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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study followed acceptable scientific practice for the time period.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1970
Report Date:
1970

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
Admin. From day 6 to 16 of gest., 2 dose groups only
GLP compliance:
no
Remarks:
prior to GLP
Limit test:
yes

Test material

Reference
Name:
Unnamed
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): EY 2333, identity verified in a separate analytical report
- Analytical purity: 98.5%

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc.
- Age at study initiation: Adult no further data
- Weight at study initiation: no data
- Fasting period before study: no
- Housing: inidividual after succesful mating
- Diet ad libitum
- Water ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
1.5 and 15 mg/l suspension
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:

VEHICLE
- Justification for use and choice of vehicle (if other than water): corn oil was used to achieve some solubility and a fine dispersion of the TS
- Concentration in vehicle: 1.5 and 15 mg/l
- Amount of vehicle (if gavage): 1 ml/100 g of bw
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:

- cohoused:
- M/F ratio per cage: 1/2
- Length of cohabitation: no data
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: sperm in vaginal smear eferred to as day 0 of pregnancy
Duration of treatment / exposure:
Daily from day 6 to day 15 of gestation
Frequency of treatment:
Daily
Duration of test:
Day 19 of gestation
Doses / concentrations
Remarks:
Doses / Concentrations:
15, 150 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
Vehicl control : 18 females
15 mg/kg bw dose group: 18 females
150 mg/kg bw dose grou: 19 females
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked: Mortality, appearance, behavoir

BODY WEIGHT: Yes
- Time schedule for examinations: At day 0, 5, 10, 15, 19.

FOOD CONSUMPTION : Yes
- rcorded prior to treatment, at two intervals during treatment and after treatment until sacrifice
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 19
- Organs examined: gross examination of uterine and visceral structures

Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included
- Gravid uterus weight: No data
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of resorptions: Yes
Fetal examinations:
- External examinations: Yes:
- Soft tissue examinations: Yes: one third of each litter
- Skeletal examinations: Yes: 2/3 of each litter
- Head examinations: Yes: in the animals used for visceral examination (1/3)
Statistics:
not reported

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No maternal deaths occurred. Appearance and behavior was comparable to controls. No test substance related gross changes observed in the pregnant animals at necropsy. One animal in the high dose group showed wheezing on day 11. One low dose group animal had sof faeces on day 19.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
>= 150 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
>= 150 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: developmental toxicity

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
All examined parameters were comparable to those of the concurrent controls.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

The number and placement of uterine implantation and resorption sites was comparable in dosed and control group animals.

The number, weight and length of life foetusses in the test substance groups was comparable to controls.

One dead fetus was found in the control group, but none in the dose groups. One control group female had three, on other one late resorption sites. Two low group females had one resorption site each.

The number of litters with resorption sites was 11/18 in controls, 7/17 in the low dose and 8/18 in the high dose group.

A few fetusses in controls and test groups appeared small in size, with similar incidence.

Visceral structures were examined by Wilson's sectioning technique in 58 control, 61 low dose and 68 high dose fetuses.

Observations in all groups included clotted blood in thoracical, abdominal and intestinal, or cranial regions, dilated renal pelvis dilated lateral brain ventricel in one control and ligh colores area of the liver in one control fetus.

No clearly test substance related differences in incidence of findings from controls were observed.

Skeletal examinations: skull, ribs, sternum, vertebrae, pelvic gridle, long bones, forepaws, hind paws evaluated. Changes observed occured with comparable incidence in dose and control groups.

Applicant's summary and conclusion

Conclusions:
The developmental toxicity study in rats receiving either 15 or 150 mg/kg bw of the test substance by gavage between day 5 and day 16 of gestation did not reveal any test substance related effects on inplantation, resorption litter size or any fetal parameters investigated in this study. Under the conditions of this study no indications of a possible developmental effect were observed.
Executive summary:

The substance was investigated for enbryotoxic and/or teratogenic effects in goups of 17 to 18 pregnant female albino rats . The test material was mixed with corn oil and administered by oral gavage at dosage levels of 15 and 150 mg/kg/day from Day 6 through Day 15 of gestation . Control animals received corn oil only.

No maternal deaths occurred. All control and test litters were delivered by Caesarean section . Appearance, behavior , body weight gain , and food consumption were comparable among control and test animals. All uterine, litter, and Caesarean data were comparable among control and test groups. There was also no compound-related effect noted with respect to external appearance, visceral anatomy, development , or skeletal structure of the fetuses. Under the conditions of this study no indications of a possible developmental effect were observed.