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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from Authorized database

Data source

Reference
Reference Type:
other: Authorized database
Title:
Reproduction and development toxicity screening test of 2-Butanone oxime/Ethyl methyl ketone oxime
Author:
Ministry of Health, Labour and Welfare", "Ministry of the Environment" and "National Institute of Technology and Evaluation
Year:
2010
Bibliographic source:
J-CHECK, 2010

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD 141
Principles of method if other than guideline:
Preliminary Reproductive Toxicity Screening Test of 2-Butanone oxime/Ethyl methyl ketone oxime in rat
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-Butanone oxime/Ethyl methyl ketone oxime

- Molecular formula (if other than submission substance): C4H9NO
- Molecular weight (if other than submission substance): 87.12 g/mole
- Substance type: Organic
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2-Butanone oxime/Ethyl methyl ketone oxime
- Molecular formula (if other than submission substance): C4H9NO
- Molecular weight (if other than submission substance): 87.12 g/mole
- Substance type: Organic

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Details on species / strain selection:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
not specified

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Remarks on MMAD:
not specified
Vehicle:
water
Remarks:
Distilled water for injection
Details on exposure:
not specified
Details on mating procedure:
not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Males, 48 days
Females, from 14 days before mating to day 3 of lactation
Frequency of treatment:
Dailly
Details on study schedule:
not specified
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
10 mg/kg bw/day
Dose / conc.:
30 mg/kg bw/day
Dose / conc.:
100 mg/kg bw/day
No. of animals per sex per dose:
Total: 96
0 mg/kg/day: 12 male, 12 female
10 mg/kg/day: 12 male, 12 female
30 mg/kg/day: 12 male, 12 female
100 mg/kg/day: 12 male, 12 female
Control animals:
yes, concurrent vehicle
Details on study design:
not specified
Positive control:
not specified

Examinations

Parental animals: Observations and examinations:
Mortality, Clinical signs, Body weight and food consumption were examined.
Oestrous cyclicity (parental animals):
not specified
Sperm parameters (parental animals):
not specified
Litter observations:
Mortality, Clinical signs and Body weight were examined.
Postmortem examinations (parental animals):
Organ weights, Gross pathology and Histopathology were examined.
Postmortem examinations (offspring):
Gross pathology were examined.
Statistics:
not specified
Reproductive indices:
Delivery index were examined.
Offspring viability indices:
not specified

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
no effects observed
Description (incidence and severity):
No clinical signs were observed in treated rats.
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No effect on survival of treated rats were observed as compared to control.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on body weight were observed in treated rats.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No effect on food consumption were observed in treated rats.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
When treated 100 mg/kg bw, significant increase in liver weights in males and heart weights in females were observed as compared to control.

When treated 30 and 100 mg/kg bw, significant increase spleen weights of male and femaler ats were observed
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Black and enlargement of spleen were observed in male and femlae rats at 30 and 100 mg/kg as compared to control.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Congestion, deposition of pigment and extramedullary hematopoiesis in the spleen, deposition of glycogen, deposition of pigment in Kupffer cells and extramedullary hematopoiesis in the liver and deposition of brown pigment in the kidney were observed in male and femlae rats at 10, 30 and 100 mg/kg
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
No effect on reproductive performnce of treated male rats were observed as compared to control.

When treated 100 mg/kg bw, significant decrease in delivery index of femlae rats were observed as compared to control.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
reproductive performance
Remarks on result:
other: No effect observed

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Description (incidence and severity):
No clinical signs were observed in treated offspring.
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Description (incidence and severity):
No effect on survival were observed in treated offspring.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on body weight were observed in treated offspring
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 specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
No effect on body weight were observed in treated offspring.
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
100 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
gross pathology
Remarks on result:
other: No effect observed

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 100 mg/kg bw for male rat and 30 mg/kg bw for P female rats and 100 mg/kg bw for F1 generation when Crj:CD(SD) male and female rats were treated with 2-Butanone oxime/Ethyl methyl ketone oxime orally by gavage.
Executive summary:

In a Preliminary Reproductive Toxicity Screening Test, Crj:CD(SD) male and female rats were treated with 2-Butanone oxime/Ethyl methyl ketone oxime in the concentration of 0, 10, 30 and 100 mg/kg bw orally by gavage. No adverse effects on survival, general condition, and body weight or food consumption throughout the administration period were observed in P and F1 generation treated rats as compared to control. Similarly, No effect on reproductive performance of treated P male rats were observed as compared to control. But, significant decrease in delivery index of P female rats were observed at 100 mg/kg bw as compared to control. Significant increase in liver weights in males and heart weights in females were observed at 100 mg/kg bw as compared to control. Significant increase spleen weights of male and female rats were observed at 30 and 100 mg/kg bw as compared to control. In addition, Black and enlargement of spleen were observed in male and female rats at 30 and 100 mg/kg as compared to control. In histopathological examination, Congestion, deposition of pigment and extramedullary hematopoiesis in the spleen, deposition of glycogen, deposition of pigment in Kupffer cells and extramedullary hematopoiesis in the liver and deposition of brown pigment in the kidney were observed in male and female rats at 10, 30 and 100 mg/kg. No effects on clinical sign and body weight were observed in treated offspring. Therefore, NOAEL was considered to be 100 mg/kg bw for male rat and 30 mg/kg bw for P female rats and 100 mg/kg bw for F1 generation when Crj:CD(SD) male and female rats were treated with 2-Butanone oxime/Ethyl methyl ketone oxime orally by gavage.