Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary source from OECD SIDS
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: OECD Guideline 412
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 83-3 (Prenatal Developmental Toxicity Study)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan/MAFF Guideline
Deviations:
no
Qualifier:
according to
Guideline:
other: U.S. EPA TSCA Guideline 40 CFR Parts 798.2450
Deviations:
no
Qualifier:
according to
Guideline:
other: EEC Guideline 92/69/EEC
Deviations:
no
Principles of method if other than guideline:
Not relevant
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Isobutyraldehyde
- Molecular formula (if other than submission substance): Not documented
- Molecular weight (if other than submission substance): Not documented
- Smiles notation (if other than submission substance): Not documented
- InChl (if other than submission substance): Not documented
- Structural formula attached as image file (if other than submission substance): see Fig. Not documented
- Substance type: Not documented
- Physical state: Not documented
- Analytical purity: Not documented
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: Not documented
- Lot/batch No.: Not documented
- Expiration date of the lot/batch: Not documented
- Radiochemical purity (if radiolabelling): Not documented
- Specific activity (if radiolabelling): Not documented
- Locations of the label (if radiolabelling): Not documented
- Expiration date of radiochemical substance (if radiolabelling): Not documented
- Stability under test conditions: Not documented
- Storage condition of test material: Not documented
- Other: Not documented

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No information provided
- Age at study initiation: 75 - 84 days old.
- Weight at study initiation: No information provided
- Fasting period before study: No information provided
- Housing: No information provided
- Diet (e.g. ad libitum): No information provided
- Water (e.g. ad libitum): No information provided
- Acclimation period: No information provided

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No information provided
- Humidity (%): No information provided
- Air changes (per hr): No information provided
- Photoperiod (hrs dark / hrs light): No information provided

IN-LIFE DATES: From: To: No information provided

Administration / exposure

Route of administration:
other: not specified
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on exposure:
Groups of 25 mated female Wistar rats were exposed to target concentrations of 1000, 2500, or 4000 ppm isobutyraldehyde for 6 hours per day, gestation day 6 through 15. Coital day 6 through post-coital day 15.
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
No information provided
Details on mating procedure:
No information provided
Duration of treatment / exposure:
6 hours per day from gestation day 6 through 15 and coital day 6 through post-coital day 15.
Frequency of treatment:
Not specified
Duration of test:
6 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
1000, 2500 or 4000 ppm
Basis:
no data
No. of animals per sex per dose:
Groups of 25 mated female rats per dose level.
Control animals:
not specified
Details on study design:
No further information

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: No data
- Time schedule: Not documented
- Cage side observations checked in table [No.?] were included. Not documented

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: Not documented

BODY WEIGHT: Yes
- Time schedule for examinations: Not documented

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- 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 data
- Time schedule for examinations: Not documented

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # Not documented
- Organs examined: Not documented

OTHER: No additional information
Ovaries and uterine content:
No information provided
Fetal examinations:
- External examinations: Yes: No data on number of litter examined.
- Soft tissue examinations: Yes: No data on number of litter examined.
- Skeletal examinations: Yes: No data on number of litter examined.
- Head examinations: No data
Statistics:
No information provided
Indices:
No information provided
Historical control data:
No information provided

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Decreased body weight gain; Lesions of nasal mucosa

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEC
Effect level:
3 mg/L air (nominal)
Based on:
no data
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEC
Effect level:
12 mg/L air (nominal)
Based on:
no data
Basis for effect level:
other: developmental toxicity

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
No substance-related effects up to and including highest exposure concentration

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Isobutyraldehyde exposure resulted in a dose-related increase in maternal toxicity, as evidenced by a significant decrease in body weight gain in dams exposed to 4000 and 2500 ppm., but not at 1000 ppm. Exposure of dams to isobutyraldehyde had no effect ongestational or litter parameters and did not induce embryo/fetal toxicity. There was no increase in fetal malformations at any exposure level, up to the highest concentration tested, 4000 ppm.

Applicant's summary and conclusion

Conclusions:
Based on the results of this study, it can be concluded that the test substance, isobutyraldehyde, did not induce any reproductive toxicity when testedin female mated Wistar rats.
Executive summary:

Garner et al. (1996) examined the potential of isobutyraldehyde to induce reproductive toxic effects when tested in groups of 25 mated female Wistar rats exposed to the test substance 6 hours per day on days 6 through 15 of gestation. The test animals were exposed to the test substance at concentrations of 1000, 2500 and 4000ppm. The results of this study indicate a dose-related increase in maternal toxicity but exposure of the dams to isobutyraldehyde had no effect on gestational or litter parameters and did not induce embryo/foetal toxicity. There was no increase in foetal malformations at any exposure level, up to the highest concentration tested. Based on the results of this study, it can be concluded that the test substance, isobutyraldehyde, did not induce any reproductive toxicity when tested in female mated Wistar rats.