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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2001
Reliability:
1 (reliable without restriction)
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

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
Remarks:
migrated information: particulates

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5 % sodium-carboxymethylcellulose (CMC-NA) aqueous solution containing 0.1 % Tween 80
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
males: from 14 days before mating and through the mating period until the day before necroscopy for a total of 37 days
females: from 14 days beformating, through the matingand gestation periods and delivery until day 4 of lactation for a total of 42 to 47 days. Non-delivering females, however, were treated until the day before necropsy.
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 300, 1000 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
12
Control animals:
yes, concurrent vehicle
Positive control:
none

Examinations

Oestrous cyclicity (parental animals):
From the first day of dosing to the start of mating, the estrous cycle was examined by collecting vaginal smears every day in the morning for all females of each group, and the mean estrous cycle length of each female was calculated. Females that had an estrous cycle length other than 4 to 6 days were judged as having irregular estrous cycles.
Statistics:
Multiple comparison test:
Body weight, body weight gain, food consumption, hematology, blood chemistry, organ weight, number of corpora lutea, number of implantations, number of offspring

Kruskal-Wallis test and Dunnett-type multiple comparison test:
Days until copulation, number of estrus stages without copulation, mean estrous cycle length, gestation length, implantation index, delivery index, live birth index, incidence of offspring with external anomaly, viability index an Day 4

Chi-square test: Histopathological findings

Fisher's exact probability test:
Incidence of females with irregular estrous cycles, copulation index, fertility index, gestation index, sex ratio (rnale/fernale), incidence of dams with externally abnormal offspring
Reproductive indices:
(1) Days until copulation: Number of days from the start of mating to detection of copulation
(2) Number of estrus stages without copulation
(3) Copulation index (%): (Number of animals with successful copulation/Number of animals paired) x 100
(4) Fertility index (%): (Number of pregnant animals/Number of animals with successful copulation) x 100
(5) Gestation length: Days until completion of delivery from Day 0 of gestation
(6) Gestation index (%): (Number of females with live offspring/Number of pregnant females) x 100
(7) Implantation index (%): (Number of implantations/Number of corpora lutea) x 100
(8) Delivery index (%): (Total number of offspring born/Number of implantations) x 100
Offspring viability indices:
(1) Live birth index (%): (Number of offspring born alive/ Total number of offspring born) x 100
(2) Viability index on Day 4 (%): (Number of live offspring on Day 4/ Number of offspring born alive) x 100

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:
effects observed, treatment-related
Description (incidence and severity):
details see section 7.5.1
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
details see section 7.5.1
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
not examined

Reproductive function / performance (P0)

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

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: Generation: P and F1 (migrated information)

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:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings:
not examined

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion