Registration Dossier

Diss Factsheets

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Several data were used in a weight of evidence approach for the assessment of developmental toxicity. The whole database was considered reliable and suffcient for assessment.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Toxicity to reproduction

No data exist for 2 -methylbutan-1 -ol on toxicity to reproduction. Therefore read-across was performed to two other members of the category. A detailed read-across justification is attached in IUCLID chapter 13.

3-methylbutan-1-ol was tested in a Combined 28-Day Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test according to OECD TG 422 and in compliance with GLP regulations (Kuraray Co. Ltd. 2008). The substance was administered to male and female Sprague-Dawley strain SPF rats by gavage at dose levels of 0 (control group), 30, 100 or 300 mg/kg bw for a total of 42 days to males (for 14 days before mating throughout the mating period up to the day before necropsy) and for a total of 41 to 53 days to females (for 14 days before mating throughout the mating and gestation periods up to day 4 of lactation) to examine its repeated dose toxicity and reproductive and developmental toxicity. For the males and females in the 0 and 300 mg/kg bw groups, a 14-day recovery period was provided after administration for 42 days to examine reversibility of the toxic changes. The females in the recovery group were not subjected to mating. There were no test article-related effects on estrous cycle, number of days until copulation, copulation index, insemination index or fertility index. There were no test article-related effects on delivery index, length of gestation period, number of corpora lutea, number of implantation sites, implantation index, index of pre-implantation loss, index of post-implantation loss, index of stillborn pups, parturition index, number of liveborn pups, live birth index or sex ratio and there were no abnormalities in the lactation condition during the lactation period. In live born pups, there were no test article-related changes in body weight, external observation, gross pathological findings or viability index on day 4 of lactation. Based on the results described above, it was judged that the no adverse effect levels for reproductive and developmental toxicity in male and female parent animals and pups were 300 mg/kg bw/day.

In addition, repeated dose toxicity was investigated in a 90 day drinking water study performed according to OECD guideline 408 with 3-methylbutan-1-ol (BG-Chemie 1990). Ten Wistar rats per sex and dose received nominal doses of 80, 340 and 1250 mg/kg bw /day 3-methylbutan-1-ol in the drinking water for 3 months. At the end of the 3-month administration period all animals were sacrificed by decapitation and were assessed by gross pathology. Subsequently, a histopathological examination was carried out including the reproductive organs. Regarding toxicity to reproductive organs, no abnormalities were found by histological analysis. Thus, the highest dose level tested, 1250 mg/kg bw/day, was the NOAEL under the conditions of the study.

These results were supported by a publication describing a subchronic study performed with pentan-1-ol. In a subchronic repeated dose toxicity study conducted equivalent to OECD guideline 408, 15 ASH/CSE rats per sex and dose received doses of 50, 150, 1000 mg/kg bw/day pentan-1-ol in corn oil by gavage for 13 weeks (Butterworth et al. 1978). At necropsy all tissues were examined for gross abnormalities including the reproductive organs. No abnormalities in the reproductive organs were found by histological analysis. Therefore, the highest dose of 1000 mg/kg bw can be seen as the NOAEL regarding reproductive toxicity of pentan-1-ol.

Taken together, there are no hints for a reproductive toxic potential, nor was any relevant systemic toxicity observed up to at least 1000 mg/kg bw subchronic exposure


Short description of key information:
Reproduction:
- oral: NOAEL = 300 mg/kg bw /day (Sprague-Dawley rat, OECD TG 422, gavage, Read-across to CAS No. 123-51-3)
- No effects on reproductive organs after subchronic exposure (NOAEL 1000mg/kg, RA to CAS 71-41-0; NOAEL 1250 mg/kg, RA to CAS 123-51-3)

Effects on developmental toxicity

Description of key information
Toxicity to reproduction (development):
- inhalative: NOAEC = 14 mg/L air (maternal and developmental) (Sprague-Dawley rat, vapour inhalation, GD 1-19) - RA to 71-41-0
- inhalative: NOAEC = 10mg/L air (developmental toxicity) = sat. vapour conc. (rat and rabbit, OECD 414) - RA to 123-51-3
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
14 000 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
Several data were used in a weight of evidence approach for the assessment of developmental toxicity. The whole database was considered reliable and sufficient for assessment.
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Developmental toxicity

No data from 2-methylbutan-1-ol studies on developmental toxicity is available. Therefore read-across with its structural analogues was done.

Developmental toxicity of 3-methylbutan-1-ol was investigated in a prenatal developmental study performed according to OECD test guideline 414 (BG-Chemie 1990). 25 Wistar rats were exposed to test substance vapours at 0.5, 2.5 and 10 mg/L air for 6 hours/day on days 6 - 15 of gestation. The number of corpora lutea, implantations, resorption sites and live fetuses per sex was recorded. Fetuses were examined for skeletal malformations or visceral abnormalities. As a result, a marginal and transient (days 6-9) retardation of bodyweight gain was observed in the dams of the highest dose group, while the fetuses did not show any embryo-/fetotoxic or teratogenic effects in all dose groups. Thus, the NOAEC was 2.5 mg/L air for maternal toxicity and 10 mg/L air for developmental toxicity.

In a similar study also performed according to OECD TG 414, Himalayan rabbits as second species were exposed to 3-methylbutan-1-ol substance vapours at 0.5, 2.5 and 10 mg/L air, 6 hours/day, on days 7 - 19 of gestation (BG-Chemie 1990). Animals were sacrificed on gestation day 29. Gravid uterus weight, number of copora lutea, implantation sites, early and late resorptions and live foetuses were recorded. All foetuses were examined for visceral and skeletal changes, including a head examination. The only effect was a decreased body weight in the high dose animals between gestation days 7 and 10, comparable to the findings in rats. In addition, signs of beginning eye irritation were observed in this group. Thus, the NOAEC was 2.5 mg/L air for maternal toxicity and 10 mg/L air for developmental toxicity in rabbits.

Developmental toxicity of pentan-1-ol was examined in a study, where 15 female, sperm-positive Sprague-Dawley rats were exposed to a concentration of 14 mg/L air, the highest vapour concentration technically achievable (Nelson et al. 1989). Thereby, the exposure duration was 7 hour/day on days 1 - 19 of gestation. At the end of the exposure period, the dams were sacrificed and ovaries and uterine content as well as fetuses were examined. The number of corpora lutea, implantations, resorption sites and live fetuses was recorded. One-half of the fetuses were examined for skeletal malformations, while the remaining fetuses were examined for visceral abnormalities. At 14 mg/L air, no overt maternal toxicity was observed. Overall feed consumption was lower than in controls, but water consumption remained unchanged. Although the weight gain was slightly decreased, this effect did not reach statistical significance. The number of corpora lutea, resorptions, gender ratio and fetal weights were also not affected by treatment. Although small reversible delays in ossification of the caudal vertebrae, the sternum, the metacarpals and the hind paw phalanges were reported, these effects were not statistically significant. In addition, no malformations of the fetuses were observed. Thus, the dose of 14 mg/L air can be seen as the NOAEC regarding maternal as well as developmental toxicity of pentan-1-ol.

Thus, no indications of a developmental toxic or teratogenic effect were seen in animal studies with two members of the pentanol category. A detailed justification for this read-across is attached in IUCLID chapter 13.

Justification for classification or non-classification

The available data are considered reliable and suitable for classification purposes under Regulation (EC) No 1272/2008 (CLP). As a result, no classification for toxicity to reproduction or developmental toxicity under Regulation (EC) No 1272/2008 is required for 2 -methylbutan-1 -ol.

Additional information