Registration Dossier

Administrative data

Endpoint:
three-generation reproductive toxicity
Remarks:
based on test type (migrated information)
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:
This data has been reviewed by the World Health Organisation (WHO) have agreed that no effects or dominant lethality was found at either dose level tested. The data is considered accurate and appropriate based on the registrants experience of the substance.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1974

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In a three-generation, oral gavage study in rats using CFC-12 (in corn oil) at average doses of 15 and 150 mg/kg per day.
GLP compliance:
not specified
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid - liquid: suspension
Details on test material:
Dichlorodifluoromethane (CFC-12) is a relatively inert, non-flammable liquid that is used mainly as a refrigerant. Its molecular weight is 120.92, its vapor pressure is 6.43 atm at 25°C, and it is quite insoluble in water (5.7 ml/100 ml at 26°C).

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Not specified

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on exposure:
In a three-generation, oral gavage study in rats using CFC-12 (in corn oil) at average doses of 15 and 150 mg/kg per day
Details on mating procedure:
Not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not specified
Duration of treatment / exposure:
Not specified
Frequency of treatment:
Not specified
Details on study schedule:
Not specified
Doses / concentrations
Remarks:
Doses / Concentrations:
15 or 150 mg/kg
Basis:
no data
No. of animals per sex per dose:
Not specified
Control animals:
not specified
Details on study design:
Male and female rats were given Freon 12 in doses of 15 or 150 mg/kg by intubation. The rats were then bred and evaluated for fertility, corpora lutea, implantation sites, resorption sites, and number of live fetuses per litter.
Positive control:
Not specified

Examinations

Parental animals: Observations and examinations:
Not specified
Oestrous cyclicity (parental animals):
Not specified
Sperm parameters (parental animals):
Not specified
Litter observations:
Not specified
Postmortem examinations (parental animals):
Not specified
Postmortem examinations (offspring):
Not specified
Statistics:
Not specified
Reproductive indices:
Fertility, corpora lutea, implantation sites, resorption sites, and number of live fetuses per litter.
Offspring viability indices:
Number of live fetuses per litter.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Details on results (P0)

No dominant lethality was found at either dose level.

Effect levels (P0)

Dose descriptor:
NOEC
Effect level:
> 150 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified

Details on results (F1)

No dominant lethality was found at either dose level.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No dominant lethality was found at either dose level. The substance is not considered to be classified for fertility effects.
Executive summary:

In a 3 generation oral study using CFC12 (in corn oil) at average doses of 15 and 150 mg/kg per day, Sherman (1974) found no adverse effects in reproductive capability as measured by the fertility index, gestation index, viability index and lactation index. No classification is applicable.