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Effects on fertility

Description of key information

No adverse effects were observed, either in the adult animals or in the offspring, at the highest dose (200 mg/kg bw) used in an OECD 422 study (28-day exposure) via the oral route.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
200 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

According to the Regulation EC 1907/2006, a two-generation reproductive toxicity study (one species, male and female, most appropriate route of administration, having regard to the likely route of human exposure) must be proposed in the REACH dossier (Annex IX) if the 28-day or 90-day study indicates adverse effects on reproductive organs or tissues. An OECD 422 study (28-day exposure) via the oral route is available which has not shown any adverse effects, either in the adult animals or in the offspring at the highest dose (200 mg/kg bw) used. Dosage levels were selected based on the results of previous studies and were provided by the Sponsor after consultation with the Study Director. In a previous 14-day toxicity study in Crl:CD(SD) rats (Stump, Draft, WIL-738003), the maximum tolerated dose was exceeded at 1000 mg/kg/day. At 300 mg/kg/day, lower mean body weight gains, reduced food consumption, adverse clinical signs, and/or changes in mean organ weights were noted for males and females. Based on these results, dosage levels of 25, 75, and 200 mg/kg/day were selected to be evaluated in the current study.


Justification for selection of Effect on fertility via oral route:
The study used for this end-point is an OECD 422 study with a supporting substance (read-across). The study has been conducted under GLP. The substance used for read-across is a structural analogue with a similar functional group and comparable phys-chem properties as the substance to be registered.

Effects on developmental toxicity

Description of key information

No adverse effects were observed, either in the adult animals or in the offspring, at the highest dose (200 mg/kg bw) used in an OECD 422 study (28-day exposure) via the oral route.

In an OECD 414 study in rabbits, no developmental toxicity was observed at the highest dose of 75mg/kg.

No developmental toxicity was also observed in rats in an OECD 414 equivalent study, but the maximum dose tested was only 10mg/kg.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
75 mg/kg bw/day
Study duration:
subacute
Species:
rabbit
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

No information is available for the registered substance. Read across has been performed to the structurally related substance PETIA, CAS 1245638 -61 -2, which has the same functional groups and is, due to the missing ethoxy elements expected to be more reactive than the registered substance.

Justification for classification or non-classification

No test item related, or adverse effects were noted at evaluation of the reproductive parameters during mating and gestation, delivery and post-partum/lactation period, under the conditions of this study.There were no adverse effects ascribed to test item administration on the F1 offspring viability, clinical signs, development or at observations following euthanasia. There were no test item-related changes observed in organ weights, at necropsy or at histopathology for the adult animals of either sex. The NOEL for effects in the offspring (F1) is considered to be 200 mg/kg bw/day.

In OECD 414 study in rabbits, there was also no indication of a developmental effect. This is supported by the results of a teratogenicity study in rats.

Therefore, there is no need to classify the substance for fertility and developmental toxicity, according to the Regulation EC 1272/2008 and the Directive 67/584/EEC.

Additional information