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EC number: 201-158-5
CAS number: 78-92-2
Secondary butanol, in a modified two-generation reproductive toxicity
study in rats, produced a reduction in fertility when administered at 3%
in drinking water, a concentration which clearly exceeded the maximum
tolerated dose level, causing significant maternal toxicity and reduced
pup survival (Cox, 1975). The non-specific systemic effects on the dams
and pups noted at 3% (4571 mg/kg/day) included significant maternal body
weight loss, kidney and liver histopathology, reduced fetal body weight
and pup survival and reduced fertility. When the
highest concentration was lowered to 2% (equivalent to 3384 and 3122
mg/kg/day for males and females, respectively) for 2 subsequent matings
(P and F1), no effect on fertility or reproduction was observed. Adult
rats exposed to 2.0% SBA showed significant kidney histopathology;
however, no adverse systemic effects were found at a dose of 1%
(equivalent to 1644 and 1771 mg/kg/day for males and females,
respectively). Thus, the overall NOAEL for the study
was 1644 mg/kg/day. This study was conducted prior to the GLPs and was
similar to OECD test guideline 416.
Secondary butanol (SBA) was studied for developmental toxicity by the oral and inhalation routes of exposure in prenatal development toxicity studies similar in design to OECD Guideline 414. An oral prenatal development toxicity study in rats, predating the GLPs, identified a NOAEL for maternal and developmental toxicity of 1644 mg/kg bw/day (1% in drinking water). An inhalational prenatal development toxicity study of SBA in rats reported a NOAEL for developmental toxicity of 3,500 ppm (10605 mg/m3). A maternal NOAEL was not identified in the inhalational study on the basis of decreased maternal food consumption and reduced body weight gain at all dose levels. Supportive information was available from an inhalational study conducted with the read across substances, methyl ethyl ketone (MEK) in mice and isopropanol (IPA) in rabbits. No evidence of teratogenicity or was observed in these studies in mice, rats or rabbits. Embryotoxic and fetotoxic effects only occurred at maternal toxic doses in these studies.
The effects of orally administered secondary butanol (SBA) on
development were evaluated in a prenatal development toxicity study that
is comparable in design to OECD Guideline 414, and predates the GLPs
(Cox, 1975). This study was part of a multi-generation reproductive
toxicity study. Both F1 males and female Wistar rats
were treated with 0 (water), 0.3, 1.0, or 2.0% SBA in drinking water
pre-mating through to gestation day 20. Increased maternal kidney weight
and renal pathology including tubular casts, tubular degeneration, and
eosinophilia at 2% (3122 mg/ bw kg/day) were reported. Fetal body
weights were also reduced at 2%. No treatment-related skeletal or
visceral malformations or variations were seen at any dose. No
treatment-related maternal or developmental toxicity was observed at an
SBA concentration of 1% (NOAEL = 1644 mg/kg/day).
The effect of inhaled SBA on development was evaluated in a prenatal
development toxicity study similar in design to OECD Guideline 414 (GLP
status not provided) (Nelson et al., 1989). Sprague-dawley
rats were exposed to SBA concentrations of 0, 3500, 5000, or 7000 ppm 7
hours/day from gestation days 0 through 20. Maternal
toxicity (evidenced by reduced food intake and reduced body weight gain)
was noted at all dose levels. An increase in resorptions and reduced
fetal weight were seen at 5000 and 7000 ppm, respectively. There were no
teratogenic effects reported at any dose level. The
NOAEC for embryotoxicity and fetotoxicity was 3500 ppm (10,605 mg/m3).
An estimated internal absorbed dose of 350 mg/kg/day was calculated to
correspond to the 3500 ppm concentration in the study. No
NOAEC was identified for maternal toxicity in the study.
Supportive information was provided by a study conducted with the read
across substance, methyl ethyl ketone (MEK)
(see "Read-across justification" attachment in Section 13 of dossier).
Another supporting study in a non-rodent species was available for the
read-across substance, isopropanol (IPA) (see "Read-across
justification" attachment in Section 13 of dossier). In this study,
pregnant rabbits were orally administered 0, 120, 240 or 480 mg/kg/day
IPA, once daily on gestation days 6 -18 (Tyl et al, 1994).
Treatement-related maternal mortality was reported (26.7% at 480 mg/kg
dose). Other adverse maternal effects included reduced weight gain, food
consumption and clinical signs indicative of alcohol intoxication. No
developmental effects were observed in the fetus. The authors concluded
that the NOAEL for developmental toxicity was 480 mg/kg/day in rabbits.
The substance does not meet the criteria for classification and
labelling for this endpoint, as set out in Regulation (EC) No. 1272/2008
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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