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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Klimisch code: 2. Reliable with restrictions. “Key study” Well described study conducted according to/or similar to OECD Test Guideline 414, ‘Prenatal Developmental Toxicity Study’

Data source

Reference
Reference Type:
publication
Title:
Absence of Dichloromethane Teratogenicity with Inhalation Exposure in Rats.
Author:
Hardin et al
Year:
1980
Bibliographic source:
Toxicology and Applied Pharmacology, Vol. 52: 22 -28.

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: vapour
Details on test material:
Technical grade dichloromethane (>97% pure)

Test animals

Species:
rat
Strain:
Long-Evans
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratory
- Age at study initiation:no data
- Weight at study initiation: 220-280 g
- Fasting period before study:
- Housing: single, in galvanized wire-mesh cages
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°F):74
- Humidity (%):no data
- Air changes (per hr):no data
- Photoperiod (hrs dark / hrs light): 12 hours

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Details on exposure:
Whole body inhalation chamber exposure to dichloromethane vapour produced by pumping liquid test substance into a heated three-neck round-bottom evaporating flask with a positive displacement pump.
Details on mating procedure:
M/F caged overnight; a positive mating was determined by a presence of sperm in a vaginal smear. Positive mating detection day was considered as pregnancy day 1.
Duration of treatment / exposure:
Dams were sacrificed on gestation day 21
Frequency of treatment:
6 h/day, 7 days/week
Duration of test:
Dams were sacrificed on gestation day 21
Doses / concentrations
Remarks:
Doses / Concentrations:
0 or 4500-ppm
Basis:

No. of animals per sex per dose:
30/ per group/per dose
Control animals:
yes

Examinations

Maternal examinations:
Clinical observations performed and frequency:
Daily observation.

body weights (measured every 4 days and including gestation Days 1 and 21, livers, number, live, dead and resorbed foetuses counted.
Fetal examinations:
Foetal: sex, body weights, external anomalies, soft-tissue defects, skeletal defects.

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Results

LOAEC maternal toxicity:

4500 ppm (effects on organ weights/increased liver weights)

LOAEC developmental toxicity:

4500 ppm (effects on fetal body weight/ decreased body weights)

 

Maternal data:

Body weight:

No treatment-related significant reductions in maternal body weights were observed.

Organ weight changes:

Exposure A and C (during gestation): statistically significant increases in relative and absolute liver weights were observed.

Fetal data:

Litter size and weights:

Exposure A and C (during gestation): statistically significantly decreased fetal body weights.

Sex ratio:

No treatment-related effects on the foetal sex ratio were observed.

 

Grossly visible abnormalities, external, soft tissue and skeletal abnormalities:

No treatment-related effects were observed.

Applicant's summary and conclusion

Conclusions:
(Study authors)
No overt teratogenic or embryotoxic effects associated with exposure to dichloromethane were seen in rats under the study conditions.

Remarks (submitter comment):
Developmental effects (i.e. reduced fetal body weight) were seen only at the maternally toxic doses of 4500 ppm (increased absolute and relative liver weights). LOAEC (maternal and developmental toxicity) =4500 ppm.