Methyltrioctylammonium chloride

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Toxicity to reproduction

No Observed Adverse Effect Level (NOAEL) for reproductive toxicity was considered to be above 25-100mg/kg/day, When male and female rats  were treated with Methyltrioctylammonium chloride (5137-55-3) orally. Thus, based on the avaliable experimental study of structurally similar read across substance No Observed Adverse Effect Level (NOAEL) was considered to be  above 25 -100mg/kg bw . Thus, comparing this value with the criteria of CLP regulation Methyltrioctylammonium chloride (5137-55-3)  cannot be classified as reproductive toxicant.

 

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is Klimicsh 2 and from authoritative database

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity

Data available for the read across chemicals was reviewed to determine the reproductive toxicity of Methyltrioctylammonium chloride (5137-55-3). The studies are as mentioned below:

Study 1

Two generation reproduction study of test material was performed on male and female Sprague Dawley CD® rats in accordance with OECD guideline 416 (1983). Although oestrus cycle, sperm parameters and sexual maturation of pups was not investigated, no reproductive effects were observed indicating indirectly no effect on these parameters. The study is considered acceptable. The test material mixed with food in dose concentration 0, 20, 50 and 100 mg /kg bw/day (0, 300, 750 and 1500 mg/kg food ).28 male and 28 female placed in each dose group. Diet starting 10 weeks before mating (F0) or at weaning (F1), throughout mating, gestation and lactation periods until scheduled necropsy. F0 rats were mated twice to produce F1a and F1b litters. Twenty-eight parents/sex of the F2 generation were selected from the F1b litters. They were mated twice to produce F2a and F2b litters. Mating was allowed for up to 21 days. Necropsy was performed on 10 pups/sex/dose from the F1a and F1b generation. Clinical signs, mortality, body weight and Food consumption were noted in each generation. No treatment-related clinical signs were observed. There were no treatment related deaths during the study. One male at each dosing level was killed due to trauma or caging accident or sacrificed moribund. Body weight gain was reduced in males and females at 100 mg/kg/day food during the premating period. Food consumption was reduced at 100 mg/kg /day during the premating period in males and females. At necropsy no treatment-related abnormalities were observed, including histopathological examinations there were no changes detected between parental animals of the treated and control groups in mating indices and pregnancy rates. No treatment-related changes were detected in litter size, live birth index, viability index, lactation index and sex ratio of the F0 offspring.  F1 pup weight gains were initially similar to those in the control group, but were significantly decreased on day 21 and 28 post-partum at 100 mg/kg /day (82-87% and 83-86% of control for F1a males and females, and 76-85% and 78-83% of control for F1b males and females, resp.). F1a and F1b pups showed no treatment-related macroscopic findings. F1 parental animals showed no treatment-related mortality or clinical signs. Body weight gain was only incidentally reduced for F1 parents. Body weights of males and females at 100 mg/kg /day were already significantly reduced at the beginning of mating due to the reduced body weight gain during their lactation period. Body weights of females were still decreased during gestation and were equal to controls at the end of lactation due 10 increased body weight gains relative to controls during gestation and lactation (F28 and F2b). Food consumption was significantly reduced at 100mg/kg /day in F1 males until week 7 and F1 females during the whole pre-mating period. No changes were noted between parental animals of the treated and control groups in mating indices, pregnancy rates and male fertility. At necropsy no treatment-related abnormalities were observed, including histopathological examination. No treatment-related changes were observed in litter size, live birth index, viability index,l actation index or sex ratio of the F, offspring (F2pups). F2apup weight gains were decreased at 100 mg/kg /day on day 21 and 28 post-partum (85-89% and 83-90% of control for males and female resp.). F2bpup weight gains were decreased at 100 mg/kg/day on day 21 and 28post-partum (85-89%and 84-86% of control).F2a andF2b pups showed no treatment- related macroscopic finding. Hence No Observed Adverse Effect Level (NOAEL) for F0 generation was considered to be 100mg/kg/day, As No treatment related changes were noted in mating behaviour, conception and gestation and the NOAEL for developmental toxicity was considered to be 50 mg/kg /day, based on decreased body weight. When female Sprague Dawley rats were treated with test material orally.

Study 2

Reproductive and development toxicity study oftest material was performed on femalewistar rats.20-22 rats /dose group were used. The test materialwas administered in dose concentration 0, 8, 25,50 mg/kg bw/day from day 5 through day 14 of gestation by gastric intubation route. All of the dams were killed on day 20 of gestation and Uterine contents examined. The foetuses were weighed, sexed and subjected to external, soft tissue or skeletal examinations.The incidence of resorption site was increased in the dams from the 50 mg/kg bw dose group. Fetal survival was reduced in 50 mg/kg bw dose group. No evidence of adverse effects on litter size , viability ot litter weight in any dose group.There were no treatment-related malformations or variations in any groups at external, soft tissue or skeletal examinations. Hence No Observed Adverse Effect Level (NOAEL) for reproductive toxicity was considered to be 25 mg/kg/day, and the dose-level of 50 mg/kg/day was considered to be the NOAEL for embryo-foetal toxicity.When femalewistar rats were treated withtest material orally.

Thus, based on the avaliable experimental study of structurally similar read across substance No Observed Adverse Effect Level (NOAEL) was considered to be above 25 -100mg/kg bw. Thus, comparing this value with the criteria of CLP regulation Methyltrioctylammonium chloride (5137-55-3)  cannot be classified as reproductive toxicant.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation Methyltrioctylammonium chloride (5137-55-3)  cannot be classified as reproductive toxicant.

If however the content of CAS # 68814-95 -9 (Repro Cat. 1B, Fertility and Development) is at or greater than 0.3 % (but less than 10 %), a classification with Repro Cat. 1B (F, D) is warranted.