Nitriles, C16-18

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

250 mg/kg bw/day

Additional information

A combined repeated dose/reproduction screening toxicity study according to OECD 422 has been performed with Dodecanenitrile. The NOAEL for reproductive effects from this study is 250 mg/kg, based on death and poor health of the females at 1000 mg/kg. At 1000 mg/kg/day, two of the ten females were not pregnant, and seven females died or were killed for ethical reasons during or directly after giving birth or by day 4 post partum, leaving just one animal that reared her pups until day 4 pp.

 

Reproductive performance: precoital time, duration of gestation, and number of implantations were not affected at 1000 mg/kg.

Short description of key information:

NOAEL = 250 mg/kg bw/day from a combined repeated dose/reproduction screening study.

Effects on developmental toxicity

Description of key information

NOAEL = 250 mg/kg bw/day from a combined repeated dose/reproduction screening study.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

250 mg/kg bw/day

Additional information

A combined repeated dose/reproduction screening toxicity study according to OECD 422 has been performed with Dodecanenitrile.

These results from Dodecanenitrile can be regarded as valid for HT-nitrile as the tested substance is actually the same: They share the same chemical structure, and only differ in the average length of the alkyl chain. Therefore the inherent toxicological mechanism is considered to be similar, only the bioavailability is assumed to be possible bigger for the nitriles with the shorter alkyl chains. Consequently, one can consider the results from Dodecanenitrile as a worst case assumption for HT-nitrile.

The NOAEL for reproductive effects from this study is 250 mg/kg, based on death and poor health of the females at 1000 mg/kg. At 1000 mg/kg/day, two of the ten females were not pregnant, and seven females died or were killed for ethical reasons during or directly after giving birth or by day 4 post partum, leaving just one animal that reared her pups until day 4 pp.

 

Developmental related effects observed included increased incidence of post implantation loss, reduced mean litter size, increased incidence of dead pups at first litter check and increased incidence of postnatal loss. Only when calculated for all dams giving birth the incidence of postnatal loss was statistically significantly increased in group 4. This increase was considered to be treatment related. When calculated for all dams with live pups on day 4 post partum the incidence of postnatal loss of the remaining single female in group 4 was not increased.

 

Examinations of pups during gross pathology did not show indications of possible congenital malformations, but then again no full histopathology has been performed on the pups.

Toxicity to reproduction: other studies

Additional information

These results from Dodecanenitrile can be regarded as valid for HT-nitrile as the tested substance is actually the same: They share the same chemical structure, and only differ in the average length of the alkyl chain. Therefore the inherent toxicological mechanism is considered to be similar, only the bioavailability is assumed to be possible bigger for the nitriles with the shorter alkyl chains. Consequently, one can consider the results from Dodecanenitrile as a worst case assumption for HTnitrile.

Justification for classification or non-classification

The combined repeated dose/reproduction screening toxicity study with Dodecanenitrile showed no effects up to levels showing maternal toxicity. Higher dose levels resulted to high maternal toxicity causing death of most of the dams, and effects seen in pups are likely subsequent to maternal toxicity. No macroscopic malformations have been observed in the pups. The highest non-lethal dose remained without effect on reproduction parameters.