Cyclohexanone oxime

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: subchronic toxicity study

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Equivalent to guidellne with limited documentation

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cyclohexanone oxime

EC Number:

202-874-0

EC Name:

Cyclohexanone oxime

Cas Number:

100-64-1

Molecular formula:

C6H11NO

IUPAC Name:

cyclohexanone oxime

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): cyclohexanone oxime
- Analytical purity: 99,5%

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles
River Breeding Laboratories (Kingston, NY, USA)
- Housing: individually

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 5

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on mating procedure:

not performed

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days (main study)

Frequency of treatment:

5 days/week

Details on study schedule:

subchronic toxicity study

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.25, 2.5 or 25 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

20 (main study)

Control animals:

yes, concurrent vehicle

Details on study design:

subchronic toxicity study

Positive control:

no

Examinations

Parental animals: Observations and examinations:

The complete range of observations and examinations is reported in chapter 7.5.1

Oestrous cyclicity (parental animals):

not examined

Sperm parameters (parental animals):

not examined

Litter observations:

not examined

Postmortem examinations (parental animals):

HISTOPATHOLOGY / ORGAN WEIGTHS
Testes and ovaries were weighed. Testes with epididymis, prostate, ovaries and uterus were examined microscopically
The complete range of observations and examinations is reported in chapter 7.5.1

Postmortem examinations (offspring):

not examined

Statistics:

Continuous variables: Bartlett's homogeneity of variance, analysis of variance, and Duncan's multiple range test.
If Bartlett's test indicated heterogeneous variance or where data were ranked or suspected to be nonparametric, Kruskall-Wallis nonparametric analysis of variance and Wilcoxan rank sum tests were used.

Reproductive indices:

not calculated

Offspring viability indices:

not calculated

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

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

Description (incidence and severity):

on reproductive organs

Other effects:

not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

not examined

Details on results (P0)

CLINICAL SIGNS AND MORTALITY
Through the first 9 weeks of the study: Highest dose males: persistent red nasal discharge, chromodacryorrhea and swollen conjuntiva (also mid dose), the effects gradually subsided and had disappeared by the end of the study
Females after 2 weeks of exposure: chromodacryorrhea (high dose) and corneal opacity (high and mid dose), which both gradually subsided but persisted at study termination

Three females of the high dose died (additionally on female of low dose group due to dosing accident)

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

>= 25 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effects observable in reproductive organs (testes with epididymis, prostate, ovaries, uterus)

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Mortality / viability:

not examined

Body weight and weight changes:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

No effects were evident in reproductive organs of animals of both sexes

Applicant's summary and conclusion

Conclusions:

The reproductive organs were unaffected in this subchronic toxicity study

Executive summary:

Groups of F-344 rats (20 per sex per dose) were treated by oral gavage with the test substance for 5 days/w for 90 days at doses of 0, 0.25, 2.5 or 25 mg/kg body weight. No histopathological alterations were observed in testes, uteri and ovaries. The main effect in this study was haematotoxicity (for a full description of study results see chapter 7.5.1).