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Survey and Health Assement of the exposue of 2-year-olds to chemical substances in Consumer Product

7 Risk Assessment

• 7.1 Selection of dose factors (NOAELs and LOAELs)
• 7.2 Use of assessment factors
• 7.3 Exposure scenarios - Method
  • 7.3.1 Route of exposure
    • 7.3.1.1 Inhalation
    • 7.3.1.2 Dermal uptake
    • 7.3.1.3 Daily ingestion
  • 7.3.2 Previous relevant product surveys
  • 7.3.3 Exposure scenarios
    • 7.3.3.1 Exposure times used
    • 7.3.3.2 Use of summer and winter scenarios
    • 7.3.3.3 Anatomic data
  • 7.3.4 Methods for the calculation of exposure
    • 7.3.4.1 Calculation of exposure
• 7.4 Calculation of risk - method
  • 7.4.1 Combination effects
• 7.5 Significant sources of exposure
  • 7.5.1 Indoor climate
    • Gunnersen et al. (2009) state that the greatest exposure to PCB used in building joints occurs due to realease to the indoor air. Gunnersen et al. (2009) conclude that although primarily non-dioxin-like PCBs are released to the indoor air, there will also be exposure to dioxin-like PCBs. The relevance of this finding should be considered in view of the fact that there is always more or less concomitant exposure to non-dioxin-like PCBs and dioxin-like PCBs.
    • The present report focusses on the dioxin-like PCBs because there is documented evidence of their endocrine disrupting effects.
  • 7.5.2 Other sources of exposure
    • 7.5.2.1 Phthalates, generally
    • 7.5.2.2 Parabens in general 99-96-7
• 7.6 Calculation of exposure
  • 7.6.1 Exposure calculations for the selected substances via the indoor climate
    • 7.6.1.1 Dust
    • 7.6.1.2 Air
    • 7.6.1.3 Comparison of dust and air
    • 7.6.1.4 Total contribution from the indoor climate
• 7.7 Risk assessment of the individual substances
  • 7.7.1 DIBP, di-isobutyl phthalate, 84-69-5
    • 7.7.1.1 NOAEL, AF and DNEL
    • 7.7.1.2 General exposure
    • 7.7.1.3 Exposure to DINP from foods
    • 7.7.1.4 Exposure from consumer products
    • 7.7.1.5 Exposure from indoor climate
    • 7.7.1.6 Combined exposure and risk
  • 7.7.2 DBP, dibutyl phthalate, 84-74-2
    • 7.7.2.1 NOAEL, AF and DNEL
    • 7.7.2.2 General exposure
    • 7.7.2.3 Exposure to DBP from foods
    • 7.7.2.4 Exposure from consumer products
    • 7.7.2.5 Exposure from indoor climate
    • 7.7.2.6 Combined exposure and risk
  • 7.7.3 BBP, benzyl butyl phthalate, 85-68-7
    • 7.7.3.1 NOAEL, AF and DNEL
    • 7.7.3.2 General exposure
    • 7.7.3.3 Exposure to BBP from foods, etc.
    • 7.7.3.4 Exposure from consumer products
    • 7.7.3.5 Exposure from indoor climate
    • 7.7.3.6 Combined exposure and risk
  • 7.7.4 DEHP, diethylhexyl phthalate, 117-81-7
    • 7.7.4.1 NOAEL, AF and DNEL
    • 7.7.4.2 General exposure
    • 7.7.4.3 Exposure from foods
    • 7.7.4.4 Exposure from consumer products
    • 7.7.4.5 Exposure from indoor climate
    • 7.7.4.6 Combined exposure and risk
  • 7.7.5 DINP, di-isononyl phthalate, 28553-12-0
    • 7.7.5.1 NOAEL, AF and DNEL
    • 7.7.5.2 General exposure
    • 7.7.5.3 Exposure to DINP from foods
    • 7.7.5.4 Exposure from consumer products
    • 7.7.5.5 Exposure from indoor climate
    • 7.7.5.6 Combined exposure and risk
  • 7.7.6 Prochloraz, 67747-09-5
    • 7.7.6.1 NOAEL, AF and DNEL
    • 7.7.6.2 Exposure from food
    • 7.7.6.3 Combined exposure and risk
  • 7.7.7 Tebuconazole, 107534-96-3
    • 7.7.7.1 NOAEL, AF and DNEL
    • 7.7.7.2 Exposure from food
    • 7.7.7.3 Combined exposure and risk
  • 7.7.8 Linuron, 330-55-2
    • 7.7.8.1 NOAEL, AF and DNEL
    • 7.7.8.2 Exposure from food
    • 7.7.8.3 Combined exposure and risk
  • 7.7.9 Vinclozolin
    • 7.7.9.1 NOAEL, AF and DNEL
    • 7.7.9.2 Exposure from foods
    • 7.7.9.3 Combined exposure and risk
  • 7.7.10 Procymidone
    • 7.7.10.1 NOAEL, AF and DNEL
    • 7.7.10.2 Exposure from foods
    • 7.7.10.3 Combined exposure and risk
  • 7.7.11 Dioxins and dioxin-like PCBs
    • 7.7.11.1 NOAEL, AF and DNEL
    • 7.7.11.2 Exposure from foods
    • 7.7.11.3 Combined exposure and risk
  • 7.7.12 Non-dioxin-like PCBs
    • 7.7.12.1 Risk assessment
  • 7.7.13 DDT
    • 7.7.13.1 NOAEL, AF and DNEL
    • 7.7.13.2 Exposure from foods
    • 7.7.13.3 Combined exposure and risk
  • 7.7.14 Propyl-, butyl-, and isobutylparaben
    • 7.7.14.1 Propylparaben, 94-13-3
    • 7.7.14.2 NOAEL, AF and DNEL
    • 7.7.14.3 Butylparaben, 94-26-8
    • 7.7.14.4 Isobutylparaben, 4247-02-3
    • 7.7.14.5 Exposure to parabens from consumer products
    • 7.7.14.6 Exposure from indoor climate
    • 7.7.14.7 Combined exposure and risk
  • 7.7.15 Bisphenol A, 80-05-7
    • 7.7.15.1 Exposure from foods etc.
    • 7.7.15.2 Exposure from consumer products
    • 7.7.15.3 Exposure from indoor climate
    • 7.7.15.4 Combined exposure and risk
• 7.8 Cumulative risk assessment of potential endocrine-like substances
  • 7.8.1 Risk assessment, overview summary
    • 7.8.1.1 Summer scenario
    • 7.8.1.2 Winter scenario
  • 7.8.2 Risk assessment, total for antiandrogenic substances
  • 7.8.3 Risk assessment, total for oestrogenic substances
  • 7.8.4 Risk assessment totalled for oestrogenic and antiandrogenic substances
  • 7.8.5 Discussion and conclusion

7.1 Selection of dose factors (NOAELs and LOAELs)

The emphasis of the cumulative risk assessment in this project is on substances with endocrine disrupting effects. Thus the choice was made to base the assessment on NOAELs (No Observed Adverse Effect Levels) and LOAELs (Lowest Observed Adverse Effect Levels) from animal experiments that have shown endocrine disrupting effects. The used NOAELs/LOAELs do not come from the critical effect of the substances, which would normally be used in the surveying reports of the Danish Environmental Protection Agency. The aim has been to select NOAELs/LOAELs that are used for endocrine disrupting effects in EU risk assessments, EFSA opinions, or other official risk assessments. In many cases the employed results come from studies where the effects have been observed after the animals have been exposed to the substances during the foetal stage. One can question the assumption of whether 2-year-old children can be expected to be equally sensitive towards endocrine disrupting effects as in the foetal stage. There is insufficient knowledge about this relationship at the present time. As long as there are no counterarguments to this, use of NOAELs/LOAELs from experiments on exposure in foetuses to formulate the risk assessment of the exposure of 2-year-old children is deemed a reasonable (although careful) approach to the problem.

7.2 Use of assessment factors

In the previous surveying projects (among others the surveying projects from 2008 and prior to that), calculation of the Margin of Safety (MoS) was employed in the risk assessment of the measured exposure concentration/dose in the individual experiment.

Instead, REACH uses a Derived No Effect Level (DNEL) value calculated on the basis of NOAEL (or similar) and relevant assessment factors.

The DNEL value can be determined on the basis of dose factors (dose descriptors) such as NOAELs or LOAELs, corrected using several assessment factors (AF). The assessment factors to be used will depend on which study the dose factor is based. The endpoint-specific DNEL value is then calculated from this (ECHA, May 2008 – R8).

The endpoint-specific DNEL value is determined on the basis of the formula:

Endpoint-specific DNEL

NOAELcorr is the corrected NOAEL value, i.e. the carefully selected NOAEL value on the basis of which the DNEL value is calculated (NOAEL corrected, R8). An LOAEL value is used instead of an NOAEL value in certain cases where an NOAEL value has not been determined.

The employed assessment factors and DNEL values are evidenced by the substance review in chapter 7.7. The assessment factors are determined based on the principles outlined in the REACH guidelines. They are adjusted to the scenario with 2-year-old children as the target group. The assessment factors employed in the calculations are given in the table below.

Table 7.1.The assessment factors (AF) employed in the calculation of DNEL.

7.3 Exposure scenarios - Method

The focus of the project is 2-year-old children's total exposure for chemical substances from consumer products, foods and the indoor climate. Exposure calculations for the selected substances have been made on the basis of the analyses that have been made for products relevant to 2-year-olds in this project, analyses of relevant products made in prior surveying projects as well as estimates of the exposure from cosmetic products, foods and the indoor climate.

Realistic worst-case exposure scenarios have been devised for the consumer products based on the EU REACH Guidance Document for risk assessments (REACH “Guidance on information requirements and chemical safety assessment” (ECHA, May 2008)) as well as “Children's toys fact sheet:^[16] to assess the risks for the consumer” from RIVM (Bremmer & Veen, 2002)^[17]. The scenarios are based on calculations of the use and predictable other uses of the products. The exposure assessment is (depending on the product type and chemical substance) based on sucking on/ingestion of the product, dermal contact and/or inhalation of volatile substances from the product or from chemical substances in the indoor climate. The exposure from the indoor climate is based on data from the literature.

For foods the starting point is 2-year-olds average food ingestion.

7.3.1 Route of exposure

7.3.1.1 Inhalation

In the risk assessment, calculations have been made for exposure to chemical substances via the indoor climate. The basis has been literature studies on chemical substances in dust and the indoor climate. In addition, 2-year-olds can be affected by inhalation of substances from several products, e.g. linens, clothing, etc.

7.3.1.2 Dermal uptake

Skin exposure (dermal exposure) must be considered relevant for all the selected product groups, as children have direct skin contact with all these products. The case considered is exposure via skin on varying places of the body, as clarified in the exposure calculations.

7.3.1.3 Daily ingestion

Ingestion via the mouth (oral exposure) is assumed to be the potentially largest problem for 2-year-olds. This age group is known for putting things in their mouths. Furthermore, they suck on their fingers. Thereby they can transfers any possible depositing from the fingers to the mouth, after they have been in contact with the products. Ingestion by these means is considered to be relevant for all product groups.

7.3.2 Previous relevant product surveys

The first phase of the project will review prior surveys/analyses of products that are relevant for 2-year-olds. The product types that the substances occur in are listed below:

The relevant, selected substances are found in:

• Baby/children duvets
• Swimming pool
• Beach ball
• Shower curtain
• Car tires for sandbox
• Books (of foam plastic)
• Indoor climate in the children's room
• Indoor climate – carpets, impregnating agents, dust, vinyl wallpaper
• Indoor climate day-care institution – laminating materials
• Scented toys
• Floor jigsaw
• Wrapping paper
• Play bags
• Toys - miscellaneous
• Lunch boxes
• Make up
• Masks
• Plasticine
• Baby changing mats/cushions
• Shoe care products
• Bottle feeder
• Swimming board
• Clothes
• Toilet paper.

The exposure for the relevant substances in these product types is thus combined with the exposure from the analysed products in this project.

For some of the products only content analyses and no migration analyses exist. Only data from migration analyses have been used in order to aovid overestimating the exposure, as this gives a more accurate assessment of the oral ingestion. Due to this lack of migration data, relevant contributions, have not been included in the total calculations,

7.3.3 Exposure scenarios

7.3.3.1 Exposure times used

Below, data has been collected for relevant exposure times (Table 7.2) for the product groups analysed in this project, as well as for the product types previously analysed.

On the basis of the available studies, realistic worst case-values have been determined for the later exposure calculations. Suitable exposure periods have been found in particular in Bremmer & Veen (2002) and DTI (2002).

Because the studies are structured differently, for the stated time intervals the best suitable category from the reference has been used, e.g. Bremmer & Veen (2002) have only one category for "pacifier”, "teething ring", “plastic toy” and “other objects”. This means that for soft toys the same time is used as for "other objects" because most soft toys that children sleep with do not belong to the category "plastic toys".

The statements in "Ingestion, 15 minutes per day (Bremmer & Veen, 2002)” of, for example, junior bedding (saliva) are average values for children (19-39 months) that suck on “other objects”. This means that the value does not represent the worst case in the group, but an average of the time that children - who put things in their mouth – have other objects in their mouth.

The corresponding values from the other study (DTI, 2002) have also been entered in the table. A total statement shows that 2-year-olds (24-36 months) sit with objects in the mouth at the most 7:42 hours/day in the daily hours, excluding eating periods and including periods with a pacifier (DTI, 2002). The corresponding average time for 2-year-olds is 1:39 hours/day, which attests to the fact that there are large individual differences.

For migration from articles, REACH R 17 (R17.3) refers to Van Engelen et al (2006). Due to the limited number of surveys and the large variations in the data, it is generally recommended to use an exposure time (sucking time) of 3 hours for toys (and other objects) that children of 0-3 years put in their mouth.

Based on the above principle and recommendations, the existence of identical categories has been taken into account in the exposure calculations, in such a way that the total oral exposure of toys and other objects together gives at most 3 hours/day, i.e. excluding pacifiers, since these are also used when sleeping. Similalry, a correction has been made for the overlap between the groups “packaging for bath soap” and “non-slip figures and mats for the bath” so that the exposure for these two groups is in total 30 min. for the bath period.

Table 7.2 Reproduces the migration analyses of the analysis programme.

Table 7.2 Overview of the relevant migration analyses compared with the exposure period

In summary, the overall times considered for a 2-year-old child's day:

• It is assumed that 2-year-old children sleep approx. 12 hours per day.
• It is assumed that 2-year-old children suck on things 11 hours per day (including pacifiers). According to Bremmer & Veen (2002), 2-3-year-old children suck on miscellaneous items at most about 11 hours per day.
• It is assumed that of the 11 hours, the 2-year-old uses about 2 hours to eat and dress.
• It is assumed that 2-year-old children bathe approx. ½ hour per day.
• There is no available information on the remaining last half hour of the day, but it is assumed that the 2-year-old is busy with another activity other than eating, bathing, playing, getting dressed and sleeping, which is included in the scenarios.

According to the CASA report (Hagendorn-Rasmussen, 2008) only a few cases have been observed in which 2-year-old children play with one item for more than half an hour per day. For the calculations, the toy with the highest exposure (migration value) has been used. This is because the data constitutes a basis of random samples and not a representative market analysis. The data basis thus gives no knowledge about the highest concentrations of the substance in the products on the market; therefore the highest migration value is used to ensure a realistic worst case. The highest migration value is therefore used as the worst-case representative for all toys throughout the day.

The majority of the previous surveys on phthalates in toys originate from before 2007, when the statutory order on phthalates came into force. In this investigation, the decision to use results from the previous surveys of toys is a conscious choice. This is despite the fact that some of the toys would be banned today because the phthalate concentrations exceed the allowed threshold limit. This decision was taken because it is realistic to believe that toys purchased prior to 2007 will still be in use in Danish homes. Toy products purchased today do not give the same exposure, becasue new toys must comply with the statutory order on phthalates. However, dermal exposure from phthalates other than DEHP, DBP and BBP can still occur if the 2-year-old plays with toys suitable for children above the age of 3, since these three phthalates are the only ones banned in all toys. The regulation on the phthalates DINP, DIDP and DNOP apply exclusively to toys that children are able to put into the mouth (i.e. the toy is smaller than a certain size).

Two-year-olds can be exposed even if they are not holding the toys in their hands. For example, this could be via inhalation, if the toy releases substances to the immediate inhalation zone, or the indoor air. Inhalation of evaporated phthalates (i.e. that contained in the indoor climate) is not generally considered to be the main exposure source. The ingestion of phthalates via dust is considered to contribute to the oral uptake. These factors in addition to the general lack of data on the evaporation of substances from toys means that only dermal uptake and oral ingestion have been included in the calculations.

If the 2-year-old holds the toy in their hand, exposure occurs not only via dermal uptake but also when the 2-year-old sucks on their fingers, which is something they do a lot. This means that we assume that the entire quantity of substance that is transferred to the fingers will either be taken up via the skin or will be sucked off the fingers. To avoid overestimating the amount ingested, it is assumed in the calculations that dermal contact with toys is at most 9 hours (the time that a 2-year-old is in contact with toys during the day) and oral ingestion occurs over 3 hours per day (the maximum time that a 2-year-old sucks on toys). A 2-year-old does not normally suck on as many things as an infant. This is accounted for in the calculations by assuming that they suck on an area that is smaller than that of the dermal contact. It is assumed and included in the calculations that the 2-year-old sucks on 50% of the area that they have dermal contact with.

7.3.3.2 Use of summer and winter scenarios

As there is a difference in the behavioural patterns of 2-year-olds in the summer half-year and in the winter half-year, a summer scenario and a winter scenario have been considered in order to include the most realistic exposure during both seasons.

It has been decided that the scenarios encompass the following:

The summer scenario encompasses:

• Contact with sunscreens
• Contact with rubber clogs (no socks are worn)
• Dermal contact with toys for 9 hours in the summer
• Ingestion of 50 mg dust (US EPA states this value for the summer scenario).

The winter scenario encompasses:

• Dermal contact with toys for 6 hours in the winter
• Contact with jackets/mittens for 3 hours.
• Ingestion of 100 mg dust (US EPA states this value for the winter scenario, when one is more indoors).

In addition both the summer and winter scenarios contain the same remaining elements, i.e.:

• Ingestion of foods
• Contact with objects other than toys, i.e. moisturising cream, bath articles and other textiles aside from winter clothing (jackets/mittens).

7.3.3.3 Anatomic data

For the exposure scenario for the risk assessment, a series of data on frequency of use, body surfaces exposed, etc. have been collected. These are given in Table 7.3. Anthropometric data (body weight, skin areas, etc.) have been used for the calculations of the exposure per kg bodyweight per day, as assumed in Bremmer & Veen, 2002. Average data for the anatomic data have been used for exposure calculations as agreed with the Danish Environmental Protection Agency. These are given in the column “used”.

Table 7.3 Overview of other data for use in the exposure scenarios for 2-year-olds

The exposure scenarios that are to be calculated are chosen on the basis of the existing results as well as the results from the analyses in this project.

7.3.4 Methods for the calculation of exposure

For the substances from the screening analyses a “Tier 1 exposure assessment” has been performed as explained in the REACH guidelines for risk assessment. This Tier 1 exposure assessment has only been performed on the substances where a value was measured from the screening analyses. A direct value cannot be measured for all the substances identified via the screening analyses, because the measurement requires that the substance be found as a reference substance in the analysis laboratory's database. This requirement was not fulfilled for all of the substances. The Tier 1 exposure gives a very rough estimate of the children's exposure, since it assumes 100% migration and 100% uptake of all substances. More detailed exposure calculations are performed for the selected substances listed in chapter 3.1.

The following chapters describe how the exposure via inhalation, dermal contact and oral contact was calculated.

7.3.4.1 Calculation of exposure

Exposure at inhalation

The exposure of 2-year-olds via the respiratory passages occurs primarily indirectly via the indoor climate or via toys that release volatile substances.

For assessment of the exposure, the general equations described in the REACH document “Guidance on information requirements and chemical safety assessment” (ECHA, May 2008) have been employed.

