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Mapping of perfume in toys and children's articles

8 Exposure scenarios

• 8.1 Selection of substances for exposure scenarios
• 8.2 Exposure of the skin
• 8.3 Exposure via inhalation
• 8.4 Data for evaluation of health conditions at exposure
  • 8.4.1 Tris(2-chlorethyl)phosphate, CAS number 115-96-8
  • 8.4.2 Tert-butanol (2-methyl-2-propanol), CAS number 75-65-0
  • 8.4.3 n-butylacetate, CAS number 123-86-4
  • 8.4.4 Butylglycol (2-butoxyethanol), CAS number 111-76-2
  • 8.4.5 Cyclohexanon, CAS number 108-94-1
  • 8.4.6 Ethylbenzene, CAS number 100-41-4
  • 8.4.7 Hexane, CAS number 110-54-3
  • 8.4.8 Methylethylketone (MEK), CAS number 78-93-3
  • 8.4.9 Methylisobutylketone (MiBK), CAS number 108-10-1
  • 8.4.10 Toluene, CAS number 108-88-3
  • 8.4.11 Xylenes, CAS number 1330-20-7

8.1 Selection of substances for exposure scenarios

To investigate a potential exposure to harmful substances when using the selected products, an analysis of migration to sweat was made of extracts from the products to elucidate a potential exposure in case of touch and skin contact. An emission analysis was also conducted to shed light on exposure via inhalation. The migration test has been carried out for 4 products intended for children below the age of three years, whereas the emission analysis was conducted for 7 products, of which 4 products were for children below the age of 3 years and 3 products were for children older than three years. The results of the two tests appear from chapter 7 and form the basis for selection of substances for further analysis of exposure in typical use scenarios.

It has been decided not to make any exposure scenarios for the sensitizing fragrances due to their already documented dangerous nature.

Exposure scenarios for absorption through the skin have been selected on the basis of migration tests made on four products especially intended for children under the age of three years (D09, D12, D14, and D15). GC/MS screening of the simulant for sweat shows occurrence of the fragrances cyclohexanon, ethylvanillin, 7-hydroxy-3,7-dimethyl octanal, piperonal and vanillin distributed among the four products in concentrations of or below 140 mg/kg (140 ppm). In addition to this, appearance of diethylphthalate and tris(2-chlorethyl)phosphate has been demonstrated.

Based on the health characteristics and classification of the substances, it is assessed that the appearance of the fragrances demonstrated in the migration test of the four products does not constitute a health risk by contact with the skin.

Tris(2-chlorethyl)phosphate is used as flame retardant in one of the products (D12) and has been detected during the migration test in high concentrations in the sweat simulant (3,000 ppm). Tris(2-chlorethyl)phosphate is under suspicion of being carcinogenic (carc3) and is assessed to constitute the highest health risk of the four tested products when in contact with the skin. On the basis of this, it has been decided to carry out an exposure scenario for the flame retardant in product D12.

The emission test shows evaporation of a wide range of organic compounds represented by for example fragrances and solvents. The function of the single substances has only been identified for the group of fragrances. The evaporation of substances is especially high for the D02 and D08 products where a large variation in the chemicals being evaporated is also seen.

When the chemical substances were selected for the inhalation exposure scenario, the content and the liberation from the products and the classification of the substances were taken into consideration. This applies to all the substances and not only the fragrances. On the basis of the health characteristics of the substances at inhalation, 10 substances have been selected for analysis of exposure scenarios. 5 of these 10 substances may probably have been used in the products as fragrances (see table 8.1).

The table below gives an overview of the selected substances and their classification (the list of dangerous substances, the Danish Environmental Protection Agency), stating in which products they occur. All the selected substances are on the list of dangerous substances of the Danish Environmental Protection Agency, whereas hexane and tris(2-chlorethyl)phosphate are also on the list of unwanted substances.

Table 8.1: Substances selected for exposure scenarios on the basis of migration and emission tests

1 Fragrance
2 Flame retardant
^ Is no longer on the Danish market

8.2 Exposure of the skin

Exposure of the skin may take place when playing with the toys where the chemical substances can get in contact with the skin via sweat. The migration analyses carried out have demonstrated that some of the chemical substances in the toys can be transferred to sweat. Via the sweat, they can subsequently get in contact with the skin. As also mentioned in section 8.1, focus will be on tris(2 chlorethyl)phosphate.

The calculation of the absorption through the skin has been made according to the principles in Technical Guidance Document (TGD 2003). The calculation has been made for children below the age of three years.

It is presupposed that the contact area is the palms of the child's hands, corresponding to 2.2 % of the total surface area (the total surface area for children is specified as 60.3 dm²). Furthermore, it is assumed that the entire migrated quantity is absorbed at the same time (n=1).

The exposure is calculated according to the following formula (TGD 2003):

(1) E = C/a * A

Calculation of the actual absorption per kg body weight is made according to the following formula (TGD, 2003):

(2) U_{der, pot} = E * n / BW

The following parameters form part of the assessment of the extent of the skin exposure:

The following data have been used to calculate the skin absorption for children:

8.3 Exposure via inhalation

When playing with toys containing fragrances and other chemical substances, an emission of volatile, organic components to the air may take place, whereupon the substances can be inhaled by the child. It is especially interesting to assess the concentration of the single substances in the volume around the child in connection with the exposure.

The emission test was conducted with 1 g material in a small chamber from which air has been sucked, corresponding to an air change of 2.9 times per hour. The results appear from table 7.4 in chapter 7 as a concentration in the air specified as µg/m³.

The obtained concentrations can be converted to a source strength, R, from the single product:

(3) R = C₀ * n₀ *V₀, where C₀ is the measured concentration in the test, n₀ is the air change in the test chamber and V₀ is the volume of the test chamber.

The source strength R is used for calculating the concentration in the air at a given exposure. It is expected that the volume around the person is 2 m³ (V) and that the air change is (n) 0.5 times per hour, which is a normal air change in a house, compare with TGD (2003).

The concentration around the person is thus:

(4) C = R / (V * n) = C₀ * n_O *V₀ /(V * n), where n is the air change in the house and V is the volume around the person.

The calculations were made for the substances that have been selected on the basis of the emission test for further estimation of a typical exposure scenario.

Outline of the applied parameters for estimating concentration in the air around a person at a given exposure:

The following data were used to calculate the concentration around the person:

The values for n₀ and V₀ are data for the test, but the values for n and V are values from TGD (2003).

8.4 Data for evaluation of health conditions at exposure

The extent of the exposure when using the products is compared with the known limit values for effects on the health. NOAEL (No Observed Adverse Effect Level) values or LOAEL (Lowest Observed Adverse Effect Level) defined in animal tests often carried out on rats or mice are used. The NOEAL values state the highest investigated concentration where adverse health impacts have not been found, either stated as the concentration in the air or as absorbed quantity. By extrapolation of NOAEL values defined in animal tests to humans, the means of exposure and the seriousness of the effects should be taken into consideration. LOAEL is the lowest investigated concentration where effects have been detected. If it is not possible to define a NOAEL value in the tests, LOAEL is used in the assessment of the risk.

To illustrate the harmful effects and expected effect levels of the selected substances, searches have been made in EU risk assessments, IUCLID and US EPA (Toxnet, Riskline, IRIS, HSDB). NOAEL values found in literature appear from the below key tables. With regard to tris(2-chlorethyl)phosphate, which was demonstrated during the migration test, NOAEL values are shown for intake, supplemented with information from a draft of the EU risk assessment of TCEP.

For substances detected during the emission test, limit values have been found in literature for content in the air of the substances in question. These are the limit values of the National Labour Inspection (AT 2002), LCI (Lowest Concentration of Interest) (EU 1997) and reference concentrations for inhalation, RfC (IRIS 2004).

The limit values of the National Labour Inspection have been stated for content in the air in a working environment (AT 2002) whereas LCI (Lowest Concentration of Interest) has been stated especially for indoor climate. The LCI values have been defined as the lowest concentration of a given substance, which, based on the present knowledge, does not cause any risk of harmful effects on human beings (EU 1997). LCI is calculated on the basis of harmful effects in the working environment and is therefore not considered a real limit value for the indoor climate, but an estimate of when it may be expected to cause inconvenience, typically mucosal irritation and skin irritation, in a given indoor climate. The LCI values are often calculated from the limit values for the working environment with a typical safety factor of 100. For teratogenic, reproduction toxic or carcinogenic substances, the safety factor is, however, 1,000.

Reference concentrations for inhalation, RfC (IRIS 2004), are an estimate of a daily exposure at inhalation where no risk of harmful effects is expected through the lifetime of a normal human being. The inhalation reference concentrations are stated on the basis of toxic effects on the respiratory system as well as effects outside the respiratory system.

Furthermore, odour thresholds values have been stated for the single substances. They are included, as focus is on fragrances, i.e. substances that may be expected to have a low odour threshold. The odour threshold values are from VOCBASE (VOCBASE, 1996).

