Classification of DEHP is unjustified
 Di(2-ethylhexyl) phthalate (DEHP) is the most widely used plasticiser for the manufacture of PVC-based plastic materials. It accounts for 30% of the European market of just over one million tons of phthalate plasticisers per year and close to 50% of the world market.
DEHP has been safely used in the manufacture of many household items and life-saving medical devices for more than 40 years. There is not one known case of anyone having suffered adverse health effects as a result.
The plasticiser industry disagrees with the decision of the European Chemicals Bureau (ECB) to classify DEHP as Category 2 for reproductive toxicity as part of the 28th Adaptation to Technical Progress of the Dangerous Substances Directive (67/548/EEC) on the grounds that it is unjustified and based on incomplete scientific evidence.
Category 2 labelling is not warranted
ECPI believes that a Category 2 classification for DEHP has been taken without due and proper consideration of the full and emerging scientific evidence.
The proposal for a Category 2 Classification is based on effects seen during studies on rats and mice. It ignores tests on monkeys during which, no such effects on fertility were seen. Toxicokinetic differences have also been seen between rodents and primates (relevant to both fertility and developmental effects) and important new studies on this aspect are expected to be available soon. It is regrettable that the Classification and Labelling Working Group did not await the results of these studies before reaching its decision.
Fertility Effects.
Some phthalates at high dose rates have been shown to cause reproductive effects in rats and mice. According to a review by the Commission of the European Communities(1) the most sensitive indicator of reproductive impairment by phthalates is testicular atrophy.
However, the evidence with regard to primates appears quite different. Results indicate that primates are resistant to the reproductive organ toxicity seen in rodents. A study by Kurata with marmosets(2) shows that repeated dosing of DEHP at up to 2500mg/kg body weight for 13 weeks resulted in no difference in testicular or prostate weight or any other aspect of the reproductive system and no differences in blood testosterone or oestradiol levels.
The Classification and Labelling guidelines (Annex VI, Dangerous Substances Directive 67/548/EEC) explicitly makes the point that toxicokinetic differences should be considered: 'even when clear effects have been demonstrated in animal studies the relevance for humans may be doubtful because of the dose administered…or where marked toxicokinetic differences exist'.
In the case of DEHP there are differences with respect to toxicokinetics between rodents and primates.
Developmental Effects.
Whilst the effects on development caused by DEHP have been seen in both rats and mice, there are toxicokinetic differences between rodents and primates which need to be taken into account.
The relevance of the rodent developmental effects compared to primates will become much clearer from a more definitive pharmacokinetic study in pregnant primates which is currently underway. Results are expected soon.
Taking into account all of these above points: clear species difference in response between rodents and primates, the toxicokinetic differences between rodents and primates, the relative dose levels and the ongoing studies, ECPI strongly believes that Category 3 classification for DEHP for reproductive effects would have been more appropriate.
Classification in Category 3 fully protects human health
Manufacturers have already classified DEHP as Category 3 which requires the St Andrews Cross symbol on the label. This classification was introduced under the industry's Responsible Care programme in 1994 in response to the modification of the classification and labelling directive. The product is not sold directly to consumers.
References
(1) Sullivan, F.M, Watkins, W.J and van der Venne, M. Th. (eds) (1993) 'The Toxicology of Chemicals' Series 2 Reproductive Toxicity, Volume 1, Summary Reviews of the Scientific Evidence, Commission of the European Communities
(2) Kurata, Y., Kidachi, F., Yokoyama, M., Toyota, N., Tsuchitani, M. and Katoh, M. (1998) Subchronic toxicity of DEHP in common marmosets: Lack of hepatic peroxisomal proliferation, testicular atrophy, or pancreatic acinar cell hyperplasia. Toxicological Sciences, 42, 49-56
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