The exposure is calculated according to the formula “Equation 15-2” from the REACH Guidance document, Chapter R.15 “Consumer exposure estimation” (ECHA, May 2008):

where

The parameters used for the calculation of the exposure via inhalation for 2-year-old are described in Table 7.2 and Table 7.3.

Dermal exposure

The exposure of the skin occurs by direct contact with the products, e.g. when the toy is held in the hand, when the clothes are worn on the body, when not wearing socks, when the child falls asleep with its cheek on its soft toy, etc. The chemical substances can come in contact with the skin via sweat. The results from the migration analyses (to artificial sweat) are used in the calculations.

The possible uptake via skin is calculated according to the formula “Equation 15-8” from the REACH Guidance document, Chapter R.15 “Consumer exposure estimation” (ECHA, May 2008). We have added a factor F_abs,, which is the fraction of substances that can be taken up via the skin. Thus, the calculated D_der value constitutes the actual amount of substances that can be taken up per kg BW per day.

The product Fc_prod • Fc_migr corresponds directly to the results from the migration analyses.

where

The parameters used for the calculation of the exposure via inhalation for 2-year-old are described in Table 7.2 and Table 7.3.

If there is no knowledge of the dermal uptake of a substance, then a worst case-scenario is used: The entire amount of substance that is given off to the artificial sweat in the exposure experiments will be dermally absorbed. Where data for the dermal uptake of a substance exists, this will be used.

Oral exposure

Oral exposure occurs when the 2-year-olds suck on their clothes, toys, pacifiers, etc. By oral exposure is understood the uptake in the body occurring after release (migration) of the substances from products and mixing in saliva. Uptake can occur via mucous membranes in the oral cavity or in the gastrointestinal tract.

The possible uptake via the mouth is calculated according to the formula “Equation 15-11” from the REACH Guidance document, Chapter R.15 “Consumer exposure estimation” (ECHA, May 2008). This formula however covers the direct ingestion of substances/products, which is why the equation has been adjusted to the present scenario with migration to the saliva simulant, i.e. where the 2-year-olds suck the products (and does not swallow them directly). D_oral below thus denotes the ingestion of the substance when the child sucks on the product.

The product Fc_prod • Fc_migr corresponds directly to the results from the migration analyses, where the following is used:

In REACH R 17 (R17.3) on the subject of migration from articles there is a reference to Van Engelen et al (2006). In the reference, a formula for the uptake of a substance from "sucking” (on p. 47) is given, whereby it is possible to calculate a factor for the migration of a substance from the item in the given case where no migration data exists for the release of a metal from the item. The reference focuses on the release of metals from items. This formula is not relevant in the present context, since there are no metals on the substance list and no migration of substances has been measured.

7.4 Calculation of risk - method

As explained above, the 2-year-olds can be exposed to the same substance via different routes of exposure – inhalation, dermal and oral exposure. According to the REACH Guidance document on consumer exposure (ECHA, May 2008 – R.15 p. 29), the exposure dose for the three different routes of exposure is summated to obtain the total exposure:

According to the REACH guidance document for risk assessment (ECHA, May 2008 – Part E p. 14), each case is assessed for health risks using the following formula, which calculates the Risk Characterisation Ratio (RCR) by using the Derived No Effect Level (DNEL):

If the RCR > 1 (i.e. the exposure is greater than the DNEL) then there is a risk. If the RCR < 1 then the exposure is considered to not pose any risk.

The basis for foods is normally the EFSA assessments of oral ingestion and the respective threshold values dictated in the legislation. However, in this report the above model has been used for the calculations.

7.4.1 Combination effects

Combination effects or cocktail effects denote the exposure to different substances that all have the same effects from many different sources. The Danish Working Environment Authority recommends that calculations consider a total (additive) effect if no specific information on the concurrent effects is availabsummated (the Danish Working Environment Authority, 2005). The simultaneous occurrence of several substances can have a strengthening (synergic) or weakening (antagonistic) effect. Demonstrating the existence of these effects requires rigorous studies with the appropriate detailed combinations of substances. In this project only the additive effects are included and considered.

New investigations show that combination effects of phthalates and other antiadrogenic substances can be calculated using the dose addition-concept (NAP, 2008; Benson 2009). This concept is also used here.

The total, i.e. additive risk is thus calculated by adding the individual substance RCR values together:

RCR total is thus an expression for the increased (cumulative) risk that the child is exposed to, for example, the effects from the entire group of potential endocrine disruptors with antiandrogenic effects.

It should be noted that the RCR value for the individual substance in toys is only included once. The largest RCR value for the substance in toys is selected and used in the calculation for a maximum of 9 hours. Overall this ensures that the contact with toys and individual substance is not included when the period of contact exceeds 9 hours per day .

RCR total is calculated:

• In an isolated fashion for the antiandrogenic substances (RCR total_{antiandrogenic})
• In an isolated fashion for the oestrogen-like substances (RCR total_oestrogen).

7.5 Significant sources of exposure

In the following section the significant sources of exposure for some of the prioritised substances from selected literature are discussed.

7.5.1 Indoor climate

According to Rudel et al, 2003, indoor air has been identified as one of the most significant sources of exposure to chemical substances. Indoor air appears to contain significantly higher concentrations of chemical substances than outdoor air. For young children the most important exposure pathway appears to be house dust.

A series of the selected substances are found in the indoor air as they are released by miscellaneous furniture and consumer products in the home, and can thus be measured in both the dust as well as the indoor air. Several more recent investigations on the content of potential endocrine disruptors in the indoor climate are reviewed, and the tables below give an overview of the data presented in the sources. There are most references in the open literature for the measurement of the content of phthalates in dust. Europe has for a number of years had legislation prohibiting the use of certain phthalates in toys (first a ban in toys for children aged 0-3 years, now a ban in all toys) but this is not reflected in the investigations, since phthalates in dust in the indoor climate in the US and European countries are at the same level (shown in Hwang et al, 2008, among other sources). For instance, the highest measured concentrations of DEHP have been made in Sweden (Bornehag et al, 2005).

Only one American investigation was found in which several potential endocrine disruptors were measured in both the dust indoors and the indoor air, and a few surveys on PCB in dust and indoor air. A Danish survey on PCB in Danish buildings was recently published in March 2009 (Gunnarsen et al, 2009).

Gunnersen et al. (2009) state that the greatest exposure to PCB used in building joints occurs due to realease to the indoor air. Gunnersen et al. (2009) conclude that although primarily non-dioxin-like PCBs are released to the indoor air, there will also be exposure to dioxin-like PCBs. The relevance of this finding should be considered in view of the fact that there is always more or less concomitant exposure to non-dioxin-like PCBs and dioxin-like PCBs.

The present report focusses on the dioxin-like PCBs because there is documented evidence of their endocrine disrupting effects.

Several PCB concentration measurements have been made in the indoor climate (dust and air), but most have focussed on measurements in buildings (e.g. schools) where there is awareness that the building is contaminated with PCB. The levels in these buildings can be extremely high, even above 40 µg/m3 in air and 980 µg/g in dust (Weis et al, 2003). For the exposure calculations in this project, we have chosen to use values found in common households, (Rudel et al, 2003; Gunnarsen et al, 2009). There are no investigations showing whether PCB found in day-care institutions resembles the data for common households or public buildings (which normally have a significantly higher content of PCB in dust and indoor air).

Danish values are used in the exposure calculations where possible, but these are only available for PCB and DEHP (in dust). For DEHP, the Danish value was used for the 95^th and 50^th percentile but not for the maximum value, which was not given. The maximum value of DEHP in dust (> 40,000 µg/g) comes from an investigation of household dust in Swedish homes (Bornehag et al, 2004). The same Swedish survey has lower values for both the 95^th and 50^th percentile when compared to the Danish survey (4069 and 770 µg/g in dust, respectively, (Sweden) versus 7063 and 858 µg/g, respectively, (Denmark)). The Swedish survey (346 measurements) is significantly larger than the Danish survey (23 measurements). The figures from studies on household dust in Swedish homes are used for the DBP phthtalate (Bornehag et al, 2005), as no figures are available for Danish homes.

As is apparent from the data in Table 7.4, there is a very large difference between the 50^th and 95^th percentile, and the maximum values of phthalates measured in in dust. This illustrates the large differences in the levels that exist and, thus also the levels that will occur in Danish households. Thus, exposure calculations have been made for the 50^th and 95^th percentiles, as well as for the maximum value, in order to illustrate the large range and its significance for the risk.

Table 7.4 Overview of the amounts of various potential endocrine disruptors in dust in the indoor climate.

ND = Not detected (below the detection threshold)
*) Note that some surveys provide a median value and others a 50^th percentile. This is an expression of the same value, since the 50th percentile is also called the median, a measure of centrality, i.e. the value where half of the values lie below and the other half of the values lie above. The median is thus not (necessarily) the same value as the average.

The majority of the surveys focus on the content of phthalates in the dust of the indoor climate. Two American surveys were found that measured the concentration of phthalates in the indoor air; one study that also measured other potential endocrine disruptors in the indoor air; two American surveys measuring PCB in the indoor air; and a new Danish survey that measures PCB in the indoor air. It should be noted that the measurement of the indoor air can include the airborne particles (e.g. swirled up) and gases/steam. The results are reproduced in the table below.

Table7.5 Overview of the amounts of various potential endocrine disruptors in the indoor air.

Small children have a particularly high ingestion of dust, since they crawl around on the floor, put dirty fingers in their mouth, as well as suck on toys and other objects. But this depends entirely on behaviour, hygiene and actual conditions. According to Survey Report no. 75, babies that crawl around the floor can in certain cases have a daily ingestion of dust and earth of up to 10 grams.

Normally it is estimated that children consume 200 mg earth/day when establishing earth quality-criteria (corresponding to the 95^th percentile) and 100 mg earth/day as a daily average (Note by the Kriteriegruppen, 2004; Danish Environmental Protection Agency, 2006). US EPA uses the same value of 200 mg earth/day for children as a conservative estimate, 100 mg earth/day as an average value and up to 400 mg earth/day if 95% of children are to be taken into account (95^th percentile) (Nielsen et al, 2008).

Gunnarsen et al 2009, states without referring to the sources that the different sources state that household dust exposure makes up approx. 55% in relation to ingestion of earth. US EPA has assessed that a 2½-year-old child has a daily ingestion of 100 mg household dust in the winter and 50 mg in the summer, when the child spends more time out of doors (US EPA, 1997). In Germany the estimate used is a daily ingestion of dust of 20-100 mg for 1-6-year-old children (Seifert et al in Jensen and Knudsen, 2006).

The CSTEE (Scientific Committee on Toxicity, Ecotoxicity and the Environment) has expressed in an opinion for an assessment report that it is reasonable to use a daily ingestion of earth and/or dust of 200 mg/day (CSTEE, 2003).

On the basis of using between 100 and 200 mg earth when establishing earth quality-criteria, coupled with the fact that several sources state similar values for the ingestion of household dust, it has been decided to use a daily ingestion value of 100 mg dust (for the winter scenario). A value of 50 mg household dust/day (for the summer scenario) is used in order to account for a possible lower ingestion during the summer.

7.5.2 Other sources of exposure

7.5.2.1 Phthalates, generally

The human exposure to phthalates from foods is estimated via the EFSA assessment and the report from Müller et al (2003). This estimate is aimed at Danish conditions and encompasses the group of 1-6-year-olds, to which the target group of 2-year-olds belongs.

Data on exposure have been searched for in the literature from 2003 until the present day. It should be noted that phthalates can have been replaced with other substances in the meantime, e.g. in household plastic film and screw caps, and that from 2008 lower threshold limits have been set for set-off from food contact materials and articles.

One of the references found, Schettler (2006), highlights medicinal devices as a source of phthalates due to the use of phthalate-softeners (Schettler, 2006). However, these sources must be considered as sporadic, and do not occur commonly in the 2-year-old population in general, therefore these sources have not been taken into account in this report.

Schettler (2006) also points at oven baking of plasticine as a source of inhalation of phthalates, which can be relevant for 2-year-olds. The release of phthalates from baking Sculpey and Fimo-plasticine with 3.5 and 14% phthalates, respectively, resulted in indoor air concentrations of 32-2667 µg/m3 for BBP; not detected to 6670 µg/m3 for DNOP; and 6.05-4993 µg/m3 for DEHP. At inhalation of 1 m3 in an hour, which according to the US EPA is realistic for children under 18 years (for short-term exposure), the maximum inhalation exposure to be used is 2667 µg BBP, 6670 µg DNOP and 4993 µg DEHP (Schettler, 2006).

With regard to dust, reference is made to a survey from 2004 in which the concentration of DEHP in household dust was investigated together with the content of DEHP metabolites in children's urine. No correlation was found between the amount in urine and the amount in household dust, which according to the survey indicates that household dust does not constitute a significant source of the total DEHP exposure. The age of the children examined is not stated in the survey. It makes a significant difference if one is dealing with young children, because it must be assumed that their ingestion of dust is larger than that of older children.

A second survey from 2003 found a significant correlation between exposure via air, measured with person-borne measuring devices, and release of DEP, DBP and BBP in women's urine (Schettler, 2006). This indicates that inhalation can be a significant exposure pathway for the low-molecular-weight phthalates in women, but provides no information on 2-year-olds.

A recent Norwegian survey by Rakkestad et al. (2007) has found phthalates in household dust on university premises, in schools, in day-care institutions and households related to the particle size. The most dominating phthalate is DBP, both on the PM₂₅ and the PM₁₀1⁹-fraction. The highest levels of total-phthalates were found in a children's room, a day-care institution, two schools as well as a computer room. The relative share of total-phthalates was approx. 1.1% for both particle-size fractions. Despite the fact that DBP can be found in car tires, Rakkested et al. (2007) performed an analysis on DBP in household dust and have concluded that it does not originate from car tires, but that the sources are to be found in indoor materials.

7.5.2.2 Parabens in general 99-96-7

In foods

The use of methyl-, ethyl- and propylparabens as additives in certain foods was permitted until 15 February 2008. Propylparaben has since been banned as an additive, but only methyl- and ethylparabens are still allowed, although only in the following foods:

• Jelly coat of meat products and pâté: 1000 mg/kg.
• Surface treatment of dried meat products: as much as is necessary (q.s.).
• Grain- or potato-based snacks, nuts and comfiture (except chocolate): 300 mg/kg
• Liquid supplements: 2000 mg/kg.

Parabens are not, and were not, permitted in beverages.

Parabens have the following E numbers:

• Methylparaben: E218 and E219 (Na salt).
• Ethylparaben: E214 and E215 (Na salt).
• Propylparaben: E216 and E217 (Na salt).

A rough estimate of the ingestion in the EU for adults and children has shown that an ADI of 10 mg/kg BW/day is not exceeded (NNT, 2000). In 2004 the EFSA reviewed the ADI of parabens and found that propylparaben could no longer be included in the ADI of 10 mg/kg BW/day (EFSA, 2004). The EFSA could at that time not establish an ADI for propylparaben (EFSA 1-26). The use of propylparaben in foods was thus banned after the 15 February 2008.

Parabens (4-Hydroxybenzoic acid, its salts and esters) may be used in products regulated by the statutory order on cosmetics in amounts up to 0.4% by product weight for one ester and up to 0.8% for mixtures of esters (calculated as the acid) (BEK 422, 2006).

It is very difficult to estimate the exposure via skin, since there is disagreement on how much can be absorbed via the skin. In the most recent statement on parabens by the SCCP from 2008, the industry assesses that the absorption of unreacted butylparaben is approx. 1% of the content in the formulations that come into contact with the skin (SCCP, 2008). It is thought that the skin is capable of converting parabens to conjugated metabolites, and that the metabolites can subsequently be found in the urine, but so far, no safe methods exist to correlate the amount of metabolite in the urine with oral exposure and exposure via skin (Ye, 2006).

Darbre and Harvey (2008) points to the fact that certain surveys suggest that after multiple applications on the skin, parabens may accumulate in the skin and later be absorbed therefrom, either in the unreacted form or as miscellaneous metabolites. The SCCP have in their statement chosen to disregard the survey (El Hussein et al., 2007) which the claim is based on, because the survey is thought to be vitiated by errors and omissions.

Darbre and Harvey (2008) further suggest that there are significant variations in the conversion of parabens (esterase activity) in the liver amongst individuals, which is probably reflected in the skin. Ethanol in formulations for application on skin has been shown to increase the absorption of parabens through the skin, inhibit the hydrolysis of methylparaben to p-hydroxybenzoic acid (the common metabolite of all parabens) as well as promote transformation (transesterification) of methylparaben to butylparaben.

Studies have also been performed on moisturising creams containing 2% butylparaben, where skin absorption has been shown to occur. According to current legislation, only 0.4% butylparaben is permitted as an affitive to creams which complicates the interpretation of the results (Darbre P and Harvey PW 561-78). Given the data currently available it is not possible to give accurate and meaningful quantitative estimates for exposure to parabens via the skin.

The SCCP is awaiting new data from the industry on the dermal uptake of parabens.

In consumer products

Propylparaben, butylparaben and isobutylparaben, which have been selected for exposure calculations in this project due to their oestrogen-like effects in animal experiments, are included in common cosmetic products but, from previous studies, have also been identified in makeup kits for children sold in toy stores. Parabens are thus expected to be found in products like Shrovetide/Halloween makeup, etc.

In Survey Project no. 88 on cosmetic products for children, parabens were identified in a large numbers of the 208 different cosmetic products for children, where the content labelling was reviewed (Poulsen & Schmidt, 2007):

• Methylparaben (in 79 products) – is not surveyed further here
• Propylparaben (in 70 products)
• Butylparaben (in 48 products)
• Ethylparaben (in 46 products) – is not surveyed further here
• Isobutylparaben (in 39 products).

7.6 Calculation of exposure

As described in the chapter on exposure calculations, these have been performed for a summer scenario and a winter scenario because it is assumed that there is a difference between the duration of the dermal contact with toys in the summer and winter periods, as well as a difference in the contact with other products like sunscreens and rubber clogs.

In the calculations it is assumed that there is both dermal and oral contact with the products. For toys it is assumed that there are 9 hours of dermal contact and 3 hours of oral contact (in the summer scenario). This is only valid for toys and similar items that the child alternately holds and sucks. For footwear, for example, the calculation encompasses dermal exposure but not oral intake.

For each substance, the assumptions in the calculations on pre-existing data are described. No mention was made of the weight of the products in the existing data, hence it was necessary to use an estimate of this weight in the calculations. Likewise, the percentage of the products that the 2-year-old is in contact with was estimated. It was estimated that the 2-year-old sucks an area smaller than the area of dermal contact, i.e. in the calculation it is assumed that the child sucks 50% of the area with which it has dermal contact.

Another problem is that most of the data that exists from earlier studies are quantitative analyses of the contents of the material, but not of the substances released (migration). Therefore, migration analyses have only been performed in very few cases. The migration data that is available has been used in the calculations, where applicable.

When using migration data measured over a short period (often a few hours) it is assumed that the migration from the product occurs at a constant rate. For some products this means an overestimate of the daily ingestion of the substance that migrates from the product. This will be valid for erasers and bath mats, for example, products with which there is contact for a longer period of time. The measured migration does not continue indefinitely since more substance than that contained in the product cannot migrate. For products such as toys, rubber clogs, pacifiers, jackets and mitts, the calculation results more closely reflect the actual situation, because these are product groups from which new products are used constantly, thus exhibiting new migration. Children constantly get new toys, new clothes and shoes because they outgrow the old.

There is a difference between the calculation results and the numbers that the individual surveys stated for exposure contribution from air, dust, toys and foods, for example. These numbers vary quite naturally, as a consequence of the variations in the data employed in the surveys, the measurement methods used, biological variations, and the differences in the methods used to calculate the results. For example, in the EU risk assessments (RAR) values are given for indoor air (aerosol + gas phase) that do not include indoor climate dust, whereas other sources have included the contribution from dust. In addition, there are differences in how the sources have included respirable dust (i.e. swirled up in air) and the dust that is ingested in by finger sucking.

