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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Abstract only available; suitable only as part of a WoE assessment

Data source

Reference
Reference Type:
publication
Title:
A teratology screening study in rats with n-hexanol
Author:
Rodwell DE, Mercieca MD, Rusch CM & Tasker EJ
Year:
1988
Bibliographic source:
Toxicologist 8(1):213 (1988)

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
n-Hexanol
IUPAC Name:
n-Hexanol
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): n-hexanol

Test animals

Species:
rat
Strain:
other: COBS CD
Details on test animals or test system and environmental conditions:
25 mated female COBS CD rats per group..

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
N-hexanol was mixed with corn oil and administered by oral gavage at doses of 200 or 1000 mg/kg bw/day. Each group consisted of 25 mated female COBS CD rats. Ten consecutive daily doses were administered over gestation days 6-15, in a dose volume of 5 ml/kg bw.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No information
Details on mating procedure:
No data
Duration of treatment / exposure:
ten days GD 6-15
Frequency of treatment:
daily
Duration of test:
dams terminated on gestation day 20
Doses / concentrations
Remarks:
Doses / Concentrations:
200 or 1000 mg/kg bw/day
Basis:
nominal conc.
No. of animals per sex per dose:
25 mated females per group
Control animals:
no
Details on study design:
No further details available

Examinations

Maternal examinations:
Throughout gestation the rats were observed for appearance and behaviour, and bodyweights were recorded. On gestation day 20 intrauterine survival was evaluated following Caesarean section and foetal development indices – bodyweight, external, skeletal and visceral morphology – were assessed.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: intrauterine survival and foetal development indices
Fetal examinations:
On gestation day 20 intrauterine survival was evaluated following Caesarean section and foetal development indices – bodyweight, external, skeletal and visceral morphology – were assessed.
Statistics:
No data
Indices:
No information presented on how foetal development indices were determined
Historical control data:
No data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes. Remark: 1000 mg/kg bw/day

Details on maternal toxic effects:
Maternal toxicity was only evident at 1000 mg/kg bw/day – indicated by clinical signs and decreased maternal bodyweights during the treatment period.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects. Remark: No embryotoxicity or teratologic effects were observed at either dose level.

Details on embryotoxic / teratogenic effects:
No embryotoxicity or teratologic effects were observed at either dose level.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Mean foetal bodyweight was slightly decreased at 1000 mg/kg bw/day, but weights were within the laboratory historical range. An increase in the number of litters with the foetal variant ‘malaligned sternebrae’ occurred at the low dose level, 200 mg/kg bw/day. The incidence of this variation in the high dose group was similar to incidence in the controls.

Applicant's summary and conclusion

Conclusions:
Maternal toxicity and developmental toxicity were evident at the highest dose level of 1000 mg/kg bw/d; there is no evidence for specific developmental toxicity.
Executive summary:

The potential maternal, embryotoxic and teratologic effects of N-hexanol were evaluated. N-hexanol was mixed with corn oil and administered by oral gavage at doses of 200 or 1000 mg/kg bw/day. Each group consisted of 25 mated female COBS CD rats. Ten consecutive daily doses were administered over gestation days 6-15, in a dose volume of 5 ml/kg bw. Throughout gestation the rats were observed for appearance and behaviour, and bodyweights were recorded. On gestation day 20 intrauterine survival was evaluated following Caesarean section and foetal development indices – bodyweight, external, skeletal and visceral morphology – were assessed. No embryotoxicity or teratologic effects were observed at either dose level. Maternal toxicity was only evident at 1000 mg/kg bw/day – indicated by clinical signs and decreased maternal bodyweights during the treatment period. Mean foetal bodyweight was slightly decreased at 1000 mg/kg bw/day, but weights were within the laboratory historical range.  An increase in the number of litters with the foetal variant ‘malaligned sternebrae’ occurred at the low dose level, 200 mg/kg bw/day. The incidence of this variation in the high dose group was similar to incidence in the controls. The 200 mg/kg bw/day dose level was considered a no-effect level. Maternal toxicity and developmental toxicity were evident at the highest dose level of 1000 mg/kg bw/d; there is no evidence for specific developmental toxicity.