Ethyl hexanoate

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-08-25 to 2017-02-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl hexanoate

EC Number:

204-640-3

EC Name:

Ethyl hexanoate

Cas Number:

123-66-0

Molecular formula:

C8H16O2

IUPAC Name:

ethyl hexanoate

Test material form:

liquid

Results and discussion

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse treatment-related effects of toxicological significance were observed.

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

This study was conducted to evaluate the potential toxicities of the test substance in the general systemic and reproductive/development when administered via oral gavage to Sprague-Dawley rats with dose levels of 0, 100, 300 and 1000 mg/kg. There were no test item-related adverse effects in general effects and reproduction/development up to 1000 mg/kg. Therefore, the No Observed Adverse Effect Levels (NOAELs) for general toxicity effects and reproduction/developmental toxicity are considered to be at least 1000 mg/kg/day.

Executive summary:

This study was conducted to evaluate the potential toxicities of a test substance, regarding general systemic effects and reproductive/developmental toxicity. The test item was administered by oral gavage to Sprague-Dawley rats (12 animals per sex per group) at dose levels of 0, 100, 300 and 1000 mg/kg with a dose volume of 2 mL/kg. Males and females were dosed for two weeks prior to mating and continued through the day before sacrifice in males (at least 50 days), and continued through the lactation day 13 in females. Additional animals in the recovery groups 0 and 1000 mg/kg (6 animals per sex per group) received the test substance, but were not mated. Afterwards, they were assigned to 2 weeks of recovery period after the completion of the test item administration.

No deaths or moribund animals occurred in any group throughout the study. Test item-related salivation was observed in both sexes at 1000 mg/kg; however, it was not considered to have toxicological relevance since it was considered to be attributed to the palatability of the test item. At 1000 mg/kg, test item-related changes were also observed including increased prothrombin time (up to 1.11-fold of the control) in both sexes and increased kidney weight (1.13-fold of control) in females. However, it was not considered to have toxicological relevance since there was no correlated microscopic findings. In addition, in males in all test item-treated groups, decreased gamma glutamyl transpeptidase (up to 32% of control) was observed. However, it was not considered to have toxicological relevance since there was no correlated microscopic finding.

No test item-related change was observed in oestrus cycle, precoital time, fertility data, reproductive and littering findings, F1 pups clinical signs, body weight, anogenital distance, nipple retention and external examinations. Test item-related increase in T4 was observed in adult males (1.14-fold of control) and pups (1.20-fold of control) at 1000 mg/kg. However, it was not considered to have toxicological relevance since there were no correlated changes in other parameters including microscopic findings of thyroids (with parathyroids).

In conclusion, no test item-related adverse effects for general toxicity effects and reproductive/developmental effects were observed up to 1000 mg/kg. Therefore, the No Observed Adverse Effect Levels (NOAELs) for general toxicity effects and reproduction/developmental toxicity are considered to be at least 1000 mg/kg/day.