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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:
experimental study
Adequacy of study:
key study
Study period:
2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed in accordance with the OECD guideline 421, and in compliance with GLP standard.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
Deviations:
not specified
Principles of method if other than guideline:
NA
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): 4,4'-Oxybis(benzenesulfonyl hydrazide)
- Analytical purity: no data
- Purity test date: 99.3 wt%
- Lot/batch No.: 403650

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
no data
Details on mating procedure:
no data
Duration of treatment / exposure:
Male: total of 46 days beginning 14 days before mating
Female: From 14 days before mating to day 4 of lactation throughout the mating and pregnancy period
Frequency of treatment:
daily
Details on study schedule:
no data
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 3, 10, 30 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
no data
Positive control:
no

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: No data


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: All animals were observed twice a day

BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were recorded in males and females on days 1, 2, 5, 7, 10, and 14 of the administration during the pre-mating period. Thereafter, males were weighed on the days 21, 28, 35, 42, and 46 of the administration, and the day of necropsy. Females were weighed on days 0, 1, 3, 5, 7, 10, 14, 17, 20 of gestation and on day 0, 1, and 4 of lactation, and the day of necropsy (day 5 of lactation).

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Means of food consumptions were calculated for each rat per day.
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No

OTHER:
CAGE SIDE OBSERVATIONS: Yes / No / No data
- Time schedule:
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:

BODY WEIGHT: Yes / No / No data
- Time schedule for examinations:

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data
- Time schedule for examinations:

OTHER:
Oestrous cyclicity (parental animals):
Yes
Sperm parameters (parental animals):
Not examined
Litter observations:
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes

PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 / F3] offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities,

GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities
Postmortem examinations (parental animals):
SACRIFICE
no data

GROSS NECROPSY
- Gross necropsy consisted of: At necropsy, all animals were macroscopically examined external condition.

HISTOPATHOLOGY / ORGAN WEIGHTS
The following organs were weighted; brain, heart, liver, kidneys, adrenals, thymus, testes, epididymides, and ovaries.
The main organs of all animals were fixed in 10 % neutral buffered formalin. The testes and epididymides were fixed with Bouin’s solution and preserved in 70 % alcohol. The reproductive organs (ovaries, epididymides, and testes) in the control and highest dose groups were performed on histological examination.
Postmortem examinations (offspring):
no data
Statistics:
Statistical analysis was performed using the one-way ANOVA and Kruskal-Wallis’s test. Dunnett’s test’s test and Mann-Whitney’s U test were used for post-hoc comparison. Statistical analysis of fetuses was carried out using the litter as an experimental unit.
Reproductive indices:
•Estrous cycle: normality (%), length (day)
•Copulation index (%) = (No. of pairs with successful copulation / No. of pairs mated) X 100
•Fertility index (%) = (No. of pregnant rats/No. of pairs with successful copulation) X 100
•Gestation index (%) = (No. of females with live pups / No. of pregnant females) X 100
•Gestation length (day)
•Nursing index (%) = (No of females nursing live pups on day 4 of lactation / No. of females with live pups delivery) X 100

•Implantation index (%) = (No. of implantations / No. of corpora lutea) X 100

•Delivery index (%) = (No. of pups born / No. of implantations) X 100
Offspring viability indices:
•Sex ratio of life pups = No. of male pups born / No. of female pups born
•Live birth index (%) = (No. of live pups on day 0 of lactation /No. of pups born) X 100
•Viability index on day 4 of lactation (%) = (No. of live pups on day 4 of lactation / No. of live pups on day 0 of lactation) X 100

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
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
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
not specified

Reproductive function / performance (P0)

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

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
no data

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
Body weight gain and food consumption in all groups were not affected by the test article administration.

TEST SUBSTANCE INTAKE (PARENTAL ANIMALS)
no data

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
No compound-related effects were observed in reproductive and developmental parameters.

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
no data

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
No compound-related effects were observed in reproductive and developmental parameters.

ORGAN WEIGHTS (PARENTAL ANIMALS)
The relative weight of the kidneys was significantly increased at 10 mg/kg bw/day. Significant increases in the absolute and relative weights of the kidneys in both sexes and in the relative weight of the liver in males were found at 30 mg/kg bw/day.

GROSS PATHOLOGY (PARENTAL ANIMALS)
no data

HISTOPATHOLOGY (PARENTAL ANIMALS)
There was no relevant change in comparison to the control.

Effect levels (P0)

Key result
Dose descriptor:
NOEL
Effect level:
30 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effect on reproductive parameters (male/female) at highest tested dose level.

Results: P1 (second parental generation)

Effect levels (P1)

Key result
Dose descriptor:
NOAEL
Effect level:
30 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effect on reproductive parameters (male/female) at highest tested dose level.

Results: F1 generation

General toxicity (F1)

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

Details on results (F1)

VIABILITY (OFFSPRING)
No compound-related effects were observed in reproductive and developmental parameters.

Effect levels (F1)

Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
30 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effect on reproductive parameters (male/female) at highest tested dose level.

Overall reproductive toxicity

Key result
Reproductive effects observed:
no
Treatment related:
no
Dose response relationship:
no

Applicant's summary and conclusion

Conclusions:
The toxicity to reproduction of OBSH was evaluated in a reproduction/debelopmental toxicity screening test. The study was performed in accordance with the OECD guideline 421.
The NOEL for repeated dose toxicity in parents was considered to be 3 mg/kg bw/day, and the NOEL for reproductive and developmental toxicity was 30 mg/kg bw/day.
Executive summary:

The toxicity to reproduction of OBSH was evaluated in a reproduction/developmental toxicity screening test. OBSH was administered to rats by oral gavage at doses 0, 3, 10 or 30 mg/kg bw/day. The study was performed in accordance with the OECD guideline 421.

The NOEL for repeated dose toxicity in parents was considered to be 3 mg/kg bw/day, and the NOEL for reproductive and developmental toxicity was 30 mg/kg bw/day.