8.4.1 Tris(2-chlorethyl)phosphate, CAS number 115-96-8

Exposure to tris(2-chlorethyl)phosphate has been investigated in mice and rats. The tests show effects on liver and kidneys. By repeated intake (oral dosing or via a pump directly to the stomach), NOAEL values of 88-400 mg/kg body weight/d have been demonstrated. During an investigation of effects in the foetal stage of rats, NOAEL of 200 mg/ kg body weight/d has been found for the mother animal (IUCLID 2000), observed as a reduction in the food intake. No significant effects on the foetus were demonstrated.

At present, TCEP is being risk assessed in EU with Germany as rapporteur country. The results of the health assessment is available as first draft. From this a LOAEL of 12 mg/kg body weight/d appears as the lowest toxicity value and used as basis for the risk assessment (RAR 2004). The LOAEL values has been found by repetitive intake of TCEP in test with mice over a period of 18 months, where injuries to the kidneys were observed. A NOAEL value for these effects was not determined (RAR2004).

Table 8.2: NOAEL values found in literature for Tris(2-chlorethyl)phosphate selected on the basis of the migration test

8.4.2 Tert-butanol (2-methyl-2-propanol), CAS number 75-65-0

Effect from inhalation of tert-butanol has been investigated in tests for illustration of foetal malformation of rats. During the tests, reduction in food intake and loss of weight were observed for the mother as well as reduction in the bone formation of the foetus. NOAEL was determined at 6,053 mg/m³ (2,000 ppm) for the mother animal and at 15,133 mg/m³ (5.000 ppm) for the foetus (IUCLID 2000).

Table 8.3: NOAEL values found in literature for Tert-butanol selected on the basis of the emission test

Limit values and odour threshold for tert-butanol:

Limit value (AT 2002): 150 mg/m³
LCI (EU 1997): 1 mg/m³
RfC (IRIS 2004): -
Odour threshold (VOCBASE 1996): 70,000 µg/m³

8.4.3 n-butylacetate, CAS number 123-86-4

Only a few tests for determination of NOAEL at inhalation of n-butylacetate have been found in literature. Effect on the foetal stage was investigated during tests with rats and rabbits. There were no significant effects on the foetus at the tested concentration of 7,230 mg/m³ (1,500 ppm), whereas the mother animals showed reduced food intake and loss of weight (IUCLID 2000).

Table 8.4: NOAEL values found in literature for n-butylacetate selected on the basis of the emission test

Limit values and odour threshold for n-butylacetate:

Limit value (AT 2002): 710 mg/m³
LCI (EU 1997): 7 mg/m³
RfC (IRIS 2004): -
Odour threshold (VOCBASE 1996): 47 µg/m³

8.4.4 Butylglycol (2-butoxyethanol), CAS number 111-76-2

NOAEL values determined during inhalation studies by repeated exposure of rats and guinea pigs are in the interval of 98-610 mg/m³ (IUCLID 2000, IRIS 2004). Effects on the blood, liver and kidneys were demonstrated. Also effects on the foetus at exposure of the mother animal were observed during pregnancy and NOAEL for the foetus was determined at 970 mg/m³ (IUCLID 2000).

Table 8.5: NOAEL values found in literature for butylglycol selected on the basis of the emission test

Limit values and odour threshold for butylglycol:

Limit value (AT 2002): 98 mg/m³
LCI (EU 1997): 1 mg/m³
RfC (IRIS 2004): 13 mg/m³
Odour threshold (VOCBASE 1996): 5 µg/m³

8.4.5 Cyclohexanon, CAS number 108-94-1

Only few data are available for health effects at inhalation of cyclohexanon. A test of volunteers exposed to different levels of cyclohexanon in the air showed that most of the volunteers complained about irritation of the eyes, nose and throat at concentrations of 300 mg/m³, whereas a concentration of 100 mg/m³ was considered acceptable (Riskline 2004). A long-term study with rabbits demonstrated injuries to the central nervous system after repeated exposure. A NOAEL of 2,450 mg/m³ (Riskline 2004) was determined. An 8 hours time-weighted average limit value is specified as 20 mg/m³ intended for a working environment (Riskline 2004).

Table 8.6: NOAEL values found in literature for cyclohexanon selected on the basis of the emission test

Limit values and odour threshold for cyclohexanon:

Limit value (AT 2002): 40 mg/m³
LCI (EU 1997): 1 mg/m³
RfC (IRIS 2004): -
Odour threshold (VOCBASE 1996): -

8.4.6 Ethylbenzene, CAS number 100-41-4

Changes to liver and kidneys as well as weight changes were observed in mice and rabbits repeatedly exposed to gaseous ethylbenzene in concentrations of 100-3,350 mg/m³ (23-750 ppm). Changes in the blood composition were observed at 100 mg/m³. NOAEL was determined in the interval of 10-2,370 mg/m³ (2.3-500 ppm) (IUCLID 2000).

