Registration Dossier

Administrative data

Endpoint:
two-generation reproductive toxicity
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
Deviations:
yes
Remarks:
Only 3 applications per week; no or only partial examination of oestrous cycle and sperm parameters.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
As described in guideline.

Administration / exposure

Route of administration:
dermal
Vehicle:
water
Details on exposure:
Dose volume: 1 mL/kg bw
Details on mating procedure:
As described in guideline.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
No data.
Frequency of treatment:
3/week (except during mating)
Details on study schedule:
P: 119 days of dosing
F1: 133 days of dosing
Doses / concentrationsopen allclose all
Dose / conc.:
0 other: % nominal in water
Dose / conc.:
1 other: % nominal in water
Dose / conc.:
10 other: % nominal in water
Dose / conc.:
25 other: % nominal in water
Dose / conc.:
0 other: mg/kg bw/day nominal in water
Dose / conc.:
10 other: mg/kg bw/day nominal in water
Dose / conc.:
100 other: mg/kg bw/day nominal in water
Dose / conc.:
250 other: mg/kg bw/day nominal in water
No. of animals per sex per dose:
30 (P)
20/40 (male/female; F1)
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
As described in guideline.
Oestrous cyclicity (parental animals):
Not examined.
Sperm parameters (parental animals):
Weight and histopathology are missing.
Litter observations:
No individual weighing of pups.
Postmortem examinations (parental animals):
As described in guideline.
Postmortem examinations (offspring):
As described in guideline.

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
no effects observed
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:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Details on results (P0)

In the highest dose, body weights of both males and females in both treated generations were sporadically and not always statistically significant decreased compared to controls.
At necropsy organ weight differences in liver, lung, kidney and heart were observed in the F1 generation, but no pathological findings were associated with the affected organs.

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Remarks:
reproduction
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No treatment-related effects observed.
Dose descriptor:
NOAEL
Remarks:
development
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No treatment-related effects observed.
Dose descriptor:
NOEL
Remarks:
systemic
Effect level:
100 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: Changes in body weight and organ weights without associated pathological findings.
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: Changes in body weight and organ weights without associated pathological findings.

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:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed

Effect levels (F1)

open allclose all
Dose descriptor:
NOAEL
Remarks:
reproduction
Generation:
F1
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No treatment-related effects observed.
Dose descriptor:
NOAEL
Remarks:
development
Generation:
F1
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No treatment-related effects observed.

Results: F2 generation

Effect levels (F2)

Dose descriptor:
NOAEL
Remarks:
development
Generation:
F2
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No treatment-related effects observed.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion