Butyl (S)-2-hydroxypropionate

Toxicity to reproduction

Administrative data

Endpoint:

fertility, other

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Data source

Reference

Reference Type:

review article or handbook

Title:

SIDS Initial assessment reports for SIAM 13 - n-Butyl Alcohol (CAS Nr 71-36-3)

Author:

OECD SIDS

Year:

2001

Bibliographic source:

https://hpvchemicals.oecd.org

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: The potential testicular toxicity of n-butyl acetate was examined in a 14-weeks inhalation study with male rats.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-butyl acetate

EC Number:

204-658-1

EC Name:

N-butyl acetate

Cas Number:

123-86-4

Molecular formula:

C6H12O2

IUPAC Name:

butyl acetate

Specific details on test material used for the study:

no specified

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

not specified

Administration / exposure

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Details on exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 weeks

Frequency of treatment:

6 hours per day

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 ppm (nominal)

Remarks:

Control

Doses / concentrations 2

Dose / conc.:

500 ppm (nominal)

Remarks:

low concentration

Doses / concentrations 3

Dose / conc.:

1 500 ppm (nominal)

Remarks:

mid concentration

Doses / concentrations 4

Dose / conc.:

3 000 ppm (nominal)

Remarks:

high concentration

No. of animals per sex per dose:

Total number of animals: 40

Control animals:

yes, concurrent no treatment

Details on study design:

not specified

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: No data

WATER CONSUMPTION AND COMPOUND INTAKE: No data

Postmortem examinations (parental animals):

At necropsy, right testes (n= 40) were prepared for histological examination and left testes and left epididymis (n= 40) from the same animal were frozen and processed for determination of sperm concentrations.

Statistics:

not specified

Reproductive indices:

not specified

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not examined

Mortality:

not specified

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

not specified

Details on results (P0)

Overall there was no evidence of male reproductive toxicity at any exposure concentration based on lack of significant differences between treatments and controls for testicular spermatid head counts and epididymidal spermatozoa counts as endpoints of toxicity. Overall weight gains for 3000 ppm exposure groups were 64% and 59% of controls for males and females, respectively. Overall weight gains for 1500 ppm exposure groups were 82% and 74% of controls for males and females, respectively. No significant differences in weight gain at 500 ppm vs. control.

Effect levels (P0)

Dose descriptor:

NOAEL

Remarks:

male reproductive toxicity

Effect level:

3 000 ppm (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

reproductive function (sperm measures)

Target system / organ toxicity (P0)

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

There was no evidence of testicular toxicity in male rats exposed via inhalation to 0, 500, 1500, or 3000 ppm of n-butyl acetate (6 hrs/day) for at least 65 exposures over 14 weeks. Therefore, the NOAEL for male reproductive toxicity following repeated inhalation exposure was determined to be 3000 ppm.

Executive summary:

In a repeated dose toxicity study, male rats were exposed via inhalation to 0, 500, 1500, or 3,000 ppm (6 hrs/day) for at least 65 exposures over 14 weeks. At necropsy, right testes (n=40) were prepared for histological examination and left testes and left epididymis (n=40) from the same animal were frozen and processed for determination of sperm concentrations.

Overall weight gains for 3000 ppm exposure groups were 64% and 59% of controls for males and females, respectively. Overall weight gains for 1500 ppm exposure groups were 82% and 74% of controls for males and females, respectively. No significant differences in weight gain at 500 ppm vs. control.

Furthermore, there was no evidence of male reproductive toxicity at any exposure concentration based on lack of significant differences between treatments and controls for testicular spermatid head counts and epididymal spermatozoa counts as endpoints of toxicity. Therefore, a NOAEL for male reproductive toxicity following repeated exposure was 3000 ppm.

It should also be mentioned that the rapid in vivo hydrolysis of n-butyl acetate to 1-butanol makes this study directly applicable to 1-butanol exposures.