Environmental and Health Assesment of Alternatives to Phthalates and to
flexible PVC

English Summary 

Phthalates and PVC 
Phthalates are a group of plasticisers, which among others is used for manufacturing of soft PVC. In recent years laboratory experiments have shown that some of the phthalates may have toxicological and ecotoxicological effects, e.g. impaired capacity for reproduction in laboratory animals Effects are seen at levels, which give rise to concern in relation to exposure of man and environment. Five phthalates are under risk assessment in the EU. In Denmark a plan for 50% reduction over the next 10 years has been adopted. Other countries like Sweden and Germany have a similar objective. It is therefore to be expected that the need for alternatives to the existing plasticisers will grow in the near future. In this report a range of alternatives to phthalates and flexible PVC has been assessed with respect to their inherent properties and potential risk for humans and the environment.

Evaluated substances and materials
The Danish Environmental Protection Agency (DEPA) had in advance se-lected five substances and in concert with the industry another six sub-stances were selected as examples for the remaining groups of alternative plasticisers. Also two polymeric materials were selected as alternatives to flexible PVC. A data search in readily available databases was performed at first. On this basis preliminary data sheets were produced for the physico-chemical, health and environmental properties of the substances. A possible substitution pattern expected for phthalates in Denmark was developed based on information from the Danish Product Register, suppliers and the industry.

Exposure, health and environmental properties
Key data for the assessment of toxicological effects in man and the envi-ronment were identified. For these data additional information was obtained in the original literature and presented in more detail in the main report.

Screening of health and environmental effects are based on inherent properties. The risk to man and environment is illustrated through two possible exposure scenarios: one scenario based on an expected substitution pattern and another scenario based on substitution of the total consumption of phthalates for a particular use with the actual plasticiser. The estimation and comparison was carried out according to principles of the EU Technical Guidance Document. Exposures were determined using the EASE and EUSES models, which were supplied with substance data and amounts for the chosen exposure conditions. The physical dimensions of the regional scenario were set at values representative for Denmark.

Table 1.1 The registered use of the selected substances as plasticisers in the selected product groups. Data obtained from the Danish Product Register. The polyester plasticiser (polyadipate) was not included due to lack of CAS no.

* Not found in the Product Register.

Migration and volatility
The key parameters with respect to release of plasticisers under polymer production and consumer use, are potential for evaporation and migration out of the PVC polymer. Some data exist for volatility, but only few data have been identified on migration potential for the substitutes.

Assessment of polymer materials
The assessment principles in the EU Technical Guidance Document are only applicable for substances. The polyadipate plasticiser and the two materials are assessed based on their monomers and oligomers as well as on general properties of polymers. Based on the obtained data it is estimated that the polyadipate and the two materials will have no immediate effects in the con-sumer use situation or in the environment.

Assessment of substances
A comparative assessment of the substances is difficult, as only few and often different parameters are available for some of the substances. Quantita-tive ranking is not a possibility with the available data set presented for the substances. In the following two tables (Table 1.2 and Table 1.3) a summation of the inherent hazardous properties and the potential risks from use of the suggested alternatives are presented.

The selected key properties (inherent properties) with rspect to humans are those effects, which manifest themselves immediately after exposure and chronic effects, which may arise from a single or repeated exposure. For these properties it is evaluated whether thay fulfil the criteria for classification according to the EU regulations. Key properties with respect to the en-vironment are persistence, bioaccumulation and aquatic toxicity. For those parameters it is also evaluated whether they fulfil the EU classification crite-ria for the aquatic environment.

The assessment of the risks to man and environment in relation to the inves-tigated substances is summarised in Table 1.3. The assessment of the risk to humans is based on a comparison between the estimated exposure and the established or suggested Acceptable Daily Intake (ADI). The asssessment of the risk to the environment is based on a comparison between the predicted environmental concentrations (PEC) in the aquatic environment and predicted no-effect concentrations (PNEC).

Physical-chemical properties and exposure
Several of the substances are considered to have lipophilic properties based on measured or estimated LogPow values. Consequently they are expected to have a high tendency for accumulation in animals and plants.

Health assessment
Di(2-ethylhexyl) phosphate, tri(2-ethylhexyl) phosphate, tri-2-ethylhexyltrimellitate and dioctyl sebacate fulfil the criteria for classifica-tion with regard to acute toxicity or local effects. Based on the available lit-erature di(2-ethylhexyl) phosphate should be classified as Corrosive (C) and Harmful (Xn) with the risk phrases R34 (Causes burns) and R21 (Harmful in contact with skin). This classification was suggested by Bayer AG (Bayer, 1993) and is supported by the toxicological findings in the literature. Tri(2-ethylhexyl) phosphate fulfils the criteria for classification as Irritant (Xi) with the risk phrase R36/38 (Irritating to eyes and skin) also according to Bayer AG (1993). Tri-2-ethylhexyltrimellitate fulfils the classification crite-ria with respect to acute toxicity as Harmful (Xn) with the risk phrase R20 (Harmful by inhalation) and dioctyl sebacate as Harmful (Xn) with the risk phrase R22 (Harmful if swallowed) based on LC50 and LD50 values. On the basis of the limited amount of data it has not been possible to evaluate all effects with respect to classification. For some of the substances data on effects from repeated dosing are available, but none of the investigated substances have been shown to cause serious systemic effects e.g. on organs, heredity, foetuses, or the like.

