Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

In a screening reproductive toxicity study (according to OECD guideline 421), rats were exposed to 3, 10, 30 mg/kg (nominal in water) via topical application. No systemic, reprotoxic or developmental effects were observed: a NOAEL of 30 mg/kg bw/day was derived.

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

In a screening reproductive toxicity study (according to OECD guideline 421), rats were exposed to 3, 10, 30 mg/kg (nominal in water) via topical application. No systemic, reprotoxic or developmental effects were observed: a NOAEL of 30 mg/kg bw/d was derived.

An extended one generation reproductive toxicity study is deemed not required as there is sufficient weight of evidence from the OECD 421 screening reproductive study on POPDA to conclude that there were no effects on reproduction at the highest concentration tested (30 mg/kg/day via topical application).

Moreover, the substance is corrosive; therefore, testing at higher concentrations is not justifiable. In addition, reproductive tissues (including testes, seminal vesicles, epididymides, prostate, ovaries, uterus, cervix and vagina) were examined for gross pathology in the 90-day repeated dose study and no adverse effects were noted.

This endpoint is considered to have been adequately tested through the use of the screening study.

Effects on developmental toxicity

Description of key information
The NOAEL for embryo-fetal survival, development and growth is set at 115 mg/kg/day when POPDA is administered during organogenesis in the rabbit.
    
    
    
    
    
    
    
    
    
    
    
    
    

An embryo-fetal development study with daily administration of PODPA in rabbits at dose levels 15, 50 and 115 mg/kg/day was performed. Based on the results of this prenatal developmental toxicity study, it was concluded that the NOAEL of POPDA for maternal toxicity was 50 mg/kg/day as the higher dose of 115 mg/kg/day elicited low food consumption that directly resulted in a single mortality, and elicited clinical signs relating to inappetance and overall body weight loss during gestation compared with body weight gain in all other groups. The NOAEL for embryo-fetal survival, development and growth is set at 115 mg/kg/day when POPDA is administered during organogenesis in the rabbit.

Based on the results of this OECD414 study, the NOAEL of POPDA for maternal toxicity was 50 mg/kg/day as the higher dose of 115 mg/kg/day elicited low food consumption that directly results in a single mortality, and elicited clinical signs relating to inappetance and overall body weight loss during gestation compared with body weight gain in all other groups. The NOAEL for embryo-fetal development and growth is set at 115 mg/kg/day when POPDA is administered during organogenesis in the rabbit.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
115 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 adverse effects on development were demonstrated in a reproductive/developmental toxicity screening study (OECD 421), with POPDA administered up to 30 mg/kg/day via dermal application. The substance is demonstrated to be corrosive. Therefore, testing at higher concentrations is not justifiable. In addition, reproductive tissues (including testes, seminal vesicles, epididymides, prostate, ovaries, uterus, cervix and vagina) were examined for gross pathology in the 90 -day repeated dose study and no adverse effects were noted.

A combined pilot and preliminary embryo-fetal development study was performed in rabbits with daily administration from day 6 to 28 after mating of POPDA at 75 or 150 mg/kg/day (pilot phase) or 115 or 150 mg/kg/day (preliminary phase). Mortality was observed as a direct result of a sustained period of very low food intake, hence 150 mg/kg/day is considered too high to investigate in the main embryo-fetal development study. The dose level of 115 mg/kg/day is considered appropriate as high dose, as no premature mortality in this study is observed.

An embryo-fetal development study with daily administration of POPDA via oral gavage in rabbits at dose levels 15, 50 and 115 mg/kg/day was performed. Based on the results of this prenatal developmental toxicity study, it was concluded that the NOAEL of POPDA for maternal toxicity was 50 mg/kg/day as the higher dose of 115 mg/kg/day elicited low food consumption that directly resulted in a single mortality, and elicited clinical signs relating to inappetance and overall body weight loss during gestation compared with body weight gain in all other groups. The NOAEL for embryo-fetal survival, development and growth is set at 115 mg/kg/day when POPDA is administered during organogenesis in the rabbit.

A developmental toxicity study in a second species (in this case, the rat) is deemed not required as 1) there were no adverse effects in a reproductive toxicity study (OECD 421) in rat via dermal application, 2) there were no adverse effects in a developmental toxicity study in rabbit (OECD 414) via oral gavage and 3) no adverse effects, incl on reproductive tissues, in a 90 -day repeated dose toxicity study were observed. Moreover, the rabbit is described as a more sensitive species compared to the rat, prone to elicit effects on reproduction and development, with a higher predictive value to effects in human. As no effects are expected when testing the developmental toxicity potential of POPDA in rat, further testing will not result in additional information.

.

Toxicity to reproduction: other studies

Additional information

This information is not available. However, this is not required under REACH.

Justification for classification or non-classification

Based on the available data and according to the criteria of the CLP Regulation, the substance should not be classified for toxicity to reproduction.