Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

There is currently no data available for CAS 85566 -16 -1 or its structural analogues adressing this endpoint. However, there is a testing proposal for an OECD 443 guideline EOGRT study for the read-across substance CAS 27458 -92 -0 currently under evaluation. Together with an OECD 422 guideline screening study to be conducted with CAS 85566 -16 -1 in the first half of 2021, a future read-across will be feasible to adress this endpoint.

Effects on developmental toxicity

Description of key information

No adverse effects on embryotoxicity or teratogenicity was observed with the two structural analoques.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
750 mg/kg bw/day
Species:
rat
Additional information

The potential of alcohols C13 - 15 branched and linear to induce developmental toxicity was deduced from the structural analogues with CAS numbers 27458 -92 -0 (BASF SE, 2003 & 2020) 10042 -59 -8 (BASF SE, 2004).

Developmental toxicity of CAS 27458-92-0 was examined in a GLP-study (according to OECD 414), where 25 Wistar rats (per dose) were administered 60, 250 and 750 mg/kg bw of test material orally via gavage. The administration was daily from day 6 through day 19 post coitum. On gestation day 20, the dams were sacrificed and ovaries and uterine content as well as fetuses were examined.There were no substance-related or spontaneous mortalities in any of the groups. Some signs of maternal toxicity at 750 mg/kg body weight/day were detected. Clinically, transient salivation (in all rats), urine smeared fur (in 4 dams), and reduced food consumption at initiation of treatment was observed at the high dose level. Clinical pathology revealed increased alanine aminotransferase activities, decreased total protein and globulin concentrations, and increased triglyceride levels in the serum of the high dose females. These changes, which were accompanied by statistically significantly increased absolute and relative liver weights (about 14% or 18% respectively above control values), are indicative for a mild adverse effect on the liver. The only substance-induced finding on the mid dose dams (250 mg/kg body weight/day) consisted in transitory salivation in 17 out of 25 rats, which, by itself and if seen in isolation, is not assessed as an adverse or toxic effect. No substance-induced effects on the dams occurred at the low dose level (60 mg/kg body weight/day). The oral administration of the test substance to the dams at all 3 dose levels (60, 250 and 750 mg/kg body weight/day) had no influence on the gestational parameters and evoked no signs of prenatal developmental toxicity and in particular no indications for teratogenicity at the 3 dose levels tested. Placental and fetal body weights were unaffected and the external, soft tissue and/or skeletal (including cartilage) examinations of the fetuses revealed no biologically relevant differences between the control and the substance-treated groups (i.e. 60, 250 and 750 mg/kg body weight/day). Based on these results, the NOAEL for maternal toxicity is 250 mg/kg body weight/day, while it is 750 mg/kg body weight/day for prenatal developmental toxicity.

Additionally, the developmental toxicity of test substance CAS 10042-59-8 wasexamined in a reliable GLP-study (according to OECD 414), where 25 Wistar rats (per dose) were administered an aqueous emulsion of 50, 200 and 600 mg/kg bw test material orally via gavage. The administration was daily from day 6 through day 19 post coitum. On gestation day 20, the dams were sacrificed and ovaries and uterine content as well as fetuses were examined. At 600 mg/kg bw signs of maternal toxicity like clinically salivation and discomfort, reduced food consumption, reduced absolute and net body weight gain and increased water consumption were recorded. Clinical pathology revealed slight changes such as mild thrombocytopenia and marginal changes in electrolyte levels in the peripheral blood of the high dose dams. Organ weight determination revealed an increased absolute and relative liver weight. Also, at mid dose level (200 mg/kg bw) were still some signs of maternal toxicity such as salivation, reduced absolute and net maternal body weight gain as well as a slightly increased relative liver weight recorded (NOAEL for maternal toxicity = 50 mg/kg bw). The increase in the absolute and relative liver weight (200 and 600 mg/kg bw) is likely to be associated to a peroxisome proliferation and has therefore no human hazard. The oral administration of the test material to dams at all 3 dose levels had no influence on gestational parameters. Conception rate, mean number of corpora lutea, total implantations, resorptions and live fetuses, fetal sex ratio or values calculated for pre- and postimplantation losses were unaffected by the treatment. There was a statistically significant reduction of mean fetal body weight at the high dose level (600 mg/kg bw) of about 11% below the corresponding control value. Since this value was still in the range of historical control data, the finding is assessed to be secondary to the distinct maternal toxicity that has been observed in the appropriate dams. The mean fetal body weights in low and mid dose (50 and 200 mg/kg bw) were not influenced by the test substance. No toxicologically relevant influence of the test substance on mean placental weights was noted. The external, soft tissue and/or skeletal examinations of the fetuses revealed no malformations which might be related to the test substance and no specific malformation pattern was found. A slight increase of the overall incidence of skeletal variations was noted at high dose level (600 mg/kg bw), but also these findings are considered as secondary to maternal toxicity and not relevant in terms of developmental toxicity. Therefore the NOAEL for embryotoxicity/teratogenicity and fetotoxicity was 600 mg/kg bw.