7.6.1 Exposure calculations for the selected substances via the indoor climate

In the following chapter the exposure to the selected substances via the indoor climate is calculated. In order to calculate the risk of exposure to chemical substances from the indoor climate, the NOAEL and DNEL are used. These values are given in the chapters on the individual substances. For PCBs, only exposure has been calculated, because it is not known whether these are dioxin-like PCBs or non-dioxin-like PCBs, and the NOAEL and effects for the two substance groups are different.

7.6.1.1 Dust

For the calculations of the exposure of the 2-year-old children to the selected substances via indoor climate dust, an oral ingestion of 50 or100 mg household dust is used for the summer and winter scenario, respectively. The daily exposure per kg body weight is obtained by multiplying the 50 or 100 mg household dust by the maximum measured concentration of the substances in the household dust and dividing it by 15.2 kg, which is the average weight for a child of age 2 years. The calculations assume 100% ingestion, since it is assumed that the 2-year-old ingests the dust by finger sucking. Furthermore, when these values were discussed in chapter 7.5.1, the values were given in terms of daily oral ingestion of dust.

Not many data have been obtained concerning the question of whether all the dust is absorbed or whether some dust is excreted in an unreacted fashion. Wormuth et al (2006) refers to an older source (Hawley, 1985) in which it is stated that a matrix of earth reduces the uptake of a specific chemical to about 15% ^[20]. If this source (Hawley, 1985) is further examined, the 15% originate from dermal contact (uptake). The same source states that a matrix of earth reduces the uptake of a chemical by 50%. In the source it is stated that this factor will be different for every substance. In a more recent article on brominated flame retardants (PBDEs) and experiments on rats, it was discovered that PBDE is easily taken up from dust and distributed in rats. On that basis, the survey concludes that household dust is a source of human PBDE exposure, which it is necessary to take into account (Huwe et al, 2008). DEHP is easily taken up, and experiments on rats appear to indicate that the method of application does not matter, which implies the uptake should be the same regardles of whether ingestion is via sucking on toys or via ingestion of dust. These numbers are substantiated by Björklund et al. (2009) that used intake of between 100 and 200 mg dust/day for young children (toddlers), and 100% absorption of PFOS/PFOA from the dust that is ingested. Based on this the possibility of all the substance in the dust being taken up cannot be excluded.

Tabel 7.6 Daily ingestion of selected substances via household dust based on maximum measured values for the indoor climate.

Example calculation for DEHP:

Daily ingestion of

= 266.2 µg/kg BW/day

The RCR value exceeds 1 for DEHP, DBP and PCBs when using the maximum values (and the 95th percentile for DBP), irregardless of whether an ingestion value of 50 or 100 mg dust/day is used.

It should be noted that the stated max. concentration of PCB in dust comes from American surveys. In addition, it appears that the stated maximum values for PCBs are not normal. In the American study, measurements were made in 120 households, and the median value is stated to be below the detection threshold of 0.2 µg/g. The median is the middle value in the survey; this means that in at least half of the households the measured levels of PCB were under the detection threshold. A 95^th percentile was not given in the study.

The use of PCB has been banned for some years. A single Danish survey was found that also covers normal households. The measurements from 5 different Danish households with PCB in the building materials yielded results that are approx. 1000 times below the maximum measured American value. It should be noted, however, that the Danish study does not cover a representative sample of Danish households (it only uses measurements from 5 households), whereas the American survey, with its 120 measurements, gives a more reasonable representation of the possible differences.

For the calculations of PCB taken in via dust from Danish homes, only 5 measurements from private households were made, and no measurements were made in public buildings. In public buildings, the measured concentrations of PCB in dust have been up to 10 times higher.

The 95^th percentile:

A number of studies do not state the maximum measured concentration, but only the 95^th percentile. However, there can be significant differences between the 95^th percentile and the maximum values (Rudel et al, 2003), which can be discerned from the table, in which, according to Bornehag et al. 2004, the difference between the maximum measured value of DEHP and the 95^th percentile is a factor of 10.

The same calculation (where applicable) has thus also been performed for the 95^th percentile, provided the value is available (which is not the case for PCB, DBP, butylparaben and Bisphenol A).

Table 7.7 Daily ingestion of selected substances via household dust on the basis of measured values for the indoor climate (95^th percentile values).

When the 95^th percentile for the few Danish and Swedish studies is used for DEHP and DBP, respectively, the exposure calculations show that the RCR value is less than 1.

The 50^th percentile

The corresponding calculation has been performed using the 50^th percentile value, giving the corresponding picture:

Tabel 7.8 Daily ingestion of selected substances via household dust based on measured values for the indoor climate (50^th percentile values).

*) Note that some surveys provide a median value or a 50^th percentile. This is an expression for the same value, i.e. the value where one half of the values lie below and the other half of the values lies above.

It should be noted that the value of the 50^th percentile for PCB that was used is greater than the maximum value by a factor of 5 in the Danish study on households, but approximately 2½ times smaller than the maximum measured in a Danish public building (Gannarsen et al, 2009) that could represent some of the institution buildings which 2-year-olds stay in. In the new Danish survey only 10 random samples were performed (5 from Danish households and 5 from public buildings), which is why the measured results must be viewed with considerable reservations.

7.6.1.2 Air

According to the REACH Guidance document, Chapter R.15 “Consumer exposure estimation” (ECHA, May 2008), 2-3-year-old children inhale 7 m3 air per day.

A normal Dane spends on average 80 to 90% of the time inside (Luk luften ind, 2007). This corresponds to between 19.2 and 21.6 hours per day. 2-year-old children will often spend more time outdoors than an average Dane (some even take a nap outside). In the calculations it is assumed that 2-year-old children on average spend 19 hours inside per day and that the respirable fraction for all substances is 1 (100%). Hereafter it is possible to calculate the daily ingestion via inhalation using the formula given in Chapter 1 “Exposure Scenarious – methods”, which is reproduced below.

where

The values used in the calculations, as well as the results of the calculations are presented in Table 7.8. It can be seen that none of the substances exceed the RCR value of 1. However, the contribution from the indoor air needs to be added to the contribution via the dust in order to obtain the total exposure via the indoor climate.

Tabel 7.9 Daily ingestion of selected substances via the indoor air based on maximum measured values for the indoor climate

Example calculation for DEHP:

Daily ingestion of DEHP

= 0.36 µg/kg BW/day

The corresponding values for the 95^th and 50^th percentiles / median values are given in the table below.

Tablel 7.10 Daily ingestion of selected substances via the indoor air based on the 95^th percentile values for the indoor climate.

Table 7.11 Table . Daily intakeingestion of selected substances via the indoor air on the basis of the 50^th percentile values for the indoor climate.

Once again it should be noted that the used maximum value for PCB is greater than the maximum value measured in the Danish survey by a factor of 3, whereas the used 50^th percentile for PCB is approximately equal to the maximum value measured in the Danish survey based on private households (Gunnarsen et al, 2009). On the other hand, the maximum measurement from the Danish survey on public buildings is approx. 1.5 times greater than the values used from the American households.

7.6.1.3 Comparison of dust and air

If the daily exposure concentrations from deposited dust are compared with the daily exposure concentration from the indoor air, it can be seen that the contribution from the deposited dust constitutes the largest part of the daily exposure. For phthalates the exposure occurs mostly via the deposited dust, whereas for PCBs and butylparaben the indoor air contributes a few percent, which may also include the air-borne dust particles.

Table 7.12 Daily exposure concentration from air as percent of daily exposure concentration from dust (for the max. conc. At 100 mg dust ingestion)

7.6.1.4 Total contribution from the indoor climate

The total contribution from the indoor climate is the sum of the contribution from the dust and from the air. The total contribution from the indoor climate is given in the table below for both the 50^th percentile and the 95^th percentile.

Table 7.13 Daily contribution of selected substances via the indoor climate (dust and air) based on the 95^th percentile (or the max. value if no 95^th percentile is available) and 50 or 100 mg dust, respectively.

Table 7.14 Daily ingestion of selected materials through the indoor climate (dust and air) based on the 50^th percentile and 50 or 100 mg dust, respectively

A common factor for all the studies is the extremely large variation between the different measurements – e.g. from just detectable and up to > 40,000 µg/g DEHP in Swedish house dust. There are some households in which the concentration of phthalates is relatively high and will contribute more to the total exposure to endocrine disruptors.

7.7 Risk assessment of the individual substances

The risk assessment of the selected substances is based on the NOAEL/LOAEL values and the assessment factor (AF), that the Danish Environmental Protection Agency has chosen in conjunction with the Food Institute DTU. The NOAEL/LOAEL values are based on endocrine disrupting effects, but not on the critical effects that the Danish Environmental Protection Agency traditionally uses to make risk assessments.

The aim has been to select NOAEL/LOAEL values that are used for endocrine disrupting effects in the EU risk assessments, EFSA opinions or other official risk assessments. In many cases, the employed results come from studies where the effects have been observed after the animals have been exposed to the substances during the foetal stage. One can question the assumption of whether 2-year-old children can be expected to be equally sensitive towards endocrine disrupting effects as in the foetal stage. There is insufficient knowledge about this relationship at the current stage. As long as there is no counter-evidence for this, then the use of NOAELs/LOAELs from experiments with exposure of foetuses to formulate the risk assessment of the exposure of 2-year-old children is deemed a reasonable (although careful) approach to the problem.

The group of antiandrogenic substances comprises:

• DIBP, di-isobutyl phthalate, 84-69-5
• DBP, dibutyl phthalate, 84-74-2
• BBP, benzyl butyl phthalate, 85-68-7
• DEHP, diethylhexyl phthalate, 117-81-7
• DINP, di-isononyl phthalate, 28553-12-0
• Prochloraz, 67747-09-5
• Tebuconazole, 107534-96-3
• Linuron, 330-55-2
• Vinclozolin, 50471-44-8
• Procymidone, 32809-16-8
• PCBs
• Dioxins
• DDT.

The group of oestrogen-like substances comprises:

• Propylparaben, 94-13-3
• Butylparaben, 94-26-8
• Isobutylparaben, 4247-02-3
• Bisphenol A, 80-05-7.

The calculations and risk assessment are performed for each substance in the following section.

7.7.1 DIBP, di-isobutyl phthalate, 84-69-5

Table 7.15 Identification of DIBP

Chemical name	di-isobutyl phthalate
CAS no.	84-69-5
EINECS no.	201-553-2
Molecular formula (gross)	C16-H22-O4
Molecular structure
Molecular weight	278.3435
Synonyms	Diisobutyl phthalate, 1,2-Benzenedicarboxylic acid, bis(2-methylpropyl) ester, DIBP
Classification	Repr. Cat. 2; R61 - Repr. Cat. 3; R62 (EU, ESIS, 2009)

7.7.1.1 NOAEL, AF and DNEL

For DIBP a NOAEL of 125 mg/kg BW/day (LOAEL 250 mg/kg/d) for anti-androgenicity is chosen, based on reduced anogenital distance (AGD) and increased retention of nipples in offspring of rats exposed during pregnancy (Sallenfait et al., 2008).

The combined assessment factor is set to 100 based on a factor 2.5 for general interspecies differences, 4 for allometric scaling between rats and humans, and 10 for intraspecies differences.

Thus, DNEL for DINP becomes 1.25 mg/kg BW/day (NOAEL/AF).

7.7.1.2 General exposure

Wormuth et al. (2006) estimates a daily internal exposure of approx. 0.08-4 µg/kg BW with a median of approx. 0.8 µg/kg BW/day for 1-3-year-olds. Approx. 60% of the exposure comes from foods, 30% from sucking on things like toys and 10% from inhalation of air. Note that the data basis for assessment of the exposure from foods is very limited.

7.7.1.3 Exposure to DINP from foods

DIBP in foods can stem from the environment as well as from use in materials in contact with food.

The exposure estimate of Wormuth et al. (2006) is 60% exposure via food of an internally totalled exposure of approx. 0.08 – 4 µg/kg BW with a median of approx. 0.8 µg/kg BW/day for 1-3-year-olds. This gives a 50^th percentile of 0.48 µg/kg BW/day and a maximum exposure of 2.4 µg/kg BW/day.

Neither EFSA, Müller et al. (2003) nor the EU RAR gives data for the exposure to DIBP via foods, and therefore the Wormuth et al. estimate is used in the total calculations for this report.

7.7.1.4 Exposure from consumer products

DIBP has been found through earlier surveys and in two of the examined product groups in this project. The table below presents the products in which DIBP has been found in this project, and previously.

Table 7.16 occurrence of DIBP in consumer products

As the table shows, DIBP was found in toys that were examined from 2004 onwards, (i.e. published in the year 2004 or later, so the surveys themselves are probably from 2003 and later). The study on rubber pacifiers is from 1999.

DIBP was not included in the previous statutory order on Phthalates (BEK 786, 2006), which came into force on 16 April 2007 (BEK 1074, 2006).

Measured values and migration values

The two tables below present the measured values of DIBP in the various products previously examined, and the products studied in this project.

As the first table illustrates, migration of DIBP is only measured in rare cases in the products tested in earlier surveys.

Table 7.17 Overview of surveys analysing for content of DIBP

Click here to see Table 7.17

Table 7.18 Overview of findings of DIBP in the products analysed in this project

n.a.: Product or material not selected for analysis.

The earlier surveys have supplied information on the contents of DIBP in eight different consumer products. The measured concentrations vary between 2.9 (sword of foam plastic) and 314 mg/kg (floor jigsaw).

In baby changing mats/cushions up to 70 mg/kg of DIBP has been found (However, this value includes both DIBP and DBP, indicating that a conclusive identification had not been made). DIBP has also been found in rubber pacifiers at a level of 1 µg per pacifier.

In the earlier surveys, migration analyses were only conducted for wooden toys, an eraser and a play bag. The highest migration values were identified in wooden toys (jigsaws) and a play bag at 14 and 15 mg/kg respectively.

In this project DIBP has been identified in the outer material of a jacket at a concentration of 18 mg/kg and in a rubber clog at a concentration of 670 mg/kg. Migration analyses have been conducted for both products and the values amount to 0.04 mg/kg (outer material, jacket) and 84 mg/kg (rubber clog), respectively.

In this project five different types of rubber clogs have been analysed for phthalate contents. Phthalate content has been identified in three of the five clogs:

• DEHP
• DBP and DEHP and finally
• DIBP and DEHP

Migration analyses have been conducted on two of these rubber clogs (those with the highest contents). Here the results showed that migration of DBP and DIBP occurs (in two different rubber clogs). No migration of DEHP has been demonstrated.

Calculation of exposure - toys

For toys the highest migration value is measured at 15 mg/kg for a play bag.

As noted in the chapter “Exposure scenarios - method”, the calculations assume that dermal contact occurs with the toy for 6 hours in the winter and 9 hours in the summer and that oral ingestion occurs for 3 hours in both scenarios. The maximum level measured in toys is used as a standard value for calculations in all toys, meaning that this worst-case scenario toy is assumed to be used by the 2-year-old during the assumed contact period. Since data for dermal absorption of DIBP is lacking, data concerning DBP is used. DBP and DIBP are similar in several respects, namely in molecular structure, molecule weight and log Kow (estimate from the Danish Environmental Protection Agency), which suggest that the dermal absorptions are alike. Therefore a value of 10% absorption through the skin has been assumed.

It is furthermore assumed that the weight of the play bag is 50 g (a guess, since the value was not stated in the report), and that the 2-year-old is in contact with 10% of the surface area of the play bag and sucks on half of this area. The measured migration of 15 mg/kg is measured over a period of 4 hours and therefore the result has been corrected by a factor 4.

Hence, the value of the exposure from toys on 2-year-olds is:

Daily ingestion of DIBP from toys = dermal absorption (9 hrs) + oral absorption (3 hrs)

= 2.96 µg/kg BW/day

Similarly, a corresponding RCR value of 0.0024 (i.e. a daily ingestion less than the DNEL value of 1250 µg/kg BW/day) can be obtained.

Calculation of exposure - other objects

Exposure from other products containing DIBP may occur (in addition to the exposure from toys and the indoor climate). For instance, this could be from erasers (mainly if there are older siblings in the household), baby changing mats/cushions, pacifiers and rubber clogs. However, no migration data has been found for DIBP in either pacifiers or baby changing mats/cushions.

Eraser

In the calculations it has been assumed that there is contact with the eraser for 1 minute a day (only if any possible older siblings are doing their homework). In Survey Report no. 84 it is stated that a migration of 1.5 mg/g (per 4 hours) occurs and that the eraser weighs 21.1 g. It is assumed that there is contact with 50% of the eraser.

Baby changing mats/cushions

In Survey Report no. 90 concerning baby products, a migration analysis is conducted for baby changing mats/cushions and data is only stated for DINP, so it is assumed that there has been no migration of DIBP.

Rubber clogs

In this project, migration analyses have been conducted on rubber clogs. A migration of 84 mg/kg for DIBP is found over a period of 6 hours, which is the period of time the rubber clogs are assumed to be worn each day. The weight of the pair of rubber clogs is 64.8 g. Contact with 20-40% of the clog is assumed, as well as the worst case scenario that the child wears no socks with the clogs. Since data for DIBP is lacking, data concerning DBP is applied instead. Therefore a value of 10% absorption through the skin has been assumed. It has furthermore been assumed that the rubber clogs are used for 4-10 hours a day (both indoors as slippers and outdoors).

For the remaining objects, the exposure values are the following:

Table 7.19 Daily ingestion of DIBP from other objects based on measured migration values

Click here to see Table 7.19

7.7.1.5 Exposure from indoor climate

The exposure calculation for DIBP through the indoor climate is presented and calculated in the section concerning indoor climate and is reproduced in the table below.

Table 7.20 Daily ingestion of DIBP through the indoor climate (dust and air) based on 95^th percentile

Table 7.21 Daily exposure to DIBP through the indoor climate (dust and air) based on 50^th percentile

The result shows that the RCR value is less than 1, which indicates that there will be no risk of endocrine distrupting effects caused by exposure to DIBP through the indoor climate, whether the dust ingestion contributes 50 or 100 mg dust.

In the table below the various contributions to DIBP are summarised.

7.7.1.6 Combined exposure and risk

Table 7.22 Daily ingestion of DIBP from various sources

*) Due to a larger number of decimals in the calculations in the complete tables in section 7.88, this 0.006 is rounded up to 0.01 in Table 7.879
**) The number is not found in section 7.88, because only the max values for shoes are applied in the totalled tables in the relevant places.

The combined result for DIBP shows that the RCR value is far less than 1 and therefore, under the assumptions applied in the report, no risk has been identified in either summer or winter time as a result of the combined exposure to DIBP through foods, indoor climate, shoes and other objects included in the present survey.

7.7.2 DBP, dibutyl phthalate, 84-74-2

Table 7.23 Identification of DBP

Chemical name	Dibutyl phthalate
CAS no.	84-74-2
EINECS no.	201-557-4
Molecular formula (gross)	C16-H22-O4
Molecular structure
Molecule weight	278.3435
Synonyms	Dibutyl phthalate, 1,2-Benzenedicarboxylic acid, dibutyl ester, DBP, Elaol
Classification	REP2;R61 REP3;R62 N;R50 (List of hazardous materials)

7.7.2.1 NOAEL, AF and DNEL

For DBP an LOAEL of 2 mg/kg BW/day (no NOAEL identified) has been chosen for its antiandrogenic effects, based on effects on gamete development and development of mammary tissue in a development study in rats (Lee et al., 2004 in EFSA opinion: EFSA (2005)).

The combined assessment factor is set to 300 based on a factor of 2.5 for general interspecies differences, 4 for allometric scaling between rats and humans, 10 for intraspecies differences, and 3 for LOAEL to NOAEL.

Thus, DNEL for DBP becomes 0.0067 mg/kg BW/day (LOAEL/AF).

7.7.2.2 General exposure

Müller et al (2003) estimates a total exposure of approx. 400 µg/kg BW/day for 1-6-year-olds. Practically all of the exposure is oral, as only approx. 0.4 µg/kg BW/day can be attributed to inhalation.

