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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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
OECD guideline 422. GLP study.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Physical state: a blue powder

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1.0% Methylcellulose
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
42 Days for males14 Days before mating to day 4 of lactation for females
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
100 mg/kg bw/day (actual dose received)
Dose / conc.:
300 mg/kg bw/day (actual dose received)
Dose / conc.:
1 000 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
12 male animals per group12 female animals per group
Control animals:
yes

Examinations

Parental animals: Observations and examinations:
GENERAL STATE: Yes (appearance, behaviour, mortality)- Time schedule: Daily DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: Before and after treatment, once a week. BODY WEIGHT: Yes - Time schedule for examinations: WeeklyFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes- Time schedule for examinations: Weekly
Oestrous cyclicity (parental animals):
- Estrous cycle
Sperm parameters (parental animals):
- Number of cells in seminiferous epithelia, testis weight, seminal vesicle weight and epididymis weight.
Litter observations:
PARAMETERS EXAMINEDThe following parameters were examined in offspring:number of pups born, delivery index (%), number of pups alive on Day 0 of lactation, live birth index (%), sex ratio, number of pups alive on Day 4 of lactation, viability index (%), body weight of live pups on Day 0. GROSS EXAMINATION OF DEAD PUPS:yes, for external and internal abnormalities
Postmortem examinations (parental animals):
GROSS PATHOLOGY: Yes ORGAN WEIGHTS: YesHISTOPATHOLOGY: Yes
Postmortem examinations (offspring):
GROSS NECROPSY: yes
Reproductive indices:
Copulation index Fertility index Implantation indexGestation index
Offspring viability indices:
- Viability index

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
no effects observed
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
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Details on results (P0)

The parental animals exhibited no alterations in reproductive parameters.

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Remarks:
maternal toxicity
Effect level:
>= 300 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
histopathology: non-neoplastic
Key result
Dose descriptor:
NOAEL
Remarks:
reproduction toxicity
Effect level:
>= 1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive function (oestrous cycle)
reproductive function (sperm measures)
reproductive performance

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Description (incidence and severity):
99.5%
Body weight and weight changes:
no effects observed
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed

Details on results (F1)

There were no significant differences in offspring parameters.

Effect levels (F1)

Key result
Dose descriptor:
NOAEL
Remarks:
offspring development
Generation:
F1
Effect level:
>= 1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
organ weights and organ / body weight ratios
histopathology: non-neoplastic

Overall reproductive toxicity

Reproductive effects observed:
no

Applicant's summary and conclusion

Conclusions:
The results were:-NOAEL maternal toxicity >= 300 mg/kg bw /day-NOAEL reproductive toxicity>= 1000 mg/kg bw/day-NOAEL offspring development >= 1000 mg/kg bw/day
Executive summary:

The aim of the test was to study the reproductive and developmental toxicity in rats (12 males and 12 females) in a combined repeated dose toxicity study with the reproductive / developmental toxicity screening test at doses of 100, 300 and 1000 mg/kg bw/day.

The test was performed according to OECD Test Guideline 422.

The results were:

-NOAEL maternal toxicity >= 300 mg/kg bw /day

-NOAEL reproductive toxicity>= 1000 mg/kg bw/day

-NOAEL offspring development >= 1000 mg/kg bw/day