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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Taken from publically available data, and is considered accurate based on the registrants experience of the substance, and relates to chronic results. Conducted on a mixture containing the substance. Please note that a carcinogenicity study on the substance also exists; this is detailed below under Section 7.7.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1973

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
See "details on study design" listed below.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
Not specified

Test animals

Species:
other: mice & dogs
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Not specified

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Remarks on MMAD:
MMAD / GSD: Not specified
Details on inhalation exposure:
Not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Dose concentrations are provided on the basis of calculated values.
Duration of treatment / exposure:
30 female mice were exposed for 23 months.
Adult dogs were exposed for 1 year.
Frequency of treatment:
30 female mice were exposed by inhalation 5 days/week.
Adult dogs were exposed 7 days/week.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 or 970 mg/kg-Mice.
Basis:
other: calculated value
Remarks:
Doses / Concentrations:
2240 mg/kg-Dogs
Basis:
other: calculated value
No. of animals per sex per dose:
30 female mice used in one experiment.
6 dogs in total, 3 of each sex used in the second experiment.
Control animals:
not specified
Details on study design:
In long term inhalation toxicity studies by Smith & Case (1973) mice and dogs were exposed regularly for brief periods to high levels of mixtures of CFC-11, CFC-12, CFC-114 and CFC-113 (ration of 24:49:25:1.1) and CFC-11, CFC-12, CFC-114 and Span 85, an emulsifier (24.5:50:25:0.5) respectively. In this study, 30 female mice were exposed by inhalation 5 days/week at levels of 0 or 970 mg/kg (calculated value) per day for 23 months. Dogs (3 of each sex) were likewise exposed 7 days/week at levels of 0 or 2240 mg/kg (calculated value) per day for 1 year.
Positive control:
Not specified

Examinations

Observations and examinations performed and frequency:
Haematology, blood chemistry, and urinalysis - frequency not specified.
Sacrifice and pathology:
Performed but further information not specified.
Other examinations:
Not specified
Statistics:
Not specified

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
In this study 30 female mice were exposed by inhalation. No signs of toxicity were observed during the study and there was no evidence of lung tumours after the 23 months of exposure. When adult dogs (three of each sex) were exposed, some signs of toxicity, such as slight depression or drowsiness, were observed in dogs immediately after dosing but lasted only a few minutes. Tissue sections of the lungs did not show signs of toxicity or irritation from inhalation. Also, no changes were observed in haematology, blood chemistry, or urinalysis.

Effect levels

open allclose all
Dose descriptor:
NOEC
Effect level:
> 970 other: mg/kg per day
Based on:
other: calculated value
Sex:
not specified
Basis for effect level:
other: Mouse data
Dose descriptor:
NOEC
Effect level:
> 2 240 other: mg/kg per day
Based on:
other: calculated value
Sex:
male/female
Basis for effect level:
other: Dog data

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Mice-No signs of toxicity were observed during the study and there was no evidence of lung tumours after the 23 months of exposure.
Dogs-Tissue sections of the lungs did not show signs of toxicity or irritation from inhalation. Also, no changes were observed in haematology, blood chemistry, or urinalysis.
Executive summary:

The toxicity of CFC-12 following repeated exposure by inhalation has been studied in the mouse and dog. In long-term inhalation toxicity studies by Smith & Case (1973), mice and dogs were exposed regularly for brief periods to high levels of mixtures containing CFC-12, at 49% and 50%, respectively. In this study 30 female mice were exposed by inhalation 5 days/week at levels of 0 or 970 mg/kg (calculated value) per day for 23 months. No signs of toxicity were observed during the study and there was no evidence of lung tumours after the 23 months of exposure. When adult dogs (three of each sex) were exposed 7 days/week at levels of 0 or 2240 mg/kg (calculated value) per day for 1 year, some signs of toxicity, such as slight depression or drowsiness, were observed in dogs immediately after dosing but lasted only a few minutes. Tissue sections of the lungs did not show signs of toxicity or irritation from inhalation. Also, no changes were observed in haematology, blood chemistry, or urinalysis.

On the basis of the dose levels noted in approximately 50% CFC-12 dose levels, no classification is required