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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Additional information

There were no reproduction/developmental toxicity studies conducted with dibutyl terephthalate identified. There are two-generation reproductive toxicity studies available for the analogue materials terephthalic acid and n-butyl acetate. Developmental toxicity studies are available forn-butanol and terephthalic acid.

Reproductive Toxicity

In a two-generation reproductive toxicity study, male and female rats were fed diets containing 0, 1000, 5000 or 20000 ppm terephthalic acid for 10 weeks at which point animals were mated and allowed to rear F1 litters to weaning. This breeding program was repeated with the F1 parents to produce a F2 litter after a 10-week premating period. Test diets were administered continuously. Dietary administration did not result in any effects on reproductive performance. Irritant bladder changes were present in males and females receiving 20000 ppm. The only effect noted at 1000 ppm was a decrease in kidney weights in adults and pups. In an independent review by the UK Committee on Toxicity (COT), the histopathological changes in the urinary bladders and kidneys corresponding to 5000 ppm of terephthalic acid in the diet was considered to represent a clear no adverse effect level (NOAEL) for toxicity. The NOAEL for effects on reproduction and developmental toxicity was 20000 ppm.

In a two-generation reproductive toxicity study, male and female rats were exposed to n-butyl acetate, rats were exposed by inhalation for 6 h/day, 7 days/week for at least 70 consecutive exposures at 750, 1500 or 2000 ppm for F0, F1 and F2 generations. The F0 and F1 females continued to be exposed throughout mating and gestation through gestation day 20. On lactation days 1-4, F0 and F1 maternal animals received 3 equal gavage doses, approximately 2 hours apart, to mimic the internal dose expected from inhalation exposure. There were no functional effects on reproduction for any exposed group. Adverse effects in pups were limited to exposure-related growth retardation, as evidenced by lower mean pup weights and delays in post-weaning developmental landmarks. General systemic toxicity was present at the 1500 and 2000 ppm exposure levels and consisted in decrements in mean body weights, body weight gains and food consumption. Thus, the 750 ppm exposure level was considered to be both the NOAEC for both developmental toxicity and for general systemic toxicity in adult rats.

Short description of key information:
Two generation reproductive toxicity studies in rats with the read across chemicals, terephthalic acid and n-butyl acetate, indicate a lack of adverse effects on reproductive organs in either sex of rats and no adverse effects on any reproductive or developmental parameters.

Effects on developmental toxicity

Description of key information
Developmental toxicity studies performed with the read across chemicals, terephthalic acid and n-butanol, indicate no selective developmental toxicity.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
5 654 mg/kg bw/day
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
10 mg/m³
Additional information

Rats were administered n-butanol in the drinking water at 0.2, 1.0 or 5.0% (314, 1454 or 5654 mg/kg bw/d) on days 0 through 20 of pregnancy. A significant decrease in maternal body weight gain accompanied by reduced food and water consumption was present at the 5% dose level. Fetal weights were significantly lowered at the 5.0% dose level. Increased numbers of fetuses with skeletal variations and decreased degrees of ossfication were observed at the 5% dose level, however, there were no increases in the incidences of fetuses with external, skeletal or internal abnormalities. It was concluded that n-butanol is a developmental toxicant only at maternally toxic dose levels.

Rats were administered n-butanol by inhalation at 0, 10.8, 18.5 or 24.7 mg/L (0, 3500, 6000 or 8000 ppm) for 7 h/day on days 1-19 of gestation. There was no effect observed on mean numbers of corpora lutea/litter, mean resorptions/litter, mean numbers of fetuses/litter or sex ratios. Fetal weights were slightly decreased at the two highest concentrations. External fetal malformations were not observed. There were no differences in malformation rates (skeletal or viceral) or in rates of commonly observed variations. The NOAEC for fetotoxicity and maternal toxicity was 10.8 mg/L. The NOAEC for teratogenicity was 24.7 mg/L.

Terephthalic acid was administered by aerosol inhalation to rats at concentrations of 0, 1.0, 5.0 or 10.0 mg/m3 for 6 h/day on gestation days 6 to 15. Exposures resulted in no significant toxic or teratogenic effects in the dams or fetuses.

Justification for classification or non-classification

In two-generation reproductive toxicity studies with the analogue materials, terephthalic acid and n-butyl acetate, there were no adverse effects on reproductive organs in either sex of rats and no adverse effects on any reproductive or developmental parameters. In addition, the analogue materials,n-butanol and terephthalic acid, were not selective developmental toxicant in rats after administration in the drinking water or following inhalation exposures (n-butanol) or aerosol inhalation (terephthalic acid). Based on these results, dibutyl terephthalate is not considered a reproductive toxicant and is not selectively toxic to the fetus. It is not classified for “Reproductive/Developmental Toxicity” according to GHS guidelines.