Registration Dossier

Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
fertility, other
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
unknown
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary literature

Data source

Reference
Reference Type:
publication
Title:
ε-Caprolactam / Toxikologisch-arbeitsmedizinische Begründungen von MAK-Werten
Author:
DFG (Deutsche Forschungsgemeinschaft)
Year:
1990
Bibliographic source:
WILEY-VCH GmbH, Weinheim

Materials and methods

Principles of method if other than guideline:
Method not described
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no further details described

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
no further information

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: test item was mixed in diet
Details on exposure:
no further information
Details on mating procedure:
no further information
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no further information
Duration of treatment / exposure:
Duration of treatment: exposed over a period of 3 generations
Frequency of treatment:
daily ad libitum (via food intake)
Details on study schedule:
no further information
Doses / concentrations
Remarks:
Doses / Concentrations:
1000; 5000; 10000 mg/kg diet
Basis:
nominal in diet
mg/kg diet
No. of animals per sex per dose:
no information
Control animals:
not specified
Details on study design:
no further details
Positive control:
no data

Examinations

Parental animals: Observations and examinations:
food consumption; body weight gain; birth behaviour
Oestrous cyclicity (parental animals):
no data
Sperm parameters (parental animals):
no data
Litter observations:
no data
Postmortem examinations (parental animals):
macroscopic examinations
Postmortem examinations (offspring):
no data
Statistics:
no data
Reproductive indices:
no data
Offspring viability indices:
survival time of offspring; food consumption; body weight gain

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-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

Details on results (P0)


- at doses of 5000 and 10000 mg/kg diet: dose dependent reduction of food intake and body weight gain
- at a dose of 10000 mg/kg diet: macroscopic slightly damage of kidneys in male rats
- no effects on birth behaviour and survival of new bornsat examined

Effect levels (P0)

open allclose all
Dose descriptor:
LOEL
Effect level:
5 000 mg/kg diet
Sex:
male/female
Basis for effect level:
other: reduced food consumption and body weight increase in parents and new borns
Remarks on result:
other: Generation: all generations examined (migrated information)
Dose descriptor:
LOEL
Effect level:
500 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: calculated from the NOAEL described in the publication (5000 mg/kg diet) under assumption that the average food intake of rats is 10 g/100g bw/day
Remarks on result:
other: Generation: all generations examined (migrated information)
Dose descriptor:
NOEL
Effect level:
1 000 mg/kg diet
Sex:
male/female
Remarks on result:
other: Generation: all generations examined (migrated information)
Dose descriptor:
NOEL
Effect level:
100 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: calculated from the NOEL described in the publication (1000 mg/kg diet) under assumption that the average food intake of rats is 10 g/100g bw/day
Remarks on result:
other: Generation: all generations examined (migrated information)
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: calculated from LOEL
Remarks on result:
other: Generation: all generations examined (migrated information)

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Histopathological findings:
not specified

Details on results (F1)

- at doses of 5000 and 10000 mg/kg diet: dose dependent reduction of food intake and body weight gain
- at a dose of 10000 mg/kg diet: macroscopic slightly damage of kidneys in male rats

Effect levels (F1)

Dose descriptor:
LOAEL
Generation:
F1
Effect level:
5 000 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

no further remarks

Applicant's summary and conclusion

Conclusions:
The substance ε-caprolactam was tested over three generations of rats for its potential reproduction toxicity by oral gavage of doses of 1000, 5000and 10000 mg/kg diet. The birth behaviour of dams and the time of survival of offspring was not affected (NOEL: 1000 mg/kg diet (calculated: approx. 100 mg/kg bw/day); LOEL: 5000 mg/kg diet (calculated: approx. 500 mg/kg bw/day).
Executive summary:

The substance ε-caprolactam was tested over three generations of rats for its potential reproduction toxicity by oral gavage of doses of 1000, 5000 and 10000 mg/kg diet. A decreased food consumption and bodyweight gain was observed on doses of 5000 and 10000 mg/kg diet in dams and offspring. At 10000 mg/kg diet macroscopic slightly damages of kidneys in male rats were observed. The birth behaviour of dams and the time of survival of offspring was not affected. The NOEL was determined as 1000 mg/kg diet (calculated: approx. 100 mg/kg bw/day) and the LOEL is 5000 mg/kg diet (calculated: approx.500 mg/kg bw/day).