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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Klimisch code: 1. Reliable without restrictions. “Key study” US National Toxicology Program -sponsored study.

Data source

Reference
Reference Type:
publication
Title:
NTP Technical Report on Toxicology and Carcinogenesis Studies of Dichloromethane (Methylene Chloride) (CAS NO. 75-09-2) in F344/N Rats and B6C3Fi Mice (Inhalation Studies)
Author:
NTP
Year:
1986
Bibliographic source:
NTP TR 306, NIH Publication no. 86-2562

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Principles of method if other than guideline:
Repeated Dose Inhalation Toxicity: 90-Day Study
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: vapour
Details on test material:
Dichloromethane (>99% pure).

Test animals

Species:
rat
Strain:
other: F344/N rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Charles River Breeding Laboratory
- Age at study initiation:7 -9 weeks
- Weight at study initiation:
- Fasting period before study:no data
- Housing:stainless steel wire cages
- Diet (e.g. ad libitum):ad libitum, except for exposure time
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 21days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72 -79
- Humidity (%):43 -70
- Air changes (per hr):no data
- Photoperiod (hrs dark / hrs light):12 h

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Whole body inhalation chamber exposure to test substance vapour. Test substance (liquid form) was introduced into a heated wick vaporizer situated in the chamber fresh air duct.
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
6 h/day, 5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 525, 1050, 2100, 4200 or 8400 ppm
Basis:

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

Examinations

Observations and examinations performed and frequency:
Clinical observations performed and frequency:
Observation for mortality & morbidity: 2 times/day.

Body weights:
Measured prior to the first exposure; weekly during the study
Sacrifice and pathology:
Organs examined at necropsy & histologic examination:
Complete necropsies were performed on all animals.

Complete histologic examination was performed on high dose and control animals.

Organ weights at necropsy: liver lipid/liver weight ratio.

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
At 8400 ppm: one male and one female animal died.

BODY WEIGHT AND WEIGHT GAIN
At 8400 ppm: decrease in final mean body weight in both males (23%) and females (11%).

ORGAN WEIGHTS
Organ weight changes:
At ≥ 4200 ppm (females) and at 8400 ppm (males): statistically significant decrease in the liver lipid/liver weight ratio.


GROSS PATHOLOGY

HISTOPATHOLOGY: NON-NEOPLASTIC
At ≥ 4200 ppm (females) and at 8400 ppm (males): foreign body pneumonia described as focal accumulation of mononuclear and multinucleated inflammatory cells was observed.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Results

NOAEC = 2100 ppm

LOAEC =4200 ppm (for effects on liver and lungs observed in animals of both sexes).

Mortality:

At 8400 ppm: one male and one female animal died.

Body weight:

At 8400 ppm: decrease in final mean body weight in both males (23%) and females (11%).

Organ weight changes:

At ≥ 4200 ppm (females) and at 8400 ppm (males): statistically significant decrease in the liver lipid/liver weight ratio.

Histopathology incidence and severity:

At ≥ 4200 ppm (females) and at 8400 ppm (males): foreign body pneumonia described as focal accumulation of mononuclear and multinucleated inflammatory cells was observed.

Applicant's summary and conclusion

Conclusions:
In the present study, NOAEC = 2100 ppm based on LOAEC =4200 ppm for effects on liver and lungs observed in animals of both sexes.