Wormuth et al. (2006) estimates a daily internal exposure of approx. 0.4-40 µg/kg BW with a median of approx. 4 µg/kg BW /day for 1-3-year-olds. Approx. 55% of the exposure stems from foods, approx. 10% from ingestion of dust, approx. 2% from textiles and approx. 33% from inhalation of air. Note that the data basis for assessment of the exposure from foods is very limited.

The large difference between the two estimates could be caused by two factors:

• The Wormuth estimate is internal, meaning that only the absorbed amounts are considered.
• The Müller estimate is based on the maximal estimated exposure through the environment.

Absorption through the various exposure paths are, according to EU risk assessments and quoted by Müller et al.(2003):

• Dermal: 100%
• Oral: 100%
• Inhalation: 75%.

The RAR (risk assessment report) from the EU for DBP (European Chemicals Bureau, 2004)) which Müller quotes, states no set dermal absorption percentage, but on page 65 refers to an experiment of dermal exposure in rats, which after 24 hours results in 10-12% excretion in the urine, and 1% in the faeces. After 7 days, there is 60% excretion in the urine and 12% in the faeces, giving a total excretion of 72%. This means that absorption must range from 10 to 100%. However, on page 103, the EU RAR considers 10% dermal absorption as the worst case scenario. On the other hand, the RAR applies 100% absorption through inhalation as the default value due to lacking data. It is not known how Müller et al (2003) reaches 75%.

Therefore, in accordance with the EU RAR, the following absorptions are applied in this report:

• Dermal: 10%
• Oral: 100%
• Inhalation: 100%.

7.7.2.3 Exposure to DBP from foods

The presence of DBP in foods can originate from the environment as well as use in materials in contact with food.

Müller et al (2003) estimates a total exposure of approx. 400 µg/kg BW/day for 1 to 6-year-olds. Practically all of the exposure is oral, as only approx. 0.4 µg/kg BW/day can be attributed to inhalation. It does not show, however, how much of the oral exposure is attributed to foods. EFSA (2005) points out that over 90% of these maximal exposure values stem from the highest estimated value of exposure through the local environment, which refers to printing inks, and is thus not related to the diet itself.

Wormuth et al. (2006) estimates a daily internal exposure of approx. 0.4-40 µg/kg BW with a median of approx. 4 µg/kg BW/day for the 1-3-year-olds. Approx. 55% of the exposure stems from foods, approx. 10% from ingestion of dust, approx. 2% from textiles and approx. 33% from inhalation of air. This means that the exposure from foods can be estimated to a median of 2.2 µg/kg BW/day and a maximum of 22 µg/kg BW/day. Note that the data basis for assessment of the exposure from foods is very limited.

EFSA (2005) refers to an estimate based on “the total diet study” in the UK of an exposure through foods for adults of 60 kg at an average of 13 µg/day and the 97.5^th percentile at 31 mg/day, equivalent to 0.2 and 0.5 µg/kg BW/day for adults.

Since 2-year-olds according to the NNA(2004) (Nordic nutrient recommendations) have an energy need per body weight at approx. double that of adults, the 0.2 and 0.5 µg/kg BW/day correspond to 0.4 and 1.0 µg/kg BW/day for 2-year-olds.

EFSA (2005) also refers to another estimate based on measurements of Danish meals, in which the average and high exposures for adults were calculated at 4.1 and 10.2 µg/kg BW/day, respectively.

For the 2-year-olds this corresponds to 8.2 and 20.4 µg/kg BW/day, respectively.

Based on a principle of choosing realistic worst case results for the further calculations, an average exposure has been chosen of 8.2 µg/kg BW/day from the Danish meal survey and, as the maximal exposure from foods, 22 µg/kg BW/day from Wormuth et al. (2006).

7.7.2.4 Exposure from consumer products

DBP has been found both through earlier surveys and in some of the examined product groups in this project. The table below presents those products in which DBP has been found in this project and inearlier studies.

Table 7.24 occurrence of DBP in consumer products

As the table shows, DBP was found in toys that were examined in 2004 and onwards (meaning published in the year 2004 or later, so the surveys themselves are probably from 2003 and later). The study on plasticine is from 2002.

REACH annex XVII, entry 51 and 52 continued the prohibition of toys containing DEHP, DBP and BBP. In accordance with REACH, the concentration of DBP in a toy must not surpass 0.1% (w/w). This means that those toys examined previously could no longer be sold today due to their high concentrations of DBP. In the earlier surveys, the scented toys exceeded 0.1% DBP.

Analysis values

The two tables below display the measured values of DBP in the various products examined earlier and the products studied in this project.

As illustrated in Table 7.25, migration of DBP from the products was only measured in rare cases in the earlier surveys.

Table 7.25. Overview of earlier surveys analysing for content of DBP

Click here to see Table 7.25

Table 7.26 Overview of findings of DBP in the products analysed in this project

n.a.: Product or material not selected for analysis
n.s.: No screening result calculated

The earlier surveys have provided information on the contents of DBP in nine different consumer products. The concentrations measured were between 8 and 780 mg/kg (floor jigsaw), and up to 3500 mg/kg in an eraser (scented toy).

In print on clothes, levels up to 770 mg/kg were found. Additionally, up to 70 mg/kg (measured as DBP + DIBP) was found in baby changing mats/cushions and a higher content of DBP up to 16,000 mg/kg (i.e. 1.6%) was determined in vinyl floors.

In the earlier surveys, migration analyses for plasticine were performed solely by measuring release to the indoor climate (when “baking” plasticine in an oven). Here, release of up to 6 mg/kg was measured. The maximum concentration of DBP was measured at 200 mg/kg.

In this project, DBP has been identified in a zipper strap and a loose reflector piece from two different jackets. On the zipper strap, migration analysis showed that 0.51 mg DBP migrates per kg. In addition to this, DBP has been found in a pair of rubber clogs - at approx. 25,000 mg/kg, and a migration of 249 mg/kg during a migration period of 6 hours.

In this project five different types of rubber clogs have been analysed for phthalate contents. In three of the five rubber clogs, phthalates were identified:

• DEHP
• DBP and DEHP, and finally
• DIBP and DEHP

Migration analyses have been conducted on two of these rubber clogs (those with the highest contents). Here the results showed that migration of DBP and DIBP occurs (in two different rubber clogs). No migration of DEHP has been demonstrated.

Calculation of exposure - toys

With regard to toys no migration has been measured on any of the products, and therefore no calculations of exposure have been performed.

Calculation of exposure - other objects

Exposure from other products containing DBP can occur (in addition to the exposure from toys and the indoor climate). This could, for example, be from erasers (mainly if there are older siblings in the household), baby changing mats/cushions, clothes and rubber clogs. Exposure from a vinyl floor is assumed to be included in indoor climate data.

Eraser

In Survey no. 68 on scented toys, no measurement was made of migration of DBP from the eraser, and therefore no calculations of exposure have been performed.

Baby changing mats/cushions

In survey no. 90 on baby products, a migration analysis was conducted on baby changing mats/cushions. Only data concerning DINP were stated, so it is assumed that there was no migration of DBP.

Clothes

DBP was found in print on clothes in a survey by TÆNK (THINK, magazine), a survey by Greenpeace, and a recent Swedish survey. However, none of the surveys measured migration of DBP, and therefore no calculations of exposure have been performed.

In this project, a migration analysis has been conducted on a zipper strap from a jacket. Here, 0.51 mg DBP migrates per kg over a period of 3 hours. The calculations assume that the strap weighs 5 g, that approx. half of the strap is sucked and that, as described for “other objects”, it is sucked for 3 hours a day.

Rubber clogs

In this project, migration analyses have been conducted on rubber clogs. A migration of 249 mg/kg has been found for DBP over a period of 6 hours. The weight of the pair of rubber clogs is 69.0 g. Contact with 20-40% of the shoe is assumed, as is the idea that the child in the worst case scenario wears no socks with the shoes. It has been assumed that the rubber clogs are used for 4-10 hours a day (both indoors as slippers and outdoors). If the rubber clogs are only used as outdoor shoes, 4 hours is a realistic estimate of the exposure, but if the rubber clogs are used as slippers, an exposure period of 10 hours is not unrealistic. As stated earlier, it is assumed that 10% DBP is absorbed through the skin.

For the remaining objects, the exposure values are the following:

Table 7.27 Daily ingestion of DBP from other objects based on measured migration values

Click here to see Table 7.27

7.7.2.5 Exposure from indoor climate

The exposure calculation for DBP through the indoor climate is presented and calculated in the section relating to indoor climate, but is reproduced in the table below.

Table 7.28 Daily ingestion of DBP through the indoor climate (dust and air) based on 95^th percentile

Table 7.29 Daily ingestion of selected materials through the indoor climate (dust and air) based on 50^th percentile / median value

Based on the assumptions used in the calculation of the risk, there will be a relatively large exposure from DBP via the indoor climate. The calculations have, however, been based on studies of households in Sweden, as no Danish studies on concentrations of DBP in the indoor climate are available.

7.7.2.6 Combined exposure and risk

The table below summarises the various contributions to DBP.

Table 7.30 Daily ingestion of DBP from various sources

*) Due to a larger number of decimals in the calculations in the complete tables in section 7.88, these have smaller round-off deviations
**) The number is not found in section 7.88, because only the max values of shoes are applied in the totalled tables in the relevant places.

The combined result for DBP reveals that the RCR value is far above 1 in both the summer and winter scenarios. This is due to exposure to DBP from foods; shoes in themselves can constitue a risk using the assumptions made in the reports.

7.7.3 BBP, benzyl butyl phthalate, 85-68-7

Table 7.31 Identification of BBP.

Chemical name	Benzyl butyl phthalate
CAS no.	85-68-7
EINECS no.	201-622-7
Molecular formula (gross)	C19-H20-O4
Molecular structure
Molecule weight	312.3597
Synonyms	benzyl butyl phthalate, 1,2-Benzenedicarboxylic acid, butyl phenylmethyl ester, BBP, Palatinol BB
Classification	REP2;R61 REP3;R62 N;R50/53 (List of hazardous materials)

7.7.3.1 NOAEL, AF and DNEL

For BBP an NOAEL of 50 mg/kg BW/day (LOAEL 250 mg/kg/d) is chosen for its antiandrogenic effects, based on reduced anogenital distance (AGD) in offspring of rats exposed during pregnancy (Tyl et al., 2004 in an EU risk assessment: European Chemicals Bureau (2007)).

The combined assessment factor is set to 100 based on a factor 2.5 for general interspecies differences, 4 for allometric scaling between rats and humans and 10 for intraspecies differences.

Thus, DNEL for BBP becomes 0.5 mg/kg BW/day (LOAEL/AF).

7.7.3.2 General exposure

Müller et al. (2003) estimates an oral exposure of 5.9 µg/kg BW/day and an inhalation exposure of 0.12 µg/kg BW/day for 1-6-year-olds. The estimate for oral exposure is based on measured values in the environment (including foods).

Wormuth et al. (2006) estimates a daily internal exposure of approx. 0.02-6 µg/kg BW with a median of approx. 0.4 µg/kg BW/day. Approx. 18% of the exposure stems from foods, approx. 2% from sucking on things such as toys, approx. 75% from ingestion of dust and approx. 5% from inhalation of air. Note that the data basis for assessment of the exposure from foods is very limited.

Absorption through the various exposure paths are, according to EU risk assessments (European Chemicals Bureau, 2007) and quoted by Müller et al.(2003):

• Dermal: 5%
• Oral: 100%
• Inhalation: 100%.

7.7.3.3 Exposure to BBP from foods, etc.

BBP can be found in foods both as a result of dispersion in the environment and as a consequence of migration from materials in contact with food, in which it is used as a softener.

Müller et al. (2003) estimates an oral exposure of 5.9 µg/kg BW/day and an inhalation exposure of 0.12 µg/kg BW/day for the 1-6-year-olds. The estimate for oral exposure is based on measured values in the environment (including foods). It does not state, however, how much of the oral ingestion that can be attributed to foods.

Wormuth et al. (2006) estimates a daily internal exposure of approx. 0.02-6 µg/kg BW with a median of approx. 0.4 µg/kg BW/day for 1-3-year-olds. Approx. 18% of this exposure stems from foods, approx. 2% from sucking on things such as toys, approx. 75% from ingestion of dust and approx. 5% from inhalation of air. This means that the exposure from foods should to contribute with 0.07 µg/kg BW/day as a median and 1.1 µg/kg BW/day as the highest value.

EFSA (2005a) refers to an estimate based on data on diet and foods from the UK and Denmark, in which the exposure to BBP through foods is estimated at an average of 8 µg/day and 97.5-percentile 20 µg /kg BW/day, which for an adult corresponds to 0.1 and 0.3 µg/kg BW/day, respectively.

Since 2-year-olds according to the NNA(2004) (Nordic nutrient recommendations) have an energy ingestion per kg body weight at approx. the double of that of adults, this corresponds to 0.2 and 0.6 µg/kg BW/day respectively for the 2-year-olds.

EFSA also refers to a Danish survey that estimates an average and a high exposure for adults of 0.4 and 4.5 µg/kg BW/day, respectively.

For 2-year-olds this corresponds to 0.8 and 9 µg/kg BW/day, respectively.

Based on a principle of choosing the most realistic worst case exposures, in the further calculations the EFSA exposure numbers have been included as contributions from foods with the average 0.8 and the highest value 9 µg/kg BW/day.

7.7.3.4 Exposure from consumer products

BBP was only found in earlier surveys and has not been identified in products examined in this project. The table below states the products in which BBP has been found earlier.

Table 7.32 Occurrence of BBP in consumer products

As the table shows, BBP was found in toys that were examined in 2004 onwards (meaning published in the year 2004 or later, so the surveys themselves are probably from 2003 and later). The study on vinyl floors is from 2002.

REACH annex XVII, entry 51 and 52 continued the prohibition of sale of these toys because the concentration of BBP is too high. Plasticine had concentrations of BBP that exceeded 0.1% and according REACH, the concentration of BBP in a toy must not exceed 0.1% (w/w).

Analysis values

The two tables below display the values of BBP that were measured in the various products examined earlier.

As the table illustrates, migration of BBP is only measured in rare cases in the products tested in earlier surveys.

Table 7.33 Overview of earlier surveys analysing for content of BBP

Click here to see Table 7.33

Calculation of exposure

The earlier surveys have supplied information on the contents of BBP in two different kinds of toys - plasticine and wooden toys. The measured concentrations in plasticine are 37,000 mg/kg BBP corresponding to 3.7%. The concentration of BBP was not measured in the wooden toys.

In clothes (print on clothes) up to 22,000 mg/kg BBP has been measured and in vinyl floors up to 20,000 mg/kg BBP.

Migration analyses were performed for the earlier surveys on wooden toys and plasticine. The migration for the wooden toys was measured at 1.3 mg/kg and a migration of BBP to the indoor climate was measured of up to 1,000 mg/kg when “baking” the plasticine in the oven.

As mentioned earlier, BBP has not been identified in the products that have been examined in this project.

Calculation of exposure - toys

For toys the highest migration is measured at 1.3 mg/kg for wooden toys. The values for plasticine are not used in this context since they show release to the indoor climate and not to sweat.

As noted in the chapter “Exposure scenarios - methods”, the calculations assume that dermal contact occurs with the toy for 6 and 9 hours respectively and oral ingeston occurs for 3 hours. Furthermore, the maximum value measured in a toy is used as the standard for all toys, meaning that this worst case toy is assumed to be used during all the hours in which a 2-year-old is assumed to have contact with toys.

It is furthermore assumed that the weight of the wooden toy is 50 g (a guess, since the value is not stated in the report) and that the 2-year-old is in dermal contact with 50% of the wooden toy area and sucks on half of this area. The migration of 1.3 mg/kg has been measured over a period of 1 hour. 5% absorption through the skin is used for BBP.

The exposure from toys for 2-year-olds is thus found to be the following:

Daily ingestion of BBP from toys = oral ingestion (3 hrs) + dermal absorption (9 hrs) (summer scenario):

= 4.17 µg/kg BW/day

A corresponding RCR value of 0.008 (i.e. a daily ingestion less than the DNEL value) can be obtained.

Calculation of exposure - other objects

Exposure from other products containing BBP may occur (in addition to the exposure from toys and the indoor climate). An example could be clothes. However, no migration has been measured from clothes and therefore no calculation of exposure is performed.

7.7.3.5 Exposure from indoor climate

The exposure calculation for BBP via the indoor climate is presented and calculated in the section on indoor climate, but is reproduced in the table below.

Table 7.34 Daily ingestion of BBP through the indoor climate (dust and air) Based on 95^th percentile

Table 7.35 Daily ingestion of BBP through the indoor climate (dust and air) Based on 50^th percentile

The calculation shows that the RCR value is less than 1, which indicates that there is no risk of endocrine distrupting effects as a consequence of exposure to BBP via the indoor climate.

7.7.3.6 Combined exposure and risk

The table below summarises the various contributions to BBP.

Table 7.36 Daily ingestion of BBP from various sources

*) Due to a larger number of decimals in the calculations in the complete tables in section 7.88, these have smaller round-off deviations.

The combined result for BBP shows that the RCR value is less than 1. Based on the assumptions made, no risk exists as a result of the combined exposure to BBP through foods, indoor climate, toys and other objects included in the present survey.

7.7.4 DEHP, diethylhexyl phthalate, 117-81-7

Table 7.37 Identification of DEHP.

Chemical name	diethylhexyl phthalate
CAS no.	117-81-7
EINECS no.	204-211-0
Molecular formula (gross)	C24-H38-O4
Molecular structure
Molecular weight	390.5561
Synonyms	Bis(2-ethylhexyl) phthalate, Di(2-ethylhexyl) phthalate, DEHP, Octyl phthalate
Classification	REP2;R60-61 (List of hazardous materials)

7.7.4.1 NOAEL, AF and DNEL

For DEHP, an NOAEL of 5 mg/kg BW/day is chosen for its antiandrogenic effects, based on effects on gametes and reduced testicular weight in rats (Wolfe & Leyton, 2003 in an EU risk assessment : European Chemicals Bureau (2008)).

The combined assessment factor is set to 100 based on a factor of 2.5 for general interspecies differences, 4 for allometric scaling between rats and humans, and 10 for intraspecies differences.

Thus, DNEL for DEHP becomes 0.05 mg/kg BW/day (NOAEL/AF).

7.7.4.2 General exposure

Müller et al. (2003) estimates an oral exposure of 133.4 µg/kg BW/day, an inhalation exposure of 1.9 µg/kg BW/day and a dermal exposure of 15.9 µg/kg BW/day for 1-6-year-olds.

The oral exposure of 133.4 µg/kg BW/day is distributed between various sources in the following way:

Alternative estimates of exposure through the environment are 3.4 µg/kg BW/day, based on the measured values in the environment, and 26 µg/kg BW/day based on measured values in foods.

The estimated 100 µg/kg BW/day from the environment can be compared with the EU Risk Assessment Report (RAR), which estimates the corresponding exposure at 85 µg/kg BW/day.

Data from the EU RAR has later been used in a probability risk assessment (Bosgra et al, 2005) which has estimated the total exposure of children to 7.58-23.05 µg/kg BW/day (5-95^th percentiles) with a geometric mean of 13.19 µg/kg BW/day. The contributions to the mean of 13.19 µg/kg BW/day is distributed in the following way:

Wormuth et al. (2006) estimates a daily internal exposure of approx. 0.3-80 µg/kg BW with a median of approx. 8 µg/kg BW/day. Approx. 55% stems from foods, approx. 5% from sucking on things such as toys, approx. 37% from ingestion of dust and approx. 3% from inhalation of air. Note that the data basis for assessment of the exposure from foods is very limited.

