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Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Phase-Specific Developmental Toxicity in Mice Following Maternal Methanol Inhalation.
Author:
Bolon, B., Dorman, D.C., Janszen, D., Morgan, K.T., Welsch, F.
Year:
1993
Bibliographic source:
Fund. Appl. Toxicol. 21: 508-516

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
- examination of uterine contents are missing
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Methanol
EC Number:
200-659-6
EC Name:
Methanol
Cas Number:
67-56-1
Molecular formula:
CH4O
IUPAC Name:
Methyl alcohol

Test animals

Species:
mouse
Strain:
CD-1

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
no data on mating procedure
Duration of treatment / exposure:
gestation days:
6-15 or 7-9 or 9-11
Frequency of treatment:
6 hours/day
Duration of test:
up to day 17 of gestation
No. of animals per sex per dose:
20-27 pregnant mice per dose group
Control animals:
yes, sham-exposed

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
not specified
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
not specified
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined

Maternal developmental toxicity

Number of abortions:
not examined
Pre- and post-implantation loss:
not examined
Total litter losses by resorption:
not examined
Early or late resorptions:
no effects observed
Dead fetuses:
not examined
Changes in pregnancy duration:
not examined
Changes in number of pregnant:
not examined

Effect levels (maternal animals)

open allclose all
Key result
Dose descriptor:
NOAEC
Effect level:
6.65 mg/L air (nominal)
Basis for effect level:
other: maternal toxicity
Key result
Dose descriptor:
LOAEC
Effect level:
13.3 mg/L air (nominal)
Basis for effect level:
other: maternal toxicity

Maternal abnormalities

Key result
Abnormalities:
effects observed, treatment-related

Results (fetuses)

Fetal body weight changes:
no effects observed
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
not examined
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
not examined
Skeletal malformations:
effects observed, treatment-related
Description (incidence and severity):
neural tube defects, cleft palate
Visceral malformations:
effects observed, treatment-related
Description (incidence and severity):
renal pelvic dilatation
Details on embryotoxic / teratogenic effects:
Details on embryotoxic / teratogenic effects:
GD at 6-15 for 6h/day: Reduced foetal body weights and increased incidences of resorptions,neural tube defects, cleft palate and digit malformations were observed.
GD at 7-9 for 6h/day: The incidence of resorptions, neural tube defects and cleft palate, but not the incidence of digit malformations, was increased whereas the number of live foetuses was decreased.
GD at 9-11 for 6h/day: Only cleft palate and digit malformations but no neural tube defects were observed.

Effect levels (fetuses)

Key result
Dose descriptor:
LOAEC
Effect level:
6.65 mg/L air (nominal)
Basis for effect level:
other: embryotoxicity

Fetal abnormalities

Key result
Abnormalities:
effects observed, treatment-related

Overall developmental toxicity

Key result
Developmental effects observed:
yes
Lowest effective dose / conc.:
6.65 mg/L air (nominal)
Treatment related:
yes
Relation to maternal toxicity:
developmental effects as a secondary non-specific consequence of maternal toxicity effects
Dose response relationship:
not specified

Applicant's summary and conclusion

Conclusions:
The data suggest that the spectrum of teratogenic effects is dependent on the number of methanol exposures and the stage of embryogenesis.
Major methanol-induced events included malformations of the brain, eyes, and the urinary tract as well as decreased foetal weight. External abnormalities of the calvaria, hard palate, jaw, and tail also suggest a detrimental methanol-related effect on the axial skeleton.