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Administrative data

Key value for chemical safety assessment

Effects on fertility

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

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (Lewis, 2005) was conducted with cis-2-pentenenitrile according to the OECD test guideline No. 422 and in compliance with GLP. Crl:CD®(SD)IGS BR rats (10/sex/dose level) were dosed once daily by gavage at dose levels of 0, 1, 3, or 10 mg/kg bw/day (dose volume of 10 mL/kg in deionized water) for approximately 28 days prior to cohabitation and during the cohabitation period.

The results of this study were:

No effect was considered to be dose-related to the treatment based on the following parameters:

- Mortality and clinical signs of toxicity in P1 males and females

- Body weight and body weight gain in P1 males

- Food consumption in P1 males and females

- Functional observational battery, motor activity, or grip strength in P1 males and females

- Hematology and coagulation parameters in P1 males and females

- Mating, precoital interval, fertility, gestation length, corpora lutea, number of implantation sites, and implantation efficiency in the P1 generation

- Number of pups born, born alive, alive on day 4, sex ratio, and survival indices during the lactation period in F1 litters

- Clinical observations and mean pup weights during lactation in F1 litters

- Organ weights and gross pathology in P1 males and females

- Microscopic pathology in P1 males

 

Effects considered to be dose-related to treatment were limited to the 10 mg/kg bw/day group including:

Adverse effects:

- Degeneration of the olfactory mucosa in Level II of the nose in P1 females

Non-adverse effects:

- Decreased body weight, body weight gain, and food efficiency in P1 females (transient effects)

- Increased albumin in P1 males and females (not of toxicological concern in the absence of othe biochemical changes)

 

Conclusion:

Under the conditions of this study, the no-observed-adverse-effect level (NOAEL) for systemic toxicity in P1 rats was 3 mg/kg bw/day, based on degeneration of the olfactory mucosa in P1 females at 10 mg/kg bw/day.

However, no effects on fertility or development were observed in rats. Therefore, the NOAEL for fertility was considered as greater than 10 mg/kg bw/day, the highest tested dose.

 


Short description of key information:
Key study: kr 1, OECD 422, GLP:
-NOAEL parental = 3 mg/kg bw/day based on the degeneration of the olfactory mucosa of F1 females at 10 mg/kg bw/d.
-NOAEL reproduction > 10 mg/kg bw/d (no effect at the highest dose tested).
-NOAEL developmental > 10 mg/kg bw/d (no effect at the highest dose tested).
-NOAEL fertility > 10 mg/kg bw/d (no effect at the highest dose tested).

Effects on developmental toxicity

Description of key information
Key study: kr 1, OECD 422, GLP:
-NOAEL parental = 3 mg/kg bw/day based on the degeneration of the olfactory mucosa of F1 females at 10 mg/kg bw/d.
-NOAEL developmental > 10 mg/kg bw/d (no effect at the highest dose tested).
Additional information

The OECD 422 guideline study of Lewis (2005) provide initial information on possible effects on development of the conceptus even if it offers only limited means of detecting postnatal manifestations. In this study, no effect was noticed on development in utero, therefore the NOAEL developmental is considered to be greater than 10 mg/kg bw/d (i.e. the highest dose tested).

Justification for classification or non-classification

Cis-2 -pentenenitrile is not classified for reproductive effect according to the CLP regulation (1272/2008) and to the Directive 67/548/EC.