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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

No sub-chronic 90-day toxicity study in rat with the registration substance (target substance) is available. As described in more detail in the read-across justification and based on the consistency in effects seen in the comparative 14 day-repeated dose studies performed with both the target as well as the source substance coupled with knowledge on metabolism, it is reasonable to read-across the information from the available 90-day study on the mixed n:2 FTOH to address the data gap for the registration substance.

The NOAEL in a 90-day repeated oral dose study in rats with Fluoroalkylethanol mixture is 25 mg/kg/day and will be used as conservative NOAEL also for the registration substance.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
25 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Two 14-day repeated dose oral toxicity studies with a 14-day recovery phase, one with the test substance (target) and one with the source substance are available. A 90-day repeated dose oral toxicity study with mixed perfluoro-alkylethanol FTOH (source substance) was used as a read across study to fill the data gap on sub-hronic reated dose toxicity for the test substance registered. The underlying hypothesis for the read-across between the test substance and mixed n:2 FTOH is that the test substance is transformed metabolically to the mixed perfluoro-alkylethanol FTOH of different chain length. Additionally, based on the consistency in effects seen in the repeated dose studies performed with both the target as well as source substance coupled with the knowledge of the metabolism, it is reasonable to read-across the information from the 90-day study on mixed perfluoro-alkylethanol FTOH to address the data gap for the test substance.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a 14-day repeated dose oral gavage study with the registration substance (target substance) rats were treated at dose levels of 0, 65, 160, 400 and 1000 mg/kg bw/day followed by a 14-day recovery period. During the treatment period of the study no death occurred, no toxicological relevant clinical signs were observed and body weight was within the range of variations for this strain. No relevant changes in hematological parameter were observed. A decrease in cholesterol in treated male groups below historical laboratory data was detected. Liver weights were increased dose dependently in male and females. This increase was less prominent after a 14-day recovery period but still present. Thymus weights decreased slightly in male and female treatment groups. Light changes in thyroid/parathyroid weights (decrease in males, increase in females) after the 14-day treatment period were no longer seen after the recovery period and not considered to be of toxicological relevance. These results obtained with the target substance are in good agreement with data obtained with the n:2 FTOH mixture (source substance). In this comparative study with equal study design doses of 0, 65, 160, 400 and 1000 mg/kg bw/day were applied to rats and resulted in an identical toxicity profile. Like for the target substance the only significant effect seen was a decrease in cholesterol in treated male animals of all dose groups. Based on the very consistent and comparable results from this comparative testing, read across from the n:2 FTOH mixture as source molecule to the registration substance as target molecule is supported. The findings on liver weights are explainable as adaptive response due to the known peroxisome proliferation potential which has also been reported in a 90-day repeated dose toxicity study with the source substance.

Thus, the results reported above are in good agreement with the data obtained in a 90-day repeated dose toxicity study with the n:2 FTOH mixture (source substance) which is used here as read across. In the sub-chronic toxicity study rats were administered an FTOH mixture [F(CF2)xC2H4OH, x = 3 to 6] by oral gavage at 0, 25, 100 or 250 mg/kg/d. One- and three-month recovery groups were also included to assess the reversibility of any toxic effects. No test substance-related mortality or neurotoxicity occurred. The NOAEL was set to be 25 mg/kg/d, based on increased hepatic peroxisomal beta-oxidation and the degeneration and/or disorganization of enamel organ ameloblast cells in males and females administered 100 mg/kg/d and above. In males additionally body weight decrements were observed which could be attributed to alterations to the teeth caused by fluorosis and therefore, decreased ability of animals to eat pelleted chow.

Despite the above discussed findings the conservative NOAEL of 25 mg/kg/day is taken for the substance registered.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
NOAEL is based on read across to the 90-day study with n:2 Fluoroalkylethanol mixture (source substance). 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.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
The test material is produced under strictly controlled conditions in dedicated sites and handled in industry exclusively. There are no spraying operations. The vapour pressure of the test substance registered is low. Thus neither exposure nor risks are expected via inhalation route.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
The test material is produced under strictly controlled conditions in dedicated sites and handled in industry exclusively. There are no spraying operations. Thus neither exposure nor risks are expected via inhalation route. The vapour pressure of the test substance registered is low.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
The test material is produced under strictly controlled conditions in dedicated sites and handled in industry exclusively. There are no spraying operations. Thus neither exposure nor risks are expected via dermal route. Further, the molecular weight range of the test-substance is between 418 and 718 and therefore, not expected to pass the skin layers and become systemically available in huge amounts.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
The test material is produced under strictly controlled conditions in dedicated sites and handled in industry exclusively. There are no spraying operations. Thus neither exposure nor risks are expected via dermal route. Further, results of two guidline conform skin irritation studies indicates the test substance as not irritant.

Justification for classification or non-classification

In the sub-chronic 90-day toxicity study with the source substance, liver weight parameters were elevated at all dose levels. However, hepatic enzyme levels were not elevated and no histomorphologic evidence of hepatocellular damage was observed. Thus liver function is not affected by those changes. It can be therefore concluded that hepatocellular hypertrophy and the associated increase in liver weights were considered to be a test-substance related physiologic response to metabolism of a xenobiotic and not toxicologically adverse.

Increased kidney weights and renal hypertrophy (100 and 250 mg/kg/day male dose groups only) were also observed at all dose levels. However there was no histomorphologic evidence of hepatocellular or renal damage or alterations of hepatic or renal clinical pathology parameters observed. Functional changes can therefore also be excluded.

The tooth alterations reported in this study are consistent with fluoride toxicosis in which the ingestion of too much fluoride can lead to dental fluorosis (Maurer et al. 1990). Such effects were considered by the U. S. EPA to be a cosmetic effect rather than a health effect when deriving the MCL (maximum contaminant level) for fluoride in drinking water (Kaminsky et al. 1990). Fluoride at these concentrations (i.e. about 1 mg/L) also contributes to reduced dental caries formation, which is a beneficial effect.

Observed increases in thyroid hypertrophy after 90-day of continuous treatment at 100 and 250mg/kg/day with the source substance was minimal and not associated with proliferative thyroid lesions. After one month recovery the thyroid hypertrophy was no longer observed in rats at all dose levels, although alterations in thyroid colloid persisted in the one and three month recovery animals.Altered colloid described as clumped or granular has been reported to occur spontaneously in Spraque-Dawley rats with increasing incidence correlating to increasing age (Rao-Rupanagudi et al 1991). In general such findings in rodents are not relevant for human health risk assessment.

The effects on liver, kidney, and thyroid noted in the 90-day study are not considered to be of toxicological relevance and do not indicate the need for target organ classification. Based on the CLP guidance, the following criteria should be considered before classification is applied for effects that occur at doses below ≤ 100 mg/kg/day in a rat sub-chronic study:

(a) morbidity or death resulting from repeated or long-term exposure. Morbidity or death may result from repeated exposure, even to relatively low doses/concentrations, due to bioaccumulation of the substance or its metabolites, and/or due to the overwhelming of the de-toxification process by repeated exposure to the substance or its metabolites;

(b) significant functional changes in the central or peripheral nervous systems or other organ systems, including signs of central nervous system depression and effects on special senses (e. g. sight, hearing and sense of smell);

(c) any consistent and significant adverse change in clinical biochemistry, haematology, or urinalysis parameters;

(d) significant organ damage noted at necropsy and/or subsequently seen or confirmed at microscopic examination;

(e) multi-focal or diffuse necrosis, fibrosis or granuloma formation in vital organs with regenerative capacit