A more recent and more precise estimate based on measurements of metabolites in the urine of 31 German 2-4-year-olds is 0.4-409 µg/kg BW/day with a median of 5.7-10.7 µg/kg BW/day and a 95th percentile of 23.4-45 µg/kg BW/day, depending on the calculation in relation to the creatinine exretion or urine volume (Wittassek et al., 2007). Boys in this age group are more exposed than girls. 1 out of 17 boys, but no girls, exceeded the TDI set by EFSA at 50 µg/kg BW/day. In total 239 2-14-year-olds were examined. The exposure is highest among the 2 to 4-year-olds and drops as they get older, though not that much within the age group of below 8 years. A few children in the age group 9 to 11-year-olds still demonstrate high exposure.

Absorption through the various exposure paths are, according to EU risk assessments (European Chemicals Bureau, 2008), and quoted by Müller et al. (2003):

• Dermal: 5%
• Oral: 100%
• Inhalation: 100%.

7.7.4.3 Exposure from foods

DEHP can be found in foods both as a result of dispersion in the environment and as a consequence of migration from materials in contact with food, in which it is used as a softener.

Müller et al. (2003) estimates an oral exposure for the 1-6-year-olds of 133.4 µg/kg BW/day out of which the 100 µg/kg BW/day are assessed to stem from foods. They also present an alternative estimate of 26 µg/kg BW/day, based on measured values in foods.

The estimated 100 µg/kg BW/day from the environment can be compared with the EU Risk Assessment Report (RAR), which estimates the corresponding exposure at 85 µg/kg BW/day.

Data from the EU RAR has later been used in a probabilistic risk assessment (Bosgra et al, 2005) which has estimated the contribution from foods to be

12.84 µg/kg BW/day (50^th percentile).

Wormuth et al. (2006) estimates a daily internal exposure of approx. 0.3-80 µg/kg BW with a median of approx. 8 µg/kg BW/day for the 1 to 3-year-olds. Approx. 55% are thought to stem from foods, giving a median of 4.4 µg/kg BW/day and a high exposure of 44 µg/kg BW/day.

EFSA (2005b) refers to an estimate based on a “total diet” survey from the UK, in which the exposure to DEHP from foods is estimated at an average of 2.5 µg/day BW/day and a high exposure of 5 µg /kg BW/day for adults.

Since 2-year-olds according to the NNA(2004) (Nordic nutrient recommendations) have an energy consumption per kg body weight at approx. the double of that of adults, the 2.5 and 5 µg/kg BW/day for adults correspond to 5 and 10 µg/kg BW/day, respectively, for the 2-year-olds.

EFSA also refers to an estimate based on analyses of Danish meals, in which the exposure for adults was found to be 4.3 and 15.7 µg/kg BW/day for the uppermost average interval and the high percentile respectively.

For the 2-year-olds this corresponds to 8.6 and 31.4 µg/kg BW/day, respectively.

Based on a principle of choosing realistic worst case values to be used in the further calculations, the 8.6 µg/kg BW/day from the Danish meal survey is used as the median and the 44 µg/kg BW/day from Wormuth et al. is used as the high exposure via foods.

7.7.4.4 Exposure from consumer products

DEHP has been found in earlier surveys, and in a few of the examined product groups in this project. The table below states the products in which DEHP has been found in earlier surveys, and in this project.

Table 7.38 occurrence of DEHP in consumer products

As the table shows, DEHP was found in quite a few toys that were examined in 2004 and onwards (meaning published in the year 2004 or later, so the surveys themselves are probably from 2003 and later). Plasticine, shower curtains, floorings with vinyl and vinyl wallpaper were examined in 2002 (2001).

A new statutory order on Phthalates (BEK 855, 2009) came into effect in September 2009, which continued the prohibition of sale of those toys examined previously due to their high concentrations of DEHP. In accordance with the current statutory order on phthalates, the concentration of DEHP must not exceed 0.1% (w/) in toys.

In this project we have chosen to include the results from the earlier surveys of toys in spite of changes in the legislation. The reason for this is partly that families with several children may have bought toys years ago that their 2-year-olds are playing with today, and partly that the concentrations found in the earlier surveys of toys do not in all instances exceed the value 0.1%. That means that in several instances the levels in question would also be legal today. However, six out of 25 toy items in the earlier surveys do exceed the today set limit of 0.1% DEHP.

Analysis values

The two tables below display the measured values of DEHP in both the various products previously examined and the products from this project.

As the first table illustrates, migration of DEHP is only measured in rare cases in the products tested in earlier surveys.

Table 7.39 Overview of earlier surveys analysing for content of DEHP

Click here to see Table 7.39

Table 7.40 Overview of findings of DEHP in the products analysed in this project

n.a.: Product or material not selected for analysis.
n.s.: No screening result calculated
n.d.: Material not demonstrated above the detection threshold

Calculation of exposure

The earlier surveys provide information on the content of DEHP in 25 different types of consumer products. The measured concentrations vary from 1.9 mg/kg (mask of foam plastic) to as high as 191,000 mg/kg DEHP in a football.

In print on clothes, levels are found up to 170,000 mg/kg corresponding to 17%. Furthermore, levels have been found between 6100 and 440,000 mg/kg (corresponding to 44%) in erasers and levels of DEHP in indoor climate dust have been found at approx. 7-8000 mg/kg (see section on indoor climate for additional details). Carpet tiles, vinyl floorings and vinyl wallpaper contain large quantities of DEHP, the exact percentages being 9%, 16% and 10%, respectively. Small quantities of DEHP have also been identified in a lunch box. Finally, DEHP content has been identified in bath soap packaging.

Migration analyses were only performed in the earlier surveys on lamination materials, play bags, erasers, toys (Bratz doll), plasticine, wooden toys and bath soap packaging. Here the migration falls between 2.4 (play bags) and 5.1 (wooden toys) mg/kg. The migration of the 5.1 mg/kg was measured in a hammer bench with 6 “nails”, executed in beech, but it is not stated from where precisely in the hammer bench DEHP migrates. For example, it might stem from a rubber band on the plate, where the wooden nails are placed or some other place the child will not suck at frequently. For that reason this value is ignored in the basis for the calculations. The highest value, of 23 mg/kg, is found for plasticine but describes release to the indoor climate. The migration of the 2.4 mg/kg from a play bag has therefore been applied as the highest migration measured in the earlier surveys.

In the analyses in this project DEHP has been identified in labels on mittens with concentrations of up to 14.7%, in loose reflector pieces on jackets up to 21.3%, in rubber clogs up to 1.6%, in the coverage of pacifiers in small concentrations (275 mg/kg), in soap packagings up to 8% and in shower mats up to 12.9% DEHP. On most of these products migration analyses were also performed, showing that in rubber clogs and pacifiers no migration occurs beyond the detection threshold (detection threshold 2 mg/kg). The migration is highest for shower mats, in which it is 25 mg/kg.

Calculation of exposure – toys

For toys, the highest migration value has been measured at 2.4 mg/kg for play bags. A higher migration was measured from plasticine (into the indoor air, but this value is assumed to be included in the values from the indoor climate (see section on indoor climate). The value from the play bag stems from an earlier survey. It is applied in spite of the fact that the total concentration in this play bag exceeds the current limit for DEHP in toys of 0.1%, because it is assumed that the play bag might have been bought before the limit value came into effect and may still be used.

As noted in the chapter “Exposure scenarios - methods”, the calculations assume that dermal contact occurs with the toy for 6 and 9 hours (winter and summer scenarios) and oral ingestion occurs for 3 hours. The maximum level measured in a toy is furthermore used as the calculation value for all toys, meaning that this worst case value for toys is assumed to be used during all the hours that a 2-year-old is assumed to have contact with toys.

It is furthermore assumed that the weight of the play bag is 50 g (a guess, since the value is not stated in the report) and that the 2-year-old is in dermal contact with 10% of the area of the play bag containing migrating DEHP and sucks on half of this area. The measured migration of 2.4 mg/kg is measured over a period of 4 hours and therefore the result needs to be corrected by a factor 4. Absorption of 5% is used for dermal absorption.

Hence, the value of the exposure from toys on 2-year-olds becomes (summer scenario):

Daily ingestion of DEHP from toys = oral ingestion (3 hrs) + dermal absorption (9 hrs)

= 0.38 µg/kg BW/day

A corresponding RCR value of 0.008 (i.e. a daily ingestion less than the DNEL value) can be obtained.

Calculation of exposure – other objects

Exposure from other products containing DEHP can occur (in addition to the exposure from toys and the indoor climate). This could be, for example, from erasers (mainly if there are older siblings in the household), the shower mat in the bath tub, bath soap packaging and jackets/mittens. DEHP has furthermore been identified in lunch boxes, but this contribution is assumed to be contained in the figures from foods.

Eraser

In these calculations it is assumed that there is contact with the eraser for 1 minute a day (only when possibly older siblings are doing their homework). In survey no. 84 (Svendsen et al, 2007), it is stated that a migration of 1 mg/g (per hour) occurs and that the eraser weighs 14.4 g. It is assumed that there is contact with 50% of the eraser.

Shower mat

Shower mat 7-1 has a migration of 25 µg/g and weighs 202.2 g. The calculations assume that there is contact with 25% of the area of the shower mat. Instead, an area the size of a baby’s bottom might be used, i.e. 0.038 m2, but at some point parts of legs and hands will also touch the shower mat. A contact period of 30 minutes is assumed, meaning the period of time the child sits on the mat in the bath and since everything takes place in water, a retention factor of 0.01 is applied. The retention factor has been introduced by the SCCNFP to account for products that leave behind a residue when used and washed off after use, i.e. for shampoo products, body shampoos and similar rinse-off products (SCCNFP 0690 (2003)). Since this exposure is in the bath tub it is permissible to use the retention factor in this context too. It is only assumed that dermal exposure occurs, i.e. the result is corrected because only 5% of DEHP is absorbed through the skin.

Bath soap packaging

Soap packaging no. 6-5 has a content of DEHP of 80 mg/g corresponding to 8%. The Danish Safety Technology Authority has assessed this soap packaging to be a toy, so the product thus violates the limit of 0.1% set by the statutory order on Phthalates. The migration to sweat has been measured at 2 µg/g (during ½ hour). No migration to saliva has been demonstrated (i.e. the value is below the detection threshold), so only dermal absorption has been assumed. The soap packaging weighs 4 g. A contact period of 30 minutes is assumed. The child is assumed to have contact with 75% of the area of the bath packaging, which is not very large. It might be relevant to apply a dilution factor as well, since the exposure occurs in a bath tub, but because playing often occurs above the water, a worst case calculation has been made without dilution.

The calculation appears in the table below and shows an RCR value for the soap packaging of 0.0002, i.e. far below 1 and therefore not posing a risk. The value furthermore represents the smallest contribution of DEHP from the consumer products. This small contribution has not been included in the complete calculations because the product is now illegal. and is expected to be withdrawn from the market.

Jackets/mittens

The highest migration measured is 0.68 µg/g (during 3 hours) from the label with product name on a mitten. This mitten weighs a total of 8 g. It is assumed, as described in the section “Exposure calculations – method”, that the 2-year-old maximally sucks on mittens for 2 hours and 58 minutes (rounded up to 3 hours) each day. It may not be entirely realistic that the 2-year-olds suck on the label with the product name in the middle of the mitten, but DEHP has also been found (a migration of 0.27 µg/g) in the outer material of a mitten. The child is assumed to suck on approx. 5% of the weight of the mitten.

For the remaining objects, the exposure values are the following:

Table 7.41 Daily ingestion of DEHP from other objects based on measured migration values

* = dilution factor through bath water

F_abs = Relative amount of product taken up via dermal contact. Is used solely for products where the only factor to be considered is dermal contact (such as the shower mat). Oral absorption must be accounted for in all other products and the absorption percentage is thus 100%

7.7.4.5 Exposure from indoor climate

The exposure calculation for DEHP via the indoor climate is presented and calculated in the section on indoor climate, but is reproduced in the table below.

Table 7.42 Daily ingestion of DEHP through the indoor climate (dust and air) based on 95th percentile

Table 7.43 Daily ingestion of DEHP through the indoor climate (dust and air) based on 50^th percentile

The calculation shows that at least 95% of the 2-year-olds will be exposed to concentrations of DEHP via the indoor climate that,with the assumptions made, will not pose a risk if 100 mg of dust is consumed per day. Note however that in bigger surveys than the Danish (which forms the basis of these calculations) levels of DEHP have been seen in the indoor climate high enough to pose a risk for 2-year-olds with the assumptions made.

7.7.4.6 Combined exposure and risk

In the table below, the various contributions to DEHP are summarised. The tables are distributed according to the summer and winter scenarios as described earlier.

Table 7.44 Daily ingestion of DEHP from various sources

The combined result for DEHP shows that the RCR value is above 1 in both the summer and winter scenarios when the 95^th percentile is considered, but that the RCR is below 1 when the 50^th percentile is considered.

7.7.5 DINP, di-isononyl phthalate, 28553-12-0

Table 7.45 Identification of DINP.

Chemical name	Di-isononyl phthalate
CAS no.	28553-12-0
EINECS no.	249-079-5
Molecular formula (gross)	C26-H42-O4
Molecular structure
Molecular weight	418.6093
Synonyms	1,2-Benzenedicarboxylic acid, diisononyl ester, DINP, Palatinol DN
Classification	-

7.7.5.1 NOAEL, AF and DNEL

For DINP an NOAEL of 276 mg/kg BW/day (LOAEL 742 mg/kg/day) is chosen for its antiandrogenic effects, based on reduced testicular weight in mice (Aristech, 1995 in an EU risk assessment: European Chemicals Bureau (2003)).

The combined assessment factor is set to 175 based on a factor of 2.5 for general interspecies differences, 7 for allometric scaling between mice and humans, and 10 for intraspecies differences.

Thus, DNEL for DINP becomes 1.6 mg/kg BW/day (NOAEL/AF).

7.7.5.2 General exposure

Müller et al. (2003) estimates a total oral exposure of 63.4 µg/kg BW/day, an inhalation exposure of 0.05 µg/kg BW/day, and a dermal exposure of 1.6 µg/kg BW/day.

The oral exposure of 63.4 µg/kg BW/day is distributed in the following way:

This can be compared with the estimate in the EU Risk Assessment Report, in which the total oral exposure for 3-6-year-olds is 20 µg/kg BW/day. However, in this case the bioaccessibility (the absorption) has been factored in.

Wormuth et al. (2006) estimates a daily internal exposure of approx. 0.02-90 µg/kg BW with a median of approx. 9 µg/kg BW/day. Approx. 95% stems from sucking on things such as toys and 5% from ingestion of dust.

Schettler (2006) refers to surveys in the USA, which have estimated the exposure to DINP through children’s contact with toys to 5.7-44 µg/kg/day depending on assumptions and statistical techniques. The 99^th percentile estimate is at 40-173 µg/kg/day (Schettler, 2006). DINP is used primarily in toys in the USA.

Absorption through the various routes of exposure is for young children, according to EU risk assessments (European Chemicals Bureau, 2003) and quoted by Müller et al. (2003):

• Dermal: 0.5%
• Oral: 100%
• Inhalation: 100%.

7.7.5.3 Exposure to DINP from foods

DINP can find its way into foods through dispersion in the environment and absorption into domestic animals, fish and crops, or through migration from usage in materials in contact with food.

The exposure estimates stated above (below 7.7.5.2) demonstrate that the exposure through foods must be assumed to be negligible for 2-year-olds in relation to the exposure that is possible through toys.

EFSA (2005c) estimates that as worst case the exposure through foods is 10 µg/kg BW/day.

Therefore, based on these EFSA estimates the calculations apply 0 µg/kg BW/day as 50^th percentile and 10 µg/kg BW/day as contribution from foods.

7.7.5.4 Exposure from consumer products

DINP was found both in the earlier surveys and in some of the examined product groups in this project. The table below states the products in which DINP has been found earlier and in this project.

Table 7.46 occurrence of DINP in consumer products

DINP was found in toys that were examined in 2004 and onwards (meaning published in the year 2004 or later, so the surveys themselves are probably from 2003 and later). The study on plasticine is from 2002.

REACH annex XVII, entry 51 and 52 continued the prohibition af sale of the toys examined previously because of the high concentrations of DINP. In accordance with REACH, the concentration of DINP must not exceed 0.1% (w/w) in toys children are able to put into their mouths.

Analysis values

The two tables below present the measured values of DINP in the various products previously examined, and the products examined in this project.

As the first table illustrates, migration of DINP is only measured in rare cases in the products tested in earlier surveys.

Table 7.47 Overview of earlier surveys analysing for content of DINP

Click here to see Table 7.47

Table 7.48 Overview of findings of DINP in the products analysed in this project

n.s.: No screening result calculated
n.d.: Material not demonstrated above the detection threshold

Calculation of exposure - toys

The earlier surveys provide information on the content of DINP in 27 different consumer products.^[25] The measured content concentrations fall between 5.1 mg/kg (polystyrene book) and 334,000 mg/kg corresponding to 33% (in dolls)2.

In printed clothes, the levels were found to be up to 320,000 mg/kg corresponding to 32%. Furthermore, an eraser was found to contain up to 70% DINP, but the typical percentage ranged between 30 and 50% for erasers containing DINP. In Survey Project no. 90 on baby products, contents of DINP of 3900, 144,000 and 220,000 mg/kg were found in baby changing mats (corresponding to 0.38%, 14.4% and 22%, respectively). It should be noted that the maximum value also covers the content of DiDeP.

Migration analyses were performed for the earlier investigations on plasticine, toys (Bratz doll) and baby changing mats. The migration values lie between 0.23 mg/kg (plasticine - released to the indoor climate) and 11 mg/kg (Bratz doll).

In this project DINP has been found in two stickers on mitts with concentrations of up to 86,000 mg/kg corresponding to 8.6%, in the coverage of a pacifier with a concentration of 1047 mg/kg, in a soap packaging with a concentration of 8.8% and in a bath mat with a concentration of 14.6%. Migration analyses were performed on all these products, showing that DINP does not migrate out of the products in concentrations above the detection threshold.

Calculation of exposure - toys

For toys, the highest migration value measured is 11 mg/kg for a Bratz doll.

As noted in the chapter "Exposure scenarios - methods", the calculations assume that dermal contact occurs with the toy for 6 and 9 hours,, and oral contact with the toy for 3 hours. The maximum level measured in a toy is used as the calculation value for all toys, meaning that this worst-case scenario toy is assumed to be used during all the hours that a 2-year-old is assumed to have contact with toys. ^[26]

It is furthermore assumed that the weight of the Bratz doll is 70 g (an educated guess, since the value was not stated in the report), that the two-year old is in dermal contact with 10% of the surface area of the doll and sucks on half of this area. The measured migration of 11 mg/kg is measured over a period of 2 hours, and therefore the result needs to be corrected by a factor of 2. The value used for the dermal uptake of DINP is 0.5%

Hence, the value of the exposure from toys on two-year-olds is (summer scenario):

Daily ingestion of DINP from toys = oral ingestion (3 t) + dermal uptake (9 t)

= 3.91 µg/kg body weight/day

A corresponding RCR value of 0.002 (i.e. a daily ingestion smaller than the DNEL value) can be obtained.

Calculation of exposure - other objects

Exposure from other products containing DEHP can occur (in addition to the exposure from toys and the indoor climate). This could be, for instance, from erasers (mainly if there are older siblings in the household), baby changing mats/cushions.

Eraser

Migration analyses were not done on DINP in Survey Report no. 84. The weight of the eraser with a measured content of DINP of 70% is not given. But if it assumed that DINP migrates similarly to DEHP (DINP and DEHP are both phthalates with a high molecular weight), that there was a high concentration of phthalates in both erasers, and that it is assumed that the eraser weighs 20 g (which is the typical weight for the analysed erasers), then we can make the calculation even though the result is somewhat uncertain.

In the calculations it has been assumed that there is contact with the eraser for 1 minute a day (only when any older siblings are doing their homework). It is assumed that there is contact with 50% of the surface area of the eraser.

