Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study performed according to a protocol similar to OECD guideline 414, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance code: L0212.01 (27.5% active ingredient)

Test animals

Species:
rat
Strain:
other: CD
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc, Kingston, N.Y.
- Weight at study initiation: 210-250 g
- Housing: individual stainless steel cages with raised-wire floors
- Diet: Certified Purina Rodent Chow, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
The dosing solutions were prepared as aqueous solutions at concentrations to furnish 0, 0.25, 250, or 2500 mg/kg bw/day doses of the active substance in a 10 mL/kg volume. Distilled water served as the control vehicle. All dosing solutions were stored in amber bottles and refrigerated until used.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- Impregnation procedure: cohoused
- M/F ratio per cage: 1/2
- Length of cohabitation: until conception was determined
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
Duration of treatment / exposure:
day 6 through day 15 of pregnancy
Frequency of treatment:
once daily
Duration of test:
6 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0.25, 2.5, 250, 2500 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
23-25
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations: clinical signs and mortality

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily

BODY WEIGHT: Yes
- Time schedule for examinations: days, 0, 6, 9, 12, 15 and 20 of gestation

FOOD CONSUMPTION: Yes
- Time schedule for examinations: days, 0, 6, 9, 12, 15 and 20 of gestation

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: thoracic and abdominal organs (gross examination)
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Number and location of viable and non-viable fetuses: Yes
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: Yes: all per litter
- Liver examinations: Yes: one foetus of each sex from each litter
Statistics:
The data were statistically analyzed by a computer package similar to B8944, which is contained in the Argus reproduction/teratology software package.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
All of the dams at the three highest doses had green-tinted viscera, with the discoloration being especially pronounced at the two highest dosages.
Twenty-two to twenty-four females in each group were sperm-positive, with 21-24 being confirmed as pregnant on day 0 of gestation.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
> 2 500 mg/kg bw/day
Based on:
act. ingr.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
> 2 500 mg/kg bw/day
Based on:
act. ingr.
Basis for effect level:
other: other:

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Normal pregnancies and fatal development were observed with no statistical differences among any of the characteristics measured. There were no statistically significant differences in the number of corpora lutea, implants, resorptions and (non-)viable foetuses. Hence ZPS did not have a deleterious effect on either the viability or growth of the embryo and foetus. There was no evidence of increased incidence of either external, skeletal or soft-tissue abnormalities in fetuses from dams treated with the substance. In addition, there was no evidence of discoloration in the foetal viscera, particularly of the liver, even though the viscera of the dams given the two highest doses were deeptly tinted blue-green.

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
> 2 500 mg/kg bw/day (actual dose received)
Based on:
other:
Sex:
male/female
Basis for effect level:
other: no effects

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion