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Diss Factsheets

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
three-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from OECD SIDS

Data source

Reference
Reference Type:
secondary source
Title:
SIDS Initial Assessment Profile of ε-caprolactam
Author:
OECD SIDS
Year:
2001
Bibliographic source:
OECD SIDS, 26 November 2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: as below
Principles of method if other than guideline:
Three-generation reproductive toxicity study of ε-caprolactam in Rats
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
ε-caprolactam
Cas Number:
105-60-2
Molecular formula:
C6H11NO
IUPAC Name:
ε-caprolactam
Details on test material:
- Name of test material (as cited in study report): ε-caprolactam
- Molecular formula (if other than submission substance): C6H11NO
- Molecular weight (if other than submission substance): 113.1589 g/mole
- Substance type: Organic
Specific details on test material used for the study:
- Name of test material (as cited in study report): ε-caprolactam
- Molecular formula (if other than submission substance): C6H11NO
- Molecular weight (if other than submission substance): 113.1589 g/mole
- Substance type: Organic

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Type of inhalation exposure (if applicable):
not specified
Remarks on MMAD:
not specified
Vehicle:
not specified
Details on exposure:
not specified
Details on mating procedure:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
More than 90 days.
Frequency of treatment:
Daily
Details on study schedule:
through three successive generations
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
83 mg/kg bw/day
Remarks:
ca.
Dose / conc.:
417 mg/kg bw/day
Remarks:
ca.
Dose / conc.:
833 mg/kg bw/day
Remarks:
ca.
No. of animals per sex per dose:
Not specified
Control animals:
not specified
Details on study design:
Not specified
Positive control:
Not specified

Examinations

Parental animals: Observations and examinations:
Clinical signs were observed
Oestrous cyclicity (parental animals):
Not specified
Sperm parameters (parental animals):
Not specified
Litter observations:
Gross appearance, survival, body weight, food consumption, number of pups and percentage of male pups were examined.
Postmortem examinations (parental animals):
Histopathology was examined.
Postmortem examinations (offspring):
Gross pathology and histopathology was examined.
Statistics:
Not specified
Reproductive indices:
Reproductive performance was examined.
Offspring viability indices:
Not specified

Results and discussion

Results: P0 (first parental generation)

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:
not specified
Body weight and weight changes:
not specified
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:
no effects observed
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:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Slight increase in the severity of spontaneous nephropathies occasionally accompanied by granular casts were observed in 833 mg/kg bw treated rats.
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

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
833 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
reproductive performance
Remarks on result:
other: No effect on reproductive organs or function

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: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
no effects observed
Description (incidence and severity):
No effect on gross appearance of treated rat were observed.
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No effect on survival of rat were observed.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
When treated with 833 mg/kg bw, decrease in body weight were observed in rats
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
When treated with 833 mg/kg bw, decrease in food consumption were observed in rat
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:
no effects observed
Description (incidence and severity):
No effect on kidney weight of offspring was observed.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No effect on gross pathology of offspring was observed as compared to control.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
When treated with 833 mg/kg bw, slight increase in the severity of nephropathy accompanied by the presence of granular casts in some rats were observed.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
No effect on number of pups and percentage of male pups were observed in treated rats.

Effect levels (P1)

Dose descriptor:
NOAEL
Effect level:
833 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
organ weights and organ / body weight ratios
gross pathology
reproductive performance
Remarks on result:
other: no adverse effect on reproductive organs or function

Target system / organ toxicity (P1)

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 effect on gross appearance of treated offspring were observed.
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Description (incidence and severity):
No effect on survival of offspring were observed.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
When treated with 833 mg/kg bw, decrease in body weight were observed in offspring.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
When treated with 833 mg/kg bw, decrease in food consumption were observed in offspring.
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:
no effects observed
Description (incidence and severity):
No effect on kidney weight of offspring was observed.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No effect on gross pathology of offspring was observed as compared to control.
Histopathological findings:
effects observed, treatment-related
Description (incidence and severity):
When treated with 833 mg/kg bw, slight increase in the severity of nephropathy accompanied by the presence of granular casts in some offspring were observed.
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:
833 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
organ weights and organ / body weight ratios
gross pathology
Remarks on result:
other: no adverse effect on reproductive organs or function

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

Results: F2 generation

General toxicity (F2)

Clinical signs:
no effects observed
Description (incidence and severity):
No effect on gross appearance of treated offspring were observed.
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Description (incidence and severity):
No effect on survival of offspring were observed.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
When treated with 833 mg/kg bw, decrease in body weight were observed in offspring.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
When treated with 833 mg/kg bw, decrease in food consumption were observed in offspring.
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:
no effects observed
Description (incidence and severity):
No effect on kidney weight of offspring was observed.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No effect on gross pathology of offspring was observed as compared to control.
Histopathological findings:
effects observed, treatment-related
Description (incidence and severity):
When treated with 833 mg/kg bw, slight increase in the severity of nephropathy accompanied by the presence of granular casts in some offspring were observed.
Other effects:
no effects observed
Description (incidence and severity):
No adverse effect on reproductive organs or function were observed in treated rats.

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Effect levels (F2)

Dose descriptor:
NOAEL
Generation:
F2
Effect level:
833 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
organ weights and organ / body weight ratios
gross pathology
other: Reproduction
Remarks on result:
other: no adverse effect on reproductive organs or function

Target system / organ toxicity (F2)

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 833 mg/kg bw for P, F1 and F2 generation when F344 male and female rats were treated with ε-caprolactam orally in feed through three successive generations.
Executive summary:

In a three-generation reproductive toxicity study, F344 male and female rats treated with ε-caprolactam in the concentration of 0, 83, 417, 833 mg/kg bw orally in feed through three successive generations. No clinical signs were observed in treated P rats. No effect on number of pups and percentage of male pups were observed in treated P rats. Slight increase in the severity of spontaneous nephropathies occasionally accompanied by granular casts was observed in 833 mg/kg bw treated P rats. Similarly, No effect on survival, gross appearance, number of pups, percentage of male pups and kidney weight were observed in F1, F2 and F3 offspring. Decrease in body weight and food consumption was observed in F1, F2 and F3 offspring. In addition, slight increase in the severity of nephropathy accompanied by the presence of granular casts in some offspring were observed but no adverse effect on reproductive organs or function was observed in P, F1 and F2 generation. Therefore, NOAEL was considered to be 833 mg/kg bw for P, F1 and F2 generation when F344 male and female rats were treated with ε-caprolactam orally in feed through three successive generations.