Environmental assessment
The compounds for which ecotoxicity data are available (only data for the aquatic environment available) show relativly high acute ecotoxicity, that in all cases would lead to an environmental hazard classification. The adipate would be 'Very toxic' (R50/53), tri(2-ethylhexyl) phosphate and epoxidised soybean oil isare classifiable as 'Toxic' (R51/53), and o-acetyl tributyl citrate, di(2-ethylhexyl) phosphate and tri(2-ethylhexyl) phosphate would be classified as 'Harmful' (R52/53). For the trimellitate and the sebacate, the low aqueous solubility in combination with persistence and bioaccumulation potential would lead to a classification as 'May cause long term effects in the aquatic environment' (R53).

Several substances show limited degradabililty in the environment (the trimellitate and possibly both phosphates). Some have an estimated high bioaccumulation potential (citrate, trimellitate, dibenzoate and sebacate). The trimellitate and the dibenzoate possibly combine both these environ-mentally undesired properties. It must be emphasised that this is based on estimated values for bioaccumulation, which again are based on estimated octanol-water partition coefficients. It is possible that these compounds to some extent hydrolyses in the environment and bioaccumulation will then be considerably less. Measured bioaccumulation for the adipate and the two phosphates are below the criteria for when substances are considered to bio-accumulate.It is emphasised that no data are available for any of the substitutes to evaluate possible effects in the terrestrial environment. Except for one study on the effect of DEHA no data on microorganisms has been identified for the remaining substances.

Risk for humans
The risk to humans has been investigated in exposure scenarios illustrating direct exposure to products, e.g. tubes for haemodyalisis, milk tubes, and teething rings, and in relation to the workplace scenarios. The selected workplace scenario considers aerosol generation in connection with produc-tion of floor and wall coverings using a process temperature of 200°C and eight exposure events per day. The estimated concentrations in workplace air for the adopate in this scenario were 104 times the concentration, which has been shown to result in more pronounced reactions in workers with an allergy or asthma case history. For the two phosphates the estimated con-centrations in workplace air were lower than reported concentrations from inhalation studies in the reveiwed literature. As no no-effect levels have been established for this type of exposure, the risk cannot be evaluated.

In relation to indirect exposure from the environment, the estimated con-centration is compared to the Acceptabel Daily Intake (ADI) with food. Where no established ADI is available, it is chosen to compare the concen-tration to the group ADI established/suggested for for plasticisers (based on DEHP). For the sebacate the worst case exposure is expected to exceed the suggested ADI. For the trimellitate the exposure is expected to get close to or exceed the suggested group ADI

When calculating the possible concentrations in food, it is especially root crops, which may contain considerable concentrations.

In a scenario where the exposure of children to teething rings is calculated, the citrate does reach 37% of a preliminary ADI of 1 mg/kg bw/day. This preliminary ADI is calculated by Nikiforov (1999) in relation to a prelimi-nary risk assessment prepared on behalf of the manufacturer and it is not officially recognised. A closer investigation of the exposure conditions and better data on effects may change this evaluation.

Risk for the environment
None of the five assessed substances (diethylhexyl adipate, o-acetyl tributyl citrate, di(2-ethylhexyl) phosphate, tri(2-ethylhexyl) phosphate, and tri-2-ethylhexyl trimellitate) give rise to concentrations in the aquatic environ-ment, which exceed the predicted no-effect level for the aquatic nvironment in general. For the adipate there may be a risk for the sediment compartment due to the sorptive properties of the substance combined with low degrad-ability. The risk to the aquatic environment from o-toluene sulfonamide, epoxidised soybean oil, diisobutyrate and dioctyl sebacate could not be calculated.

Terrestrial and microbial toxicity
It must be stressed that a number of the assessed substances are lipophilic and may have a high affinity for sludge particles similar to that of DEHP. Data on terrestrial toxicity are not identified. Very limited information on effects on microorganisms in the sewage treatment was found for five substances plant (effects were typically not in the tested range of concentrations).