Baby changing mats/cushions

2-year-old children will still be changed on a baby changing mat/cushion in certain situations, but can also have their diaper changed while standing. It is therefore assumed that there is dermal contact with a baby changing mat at most twice a day each time with duration of 5 minutes, i.e. a total of 10 minutes per day. The migration of DINP from the baby changing mat, measured over a period of 4 hours (which must be taken into account in the calculations), is found to have a maximum value of 6.6 µg/200 cm2

As described in chapter 7.1 it is assumed that the body surface area of a 2-year-old is 0.6 m2, i.e. 6000 cm2 It is assumed that approximately one-third of the body surface area of the 2-year-old will be in contact with the baby changing mat, i.e. migration occurs from 2000 cm2. It is assumed that there is dermal exposure solely from the baby changing mat, i.e. the result is corrected so that only 0.5% of the DINP absorption occurs via skin. For the remaining products where dermal contact is not the only factor to be taken into account, the result is 100% because oral ingestion is also considered.

For the remaining objects the exposure values are the following:

Table 7.49 Daily ingestion of DINP from other objects based on measured migration values

F_abs = Relative amount of product taken up via dermal contact. Is used solely for products where the only factor to be considered is dermal contact (like the baby changing mat). Oral uptake must be accounted for in all other products, and the uptake percentage is thus 100%

7.7.5.5 Exposure from indoor climate

The exposure calculation for DINP via the indoor climate is presented and calculated in the section on indoor climate, but is reproduced in the table below.

Table 7.50 Daily ingestion of DINP through the indoor climate (dust and air) based on the 95th percentile

Table 7.51 Daily ingestion of DINP through the indoor climate (dust and air) based on the 50th percentile

Calculations show that the RCR value is less than 1, indicating that on the basis of the assumptions made there is no risk associated with exposure to DINP via the indoor climate, neither by ingestion of 50 mg or 100 mg of dust per day.

7.7.5.6 Combined exposure and risk

In the table below the various contributions to DINP are summarised. The tables are distributed according to the summer scenario or winter scenario described earlier.

Table 7.52 Daily ingestion of DINP from various sources

The combined result for DINP shows that the RCR value is far above 1 in both the summer and winter scenarios, and therefore, under the assumptions applied in the report, does not constitute a risk.

7.7.6 Prochloraz, 67747-09-5

Table 7.53 Identification of Prochloraz

Chemical name	Prochloraz
CAS no.	67747-09-5
EINECS no.	266-994-5
Molecular formula (gross)	C15-H16-Cl3-N3-O2
Molecular structure
Molecular weight	376.6647
Synonyms	N-propyl-N-[2-(2,4,6-trichlorophenoxy)ethyl]-1H-imidazole-1-carboxamide, Dibavit, Mirage
Classification	XN; R22 - N; R50-53 (EU, ESIS)

7.7.6.1 NOAEL, AF and DNEL

For prochloraz the NOAEL of 50 mg/kg BW/day (LOAEL 250 mg/kg/d) is chosen for its antiandrogenic effects, based on increased retention of nipples in the offspring of rats exposed during pregnancy (Christiansen et al. 2009).

The combined assessment factor is set to 100 based on a factor of 2.5 for general interspecies differences, 4 for allometric scaling between rats and humans, and 10 for intraspecies differences.

Thus, the DNEL for prochloraz becomes 0.5 mg/kg BW/day (NOAEL/AF).

7.7.6.2 Exposure from food

Prochloraz (N-propyl-N-[2-(2,4,6-trichlorophenoxy)ethyl]-1H-imidazole-1-carboxamide) is a fungicide use of which is permitted on several edible crops. JMPR (2001) has determined the ADI to be 0.01 mg/kg BW/day.

Table 7.54 Findings of prochloraz in the 2008 monitoring programme of the Danish Veterinary and Food Administration (Danish Veterinary and Food Administration, 2008).

Grapefruit is presumably only consumed minimally by two-year olds, so it can be disregarded in the context of exposure.

Prochloraz is not amongst the 20 pesticides that, according to calculations by the Danish Food and Veterinary Administration, constitute the majority of the ingestion in 2007. The average ingestion is less than 0.7 µg/day/person. For a 60 kg person this corresponds to less than 0.01 µg/kg BW/day.

The caloric consumption of 2-year-olds is approximately 325 kJ/kg BW, which is roughly 3 times that of adults. If a transformation factor of 3 is used for 2-year-olds, the corresponding exposure can be derived:

Less than 0.04 µg/kg BW/day.

It should be noted that the findings in the table cannot be used to directly calculate the exposure. This is because in many cases one is dealing with results of analyses of samples that were chosen on the basis of suspicion, because the findings are not representative, and because there is always a proportion of the pesticides that will be removed upon peeling, washing and preparation. A larger exposure than the one calculated above will therefore only occur sporadically.

7.7.6.3 Combined exposure and risk

The total contribution for prochloraz that was considered in the investigation comes from foods. As it can be discerned from the tables Table 7.85-Table 7.87 the contribution from prochloraz was so minimal that it only gives a visible contribution in the total calculations for the maximum value, which constitutes 0.04 µg/kg BW/day. The contribution is too small to be reflected in the RCR values, since the calculations are with two decimals.

7.7.7 Tebuconazole, 107534-96-3

Table 7.55 Identification of Tebuconazole

Chemical name	Tebuconazole, 107534-96-3
CAS no.	107534-96-3
EINECS no.	403-640-2
Molecular formula (gross)	C16-H23-Cl-N3-O
Molecular structure
Molecular weight	307.8182
Synonyms	(RS)-1-(4-Chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1- ylmethyl)pentan-3-ol, Ethyltrianol, Fenetrazole
Classification	Rep3;R63 XN;R22 N;R51/53 Rep3;R63 XN;R22 N;R51/53 (LOFS)

7.7.7.1 NOAEL, AF and DNEL

For tebuconazole the LOAEL of 50 mg/kg BW/day (NOAEL is not identified) is chosen for its antiandrogenic effects, based on increased retention of nipples in the offspring of rats exposed during pregnancy (Christiansen et al. 2007).

The combined assessment factor is set to 300 based on a factor of 2.5 for general interspecies differences, 4 for allometric scaling between rats and humans, 10 for intraspecies differences and 3 for LOAEL to NOAEL.

Thus, the DNEL for tebuconazole becomes 0.17 mg/kg BW/day (LOAEL/AF).

7.7.7.2 Exposure from food

Tebuconazole is a fungicide use of which on a series of edible crops is allowed outside of the EU. JMPR (1994) has determined the ADI to be 0.03 mg/kg BW/day (FAO/WHO, 2006).

Table 7.56 Findings of tebuconazole in the 2007 monitoring programme of the Danish Veterinary and Food Administration (Danish Veterinary and Food Administration, 2008).

Tebuconazole is not amongst the 20 pesticides that, according to calculations by the Danish Food and Veterinary Administration, constitute the majority of the ingestion in 2007. The average ingestion is less than 0.7 µg/day/person. For a 60 kg person this corresponds to less than 0.01 µg/kg BW/day.

The caloric consumption of 2-year-olds is approximately 325 kJ/kg BW., which is roughly 3 times that of adults. If a transformation factor of 3 is used for 2-year-olds, the corresponding exposure is derived:

Less than 0.04 µg/kg BW/day.

7.7.7.3 Combined exposure and risk

The total contribution for tebuconazole that was considered in the investigation comes from foods. As it can be discerned from the tables Table 7.85 to-Table 7.87 the contribution is so minimal that it only gives a visible contribution in the total calculations for the maximum value, which constitutes 0.04 µg/kg BW/day. The contribution is too small to be reflected in the RCR values, since the calculations are with two decimals.

7.7.8 Linuron, 330-55-2

Table 7.57 Identification of linuron.

Chemical name	Linuron, 330-55-2
CAS no.	330-55-2
EINECS no.	206-356-5
Molecular formula (gross)	C9-H10-Cl2-N2-O2
Molecular structure
Molecular weight	249.0934
Synonyms	1-(3,4-Dichlorophenyl)3-methoxy-3-methylurea, Garnitan Afalon,
Classification	REP2;R61 XN;R22-48/22 CARC3;R40 REP3;R62 N;R50/53 (LOFS)

7.7.8.1 NOAEL, AF and DNEL

For linuron the NOAEL of 25 mg/kg BW/day (LOAEL 50 mg/kg/d) is chosen for its antiandrogenic effects, based on increased retention of nipples in the offspring of rats exposed during pregnancy (Christiansen et al. 2000).

The combined assessment factor is set to 100 based on a factor of 2.5 for general interspecies differences, 4 for allometric scaling between rats and humans, and 10 for intraspecies differences.

Thus, the DNEL for linuron becomes 0.25 mg/kg BW/day (NOAEL/AF).

7.7.8.2 Exposure from food

Linuron is an herbicide that is used on corn, vegetables, sunflowers and decorative greenery.

Table 7.58 Findings of linuron in the 2007 monitoring programme of the Danish Veterinary and Food Administration (Danish Veterinary and Food Administration, 2008).

Linuron is not amongst the 20 pesticides that, according to calculations by the Danish Food and Veterinary Administration, constitute the majority of the ingestion in 2007. I.e. the average ingestion is less than 0.7 µg/day/person. For a 60 kg person this corresponds to less than 0.01 µg/kg BW/day.

The caloric consumption of 2-year-olds is approximately 325 kJ/kg BW., which is roughly 3 times that of adults. If a transformation factor of 3 is used for 2-year-olds, the corresponding exposure is derived:

Less than 0.04 µg/kg BW/day.

7.7.8.3 Combined exposure and risk

The total contribution for linuron that was considered in the investigation comes from foods. As it can be discerned from Table 7.87 to Table 7.89 the contribution is so minimal that it only gives a visible contribution in the total calculations for the maximum value, which constitutes 0.04 µg/kg BW/day. The contribution is too small to be reflected in the RCR values, since the calculations are with two decimals.

7.7.9 Vinclozolin

Table 7.59 Identification of Vinclozolin

Chemical name	Vinclozolin
CAS no.	50471-44-8
EINECS no.	256-599-6
Molecular formula (gross)	C12-H9-Cl2-NO3
Molecular structure
Molecular weight	286.1102
Synonyms	1-(3,4-Dichlorophenyl)3-methoxy-3-methylurea, 3-(3,5-Dichlorophenyl)-5-ethenyl-5-methyl-2,4- oxazolidinedione, Ronilan, Ornalin,
Classification	REP2;R60-61 CARC3;R40 R43 N;R51/53 (LOFS)

7.7.9.1 NOAEL, AF and DNEL

For vinclozolin, the LOAEL of 5 mg/kg BW/day (NOAEL is not identified) is chosen for its antiandrogenic effects, based on increased retention of nipples in the offspring of rats exposed during pregnancy (Hass et al. 2007).

The combined assessment factor is set to 300 based on a factor of 2.5 for general interspecies differences, 4 for allometric scaling between rats and humans, 10 for intraspecies differences and 3 for LOAEL to NOAEL.

Thus, the DNEL for vinclozolin becomes 0.0167 mg/kg BW/day (LOAEL/AF).

7.7.9.2 Exposure from foods

Vinclozolin is a fungicide that so far has been used widely. The EFSA (2008) has recommended that the use be limited, since the theoretical maximum (TAMDI) is high, around 110-644% of the ADI.

Even though the actual ingestion value is smaller, the EFSA has recommended that residues not be tolerated in certain crops. (EFSA 1-36).

Table 7.60 Findings of vinclozolin in the 2007 monitoring programme of the Danish Veterinary and Food Administration (Danish Vveterinary and Food Administration, 2008).

Vinclozolin is not amongst the 20 pesticides that, according to calculations by the Danish Food and Veterinary Administration, constitute the majority of the ingestion in 2007. The average ingestion is less than 0.7 µg/day/person. For a 60 kg person this corresponds to less than 0.01 µg/kg BW/day.

The caloric consumption of 2-year-olds is approximately 325 kJ/kg BW., which is roughly 3 times that of adults. If a transformation factor of 3 is used for 2-year-olds, the corresponding exposure is derived:

Less than 0.04 µg/kg BW/day.

7.7.9.3 Combined exposure and risk

The total contribution for vinclozolin that was considered in the investigation comes from foods. As it can be discerned from Table 7.87 to Table 7.89 the contribution is so minimal that it only gives a visible contribution in the total calculations for the maximum value, which constitutes 0.04 µg/kg BW/day. The contribution is too small to be reflected in the RCR values, since the calculations are with two decimals.

7.7.10 Procymidone

Table 7.61 Identification of Procymidone

Chemical name	Procymidone
CAS no.	32809-16-8
EINECS no.	251-233-1
Molecular formula (gross)	C13-H11-Cl2-N-O2
Molecular structure
Molecular weight	284.1374
Synonyms	3-(3,5-dichlorophenyl)-1,5-dimethyl-3-azabicyclo[3.1.0]hexane-2,4-dione, Dicyclidine
Classification	-

7.7.10.1 NOAEL, AF and DNEL

For procymidone the NOAEL of 2.5 mg/kg BW/day (LOAEL of 12.5 mg/kg BW/day) is chosen for its antiandrogenic effects, based on decreased anogenital distance (AGD), hypospadias (malformed genitalia) as well as effects on the testes in the offspring of rats exposed during pregnancy (EFSA, 2009b).

The combined assessment factor is set to 100 based on a factor of 2.5 for general interspecies differences, 4 for allometric scaling between rats and humans, and 10 for intraspecies differences.

Thus, the DNEL for procymidone becomes 0.025 mg/kg BW/day (NOAEL/AF).

7.7.10.2 Exposure from foods

Procymidone is a fungicide which is prohibited to use within the EU.

Table 7.62 Findings of procymidone in the 2007 monitoring programme of the DanishVeterinary and Food Administration (DanishVeterinary and Food Administration, 2008).

Procymidone is amongst the 20 pesticides that, according to calculations by the Danish Food and Veterinary Administration, constitute the majority of the pesticide ingestion in 2007. The average ingestion has been calculated to be 0.7 µg/day/person (Danish Food and Veterinary Administration, 2008). For a 60 kg person this corresponds to 0.01 µg/kg BW/day.

The caloric consumption of 2-year-olds is approximately 325 kJ/kg BW., which is roughly 3 times that of adults. If a transformation factor of 3 is used for 2-year-olds, the corresponding exposure is derived fromof 0.04 µg/kg BW/day.

7.7.10.3 Combined exposure and risk

The total contribution for procymidone that was considered in the investigation comes from foods. As it can be discerned from Table 7.87 to Table 7.89 the contribution is so minimal that it only gives a visible contribution in the total calculations for the 50^th percentile value and the maximum value, respectively, each of which constitute 0.04 µg/kg BW/day. The contribution is too small to be reflected in the RCR values, since the calculations are with two decimals.

7.7.11 Dioxins and dioxin-like PCBs

Table 7.63 Identification of dioxins.

7.7.11.1 NOAEL, AF and DNEL

For dioxins, an LOAEL of 25 ng 2,3,7,8-TCDD/kg (NOAEL not identified) is chosen for its antiandrogenic effects, based on reduced semen production in rats (Faqi et al. 1998). In the study, the dose has been administered as a loading dose before mating, with a subsequent maintenance dose of 5 ng/kg BW/week.

For dioxins and dioxin-like PCBs, the EU Scientific Committee on Foods (SCF) and the FAO/WHO Expert Committee on Food Additives (JECFA) have set a tolerable daily intake (TDI) of 2 pg/kg BW for 2,3,7,8-tetrachlor dibenzo-p-dioxin (TCDD). At assessment, the animal’s body load has been converted to the body load and daily dose for humans at continuous exposure. Next, a factor of uncertainty of 3 has been used to extrapolate from an LOAEL to an NOAEL level, and a factor of uncertainty of 3.2 is used to take into account intraspecies differences.

A toxic equivalent factor is used to measure the toxicity of the various PCDDs, PCDFs and PCBs that denotes the various potencies of the substances. As the most toxic, 2,3,7,8-TCDD has been allocated a toxicity of 1.

7.7.11.2 Exposure from foods

Bergkvist et al. (2008) have estimated the exposure from six food groups combined with data on food intake for 670 people aged between 1and 24. Swedish children up to 10 years of age have a median TEQ intake that is greater than the TDI of 2 pg/kg BW/d. Younger children between 1-3 years-old revealed a median TEQ intake of 4.4 – 4.3 pg/kg BW/day, while the 95^th percentile lay between 6.6 and 8.1. Younger children have the highest exposure per kg BW, which drops with increasing age. The higher exposure is due to the fact that children consume more food than adults compared to their body weight. The youngest children in the Swedish study consumed 3-4 times more food compared to their body weight than did the average young adult.

Bergkvist et al. (2008) have estimated the exposure to dioxins and dioxin-like PCBs via foods, see table 7.64

Table 7.64 Exposure to dioxin-like substances in Swedish children aged 1-3 years (Bergkvist et al., 2008)

Therefore, in this project we have calculated the exposure to dioxin from foods for 2-year-olds as an average 4.3 pg WHO-TEQ/kg bW/day, and a maximum 8.1 pg WHO-TEQ/kg BW/day.

Bergkvist et al. calculate that average exposure via foods is distributed as 30% from diary products, 29% from fish, 12% from meat, 1% from eggs, and 28% from other fat-containing products.

7.7.11.3 Combined exposure and risk

The combined exposure and risk from dioxin and dioxin-like substances covered in this study, comes from foods. The Swedish study from 2008 states that children aged 1 – 3 years have an average intake that is twice as great as the TDI, while the maximum exceeds the TDI by four times. The RCR becomes 2 for average exposure and 4 for maximum exposure for dioxins and dioxin-like PCBs solely from foods. Any additional contribution of dioxin-like PCBs from the indoor climate arising from the use of PCB-containing building materials would therefore be undesirable as the background load of dioxins and dioxin-like PCBs from foods already exceeds the tolerable exposure.

7.7.12 Non-dioxin-like PCBs

Table 7.65 Identification of PCBs.

7.7.12.1 Risk assessment

In the report, “Sundhedsmæssig vurdering af PCB-holdige bygningsfuger” (Health-related assessment of PCB-containing building joint-filler) Gunnersen et al. (2009), it is stated that the greatest exposure to PCB used in building joint-fillers is due to releases into the indoor air. Even though there is some exposure to dioxin-like PCBs, it is primarily non-dioxin-like PCBs that liberate into the indoor air. The risk assessment performed by Gunnersen et al. (2009) is based on an NOAEL of 0.036 mg/kg/day for non-dioxin-like PCB (PCB 28) with regard to the effect on the liver and thyroid. The assessment was not performed for antiandrogenic effects. Re-assessment of the toxicology of non-dioxin-like PCBs with regard to antiandrogenic effects or oestrogenic effects lies outside the remit of this project. Its relevance should also be considered taking into account that exposure to non-dioxin-like PCBs to some extent or other always occurs in conjunction with dioxin-like PCBs. It has already been concluded for these substances, that any additional contriubtion of PCBs to the antiandrogenic effect is deemed undesirable. Any additional contribution to exposure by the non-dioxon-like PCBs must similarly be deemed undesirable.

7.7.13 DDT

Table 7.66 Identification of DDT.

Chemical name	Dichlorodiphenyltrichloroethane (DDT)
CAS no.	50-29-3
EINECS no.
Molecular formula (gross)	C14H9Cl5
Molecular structure
Molecular weight	354.48626
Synonyms
Classification	T;R25-48/25 CARC3;R40 N;R50/53 (LOFS)
Comments	The employed data sources for DDT also include the decomposition products DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene) and DDD (1,1- dichloro-2,2-bis(p-chlorophenyl)ethane).

7.7.13.1 NOAEL, AF and DNEL

For DDT, an LOAEL of 10 mg pp-DDE /kg BW/day (NOAEL is not identified) is chosen for its antiandrogenic effects, based on increased retention of nipples in the offspring of rats exposed during pregnancy (You et al. 1998).

The combined assessment factor is set to 300 based on a factor of 2.5 for general interspecies differences, 4 for allometric scaling between rats and humans, 10 for intraspecies differences, and 3 for LOAEL to NOAEL.

Thus the DNEL for pp-DDE becomes 0.03 mg/kg BW/day (LOAEL/AF).

