Hexyl acetate

Developmental toxicity / teratogenicity

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

Test material information

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.