Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Additional information
Short description of key information:
In accordance with column 2 of REACH Annex X, no two-generation reproduction toxicity study is needed since: 1) repeated dose studies did not reveal any adverse effects on the gonads or other fertility effects; 2) no teratogenic effects were observed in a prenatal developmental toxicity study (OECD 414).

Effects on developmental toxicity

Description of key information
In an oral developmental toxicity study with ZPS in rats, the NOAEL for maternal toxicity and embryotoxicity / teratogenicity in the offspring was 2500 mg/kg bw/day, the highest dose tested.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Additional information

In a GLP compliant developmental toxicity study with ZPS, performed according to a protocol similar to OECD guideline 414, female CD rats (23-25/dose) were exposed by gavage to 0, 0.25, 2.5, 250 or 2500 mg/kg bw/day from day 6 through day 15 of gestation (The Procter & Gamble Company, 1987). The pregnant rats were weighed on days 0, 6, 9, 12, 15 and 20 of gestation, and the feed consumption was measured for similar periods. On day 20 of gestation, the dams were sacrificed by CO2inhalation, and caesarean-sectioned. A gross inspection of the viscera was made, and the corpora lutea of pregnancy were counted. The uterine horns were incised and the foetuses removed, noting implantation and resorption sites. All foetuses were weighed, and inspected for external abnormalities. The sex was also determined. One foetus of each sex was randomly selected from each litter and placed in formalin for possible future histopathology of the foetal liver. One-half of each litter was randomly assigned to either soft-tissue or skeletal examinations.

Twenty-two to twenty-four females in each group were sperm-positive, with 21-24 being confirmed as pregnant on day 0 of gestation. At necropsy, all of the dams at the three highest doses had green-tinted viscera, with the discoloration being especially pronounced at the two highest dosages. There were no statistically significant differences in body weight gain and food consumption. There were no statistically significant differences in the number of corpora lutea, implants, resorptions and (non-)viable foetuses. Hence ZPS did not have a deleterious effect on either the viability or growth of the embryo and foetus. There was no evidence of increased incidence of either external, skeletal or soft-tissue abnormalities in fetuses from dams treated with the substance. Since no evidence of either discoloration of the foetal organs nor malformations were present, the foetal livers were not examined histologically.

In conclusion, the NOAEL for maternal toxicity was 2500 mg/kg bw/day. All of the dams at the three highest doses had green-tinted viscera, with the discoloration being especially pronounced at the two highest dosages, but this was not considered adverse. ZPS was not embryotoxic nor teratogenic at doses ranging from 0.25 to 2500 mg/kg bw/day. Neither was there any evidence of discoloration in the foetal livers (NOAEL for embrytoxicity / teratogenicity: 2500 mg/kg bw/day).

Justification for classification or non-classification

Based on the available data, ZPS does not need to be classified for developmental toxicity according to Annex I of Directive 67/548/EEC and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.