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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
479 mg/kg bw/day
Study duration:
subacute
Species:
rabbit
Additional information

The reproductive toxicity of DMT has been investigated in an older one-generation study in the rat (Krasavage et al, 1972;1973). Dimethyl terephthalate was administered to groups of 20 male rats in the diet for 115 days, at doses of 0, 0.25, 0.5 and 1.0%.

The male rats were then mated with twenty virgin females which had also been fed the dimethterephthalate diet for 6 days prior to mating. Male rats treated with dimethyl terephthalate showed normal mating behaviour. All treatment groups had a higher percentage of inseminations than the control group. Ninety-five to 100% of these inseminations resulted in a pregnancy with a normal gestation period and litter size. The only effect seen in pups was a statistically significant reduction in body weight at weaning compared to the control in the 0.5 and 1.0% dose groups. The NOAEL for reproductive toxicity can be considered to be 1% dimethyl terephthalate in the diet, the NOAEL for parental toxicity was 0.5% and the NOAEL for offspring toxicity was 0.25%.

Using the default conversion factors, dose levels are calculated to be approximately equivalent to 250, 500 and 1000 mg/kg bw/d.

A waiver is proposed for further testing for reproductive toxicity. Existing data for the substance, including developmental toxicity studies in rodent and non-rodent species, a one-generation reproduction toxicity study and 90-day studies using oral and inhalation exposure do not indicate any effects on the reproductive organs or on fertility or reproductive performance. Additional tetsing in a two-generation study is not justified for scientific reasons or on animal welfare grounds.

Short description of key information:
No evidence of an effect on fertility or reproductive capacity was seen in a one-generation study in the rat at dose levels up to and including approximately 1000 mg/kg bw/d. Findings in offspring were limited to bodyweight effects at weaning, likely to be attibutable to reduced dietary palatability.

Effects on developmental toxicity

Description of key information
No evidence of developmental toxicity was seen in a guideline-compliant rat study at the limit dose of 1000 mg/kg bw/d.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

Dimethyl terephthalate was administered to female Wistar rats via gavage, at a dose of 1000 mg/kg bw/d, on days 7 through 16 post-copulation (Hoechst, 1986). Controls received the vehicle alone. Dams were sacrificed on gestation day 21 for examination of uterine contents. There was no evidence of maternal toxicity. No embryotoxic or teratogenic effects were observed. The NOAEL for maternal and developmental toxicity in rats is therefore the limit dose of 1000 mg/kg bw/d.

An OECD 414 prenatal developmental toxicology study also was performed using DMT in rabbits.

There were no adverse effects on maternal survival, clinical or macroscopic findings, body weights, food consumption, clinical pathology parameters, and organ weights at 200, 400, and 600 mg/kg/day when dimethyl terephthalate (DMT) was offered in the diet (pellets) to New Zealand White rabbits. In addition, there were no test substance-related effects on intrauterine growth and survival and fetal morphology at any dosage level. Based on these results, a dosage level of 600 mg/kg/day (test substance concentration of 479 mg/kg/day), the highest dosage level evaluated, was considered to be the no-observed-adverse-effect level (NOAEL) for maternal and embryo/fetal developmental toxicity when DMT was offered in the diet (pellets) to New Zealand White rabbits.

Justification for classification or non-classification

Dimethyl terephthalate had no effects on rat reproduction, and did not result in embryotoxic or teratogenic effects, and therefore does not warrant classification according to Regulation (EC) No. 1272/2008 (CLP).