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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 from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Peer reviewed authority database (Peer review was conducted by a Japanese toxicological expert group at March 5, 2001. However, detailed information were not available). Furthermore test results were taken for the OECD SIDS Intital assessment report for C.I. Pigment Yellow 53.

Data source

Referenceopen allclose all

Reference Type:
other: Peer reviewed databse
Title:
Unnamed
Year:
2002
Reference Type:
other: OECD Substance initial assessment report (SIAR)
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
equivalent or similar 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
Details on test material:
Purity: 100 %
Lot/batch no: 4879

Test animals

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

Administration / exposure

Route of administration:
oral: gavage
Details on mating procedure:
- M/F ratio per cage: 1/1
- Length of cohabitation: 4 d
- Proof of pregnancy: vaginal plug or sperm in vaginal smear
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Exposure period: male: 46 days from 14 days prior to mating; female: 41-45 days from 14 days prior to mating to day 4 postpartum throughout mating and pregnancy
Premating exposure period (males): 14 days
Premating exposure period (females): 14 days
Frequency of treatment:
Once daily
Details on study schedule:
42 to 47 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 250, 500, 1000 mg/kg bw/day (males & females)
Basis:

No. of animals per sex per dose:
12
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: 1, 2, 3, 5, 7, 10 and 14 d; then weekly

BODY WEIGHT: Yes
- Time schedule for examinations: 1, 2, 3, 5, 7, 10 and 14 d; then weekly

Estrous cyclicity (parental animals):
Estrous cycle was determined before mating.
Sperm parameters (parental animals):
Not examined.
Litter observations:
PARAMETERS EXAMINED
The following parameters were examined in F1:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, viability index, body weight

Postmortem examinations (parental animals):
GROSS NECROPSY
ORGAN WEIGHTS
Postmortem examinations (offspring):
SACRIFICE
- The F1 offspring were sacrificed at 4 days of age.
- These animals were subjected to postmortem examinations (macroscopic examination) as follows:

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.
Reproductive indices:
Estrous cycle, copulation index (number of pairs with successful copulation/number of pairs mated X 100), fertility index (number of pregnant animals/number of pairs with successful copulation X 100), gestation index (number of females with live pups/number of living pregnant females X 100), gestation length, nursing index, number of pregnant females, corpora lutea and implantation sites, implantation index (number of implantation sites/number of corpora lutea X 100), delivery index (number of pups born/number of implantation sites X 100),
Offspring viability indices:
viability index (number of live pups on day 4/number of live pups on day 0 X 100), live birth 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:
not examined

Reproductive function / performance (P0)

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

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
No clinical signs or mortality was observed during the study period.

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
The test substance did not have any effect on body weight or food consumption.

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
No effects were observed on reproductive performances in males and females given any of the doses.

ORGAN WEIGHTS (PARENTAL ANIMALS)
Normal organ weights were observed.

GROSS PATHOLOGY (PARENTAL ANIMALS)
No gross internal lesions were observed during necropsy.

HISTOPATHOLOGY (PARENTAL ANIMALS)
No indications of treatment related findings were seen in any of the examined tissues.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day
Sex:
male/female

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

Details on results (F1)

VIABILITY (OFFSPRING)
No effects were observed on pup viability.

CLINICAL SIGNS (OFFSPRING)
No abnormal effects were observed.

BODY WEIGHT (OFFSPRING)
No treatment related effects were observed on body weight of offspring.

GROSS PATHOLOGY (OFFSPRING)
No external abnormalities or any gross internal lesions were observed.

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
>= 1 000 mg/kg bw/day
Sex:
male/female

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion