reaction mass of isomers of: C7-9-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No additional data

Additional information

The majority of the substance data set is taken from existing registrations on the substance, where the data is > 12 years old. As such, no definitive data on the reproductive toxicity of the substance is available.  There is data on developmental toxicity from another registrant, and this has been purchased and included within this dossier. 

 

Within this study, at the highest dose level, maternal toxicity was noted. At the highest dose level effects were noted such as foetal weights and visceral abnormalities which differed from the foetuses than in the control group. Nevertheless, since the foetal findings were seen at the highest tested dose which was clearly was toxic to the dams, they were considered to be attributable to maternal toxicity. In conclusion, development toxicity related to the test substance was seen, however at a dose level which clearly was toxic to the dams.

 

Within this study, maternal toxicity was noted in the study, there were no perceived developmental effects. Given the lack of definitive effects associated with reproduction and development within the developmental study, mutagenicity and repeat dose studies, it is unlikely that the substance will pose a hazard for this endpoint. Therefore, in the interests of animal welfare, it is considered justifiable to postpone assessment for this endpoint until the next tonnage level of registration. 

Short description of key information:
Discussion on proposal to waive assessment of the fertility toxicity endpoint until the next level of registration.

Effects on developmental toxicity

Description of key information

Summary of developmental toxicity / teratogenicity study

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

40 mg/kg bw/day

Additional information

The purpose of the study was to detect effects on the pregnant rabbit and development of the embryo and fetus consequent to exposure of the female to the test item from day 6 to 27 post coitum (i.e., from implantation to the day prior to Caesarean section) at doses of 0, 20, 40 or 80 mg/kg body weight/day. Mortality, clinical signs, changes in body weights and body weight gain, and changes in food consumption were recorded. The dams were sacrificed on day 28 post coitum, examined for gross lesions, and the organ weights of the liver, adrenal glands, thyroid gland and pituitary gland were recorded. The fetuses were removed by Caesarean section, examined and allocated to visceral or skeletal examination.

Whereas no indication for maternal toxicity was seen at 20 and 40 mg/kg bw/day, treatment with 80 mg/kg body weight/day, resulted in following test item related findings: The mean food consumption was reduced, at times statistically significantly, throughout the treatment period; the mean body weight gain and body weight were also reduced; post-implantation loss was statistically significantly increased and as a result, the total number of fetuses was statistically significantly reduced; one case of abortion was reported; necropsy revealed several lesions, especially in the stomach, kidneys and gall bladder.

 

Referring to developmental toxicity, no indication for developmental toxicity was seen at 20 and 40 mg/kg bw/day. At 80 mg/kg body weight/day, the mean fetal weights were statistically significantly reduced. There were more visceral abnormalities in the fetuses than in the control group. There was reduced cranial ossification, as well as reduced digit/limb ossification. The findings from the skeletal and cartilage examinations suggest a possible minor disturbance in the development of the axial skeletons of the fetuses. Nevertheless, since the fetal findings were seen at the highest tested dose of 80 mg/kg bw/day which clearly was toxic to the dams, they were considered to be attributable to maternal toxicity.

 

In conclusion, development toxicity related to the test substance was seen, however at a dose level which clearly was toxic to the dams.

Based on the results of this study, the maternal NOAEL was set at 40 mg/kg body weight/day. The NOAEL for developmental toxicity also was set at 40 mg/kg body weight/day.

Justification for classification or non-classification

The above study has been ranked reliability 1 according to the Klimish et al system. This ranking was deemed appropriate because the studies were all conducted to GLP in compliance with recognised guidelines. The majority of the information has been provided from a migrated nons file referring to studies which are more than 12 years old, with the permission of ECHA.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008).