Data availability
The data availability varies among the suggested alternatives for phthalate plasticisers and materials. For di(2-ethylhexyl) adipate, o-acetyl tributyl cit-rate, tri(2-ethylhexyl) phosphate and tri-2-ethylhexyl trimellitate information is available covering a range of results from tests on toxicological proper-ties. However, only di(2-ethylhexyl) adipate can be considered adequately covered, although some areas need further investigation. Di(2-ethylhexyl) phosphate, o-toluene sulfonamide, 2,2,4-trimethyl 1,3-pentandiol diisobuty-rate, epoxidised soybean oil, dipropylene glycol dibenzoate and dioctyl se-bacate are covered in less detail, either because of lack of information or because of inferiour quality of the tests.

For di(2-ethylhexyl)adipate a large number of studies are available covering acute toxicity, local effects, sensitisation, repeated dose toxicity, chronic toxicity, genetic toxicity, reproductive toxicity and carcinogenicity. Reviews discussing the toxicological profile of the substance are also available. In a substitution context it is however important to consider all areas which may give rise to concern, to make sure that only less hazardous substituents are introduced. Based on comparisons with the structural analogue, di(2-ethylhexyl) phthalate, for which the most critical effect is considered to be testicular toxicity, a need to address this issue for the adipate as well has been identified.

For o-acetyl tributyl citrate the available data are not sufficient for a pro-found assessment. Data on acute toxicity are sparse and other effects like carcinogenicity are not sufficiently covered for a qualified assessment.

For the two phosphates, di(2-ethylhexyl)phosphate and tri(2-ethylhexyl)phosphat, a number of studies are available, sufficient to suggest a classification of the substances for acute and local effects. Studies on lre-peated dose and chronic toxicity like reproductive toxicity and carcinoge-nicity are either not available or not sufficient for an assessment.

For tri-2-ethylhexyl trimellitate a number of studies are available covering acute and local effects. More details are however needed in order to classify the substance with regard to irritant effects. More data are also needed on repeated dose and chronic toxicity studies. Studies on reproductive toxicity are not covered at all in the reviewed literature.

O-toluene sulfonamide is sparsely covered in the literature and no data are found available on acute toxicity. Few studies are available on other effects, but not sufficient for a qualified assessment or classification. Human data are only available for related substances or combined products.

Few data are available for 2,2,4-trimethyl 1,3-pentandiol diisobutyrate. In order to make a proper evaluation of acute toxicity more detailed information is necessary. Repeated dose and chronic toxicity are not covered in the reviewed information.

A limited number of studies are available for epoxidised soybean oil. Studies on acute toxicity suggest low toxicity, but more detailed information is needed for a proper evaluation. Data on repeated dose toxicity and chronic effects as carcinogenicity are also insufficient for a qualified assessment.

No toxicological data have been found for dipropylene glycol benzoate.

Also dioctyl sebacate is sparsely covered in the available literature. Few data are available describing acute toxicity and only oral toxicity has been evaulated. Data on other effects are not sufficient for an evaluation.

No toxicological data have been found for polyester (polyadipate).

Regarding environmental properties only di(2-ethylhexyl) adipate, o-acetyl tributyl citrate, and tri(2-ethylhexyl) phosphate have a data set comprising algae, crustaceans and fish, and data on biodegradation. The remaining substances have very few or no ecotoxicological data. There are very few data on chronic endpoints, very limited data on effects on microorganisms and no data on terrestrial ecotoxicity.

Table 1.2 The inherent properties for the investigated subtances are summarised using key parametersThe inherent properties for the investigated subtances are summarised using key parameters: acute and local effects, carcinogenicity(C), genetic toxicity (M), reproductive toxicity (R), sensitisation, persistance, bioaccumulation and aquatic toxicity. If data are not available for all parameters or only from non standard test results a tentative assessment is given (shown in parentheses). For the materials an evaluation is given based on general polymer properties. The symbols: ● identified potential hazard, ○ no identified potential hazard, and – no data available

^a Foetotoxicity (reduced ossification) has been identified as the most sensitive effect in a developmental toxicity study.
^b QSAR estimates by Danish EPA leads to the classification N; R50/53 (May cause long term effects in the aquatic environment). ^c A test on reproductive effects performed on a product containing OTSA as impurity attributes effect to OTSA. No substance specific data available
^d C,M,R indicated that the effect is investigated but no effects are seen.

Table 1.3 The evaluated risks to humans or the environment are summarised for the investigated substances (polymer materials not included). The estimated exposure of humans is compared to the Acceptable Daily Intake (ADI). Predicted environmental concentrations in the aquatic environment (PEC) are compared to predicted no-effect concentrations (PNEC). "Worst case" scenarios are used. The reader is referred to the main text and the data sheets for further explanations to the table. Parentheses show an assigned ADI. The symbols: ● ratio >1 (identified potential risk), ○ ratio <1 (no identified potential risk), and –no data available.

a Dose reaches 37% of preliminary ADI in teething ring scenario.
b Tentative estimate based on only one ecotoxicity study.
c Preliminary ADI from Nikiforov (1999)
d Data set comprise only two acute values and one chronic NOEC value.