4-(vinyloxy)butan-1-ol

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-(vinyloxy)butan-1-ol

EC Number:

241-793-5

EC Name:

4-(vinyloxy)butan-1-ol

Cas Number:

17832-28-9

Molecular formula:

C6H12O2

IUPAC Name:

4-(ethenyloxy)butan-1-ol

Details on test material:

purity: 99.4%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on exposure:

After the acclimatization period, the test substance was administered orally via gavage to the F0 generation parental animals, daily at the same time in the morning (exception: no administration to animals being in labor). The treatment lasted up to one day prior to sacrifice. The animals of the control group were treated in the same way with the vehicle only (Olive oil Ph. Eur./DAB). The daily volume administered was 4 ml/kg bw/d. The calculation of
the administered volume was generally based on the most recent individual body weights.

Details on mating procedure:

In general, each of the male and female animals was mated overnight in a 1:1 ratio for a maximum of 2 weeks. Throughout the mating period, each female animal was paired with a predetermined male animal from the same test group.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The analyses of the test substance preparations were carried out at the Analytical Chemistry Laboratory of Experimental Toxicology and Ecology of BASF SE. The stability of the test substance in Olive oil Ph. Eur./DAB at room temperature was given for a period of 7 days (analytical report: Project No.: 01Y0107/098019).

Duration of treatment / exposure:

males: 30 days
females: 53 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:

Basis:
nominal in water
0, 50, 150, 450 mg/kg bw/day

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

The duration of treatment covered a 2-week pre-mating and mating period in both sexes, approximately 1 week postmating in males, and the entire gestation period as well as 4 days of lactation in females. After 2 weeks of premating treatment the F0 animals were mated to produce F1 generation pups. Mating pairs were from the same test group. Mating was discontinued as soon as sperm was detected in the vaginal smear. F0 animals were examined for their reproductive performance including determination of the number of implantation sites and the calculation of postimplantation loss for all F0 females.

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

1

Dose descriptor:

NOAEL

Effect level:

450 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: fertility

2

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: systemic toxicity (adverse clinical findings, decreased body weight gain)

Results: F1 generation

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

450 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: developmental toxicity

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

The test substance was administered orally via gavage to groups of 10 male and 10 female Wistar rats (F0 animals) at doses of 50, 150, and 450 mg/kg body weight/day. Control animals were dosed daily with the vehicle (Olive oil Ph. Eur./DAB). The duration of treatment covered a 2-week pre-mating and mating period in both sexes, approximately 1 week postmating in males, and the entire gestation period as well as 4 days of lactation in females. No adverse effects on fertility of the F0 parental animals of both sexes at dose levels of 50, 150 and 450 mg/kg bw/d were observed. The test substance caused also no impairments of the reproductive performance. Mating behaviour, conception, gestation, parturition, as well as sexual organ weights and gross and histopathological findings of these organs were not influenced. Concerning clinical pathology no treatment-related, adverse effects were observed up to a dose of 450 mg/kg bw/d. Regarding pathology there were no substance-related organ weight changes, gross lesions, or microscopic findings. Under the conditions of this study the NOAEL for reproductive performance, fertility and for developmental toxicity is 450 mg/kg body weight/day, the highest dose tested. The NOAEL for general, systemic toxicity of the test substance is 150 mg/kg body weight/day for the F0 parental animals based on adverse clinical findings (males + females) and decreased body weight gain (males) at 450 mg/kg body weight/day.