2-Propenoic acid, γ-ω-perfluoro-C8-14-alkyl esters

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

25 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

NOAEL is based on read across to the one generation reproductive toxicicity study with Fluoroalkylethanol mixture. This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In order to evaluate the reproductive toxicity of the target substance and no study on reproductive toxicity is available with the target substance, read across to data from a 1 -generation reproductive toxicity with the source substance n:2 FTOH mixture was made.

Rats (20 per sex per group) were given dosages of 0, 25, 100, or 250 mg/kg/day for a period of 74 days prior to cohabitation, and during mating, gestation, and lacatation. The fluoroalkylethanol mixture (FTOH mixture) was administered daily by gavage to Sprague-Dawley rats as a suspension in 0.5% aqueous methylcellulose. All parameters for body weight gain, food consumption, reproductive performance, clinical signs, and developmental landmarks were evaluated as per OECD guidelines. The no observed adverse effect level (NOAEL) for general toxicity as well as reproductive and offspring effects is 25 mg/kg bw/day.

There were no test substance-related effects on estrous cycle parameters in the P1 generation.

There were no test substance-related effects on sperm morphology, motility, or epididymal sperm counts in the P1 generation.

Mating and fertility indices, mean gestation length, and number of implantation sites were comparable across groups.

Short description of key information:
In order to evaluate the reproductive toxicity of the target substance, and no study on reproductive toxicity is available with the target substance, read across to data with the source substance n:2 FTOH mixture was made. In accordance with Section 1, Subsection 1.5 of REACH Annex XI, Grouping of substances and read-across approach, a reproduction toxicity study information requirement 8.7.3 in Annex IX, does not need to be conducted as the requirement is fulfilled by the one generation reproductive toxicity study for the mixed Fluoroalkylethanol (source substance). The underlying hypothesis for the read-across provided within the IUCLID Assessment Reports section, supports the read-across approach.

Effects on developmental toxicity

Description of key information

No developmental toxicity data are available for the registration substance.  A prenatal developmental toxicity study in rats with n:2 FTOH mixed alcohol (source substance) was used as a read across to fulfill the data gap for the test substance.

In order to evaluate the pre-natal developmental toxicity of the mixed fluorotelomer alcohol, groups of time-mated Sprague-Dawley female rats were administered the test substance by oral gavage in 0.5% methylcellulose as vehicle at daily dosages of 0, 50, 200, or 500 mg/kg/d on gestation days 6-20. The no-observed-adverse effect level (NOAEL) for both the dam and the fetus was considered to be 200 mg/kg bw/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The reliability of the study is 2. The study is a scientific publication and well documented.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Groups of pregnant female Sprague-Dawley rats were administered the test substance (source substance) by oral gavage in 0.5% methylcellulose as vehicle at daily dosages of 0, 50, 200, or 500 mg/kg/d on gestation days 6-20 in a prenatal developmental toxicity study according to OECD 414. The no-observed-adverse effect level (NOAEL) for both the dam and the fetus was considered to be 200 mg/kg/day.

In the developmental toxicity study, reduced maternal body weight parameters, increased perianal fur staining and increased fetal skeletal alterations (variations but no malformations) were observed at 500 mg/kg/d. There was no evidence of either maternal or developmental toxicity at 50 or 200 mg/kg/d. Minimal fetal weight reduction in the 500 mg/kg/d group were considered secondary to maternal toxicity.

Justification for selection of Effect on developmental toxicity: via oral route:
The study is a scientific publication and well documented. The read across hypothesis is based on the assumption that due to its characteristic as ester, after ingestion in mammalians the ester bound of the target chemical will be subject to metabolic cleavage into its corresponding alcohols and the acrylic acid. Thus FTAC (target) and its associated alcohols (perfluoro-alkylethanol) n:2 FTOH mixture are considered to form not only a group of structurally related analogues, but are also closely related based on metabolic pathway considerations. For details see section 13 of this IUCLID document.

Justification for classification or non-classification

No data are available for the registration substance (target substance), but data are available for the read-across material, n:2 FTOH mixture (source substance). The source substance n:2 FTOH mixture has been evaluated in a developmental toxicity study and one-generation reproduction study in rats which are published in one paper.

Litter size at birth and number of live pups per litter on day 0 and 4 of lactation, were reduced in groups administered≥100 mg/kg bw/day. Pup weights during lactation were only significantly reduced at the top dose of 250 mg/kg/day. No other adverse reproductive parameters were affected.Mating and fertility indices were comparable across groups.Although signs of developmental toxicity at higher doses were observed, the test substance (source substance) was not embryo-lethal or teratogenic in rats at doses tested. Therefore, n:2 FTOH mixture was not considered toxic to the offspring.

Based hereupon, the test substance does not need to be classified for reproductive/developmental toxicity according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.