Crotonaldehyde

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive 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: full study report available

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:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

Principles of method if other than guideline:

none

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Crotonaldehyde

EC Number:

224-030-0

EC Name:

Crotonaldehyde

Cas Number:

4170-30-3

Molecular formula:

C4H6O

IUPAC Name:

but-2-enal

Details on test material:

Lot #R6870, Batch 02 from Midwest Research Institute

recieved on Nov 20 1984 and Dec 4 1984
stored at 4C
100% purity listed on msds (98.8 % by analysis)

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

none

Administration / exposure

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

corn oil

Details on exposure:

2.5 ml gavage daily

Details on mating procedure:

males dosed 61 d prior to breeding and females dosed 31 days prior to breeding.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

98.8% purity

Duration of treatment / exposure:

Males were dosed 61 prior to breeding and terminated after breeding at day 71.
Females were sacrificed day 5 postpartum and non-pregnant at day 99 (68 days of dosing)

Frequency of treatment:

daily

Details on study schedule:

None

No. of animals per sex per dose:

20

Details on study design:

None

Positive control:

None

Examinations

Parental animals: Observations and examinations:

Male and female: no notable clinical observations.

Oestrous cyclicity (parental animals):

gulati and russel, 1987

Sperm parameters (parental animals):

gulati and russel, 1987

Litter observations:

Mean weights were the same at day 0 and day 5.
Clinical observations revealed no compound realted abnormalities.

Postmortem examinations (parental animals):

No statitistically significant changes in mean testes or epididymis weights , Compound related histomorphologic alterations wewre not observed in the testes or epididymides.
No compound related -histomorphological alterations in the ovaries, oviducts, uterus, cervix or vagina.

Postmortem examinations (offspring):

None

Statistics:

body weight gains, organ weights adn organ/body ratios of the control gruop were compared statistically to the data from the same sex of the treated groups. If variances of untransformed data were heterogeneous, analyses were performed on transformed data to achieve variance homogeneity by Levene;s test. All values were homogeneous. Group comparisons were performed routinely (Dunnett's t test) at 5% two tailed probability level unless otherwise specified

Reproductive indices:

female fertility was shown to be 83, 93, 100 and 88% in the 0, 2.5, 5 and 10 mg/kg groups respectively
male fertility showed success rates of 90, 75, 84.2 and 85 % for the 0, 2.5, 5 and 10 mg/kg groups respectively

Offspring viability indices:

gestation index = 100%
viability index = was comparable among all groups.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Details on results (P0)

None

Effect levels (P0)

1

Dose descriptor:

NOAEL

Effect level:

10 mg/kg bw/day

Sex:

female

2

Dose descriptor:

NOAEL

Effect level:

10 mg/kg bw/day

Sex:

male

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Details on results (F1)

None

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

10 mg/kg bw/day

Sex:

male/female

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:

NOAEL of 10 mg/kg bw in male and female parental animals as well as F1 generation. No LOAEL identified.

Executive summary:

In this subchronic reproductive study, 20 rats (F344) of each sex were randomized into three dose groups (2.5, 5 and 10 mg crotonaldehyde per kilogram body weight), and on control group (corn oil) and gavaged daily wiht 2.5 ml/kg until sacrifice. Males were dosed at 61 days prior to breeding. The males were terminated after breeding at Days 71 and 72. Females were dosed for 31 days prior to breeding. THe females were sacrificed at day 5 postpartum, as were the pups. Non-pregnant females were terminated at Day 99 (after 68 days of dosing).

One male from the 5 mg/kg group was found dead during week 2. There were no notable clinical observations in the males. There were no statistically significant changes in the mean testes or epididymis weights in any of the treatment groups when compared to controls. Compound-realted histomorphologic alterations were not observed in the testes or epididymides.

All females survived to scheduled sacrifice. Clininal observations in the females were not notable. There were no compound related histomorphologic alterations in the ovaries, uterus, oviducts, vagina or cervix.

Female fertility was shown to be 83, 93, 100 and 88% in the 0, 2.5, 5 and 10 mg/kg bw groups, respectively. Male fertility showed success rates (sperm or plug positive females) of 90, 75, 84.2 and 85 % for 0, 2.5, 5 and 10 mg/kg bw groups respectively.

The gestation index(number of live litters/number of pregnancies) was 100% for all groups. The viability index (number of pups surviving to day 5/number of pups born alive) was also comparative among all groups: 99.2, 100, 98.9 and 100 for the 0, 2.5, 5 and 10 mg/kg bw groups, respectively. The mean group weights of live pups taken at day 0 were similar as were mean group weights at day 5. Clinical observation in pups at days 0 and 5 did not reveal any compound-related abnormalities.

In conclusion, under conditions of this study, crotonaldehyde administered at dose levels up to 10 mg/kg from prior to breeding through delivery did not produce and toxicoloical effects in gonadal function, mating behavior and fertility of male and female F344 rats.