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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:
1982-03-17 to 1983-07-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study with detailed description of the method and the observations similar to guideline OECD 414

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
GLP compliance:
not specified
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Teratology Screen in Rats:
- Name of test material (as cited in study report): C-259
- Substance type: white
- Physical state: liquid
- Analytical purity: no data, assumed to be 100 %
- Storage condition of test material: room temperature

Range-finding: Maternal Tolerance Study in Rats:
- Name of test material (as cited in study report): C-259
- Substance type: white
- Physical state: liquid
- Analytical purity: no data, assumed to be 100 %
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
other: Crl:COBS CD(SD)BR
Details on test animals and environmental conditions:
TEST ANIMALS for the TERATOLOGY SCREEN IN RATS:
- Source: Charles River Breeding laboratories, Kingston, New York
- Age at delivery: five weeks
- Weight at study initiation: 230-245 g
- Fasting period before study:
- Housing: individually in elevated wire mesh cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 9 weeks


TEST ANIMALS for the MATERNAL TOLERANCE STUDY IN RATS:
- Source: Charles River Breeding laboratories, Kingston, New York
- Age at delivery: twelve weeks
-Mating time: maximum 16 days
- Weight at study initiation: 177-285 g
- Fasting period before study: no data
- Housing: two female rats were placed with one male rat per breeding cage.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 3 weeks

ENVIRONMENTAL CONDITIONS FOR BOTH STUDIES:
- Temperature (°C): 70-76 °F
- Humidity (%): 57% averaged
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
weekly by weighting and dillution in water
Analytical verification of doses or concentrations:
no
Details on mating procedure:
- Impregnation procedure: cohoused
- M/F ratio per cage: 1/2
- Length of cohabitation: max. 3 weeks
- After 10 days rotation of females.
- Further matings after two unsuccessful attempts: no
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
Duration of treatment / exposure:
From day 6 through 15 of gestation
Frequency of treatment:
1/day
Duration of test:
20 days
No. of animals per sex per dose:
Teratology Screen in Rats: 22 females
Maternal Tolerance Study in Rats: 6 females per group
Control animals:
other: treated with corn oil
Details on study design:
- Dose selection rationale:
The dose of 400 mg/kg was based on a preliminary "maternal tolerance study in rats" conducted at the same laboratory. (Project number: 299-533. In this preliminiary study dose levels were 40 , 200 and 400 mg/kg.
Reported effects: The mean values of food and water consumption in all dose groups were significantly higher but did not result in an higher body weights. Gross pathology lesions were reported in three rats at 40 mg/kg (1 rat with red or bright red areas in the lung, in 1 rat the kidney contained white fluid and 1 rat with distened uterus), in one rat at 200 mg/kg (1 rat with red or bright red areas in the lung ) and in two rats at 400 mg/kg (1 rat with red or bright red areas in the lung, in 2 rats the kidney contained white fluid and in 1 rat the kidney contained tan fluid ).

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily


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


FOOD CONSUMPTION: Yes
- Time schedule for examinations: 6-8, 9-11, 12-14, 15-17 and 18-20



WATER CONSUMPTION: Yes
- Time schedule for examinations: 6-8, 9-11, 12-14, 15-17 and 18-20


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Details: gross examination of each dam
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: one third per litter
- Skeletal examinations: Yes: two thirds per litter
- Head examinations: no data
Statistics:
comprehensive statistics were perfomed with the raw data
Indices:
no indices were calculated
Historical control data:
not given in the report

Results and discussion

Results: maternal animals

Maternal developmental toxicity

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

Details on maternal toxic effects:
statistically significantly (after rank transformation) increased mean foof consumption values were noted on day 9 and 18
consistently increased water consumption
Gross pathology: 19 of 22 animal had no observable gross pathology. 1 rat with renal plevis dilated, 1 rat wit cystic areas in the ovary, 1 rat with tan areas in the liver

Effect levels (maternal animals)

open allclose all
Dose descriptor:
LOEL
Effect level:
400 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
> 400 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
> 400 mg/kg bw/day
Basis for effect level:
other: developmental toxicity

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
Gross pathology: In the control group 169 out of 191 fetuses appeared normal, in the treated group this was the case for 155 out of 165 fetuses.
visceral anomalies: none
skeletal anomalies: none

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Acetaldehyde has to be considered as not teratogenic under the reported conditions. It did not induce maternal or developmental toxic effects. The NOAEL derived from this study is greater than 400 mg/kg bw/d.
Executive summary:

Acetaldehyde was investigated for teratogenic effects in 22 rats after oral administraton of 400 mg/kg bw /d from day 6 through 15 of gesation. The dose selection was based on a maternal tolerance study. It did not induce maternal or developmental toxic effects under the reported conditions. The NOAEL derived from this study is greater than 400 mg/kg bw/d.