7.7.13.2 Exposure from foods

Fromberg et al. (2005) estimated the adult daily ingestion of DDT based on measured findings in animal foods. This is expressed as the sum of DDT and its metabolites DDE and DDD.

The average ingestion of DDT from animal foods is 0.27 µg/day, the 90^th percentile is 0.46 µg/day and the 95^th percentile is 0.60 µg/day. When converted to units of kg BW for a 60 kg adult this corresponds to 0.005, 0.008 and 0.01 µg/kg BW/day, respectively.

The caloric consumption of 2-year-olds is approximately 325 kJ/kg BW., which is roughly 3 times that of adults. If a transformation factor of 3 is used for 2-year-olds, the corresponding exposure is obtained:

• Average: 0.01 µg/kg BW/day
• 90^th percentile: 0.02 µg/kg BW/day
• 95^th percentile: 0.03 µg/kg BW/day

7.7.13.3 Combined exposure and risk

The total DDT contribution that was considered in the investigation comes from foods. As it can be discerned from Table 7.87 to Table 7.89 the contribution is so minimal that it only gives a visible contribution to the total calculations for the average value (the 50^th percentile) of 0.01 µg/kg BW/day and the maximum value, which gives a total of 0.03 µg/kg BW/day. The contribution is too small to be reflected in the RCR values, since the calculations are with two decimals.

7.7.14 Propyl-, butyl-, and isobutylparaben

7.7.14.1 Propylparaben, 94-13-3

Table 7.67 Identification of propylparaben.

Chemical name	Propylparaben, 94-13-3
CAS no.	94-13-3
EINECS no.	202-307-7
Molecular formula (gross)	C10-H12-O3
Molecular structure
Molecular weight	180.2005
Synonyms	Benzyl salicylate (2-hydroxybenzoic acid, benzyl ester) (R43) Propyl p-hydroxybenzoate
Classification	-

7.7.14.2 NOAEL, AF and DNEL

For propylparaben, an LOAEL of 10 mg/kg BW/day (NOAEL is not identified) is chosen for its oestrogenic effects, based on decreased daily semen production in young rats (Oishi et al., 2002 in SCCP opinion: SCCP (2008)).

The combined assessment factor is set to 300 based on a factor of 2.5 for general interspecies differences, 4 for allometric scaling between rats and humans, 10 for intraspecies differences, and 3 for LOAEL to NOAEL.

Thus the DNEL for propylparaben is 0.03 mg/kg BW/day (LOAEL/AF).

Exposure from foods etc.

Soni et al. (2005) has calculated the possible average (PADI) and maximum (PMDI) ingestion via food for 2-4-year olds. The values are 105 and 179 mg, respectively, or 10 and 16 mg/kg BW/day, respectively, as calculated by Soni et al., using a body weight of 11 kg for the 2-4-year olds.

Propylparaben as a food additive is called E 216 or propyl-p-hydroxybenzoate, but its use was not permitted after 15 February 2008. The actual exposure through foods should therefore now be 0.

As mentioned in chapter 7.5.2.2, with the data currently available, it is not possible to obtain reliable quantitative estimates of the dermal uptake of parabens.

The industry, in its answer to the SCCP, gives an estimate of 1% absorption of unreacted butylparaben via the skin from cosmetic products, whilst a series of investigations suggest that the absorption could be higher. Due to some metabolisation in the skin the absorption presumably does not reach 100%. Therefore, the absorption is experimentally set to 10% with the condition that dermal uptake is the same for propylparaben and butylparaben.

7.7.14.3 Butylparaben, 94-26-8

Table 7.68 Identification of butylparaben.

Chemical name	Butylparaben, 94-13-3
CAS no.	94-26-8
EINECS no.	202-318-7
Molecular formula (gross)	C11-H14-O3
Molecular structure
Molecular weight	194.2271
Synonyms	Benzoic acid, 4-hydroxy-, butyl ester, Butyl 4-hydroxybenzoate, Butyl parahydroxybenzoate
Classification	-

NOAEL, AF and DNEL

For butylparaben, an LOAEL of 10 mg/kg BW/day (NOAEL is not identified) is chosen for its oestrogenic effects, based on effects on semen quality and production, as well as decreased serum testosterone levels in young rats (Oishi et al., 2001 in SCCP opinion: SCCP (2008)).

The combined assessment factor is set to 300 based on a factor of 2.5 for general interspecies differences, 4 for allometric scaling between rats and humans, 10 for intraspecies differences, and 3 for LOAEL to NOAEL.

Thus the DNEL for butylparaben is 0.03 mg/kg BW/day (LOAEL/AF).

Exposure from foods etc.

It is assumed no contributions occur via foods since the use of butylparaben as a food additive is not permitted within the EU.

As mentioned in chapter 7.5.2.2, with the data currently available, it is not possible to obtain reliable quantitative estimates of the dermal uptake of parabens.

The industry, in its answer to the SCCP, gives an estimate of 1% absorption of unreacted butylparaben via the skin from cosmetic products, whilst a series of investigations suggest that the absorption could be higher. Due to some metabolisation in the skin the absorption presumably does not reach 100%. Therefore, the absorption is experimentally set to 10%.

7.7.14.4 Isobutylparaben, 4247-02-3

Table 7.69 Identification of isobutylparaben.

Chemical name	Isobutylparaben, 94-13-3
CAS no.	4247-02-3
EINECS no.	224-208-8
Molecular formula (gross)	C11H14O3
Molecular structure
Molecular weight	194.2304
Synonyms	4-Hydroxybenzoic acid, 2-methylpropyl ester, isobutyl 4-hydroxybenzoate, 2-Methylpropyl 4-hydroxybenzoate,
Classification	-

NOAEL, AF and DNEL

For isobutylparaben, an LOAEL of 72 mg/kg BW/day (NOAEL is not identified) is chosen for its oestrogenic effects, based on increased uterus weight in mice in an uterotrophic study (Darbre et al., 2002).

The combined assessment factor is set to 525 based on a factor of 2.5 for general interspecies differences, 7 for allometric scaling between rats and humans, 10 for intraspecies differences, and 3 for LOAEL to NOAEL.

Thus the DNEL for isobutylparaben is 0.14 mg/kg BW/day (LOAEL/AF).

Exposure from food, etc.

It is assumed no contributions occur via foods since the use of isobutylparaben as a food additive is not permitted within the EU.

As mentioned in chapter 7.5.2.2, with the data currently available, it is not possible to obtain reliable quantitative estimates of the dermal uptake of of parabens.

The industry, in its answer to the SCCP, gives an estimate of 1% absorption via the skin from cosmetic products, whilst a series of investigations suggest that the absorption could be higher. Due to some metabolisation in the skin the absorption presumably does not reach 100%. Therefore, the absorption is experimentally set to 10% with the condition that the dermal uptake is equal for isobutylparaben and butylparaben.

7.7.14.5 Exposure to parabens from consumer products

The DNEL values for the parabens (0.03 mg/kg BW/day for both propylparaben and butylparaben, and 0.14 mg/kg BW/day for isobutylparaben) indicate that propylparaben and butylparaben are the most potent substances, and is the reason in the exposure calculations that a worst-case scenario is assumed with cosmetic products containing 0.4% propylparaben and 0.4% butylparaben, i.e. the maximum allowed concentrations in the products. A worst case daily exposure dose for isobutylparaben is not calculated since the maximum permitted value of paraben contents is 0.8%, and would therefore give too large a contribution when tthe additive effects of the substances are calculated. The worst case daily exposure dose for isobutylparaben will, however, be equal to the value for the other two parabens, but the RCR value will be lower (approx. 4.5 times) due to a higher DNEL value than the other parabens.

Two-year olds can be exposed to parabens from several different sources. For the exposure calculations it is assumed that the 2-year-old is exposed to parabens via the cosmetic products listed in Table 7.71 (moisturising creams/oil-based creams/lotions, sunscreens, shampoo and soap). The assumptions made during the calculations are also stated in the table.

This project surveys the contents of moisturising creams/oil-based creams/lotions and sunscreens for children on the Danish market. The use of parabens in the 32 moisturising creams/oil-based creams/lotions and the 28 sunscreens is declared in the table below.

Table 7.70 The use of parabens in moisturising creams/oil-based creams/lotions and sunscreens surveyed on the Danish market in October 2008. Each row indicates by a cross the parabens that were found in the surveyed cream or sunscreen.

From the table it can be seen that most typically methylparaben and propylparaben are used in the products (but only in 25 and 22% of the cases, respectively). Neither butylparaben nor isobutylparaben are used frequently.

No standard values for the use of creams and sunscreens have been found in the REACH Guidance Documents, but COLIPA estimates that 8 grams of body lotion/day is a realistic amount in a safety assessment of cosmetics for adults. For sun lotions, the estimate is 18 g/day (SCCP, 2006). Additionally, the typical use levels of cosmetics are stated in TGD (Appendix II, Table 14, page 242), (European Commission, 2003):

• For body lotion the typical use is stated as 7.5 g once or twice per day. In this report it assumed to be used twice a day in order to take into account children with eczema. The use of 7.5 g per application applies to adults. The use is proportionally downscaled for children by comparing the body surface of a 2-year-old and an adult.
• For sun lotions the typical use is stated as 10 g 2-3 times per day, but only for 3 weeks a year (2 weeks in the summer (full body use) and 1 week in the winter (only facial use).
• For shampoo the typical use is stated as 12 g 2-7 times per week for adults. It is assumed that children use half the amount stated. The worst case scenario is deemed to be daily use.
• For liquid soap the typical use is stated as 5 g 1-2 times per day for adults. It is assumed that children use half the amount stated. The calculations assume use once per day, since it is assumed that the 2-year-old is bathed at most once per day.

The EU Commission recommends that an adult use 36 g of sunscreen on the entire body (Recommendation by the Commission, 2006). The recommendations by the Danish Environmental Protection Agency are that children should use approx. 20 ml of sunscreen to completely cover the body, and adults should use 40 ml (The Cosmetics Guide by the Danish Environmental Protection Agency, 2008). Matas states on the sunscreen products that children should use 15-20 ml.

It is assumed that the density of sunscreens is slightly lessthan 1 (0.9 g/cm3), hence the 40 ml sunscreen recommendation is comparable with the 36 g recommendation for adults. The recommendation of the Danish Environmental Protection Agency on sunscreens is that children should use half of the recommended amount for adults. In the following calculations a value of 18 g of sunscreen is used for 2-year-olds.

With regard to the use of sunscreens in Danish day-care centres, the actual use differs widely from that described in TGD. In periods of sunshine, the message is typically that parents are responsible for applying sunscreens at home (before delivering the children) and the day-care centre applies sunscreen once again after lunch. Thus the values from TGD are not used in these exposure calculations. ^[27]

According to the UV index for the world as calculated by the DMI^[28] (Danish Meteorological Institute), Denmark will have a UV index greater than 3, which implies necessary protection against the sun from May to September. The DMI also publishes climate normals for Denmark that include the number of sunshine hours per month.^[29] The total number of sunshine hours from May to September as an average from 1961-1999 is 928 sunshine hours^[30]. If it is assumed that sunscreen is applied to a 2-year-old twice for every 12 sunshine hours (approx. 1 day) then there will be 2 x 77 applications of sunscreen.

The majority of the applications of sunscreen will primarily occur on arms and on the face. Sunscreen will only be applied to legs in the warmer periods of summer, when children possibly wear shorts. The following is therefore assumed with respect to sunscreen applications:

• Two weeks (i.e. 14 days) with applications of sunscreen to the whole body.
• Two weeks (i.e. 14 days) with applications of sunscreen to the face, arms and legs.
• During the remaining days (77 –14 -14 = 49) the application of sunscreen occurs only on arms and face.

Contrary to adults, it is not assumed that sunscreen will be needed in the winter (winter break) as described in TGD because skiing holidays will not normally involve 2-year-olds.

Some of the products are bathroom products and are washed off after use. This necessitates the use of a dilution factor (retention factor) of 0.01. The retention factor has been introduced by the SCCNFP to account for products that are diluted when used and washed off after use, i.e. for shampoo products, body shampoos and similar rinse-off products. (SCCNFP 0690 (2003)). Since this exposure is in the bath tub, it is permissible to use the retention factor in this context too.

Table 7.71 Assumptions made for the use of cosmetic products for the exposure calculations of parabens. (The values in parenthesis are calculated later)

Additionally there will be contributions from other sources such as Shrovetide/Halloween makeup, makeup, lip balm, etc., which are assumed to have a significantly smaller effect than the above mentioned sources. Finally, there is a small exposure via the indoor climate (see the calculations in the chapter on indoor climate) that contributes less than 1/10,000 of the total effect of cosmetic products.

The exposure calculations are performed by multiplying the amount of product by the fraction of parabens in the product and by the number of uses per day. The result is divided by the body weight of 15.2 kg in order to obtain the amount of parabens per kg BW per day. 10% dermal uptake is factored into the calculations. The result of the calculations is given in the table below.

Table 7.72 Daily ingestion of parabens from cosmetic products based on the maximum allowed concentrations in the products – worst case

Click here to see Table 7.72

As can be seen, the use of moisturising creams/oil-based creams/lotions and sunscreens gives an RCR value that is larger than 1. Under the assumptions made, the use of these products can pose a risk.

Other uptake data:

It is investigated whether the RCR is larger than 1 for a more moderate use of moisturising creams/oil-based creams/lotions and sunscreens, where:

• The maximum use of moisturising creams/oil-based creams/lotions on the full body is 3 times per week (say, after a shower)
• Sunscreens are used less often, i.e. only in the two months when the daily average temperature is around 20°Celsius (July and August). There are 382 sunshine days during these two months according to DMI climate normals. If it is assumed as previously that the application of sunscreen is done twice every 12 sunshine hours, then this gives 2 x 32 applications distributed in the following way:
  • One week (i.e. 7 days) with applications of sunscreen on the full body (very warm summers are rare in Denmark)
  • Two weeks (i.e. 14 days) with applications of sunscreen to the face, arms and legs.
  • During the remaining days (32 –7 -14 = 11) application of sunscreen occurs only on arms and face.
• Shampoo is used at most (i.e. the maximum number of showers): 3 times per week
• Soap is used at most (i.e. the maximum number of showers): 3 times per week

These assumptions yield the following result:

Table 7.73 Daily uptake of parabens from cosmetic products on the basis of the maximum allowed concentrations in the products – more realistic values

Click here to see Table 7.73

As can be seen, the use of moisturising creams/oil-based creams/lotions and sunscreens still give an RCR value that is 1 or larger than 1. Under the assumptions made, the use of these products can pose a risk.

Rastogi et al, 1995 has performed a survey of the content of parabens in 215 cosmetic products in Denmark. The results showed that 77% of the products contained a total of 0.1-0.97% parabens (the maximum allowed concentration is 0.8%). 99% of all the leave-on products contained parabens. The maximum concentrations of parabens were:

• Butylparaben 0.07%
• Propylparaben 0.32%
• Isobutylparaben (not considered in the survey).

If these concentrations of parabens are used on set no. 2 of the assumed uptake values (the smaller, more moderate uptake values) the RCR values still lie above 1, i.e. the use of moisturising creams/oil-based creams/lotions and sunscreens can result in endocrine disrupting effects (see Table 7.74). Furthermore contributions from any isobutylparaben that could be present should be added, since the sum of butylparaben and propylparaben in this case does not exceed the allowed value of 0.8%.

Table 7.74. Daily uptake of parabens from cosmetic products based on measured values in the products – more moderate values

Click here to see Table 7.74

As can be observed, the use of moisturising creams/oil-based creams/lotions and sunscreens still give an RCR value that is larger than 1. Under the assumptions made, the use of these products can pose a risk.

It should be pointed out that the survey of moisturising creams/oil-based creams/lotions and sunscreens on the market in this project has shown that parabens only occur in 22 and 25% of the products on the Danish market, respectively, which contrasts with the Rastologi study from 1995 (which however, was a survey of not only child creams/sunscreens) where a far greater percentage of products contained parabens. It is possible therefore to choose moisturising creams/oil-based creams/lotions and sunscreens that do not contain parabens.

Doubts as to the actual absorption of parabens:

For all of the above calculations, the value used for the absorption of parabens through the skin was 10%. This value for the absorption can be questioned as there is no reliable data available. The industry in its answer to the SCCP estimates an absorption of 1% for butylparaben, whereas a number of studies indicate that this value might be greater. The daily ingestion value of parabens has been calculated experimentally at 1, 5, 10, and 50% dermal uptake. The calculations are performed by employing the previously mentioned amounts of product, the previously measured actual values for the content of propyl and butylparaben (i.e. 0.32% and 0.07%) as well as the more realistic values for the use of moisturising creams/oil-based creams/lotions, sunscreens, shampoo and soap, i.e.:

• Use of moisturising creams/oil-based creams/lotions, shampoo and soap 3 times per week.
• The first uptake scenario for sunscreens described (i.e. 14 days of application to the whole body, 14 days of application to face, arms and legs, as well as 49 days of application of arms and face).

The values employed in the calculations are given in the table below.

Table 7.75 Values used for the calculation of the daily uptake of parabens from cosmetic products on the basis of measured concentrations in the products (variation of F_abs).

* Sunscreens are only used in the summer period, hence a daily average use for the entire year has been calculated.

Using the numbers in the table above gives the values for the daily uptake and the RCR values of dermal uptake of parabens listed in the table below. These vary between 1 and 50%. The calculations attempt to demonstrate the significance of the absorption of parabens through the skin, as due to the lack of data there is no agreement on an absolute value.

Table 7.76. The variation in the daily ingestion of parabens from cosmetic products based on measured concentrations in the products (variation of F_ABS ranging from 1 to 50%).

Click here to see Table 7.76

From the table it can be seen that the RCR value is less than 1 only for dermal absorption of parabens at values less than 5%.

7.7.14.6 Exposure from indoor climate

In reality the small contribution from the indoor climate for butylparaben of max.0003 µg/kg BW/day should be added here, but this value constitutes only a miniscule fraction in comparison to the contributions from the cosmetics, which is why it can be ignored in the calculations.

7.7.14.7 Combined exposure and risk

The different contributions of parabens for both the summer scenario and the winter scenario are summarised in the tables below, assuming that the dermal uptake of parabens is 10% (for the most realistic ingestion scenario, as described in Table 7.76).

Table 7.77 Daily absorbed dose of propylparaben from various sources

Table 7.78 Daily absorbed dose of butylparaben from various sources

As previously mentioned there is no calculated data (and hence no table) for isobutylparaben in the survey, since only the two most potent parabens were considered initially.

It should be noted that the in this project, the survey has only identified a parabens in 22 and 25% of the investigated moisturising creams/oil-based creams/lotions and sunscreens, respectively. Of these, parabens were identified in the following percentages: Isobutylparaben in 0 and 4%, butylparaben in 3 and 4% and propylparaben in 16 and 21%, respectively, of the creams and sunscreens. It is possible to choose moisturising creams/oil-based creams/lotions and sunscreens for 2-year-olds on the Danish market that do not contain parabens. This survey also shows that there has been a significant reduction in the use of parabens in cosmetic products since the Rastologi survey from 1995, which however considered cosmetic products generally and not just childcare products.

7.7.15 Bisphenol A, 80-05-7

Table 7.79 Identification of Bisphenol A.

Chemical name	Bisphenol A
CAS no.	80-05-7
EINECS no.	201-245-8
Molecular formula (gross)	C15-H16-O2
Molecular structure
Molecular weight	228.2863
Synonyms	4,4'-(1-Methylethylidene)bisphenol, 4,4'-Isopropylidenediphenol
Classification	XI;R37-41 R43 REP3;R62 (LOFS)

NOAEL, AF and DNEL

For bisphenol A, an NOAEL of 50 mg/kg BW/day (LOAEL 500 mg/kg/day) is chosen for its antiandrogenic effects, based on the effects on reproduction in mice (increased duration of pregnancy, increased incidence of undescended testes in male mice, abnormal growth of cells in the epididymis, and delayed puberty measured as separation of prepuce and penis in young males (Tyl et al., 2007 in an EU Risk Assessment: European Chemicals Bureau (2008a)).