Table 8.7: NOAEL values found in literature for ethylbenzene selected on the basis of the emission test

Limit values and odour threshold for ethylbenzene:

Limit value (AT 2002): 217 mg/m³
LCI (EU 1997): 1 mg/m³
RfC (IRIS 2004): 1 mg/m³
Odour threshold l (VOCBASE 1996): -

8.4.7 Hexane, CAS number 110-54-3

In spite of risk of hexane's harmful effect at inhalation, only few data have been found of NOAEL values determined in inhalation tests. During inhalation of hexane, irritation of the mucous membranes of the nose was observed in a test with repeated exposure and a NOAEL value of 1,762 mg/m³ (IRIS 2004) was determined. For use in a working environment (exposure in 8 hours), an average limit value of 73 mg/m³ (IRIS 2004) is stated.

Table 8.8: NOAEL values found in literature for Hexane selected on the basis of the emission test

Limit values and odour threshold for hexane:

Limit value (AT 2002): 90 mg/m³
LCI (EU 1997): 0.7 mg/m³
RfC (IRIS 2004): 0.2 mg/m³
Odour threshold (VOCBASE 1996): 79,000 µg/m³

8.4.8 Methylethylketone (MEK), CAS number 78-93-3

Loss of weight was observed in rats repeatedly exposed to MEK in the air during a period of 90 days. A NOAEL value was determined at 7,362 mg/m³ (2,500 ppm). Reduced increase in weight of pregnant rats exposed to MEK in the air during pregnancy was observed, whereas the bone formation of the foetus showed deviations (IUCLID 2000). No significant effects were detected in mice at the tested concentrations of MEK in the air of 8,834 mg/m³ (3,000 ppm).

Table 8.9: NOAEL values found in literature for methylethylketone (mek) selected on the basis of the emission test

Limit values and odour threshold for methylethylketone (MEK):

Limit value (AT 2002): 145 mg/m³
LCI (EU 1997): 1 mg/m³
RfC (IRIS 2004): 5 mg/m³
Odour threshold (VOCBASE 1996): 870 µg/m³

8.4.9 Methylisobutylketone (MiBK), CAS number 108-10-1

Inhalation of MiBK in the air showed a weight reduction of liver and kidneys of exposed rats and mice. Also changes in the blood composition of some animals were demonstrated. When testing pregnant rats, loss of weight of the mother animal was demonstrated. NOAEL for rats and mice was found in the interval of 208 - 2,080 mg/m³ (50-500 ppm) at repeated exposure to MiBK in the air (IUCLID 2000).

Table 8.10: NOAEL values found in literature for methylisobutylketone (mibk) selected on the basis of the emission test

Limit values and odour threshold for methylisobutylketone (MiBK):

Limit value (AT 2002): 83 mg/m³
LCI (EU 1997): 1 mg/m³
RfC (IRIS 2004): 3 mg/m³
Odour threshold (VOCBASE 1996): 540 µg/m³

8.4.10 Toluene, CAS number 108-88-3

Inhalation of toluene can affect the nervous system. A wide range of tests have been made with rats and mice to illustrate the effect of toluene. NOAEL values in the interval of 377-3,770 mg/m³ (100-1,000 ppm) have been determined during tests with repeated dosing. In tests carried out to investigate the effect on reproduction, NOAEL was 1,508-1,885 mg/m³ (400-500 ppm). During tests to illustrate the effects at the embryonic stage of rats, mice and rabbits, NOAEL of 500-2,830 mg/m³ (131-750 ppm) has been demonstrated for both the mother animal and the foetus (IUCLID 2000).

Table 8.11: NOAEL values found in literature for toluene selected on the basis of the emission test

Limit values and odour threshold for toluene:

Limit value (AT 2002): 94 mg/m³
LCI (EU 1997): 1 mg/m³
RfC (IRIS 2004): 0,4 mg/m³
Odour threshold (VOCBASE 1996): 644 µg/m³

8.4.11 Xylenes, CAS number 1330-20-7

During tests with mice inhaling xylenes in a mixture, reduced bone formation was observed in the foetus. No effect on the mother animal was reported. Inhalation of xylenes caused death, abortion or foetal death at concentrations of 1,120 mg/m³ (230 ppm), whereas no effects were observed at 560 mg/m³ (115 ppm) (IUCLID 2000).

Table 8.12: NOAEL values found in literature for xylenes selected on the basis of the emission test

Limit values and odour threshold for xylenes:

Limit value (AT 2002): 109 mg/m³
LCI (EU 1997): 1 mg/m³
RfC (IRIS 2004): 0.1 mg/m³
Odour threshold (VOCBASE 1996): -

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Version 1.0 March 2006, © Danish Environmental Protection Agency