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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Short description of key information:

In accordance with Column 2 of ANNEX VIII of the REACH regulation, screening for reproductive/developmental toxicity study does not need to be conducted as two inhalation pre-natal developmental toxicity studies are available.

Justification for selection of Effect on fertility via inhalation route:

In accordance with Column 2 of ANNEX VIII of the REACH regulation, screening for reproductive/developmental toxicity study does not need to be conducted as two inhalation pre-natal developmental toxicity studies are available.

Effects on developmental toxicity

Description of key information

NOAEC (maternal toxicity) = 5000 ppm = 31,000 mg/m3

NOAEC (embriotoxicity) =  50000 ppm = 310,000 mg/m3

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study.
Qualifier:
according to guideline
Guideline:
other: OECD Guideline No. 414, 1981
GLP compliance:
yes
Limit test:
no
Species:
other: Rat, Crl:CD BR
Route of administration:
inhalation
Vehicle:
other: Not applicable
Details on exposure:
Method of administration or exposure: Whole body exposure
Frequency of treatment:
Duration of exposure per day: 6 hours
Dosing regime: 7 days/week
No. of animals per sex per dose:
Number of dams and doses
25 at 0 mg/kg or mg/l
25 at 5000 mg/kg or mg/l
25 at 20000 mg/kg or mg/l
25 at 50000 mg/kg or mg/l
Details on maternal toxic effects:
Details on maternal toxic effects:
At the 20000 and 50000 ppm there were significant dose-related decreases in maternal body weight gain over the first two days of inhalation exposures. At 50000 ppm this reduction in weight gain was accompagnied by a significant reduction in maternal food consumption and occasional instances of diminished alerting responses during the inhalation exposures. No evidence of maternal toxicity was detected at 5000 ppm. There was no evidence of developmental toxicity at any level tested.
Dose descriptor:
NOAEL
Effect level:
5 000 mg/kg bw/day (nominal)
Basis for effect level:
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Details on embryotoxic / teratogenic effects:
Effects on fetus - Gross:
No compound-related effects on the incidence of early, late or total resorptions were detected. There were no dead fetuses.


No compound-related effects on mean fetal weight were detected. The values for mean fetal weight were comparable across the control and exposure group.

Effects on fetus - Soft tissue:
No compound-related effect on the incidence of fetal malformations and on the incidence of fetal variations was detected.

Effects on fetus - Skeletal:
No compound-related effect on the incidence of fetal malformations and on the incidence of fetal variations was detected.
Dose descriptor:
NOAEL
Remarks:
embriotoxicity
Effect level:
50 000 mg/kg bw/day (nominal)
Based on:
not specified
Basis for effect level:
other: fetal mortality, weight, malformation and variations.
Remarks on result:
other: NOAEL=50000 ppm (310000 mg/m3)
Abnormalities:
not specified
Developmental effects observed:
not specified
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
310 000 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
Information from migrated NONS file, as per inquiry number 06-2120010181-80-0000, permission to refer granted by ECHA.
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

In the key pre-natal developmental toxicity study (OECD 414/GLP), 1,1,1,3,3,3-Hexafluoropropane (CAS No. 690-39-1) was administered to 25 female Crl:CD BR rats via inhalation (whole body inhalation exposure ; 6 hours/day and 7 days/week )at dose levels of 5000, 20000, 50000 ppm . There were significant dose-related decreases in maternal body weight gain over the first two days at the 20000 and 50000 ppm dose levels. At 50000 ppm this reduction in weight gain was accompanied by a significant reduction in maternal food consumption and occasional instances of diminished alerting responses during the inhalation exposures. No evidence of maternal toxicity was detected at 5000 ppm. There were no substance-related effects on developmental toxicity noted at any level tested, including the incidence of early, late or total resorptions, dead foetuses, mean fetal weight, the incidence of fetal malformations and fetal variations in soft tissue and skeletal. Therefore, the established NOAEC of maternal toxicity was 5000 ppm and the NOAEC of embriotoxicity was 50000 ppm.

In the supporting pre-natal developmental toxicity study (OECD 414/GLP),1,1,1,3,3,3-Hexafluoropropane (CAS No. 690-39-1) was administered to 20 female rabbits via inhalation ( whole body exposure ; 6 hours/day and 7 days/week ) atdose levels of 5000, 20000, 50000 ppm .). There were no mortalitiesat any dose level and no substance-related effects on maternal body weight, weight gains, food consumption, clinical observations, post-mortem findings and reproductive outcome parameters. There were no substance- related effects on fetal mortality, mean fetal weight, the incidence of fetal malformation and on the incidence of fetal variations in skeletal or soft tissue. Therefore, both of the NOAEL of maternal toxicity and embriotoxicity were 7 mg/l/h/day .

Justification for selection of Effect on developmental toxicity: via oral route:

The study is not required for gases as two inhalation pre-natal developmental toxicity studies are available.

Justification for selection of Effect on developmental toxicity: via inhalation route:

The  key study (OECD 414, GLP) was conducted in the rat and indicates a higher level of concern due to adverse maternal effects (NOAEC = 31,000mg/m3). All the acute and repeated dose studies were performed in the rat, so this study was considered the most suitable. Another study (OECD 414, GLP) was conducted in the rabbit and no adverse maternal or developmental effects were noted. The NOAEL values were also provided in non-standard units (7mg/l/g/day).

Justification for selection of Effect on developmental toxicity: via dermal route:

The study is not required for gases as two inhalation pre-natal developmental toxicity studies are available.

Justification for classification or non-classification

Based on the available information in the dossier, 1,1,1,3,3,3-Hexafluoropropane (CAS No. 690-39-1) does not need to be classified for reproductive toxicity when the criteria outlined in Annex I of 1272/2008/EC are applied.

Additional information

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