Chloroethylene

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

repeated dose toxicity: inhalation

Remarks:

combined repeated dose and carcinogenicity

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” Well-defined repeated dose exposure study.

Data source

Reference

Reference Type:

publication

Title:

Inhalation Toxicity of Vinyl Chloride and Vinylidene Chloride

Author:

Lee et al

Year:

1977

Bibliographic source:

Environmental Health Perspectives, Vol. 21: 25 -32

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

Principles of method if other than guideline:

Repeated Dose Inhalation Toxicity Study

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Vinyl chloride

IUPAC Name:

Vinyl chloride

Test material form:

other: gas

Details on test material:

Vinyl chloride gas (99.8% pure)

Test animals

Species:

rat

Strain:

other: CD rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Charles River Breeding Lab
- Age at study initiation:2 month
- Weight at study initiation:no data
- Fasting period before study:no data
- Housing: stainless steel cages; 2/per cage
- Diet (e.g. ad libitum):ad libitum, except during exposure
- Water (e.g. ad libitum):ad libitum
- Acclimation period:no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C):24C
- Humidity (%):25 -60%
- Air changes (per hr):no data
- Photoperiod (hrs dark / hrs light):12 h

Administration / exposure

Route of administration:

inhalation: gas

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Exposure apparatus:3.5m3 cubical type stainless steel inhalation chambers


TEST ATMOSPHERE
The test substance gas was introduced with heated to 40C rotameters into the chamber air supply

Duration of treatment / exposure:

For up to 12 months

Frequency of treatment:

6h/day, 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 250 or 1000 ppm
Basis:

No. of animals per sex per dose:

36/sex/dose group

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

Clinical observations performed and frequency:
Observation for adverse signs.
Feed consumption was recorded weekly.

Body weights:
Measured every 2 weeks during the study

Blood:
Aortic blood was collected from 4/male/female animals at interim and final terminations.

Sacrifice and pathology:

Organs examined at necropsy & histologic examination:
Complete necropsies were performed on all animals.

Gross examination included the following organs and tissues: brain, pituitary, thyroids, respiratory tract, alimentary canal, urogenital organs, thymus, heart, liver, pancreas, spleen, mesenteric lymph nodes, body cavities.

Statistics:

no data

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS AND MORTALITY: During the first seven months of exposure: no treatment-related adverse signs were observed.

BODY WEIGHT AND WEIGHT GAIN: At 1000 ppm (females): significantly decreased body weights starting after exposure weeks 4.

FOOD CONSUMPTION: no data


WATER CONSUMPTION: no data


HAEMATOLOGY: no treatment-related effects were oserved

CLINICAL CHEMISTRY: no treatment-related effects were oserved


HISTOPATHOLOGY: NEOPLASTIC (if applicable): At ≥250 ppm: increased incidence of hemangiosarcomas in the liver and in the lung starting during the 9th month of exposure.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Results

Subchronic exposure: NOAEC = 250 ppm (LOAEC =1000 ppm –for effects on body weights observed in female rats)

 

Chronic exposure: NOAEC not determined; LOAEC =50 ppm –for increasedmortality, increased incidence of lesions.

 

Mortality and signs of toxicity:

During the first seven months of exposure: no treatment-related adverse signs were observed.

 

At 1000 ppm: 8 males and 13 females died or were terminated during 8 to 12 months of exposure.

 

At 250 ppm: 4 males and 10 females died or were terminated during 8 to 12 months of exposure.

 

At 50 ppm: 2 females died during 8 to 12 months of exposure.

 

 

Body weight:

At 1000 ppm (females): significantly decreased body weights starting after exposure weeks 4.

 

Clinical chemistry findings:

No treatment-related changes were observed in hematology, clinical blood chemistry, pulmonary macrophage count, cytogenic analysis of bone marrow culture, x-ray examination of extremities, collagen contents in liver and lung, serum ALA synthetase, urinary ALA level, serum a-fetoprotein.

Carcinogenicity:

At ≥250 ppm: increased incidence of hemangiosarcomas in the liver and in the lung starting during the 9^thmonth of exposure.

Applicant's summary and conclusion

Conclusions:

In the present study, NOAEC subchronic = 250 ppm; subchronic LOAEC =1000 ppm –for effects on body weights observed in female rats, and chronic NOAEC not determined; chronic LOAEC =50 ppm –for increased mortality, increased incidence of lesions.