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Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
20 mg/kg bw/day
Study duration:
subchronic
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

The available data from the reproductive screening study and the repeated dose toxicity studies indicate no effects on reproductive parameters relating to fertility at any dose. There are no effects observed on reproductive organs and no reduction in the number of animals succesfully mating and producing litters in the reproductive screening study.

A standard requirement for a substance manufactured or imported at levels greater than 1000 tonnes per annum is a 2 -generation reproductive study. In this particular case, the REACH substance is used as a High Temperature Heat Transfer fluid in enclosed industrial and commercial heat transfer systems. As such, the potential for exposure to workers and consumers is minimal. In the 3 month inhalation study and the OECD 422, there were no observed effects on fertility or sex organs. Therefore, no additional testing is proposed for assessing reproductive toxicity.


Short description of key information:
OECD 422 combined repeated dose/reproductive, developmental screening study (oral)
1 and 3 month repeated dose inhalation studies.

Effects on developmental toxicity

Description of key information
OECD 422 combined repeated dose/reproductive, developmental screening study (oral)
OECD 414 inhalation teratogenicity study
Both in Rats
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
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

In both the OECD 422 and the teratogenicity study, there were some developmental toxicity effects observed in the high dose animals secondary to maternal toxicity. In the OECD 422, there was some evidence (not statistically significant) of postimplantation loss in the high dose group (320 mg/kg/day). There was also a slight increase in gestation length with the majority of high dose animals delivering litters on Gestation day 22 and 23 rather than 21. One litter was born on gestation day 24, but this was a litter of 1 pup which died before postnatal day 4. In the high dose group, there was also clear evidence of maternal toxicity with decreased body weight and food consumption (systemic LOAEL of 80 mg/kg/day). It is considered that these effects on gestation length are likely to be due to maternal toxicity rather than a specific effect on development or reproductive parameters.

In the teratogenicity study, there was no evidence of embryo or fetal toxicity, but there was a significant increase in bent ribs in the high dose group compared to control. This was considered possibly treatment related; however, no other malformations were observed in this group at levels different to control. Moreover, when total malformations were considered, there was no difference to control. This study identified an increased maternal toxicity in the mid and high dose groups and some evidence of malformations, but only in conjunction of maternal toxicity. Therefore, these effects may be as a result of the general toxicity observed in the Dams rather than specific teratogenicity or developmental toxicity. With the exception of some small changes in malformation incidence, there was no evidence of embryotoxicity or fetotoxicity, that would lead to a conclusion that this substance is developmentally toxic.

It is considered that any developmental toxicity effects are likely a result of general toxicity to the dams rather than evidence of a specific reproductive or developmental effect. Together outcome of OECD 422 study does not warrant the requirement for triggered EOGRTS testing pursuant to Annex IX, Section 8.7.3. Therefore, 'benzene, ethylenated by-products from' is not considered to be a developmental toxicant.

Justification for classification or non-classification

No classification is proposed for reproductive or developmental toxicity for 'benzene, ethylenated by-products from'.