4-amino-m-cresol

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

No data are available to specifically evaluate the reprotoxic effect of the 4 -amino-3-methylphenol or its sulfate form. During the 90 days toxicity study performed on 4-amino-m-cresol sulfate, male and female reproductive organs of rats were observed. No effects were reported, thus no effect on the reproductive performance could be expected.

Effects on developmental toxicity

Description of key information

According to the result of the key study (GLP compliant, OECD guideline 414 method, Klimisch 2), the test item 4 -amino-3 -phenol sulfate did not induced maternotoxicity or embryotoxicity on this teratogenicity test. The No Observe Adverse Effect Level NOAEL was defined as the high dose level, 80 mg/kg/day for the 4 -amino-m-cresol hemisulfate, corresponding to a NOAEL of 56.8 mg/kg bw/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

56.8 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

The key study is a teratogenicity test wich was performed accordingly with OECD GLP principle and OECD guidelmine 414 method. The study was quoted as Klimisch 1. Female BOR:WISW-SPF TNo were used, they were paired with male. The presence of sperm in vaginal smear was considered as Day 0 of pregnancy. Each treatment and control group contained 24 mated females. Animals were treated once daily by oral gavage at dose levels of 0, 10, 40 and 80 mg/kg bw/day (Dose volume: 10 mL/kg bw) from Day 5 through to Day 15 of gestation. All animals were observed daily for mortality and clinical observations. Body weights were recorded. On gestation Day 20, the dams were sacrificed and examined for visceral gross pathology, cesarean-sectioned, and evidence of maternal and developmental toxicity. Numbers of live and dead fetuses were determined. Each fetus was weighed, sexed and examined externally. Fetuses were examined for visceral and skeletal alterations.

No mortality was observed in the study. No treatment-related effects in dams were noted with regard to clinical observations and postmortem findings. The body weight and the food consumption were not affected by the treatment. Gross necropsy revealed no treatment related effects. There were no treatment related effects with regard to uterus and placenta weights, the number of corpora lutea, and implantations. There were no treatment related effects with regard to reproduction e.g. litter size, foetal mortality, foetal body weight, birth position and sex ratio. The skeletal and visceral examination of the fetuses revealed no treatment related findings. Neither a statistically significant difference as compared to the concurrent control nor a dose-dependent increase in any malformation or variation was noted.

In conclusion, administration of 1-Hydroxy-3-methyl-4-aminobenzol-sulfat to female BOR:WISW-SPF TNO rats during Day 5-15 of presumed gestation, at dose levels of 0, 10, 40 and 80 mg/kg bw/day by oral gavage revealed a NOAEL of 80 mg/kg bw/day for maternal and developmental toxicity.

Based on this result on the sulfat form, the converted NOAEL for the registered substance 4 -amino-3-methylphenol was defined at 56.8 mg/kg bw/day according the read-across analogy approach.

Toxicity to reproduction: other studies

Additional information

According to the result of the key study (GLP compliant, OECD guideline 414 method, Klimisch 2), the test item 4 -amino-3 -phenol sulfate did not induced maternotoxicity or embryotoxicity on this teratogenicity test. The No Observe Adverse Effect Level NOAEL was defined as the high dose level, 80 mg/kg/day. Based on this result on the sulfate form, the converted NOAEL for the registered substance 4 -amino-3-methylphenol was defined at 56.8 mg/kg bw/day.

No data are available to specifically evaluate the reprotoxic effect of the 4 -amino-3-methylphenol or its sulfate form. During the 90 days toxicity study (Klimisch 1, OECD guideline 408 method, GLP compliant), performed on 4-amino-m-cresol sulfate, male and female reproductive organs of rats were observed (prostate gland, testes (l+ r), ovaries (l+ r) and uterus…). No effects were reported, thus no effect on the reproductive performance could be expected. The NOAEL (No observe adverse effect level) was defined as 60 mg/kg/day (for other effects than effects on reproductive parameters). Based on this result on the sulfate form, the converted NOAEL for the registered substance 4 -amino-3-methylphenol was defined at 42.6mg/kg bw/day.

For reproductive toxicity the NOAEL for developmental toxicity should be considered: 56.8 mg/kg bw/day.

Justification for classification or non-classification

According to the result of the key study (GLP compliant, OECD guideline 414 method, Klimisch 2), the test item 4 -amino-3 -phenol sulfate did not induced maternotoxicity or embryotoxicity on this teratogenicity test. The No Observe Adverse Effect Level NOAEL was defined as the high dose level, 80 mg/kg/day.

Based on this result on the sulfate form, the converted NOAEL for the registered substance 4 -amino-3-methylphenol was defined at 56.8 mg/kg bw/day.