The combined assessment factor is set to 175 based on a factor of 2.5 for general interspecies differences, 7 for allometric scaling between mice and humans, and 10 for intraspecies differences.

Hence, the DNEL for bisphenol A is 0.29 mg/kg BW/day (NOAEL/AF).

7.7.15.1 Exposure from foods etc.

Bisphenol A in polycarbonate plastics, tooth fillings and epoxy lacquer on the inner side of cans (Bisphenol –a.org., 2009).

In 2006, the EFSA (EFSA, 2009) updated its earlier assessment of bisphenol A in plastic materials in contact with foods with an exposure calculation for children. The EFSA has estimated the exposure via diet for several age groups, of which the group 1½-year-olds is the one that approaches the target group of this report: The 2-year olds

The EFSA’s conservative estimate for the 1½-year-olds is:

5.3 µg/kg BW/day

This assumes the ingestion of 2 kg of commercially processed food and beverage every day. The estimate is obtained by including the exposure via can food and foods in contact with polycarbonate (feeding bottles, service and storage containers). Exposure from the use of microwave heating of polycarbonate material or the use of drinking water from polycarbonate or epoxy coated water pipes and water containers was not included.

The NTP (2008) has calculated, on the basis of findings of bisphenol A concentrations in the urine of 90 6-8 year old girls, a median ingestion of 0.07 µg/kg BW/day, with a variation of <0.012–2.17 µg/kg BW/day. This reflects the fact that exposure comes from all sources; the environment, materials in contact with food; tooth fillings; toys; skin care products; etc.

The most important differences between the exposure of the 1½-year-old and the 6-8-year-olds are probably that the 1½-year-olds have more intense sucking habits and larger exposure via food ingestion measured compared to body weight. One can use the number for the 1½-year olds in the estimate for the 2-year-olds with the addition of the exposure via sucking and handling of toys and other items, the values of which can be found via measurements of the consumer products.

The following absorption values are used in agreement with the data given in the EU Risk Assessment (European Chemicals Bureau, 2003 a):

• Dermal: 10%
• Oral: 100%
• Inhalation: 100%.

7.7.15.2 Exposure from consumer products

Bisphenol A has not been identified in previous surveys, but is found in pacifiers as the only product group in this survey.

Values of the analysis

The table below displays the values for Bisphenol A in this project.

Calculation of exposure – other objects

In this project, Bisphenol A was identified in the coverage of two pacifiers made of polycarbonate. The measured values range between 106 and 280 mg/kg. Migration analyses of sweat and saliva were performed for both samples. A sweat simulant has been used in the analysis because the coverage of the pacifier constitutes the largest part and is in direct dermal contact with the child's skin surrounding the mouth. The results show that there is only a minor migration of Bisphenol A to sweat, with a value of 7 mg/kg for the pacifier with the higher content of Bisphenol A. This was only identified in one of the dual analyses. The detection threshold was 5 mg/kg.

Table 7.80 Overview of findings of Bisphenol A in the products analysed in this project

*: Only found in one of the samples.
n.d. Signifies that the substance has not been detected.

As described in the section “Exposure calculations – method”, it is assumed that the dermal contact with the coverage of the pacifier occurs for 7 hours and 45 minutes per day. Dermal contact occurs when sucking on the pacifier or by contact of the coverage with the mouth. It is assumed that 100% of the Bisphenol A that migrates is taken up via the skin, or is taken in directly through the mouth (pacifier in mouth) or by later sucking on the fingers. It is assumed that the child is in contact with 25% of the surface area of the pacifier.

Pacifier no. 5-3 weighs 9.6 g, of which 80% (i.e. 7.68 g) is estimated to be made up of the coverage, which is made of the material (polycarbonate) that contains Bisphenol A.

The following exposure values are obtained for the pacifier:

Table 7.81 Daily ingestion of Bisphenol A from other objects based on measured migration values

7.7.15.3 Exposure from indoor climate

The exposure calculation for Bisphenol A via the indoor climate is presented and calculated in the section on indoor climate, but is reproduced in the table below.

Table 7.82 Daily ingestion of Bisphenol A via the indoor climate (dust and air) Based on 95^th percentile

Table 7.83 Daily ingestion of Bisphenol A through the indoor climate (dust and air) On the basis of the 50^th percentile

The calculation shows that the RCR value is less than 1, which indicates that there is no risk of endocrine disrupting effects consequent to exposure to Bisphenol A via the indoor climate.

7.7.15.4 Combined exposure and risk

In the table below the various contributions to Bisphenol A are summarised.

Table 7.84 Daily ingestion of Bisphenol A from various sources

For Bisphenol A, the TDI value (based on liver damage as the toxic effects on the liver is the most sensitive endpoint) was larger than the DNEL value used (based on hormonal effects) by a factor of 10. From the table it can be discerned that the total bisphenol A contribution does not constitute a risk for either the summer scenario or the winter scenario under the assumptions made. This is in agreement with the calculations made by EFSA showing that not even infants, who have the largest bisphenol A contribution via foods, attain more than 26% of the TDI value (EFSA, 2009).

7.8 Cumulative risk assessment of potential endocrine-like substances

7.8.1 Risk assessment, overview summary

The calculated total risk for each substance is stated by the RCR values (see tables below).

The maximum RCR value is calculated in such a way that the maximum values are summated. 95^th percentile values have been used in the cases where maximum values for the substance were not available. 95th percentiles have also been used for the indoor climate, since there can be extreme differences in the maximum value and the 95th percentile.

For the other RCR column labelled "RCR (total of 50% and eventual alternative scenario)" a total of the 50% (where applicable) and the other alternative low or medium scenarios was employed. If several scenarios occur, the minimum value is used. This column thus represents neither an RCR value of 50% nor a minimum RCR value, but is an expression of a total of the remaining scenarios, that form a counterpart to the calculated maximum RCR. This has been calculated to show the range between the maximum/95^th percentile values and the alternative values.

As there is a difference in the behavioural patterns of 2-year-olds in the summer half-year and in the winter half-year, both a summer scenario and a winter scenario have been considered in order to include the most realistic exposure for both half-years.

The elements that are common to both the summer scenario and the winter scenario are included in both scenarios, in particular the following factors:

• Ingestion of foods
• Contact with objects other than toys, i.e. moisturising cream, bath articles and textiles other than winter clothing (jackets/mittens).

7.8.1.1 Summer scenario

The following factors have been included in the summer scenario (see table below):

• Contact with sunscreens.
• Contact with rubber clogs (no socks are worn).
• Dermal contact with toys for 9 hours in the summer
• Ingestion of 50 mg dust (US EPA states this value for the summer scenario).

Table 7.85 Calculation of RCR. Summer scenario with maximum value for rubber clogs. Red numbers indicate the RCR > 1

Click here to see Table 7.85

The content of phthalates in the examined rubber clogs was shown to exceed the permitted values; hence a table has been inserted that does not inlcude the contribution from these shoes. As requested by the Danish Environemntal Protection Agency, the table for toys only includes the phthalate with the maximum contribution to the RCR value for toys, in order not to use an overestimate for the exposure time for toys (in the calculations a 9 hour exposure has been used for each phthalate for toys). These calculations are given in the table below.

We compare the calculations where only one phthalate contributes to the RCR value with the calculations where all the phthalates contributed to the RCR values. It turns out that the difference is minimal, i.e. only 2 points at the 2^nd decimal place for the total of the RCR values. It should be noted that toys were found containing more than one phthalate. It is possible that the 2-year-old could be in contact with toys at home or in the childcare institution, such that exposure to phthalates is higher than that stated in the table below. Because the difference is minimal, it is not possible to interpret this from the total risk, when the value is rounded up/down to a whole number.

[1] RCR for PCBs in the indoor climate has not been calculated because the proportion that represents non-dioxin-like PCBs is highly variable. As the RCR for dioxin-like PCBs from foods alone exceeds 1, any contribution from the indoor climate is undesirable.

Table 7.86 Calculation of RCR. Summer scenario without rubber clogs and without contribution of phthalates from toys. Red numbers indicate the RCR > 1

Click here to see Table 7.86

7.8.1.2 Winter scenario

The following factors have been included in the winter scenario (see table below):

• Dermal contact with toys for 6 hours in the winter.
• Contact with jackets/mittens for 3 hours.
• Ingestion of 100 mg dust (US EPA states this value for the winter scenario, where one is more indoors).

Similarly to the summer scenario, the difference between including the contribution from toys in for the phthalate with the maximum contribution, and for all the other phthalates, in the calculations of the RCR value is minimal. The difference is only 2 points at the 2nd decimal place of the total of the RCR values. In order to avoid misinterpretations the contribution of toys from all phthalates is deliberately given in the table below. This is because the difference is minimal and cannot be read from the total risk when this result is rounded up/down to a whole number.

Table 7.87 Calculation of RCR. Winter scenario with a minimal contribution from phthalates in toys. Red numbers indicate the RCR > 1

Click here to see Table 7.87

7.8.2 Risk assessment, total for antiandrogenic substances

The total risk for each antiandrogenic substance is calculated and stated in the table below.

Table 7.88. Total RCR for antiandrogenic substances

The result shows that irregardless of whether the summer scenario or the winter scenario are considered with shoes, without shoes and with all phthalates, the RCR value for the antiandrogenic substances is much greater than 1. The significant contributions to the RCR value come the from DEHP, DBP and PCB concentrations in foods.

Any additional contribution from other sources and other substances could contribute to an even higher RCR total for the antiandrogenic substances.

7.8.3 Risk assessment, total for oestrogenic substances

The total risk for each oestrogenic substance is calculated and stated in the table below.

Table 7.89 Total RCR for oestrogenic substances

* It should be noted that the RCR value for isobutylparaben has not been calculated. This is primarily because the focus was on propyl and butylparaben, not onlybecause they are the two most potent parabens (lowest DNEL value), but also because isobutylparaben has only been identified in 1 of 60 sunscreens and creams surveyed in this project.

Since no oestrogenic substances were measured or found in either the rubber clogs or toys, the results show that irregardless of whether calculations are done on the summer scenario with or without rubber clogs, the RCR values are identical for the oestrogenic substances. For the summer scenario the RCR values are of around 3 and thus above 1. Propyl- and butylparaben in sunscreens are the most significant contributors to the RCR. The total contribution in the winter scenario is smaller than for the summer scenario, but the RCR value in the winter scenario is also above 1.

To this result one needs to add any possible contributions from other sources, for instance the use of sunscreens in the winter half-year and other cosmetic products all year around, as well as other substances that have been assessed as potential contributors to the RCR total for oestrogenic substances.

7.8.4 Risk assessment totalled for oestrogenic and antiandrogenic substances

In this section, the risk at exposure to both antiandrogens and oestrogen-like substances that affect the male reproductive system is calculated. This is based on an assumption thtat combination effects may be present when the substances’ effects are identical, even though the underlying mechanisms are different. However, to date there have been no animal studies demonstrating combined effects of antiandrogenic and oestrogen-like substances. On the rother hand, it has not been disproved, and it is normally very difficult to differentiate clearly between oestrogen-like and antiandrogenic substances, because both can induce the same type of effects; demasculinisation of the male reproductive system. In animal studies, antiandrogens can result in demasculinisation by reducing the effect of the male sex hormones, while oestrogen-like substances can result in demasculinisation by changing the balance between male and female sex hormones. Some substances that were orginally classified as oestrogen-like, have also been shown to have antiandrogenic effects, and vice-versa. Based on careful regulatory access, it is therefore assumed that concomitant exposure to two types of endocrine disruptors with similar effects can result in endocrine disrupting effects if the total risk characterisation coefficient is greater than 1.

All the antiandrogenic substances selected will be included in the total risk assessment, while only those oestrogen-like substances that result in demasculinisation of the male reproductive system will be included. Thus, propylparaben and butylparaben, which both have effects on young male rats’ sperm production, and bisphenol A, which affects descent of the testicles, development of the epididymis, and puberty in young male mice exposed during the foetal stage, will be included.

The total risk at exposure to oestrogen-like and antiandrogenic substances has been calculated and is presented in the table below.

7.8.5 Discussion and conclusion

Researchers have long known that endocrine disruptors can affect sexual development in laboratory animals. Findings in males included malformed genitals, undescended testicles to the scrotum at birth (cryptorchidism), decreased sperm quality as well as testicular cancer later in life (Sharpe, 2009). Similar symptoms have been observed in humans, and new Danish research shows that Danish girls develop breasts earlier than 15 years ago. Exposure to endocrine disruptors in the environment is suspected to be a contributory factor in the development of these syndromes in the general population (Aksglaede et al., 2009). However, in humans it is much more difficult to prove a cause-effect relationship.

A risk assessment is normally performed by assessing the exposure to a single substance in a single product. We are exposed to many different products on a daily basis, of which several contain the same chemical substances. We are also exposed to many different chemical substances that can have the same toxicological effect. This project attempts to take into account some of these combination effects.

In the past few years, surveys have shown surprising results on combination effects (also known as cocktail effects) of endocrine disruptors. A new Danish survey has revealed serious malformations in baby rats when female rats are exposed to a mixture of endocrine disruptors at concentrations which would not by themselves cause an effect. An expert workshop was held to follow up these results. Several world leaders in endocrine disruptors and combination effects met in Denmark in January 2009, where they considered on current knowledge on combination effects and possibilities for introducing legislation to address the issue. In the report from the workshop, the experts emphasise the fact that the risks posed by chemicals are currently underestimated because we do not take into account our daily exposure to a cocktail of many different substances, including endocrine disruptors. The advice from the experts is that, it is possible and necessary to include the risks of combination effects when performing a risk assessment of endocrine disruptors. The experts also refer to a so-called dose addition method that can be used until further knowledge is acquired. This project attempts to use the dose addition method for exposure to a series of substances that have been proven to exhibit endocrine disrupting effects in animal studies.

The present project has shown that if one considers the total exposure as the sum of exposure from all the products suurrounding a 2-year-old, then for certain individual substances such as DBP, dioxins and dioxin-like PCBs, and propyl- and butylparaben, the individual substance can in themselves pose a risk.

If the exposure is then assessed together with the substances that are suspected of having antiandrogenic or oestrogen-like effects, the total contribution will result in a potential risk for endocrine disrupting effects.

The current investigation is, however, based on random samples of individual consumer products and product groups. There may therefore be other chemical substances suspected of having endocrine disrupting effects, and other products on the market that contribute to this risk. In addition to the exposure contributions included in these calculations, there may be other contributing factors that could increase overall risk, including for instance:

• Potential endocrine disrupting effects like the ones stated in the screening investigations of the project in chapter 3, among these the QSAR predictions.
• Contributions from propyl, butyl and isobutylparaben in sunscreens used in the winter half-year (e.g. during winter break beach holidays).
• Contributions from propyl, butyl and isobutylparaben in other cosmetic products, which are used both in the summer and the winter. e.g. after-sun lotion, Shrovetide/Halloween makeup.
• Contribution of phthalates from other footwear, e.g. rubber sandals and rubber shoes.
• Contributions from the indoor climate in cars and other means of transport. e.g. the value of the DEHP contribution from the indoor climate in cars of 21µg/m3 as stated in the EU Risk Assessment for DEHP (European Chemicals Bureau, 2008, p. 256).
• Contributions from outdoor air, etc.

In addition, there may be a greater contribution from some of the consumer products, as some values (such as for toys) may be underestimated consequent to the estimates necessary for the weight of the products in the calculations. In addition, the actual number of products used by the 2-year-old constitutes a factor that may further contribute to the calculated risk; for example, it should be assumed that pacifiers are replaced more often than mittens and jackets.

It should also be noted that the project's calculations include many conditions that are based on estimates. This is due to the fact that there is no clear documentation in the areas concerned. Such types of estimate can produce distorted results and may mean that the overall exposure is estimated at a higher level than is actually the case, as all estimates are based on worst-case considerations. The following results are deemed to be uncertain:

• For several of the phthalates the contents in foods are based on one source, which exclusively states a total estimate and the percent-wise distribution of indoor climate, foods and other products. When generating the report, it became evident from the calculation of total exposure that this is not valid.
• For the indoor climate: Surveys from other countries such as Sweden and the US have been used where no applicable Danish surveys have been found. It is not certain whether these numbers correspond to Danish conditions.
• For propyl and butylparaben in particular, that have been included in the cumulative risk assessments, the selected LOAEL based effects have been found in a few studies conducted by a Japanese group (Oishi et al.) In the SCCP opinion from 2005, doubt is raised concerning the validity of these results and SCCP has asked the industry to provide results from developmental toxicity studies, which can determine whether or not propyl, butyl and isobutylparaben have endocrine disrupting effects in animals. The industry has subsequently attempted to repeat the studies and show that the substances do not induce endocrine disrupting effects. The studies performed by the industry have nevertheless been rejected by the SCCP on the grounds of questionable validity (SCCP, 2006a). The question of whether the three parabens are able to induce endocrine distrupting effects thus remains inconclusive. The procedure chosen for this report can therefore be perceived as rather cautious, since the work was based on studies showing the strongest endocrine disrupting effects.
• For parabens the dermal uptake is estimated at 10%. As stated several times in the report, there is currently no documentation for skin absorption, metabolism and excretion of parabens. The EU’s Scientific Committee for consumer products has stated that this documentation will be available shortly, after which a more accurate risk assessment of parabens can be performed.

Based on the present investigation it can be concluded that:

• Single effects with a high content of an endocrine disruptor, such as is seen with the content of DBP in rubber clogs may result in a critical risk for the 2-year-old.
• The contributions that 2-year-olds absorb especially from the phthalate DBP (mostly from foods, if we discount the rubber clogs) and dioxin and dioxin-like PCBs (mostly from foods and partly from the indoor climate) constitute a risk for antiandrogenic disruptions to the endocrine system.
• The contributions that 2-year-olds absorb from the parabens propylparaben and butylparaben, in particular, can constitute a risk for oestrogenic disruptions of the endocrine system. These contributions originate predominantly from cosmetic products such as moisturising creams/oil-based creams/lotions and sunscreen.

In summary, it can be concluded that there is not only a need to reduce exposure to antiandrogenic and oestrogen-like substances from foods and the indoor climate, but also from products in the studied product groups. Based on the assumptions made in this report, these contribute to both the indoor climate and to the direct exposure. A reduction of the potential cumulative risk requires knowledge of which sources are present in foods and the indoor climate. Furthermore, there is a need to reduce possible contributions from other sources, e.g. propyl, butyl and isobutylparaben in cosmetics, phthalates from other footwear (e.g. rubber clogs and rubber shoes).

[16] Bremmer HJ, van Veen MP. Children's toys fact sheet: to assess the risks for the consumer. Bilthoven: Rijksinstituut voor Volksgezonheid en Milieu, National Institute of Public Health and the Environment, 2002. (RIVM report).

[17]

[18] Migration by contact with urine is not considered in this project.

[19] Body/torso is the body without limbs and neck/head.

[20] Hawley, 1985 refers to the source Poiger & Schlatter, 1979, where the compound TCDD was given orally in ethanol to rats. After 24 hours, 26.7 % of the total dose was found in the liver. If TCDD was administered mixed with earth, half of that amount was found in the liver after 24 hours.

[21] The numbers are obtained from table 4.1

[22]

[25] The products were bought in Norway, but could have been bought in Denmark.

[26] It is stated that an arm weighs 3.5 g, a boot 16 g and a leg 5 g on http://www.miljoeogsundhed.dk/default.aspx?node=5320

[27] http://www.dmi.dk/dmi/index/verden/uv_idag.htm

[28] http://www.dmi.dk/dmi/index/verden/uv_idag.htm

[29] http://www.dmi.dk/dmi/index/danmark/klimanormaler.htm

[30] http://www.dmi.dk/dmi/index/danmark/klimanormaler.htm

[31] The total surface area of adult women is 1.69 m2 according to the TGD. We employ a total surface area for children of 0.6 m2. The amount of creams used is calculated as 7.5 g creams for an adult per time/1.69 m2 (adult) * 0.6 m2 (chiild) = 2.7 g.

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