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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Additional information

Experimental data are available to assess the effects on fertillity of Fatty acids, C18-unsatd., dimers, ethoxylated.

Valid information of the toxicological effects resulting from repeated oral-gavage administration of the test item Fatty acids, C18-unsatd., dimers, ethoxylated (NIO AD1) to rats according to OECD guideline 422 are available (BASF SE, 2013, 85R0072/12X119). Therefore Fatty acids, C18-unsatd., dimers, ethoxylated was administered in olive oil as vehicle at dosages of 100, 300 and 1000 mg/kg body weight/day to the test groups, and controls received the vehicle only. Fatty acids, C18-unsatd., dimers, ethoxylated was administered to male rats for 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. There were no unplanned deaths and no treatment related macroscopical findings. In-life observations of the animals showed decreased rearings in one male at 300 mg/kg bw/day and two males at 1000 mg/kg bw/day, and a slight decrease of body temperature in males and females at 1000 mg/kg bw/day. In the absence of any other changes, these findings were considered to be not adverse. Food consumption and body weights were generally unaffected by treatment. At histopathological examination, minimal centrilobular hepatocellular hypertrophy in the liver of high dose group males was noted that correlated with increased liver weights. This lesion was considered to be of metabolic nature. Furthermore, slight aspiration pneumonia in low dose group animals and slight to moderate aspiration pneumonia in animals from the intermediate and high dose groups could be attributed to treatment, most likely due to accidental uptake by regurgitation of the test item. A slightly higher incidence and/or severity grade of pneumonia was recorded in animals at a dose level of 300 and 1000 mg/kg bw/day, may be explained by an increased viscosity of the test item/vehicle with increasing concentration of the test item. No effects on mating performance and fertility were observed at any dose level. Mean number of corpora lutea per dam (determined at necropsy) was not affected by treatment with the test item and no effects on implantation rate or post-implantation loss were observed at any dose level. No test item-related findings were noted for pups during first litter check and lactation at any dose level. No findings were noted at macroscopic examination of F1 pups at any dose level.  

The NOAEL(No Observed Adverse Effect Level)for systemic toxicity was considered to be 1000 mg/kg bw/day.

The NOEL for reproduction/developmental toxicity was considered to be 1000 mg/kg body weight/day.

Key study assignment:

As there is only one reliable and relevant study investigating the reproductive toxicity of Fatty acids, C18-unsatd., dimers, ethoxylated. this study is integrated as key study.

 

Assessment of toxicity on reproduction:

No adverse findings regarding reproduction (e.g. mating performance and fertility, number of corpora lutea, effects on implantation, maleformation at macroscopic examination etc.) were observed in a combined subacute toxicity / reproduction screening study (OECD 422). Only slight adaptive effects in the liver could be observed in the highest dose group. These effects were rated as a adaptive effect due to metabolism of the substance but not rated to be adverse.

Therefore the NOAEL for development , reproduction and systemic toxicity was established at the highest tested dose (1000mg/kg bw/day)

 

In summary results from a combined subacute toxicity / reproduction screening study did not reveal any reason of concern for offspring and for parent animals with respect to developmental toxicity or fertility up to and including the limit dose (1000mg/kg bw). Since significant scientific evidence for a lack of reproduction toxic effects of the substance is drawn from these results and an additional two generation study or a teratogenicity study at these max. concentration, is not expected to add any further relevant knowledge on this endpoint. No additional study is therefore propose due to animal welfare aspects.


Short description of key information:
Effects on fertility
subacute toxicity / reproduction screening, rat, OECD 422: no adverse effects, NOAEL parental toxicity, fertility and development >= 1000 mg/kg bw/day test (BASF SE, 2013, 85R0072/12X119).

Justification for selection of Effect on fertility via oral route:
Most adequate and reliable result, see discussion.

Effects on developmental toxicity

Description of key information
Developmental toxicity
subacute toxicity / reproduction screening, rat, OECD 422: no adverse effects, NOAEL parental toxicity, fertility and development >= 1000 mg/kg bw/day test (BASF SE, 2013, 85R0072/12X119).
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Additional information

There are no valid, reliable and relevant studies available assessing the effects on developmental toxicity of Fatty acids, C18-unsatd., dimers, ethoxylated.

Nevertheless as no maleformation or other adverse effects on offspring are reported in a OECD 422 study (BASF SE, 2013, 85R0072/12X119) up to the highest test dosage (1000mg/kg bw/day) no additional information is expected if a teratogenicity test is performed at that concentration. According to Annex XI REGULATION (EC) No 1907/2006 chapter 1.2 "weigh of evidence .... Where sufficient weight of evidence for the presence or absence of a particular dangerous property is available:.....—further testing on vertebrate animals for that property shall be omitted...." further testing (two generation or teratogenicity study) is not strongly suggested and therefore not proposed.

Justification for classification or non-classification

As there is, in result, no evidence for reproduction toxicity potential from a human or animal study the test material does not fulfil the requirement according to GHS (Regulation (EU) 1272/2008) or DPD (67/548/EEC) to be labelled as reproductive toxicant.

 

Labelling reproductive toxicant:

GHS: no labelling

DSD: no labelling