Further, CAS 27458-92-0 was administered to 25 pregnant New Zealand White rabbits (per dose) in a prenatal developmental toxicity study (according to OECD 414), daily by stomach tube from implantation to one day prior to the expected day of parturition (GD 6-28). Clinical observations and records of food consumption and body weight/body weight gain revealed no toxicologically relevant difference between the animals receiving 25 or 75 mg/kg bw/d Isotridecanol and the controls. The high dose of 250 mg/kg bw/d produced a decrease of food consumption as well as body weight/body weight gain during the first two of three treatment weeks. Although the animals partly compensated the lower food intake in the last treatment week, the high-dose does consumed overall 8% less food and had peak food consumption decreases of 31% compared to the concurrent control does during the treatment period (GD 6-28). Accordingly, lower food intake resulted in weight loss (-16.6 g vs. 28.4 g in the control) at the beginning of treatment, and the high-dose body weight remained below control during most of the treatment period. Only towards the end of treatment the high-dose mean body weights recovered and were comparable to the control again. If calculated for the treatment period (GD 6-28), the high-dose does gained about 8% less weight in comparison to the control does (without attaining statistical significance). Concerning clinical pathology, no treatment-related, adverse effects were observed up to a dose of the test compound of 250 mg/kg bw/d. Concerning pathology, significantly increased absolute and relative kidney weights in test groups 2 and 3 as well as absolute and relative liver weights in test group 3 were regarded as treatment-related. 

There were no test substance-related and/or biologically relevant differences between thedifferent test groups in conception rate, in the mean numbers of corpora lutea and implantation sites or in the values calculated for the pre- and the post-implantation losses, the numbers of resorptions and viable fetuses. Similarly, no influence of the test substance on uterine weight, placental weight, fetal weight and sex distribution of the fetuses was noted at any dose. All differences observed are considered to reflect the normal range of fluctuations for animals of this strain and age. Fetal examinations revealed no toxicologically relevant adverse effects of the test substance on embryofetal development.

Under the conditions of this prenatal developmental toxicity study, the oral administration of Isotridecanol to pregnant New Zealand White rabbits from implantation to one day prior to the expected day of parturition (GD 6-28) caused evidence of systemic maternal toxicity at the high-dose level of 250 mg/kg bw/d, such as decrease of food consumption and body weight/body weight gain during major parts of the treatment. In conclusion, the no observed adverse effect level (NOAEL) for maternal toxicity is 75 mg/kg bw/d.As there was no evidence of toxicologically relevant adverse effects of the test substance on embryofetal development, the no observed adverse effect level (NOAEL) for prenatal developmental toxicity is 250 mg/kg bw/d.

Justification for classification or non-classification

Based on the available information the substance does not need to be classified for developmental toxicity, as in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.