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Endpoint summary

Description of key information

A toxicokinetic assessment was conducted in accordance with REACH Annex VIII 8.8.1. The substance 1,1,1,3,3,3-Hexafluoropropane  (CAS No. 690-39-1)  is a gas  at room temperature and standard pressure.. It is a mono constituent organic substance (>= 99.6%) with <= 0.4% impurities.

There is no human data available and an unreliable study on the toxicokinetics study of the substance is provided by ECHA via an inquiry result. The toxicokinetic assessment is based on data from in vivo animal models and physicochemical data. In vivo studies covering the inhalation route are available (toxicokinetics, acute toxicity, two-week and 90-day repeated dose toxicity and developmental toxicity). There are no studies covering the oral and dermal route available as the substance is a gas. For further details on study summaries, reference is made to the appropriate sections in the IUCLID 5 registration dossier.

Based on the physicochemical properties and information in the dossier, oral and dermal absorption is not considered relevant and absorption via inhalation may be expected. The distribution of the substance may be expected to be wide but will be influenced by its potentially low blood solubility. There is no evidence to indicate if the substance is metabolised. The substance is expected to be excreted unchanged in exhaled air or in the urine. The absorption rate of 100% (inhalation) is accepted for chemical risk assessment purposes.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - inhalation (%):

100

Additional information

Physicochemical properties

In accordance with the ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7C Section R.7.12 (Endpoint Specific Guidance), the physicochemical properties can provide an insight into the potential behaviour of 1,1,1,3,3,3-Hexafluoropropane in the body. This information can be combined with the in vivo study data for the toxicokinetic assessment.

Absorption:

Oral/GI absorption

Oral/GI absorption is not a relevant route of exposure, as the substance 1,1,1,3,3,3-Hexafluoropropane is a gas.

Respiratory absorption-Inhalation

The substance 1,1,1,3,3,3-Hexafluoropropane is a gas with a very high vapour pressure (249 kPa at ambient temperature) which indicates that uptake via inhalation is the likely route of exposure. As 1,1,1,3,3,3-Hexafluoropropane is moderately water soluble (724 mg/L) and has a moderate value of log P (1.12 @ 20 °C), this suggests it can pass through the alveolar cell membrane by simple passive diffusion. The main physicochemical determinant of absorption for gases is the solubility of the gas in blood, measured by the blood: gas partition coefficient. This partition co-efficient is not available in the dossier, but is assumed to be low though the moderate water solubility of the substance would increase the amount absorbed per breath.

In the acute inhalational toxicity study, no mortalities were noted and the LC 50 was > 457000 ppm (2833400 mg/m3). In the subchronic repeated dose toxicity key study, the one notable substance-related effect was a diminished response to an alerting stimulus during exposure in the 50000 ppm dose level in all animals for 1 week. The NOAEC was 124,000 mg/m3. In the developmental toxicity key study, the only effect of note was significant dose-related decreases in maternal body weight gain over the first two days at the 20000 and 50000 ppm dose levels. The maternal NOAEL was 31,000 mg/m3 (20,000 ppm). There were no substance-related effects on developmental toxicity noted at any level tested. The developmental NOAEC was 310,000 mg/m3 (50,000 ppm). The physicochemical data together with the in vivo studies indicate that some absorption via the inhalation route may be expected. For chemical safety assessment purposes, an inhalation absorption rate of 100% is accepted as the blood: gas co-efficient is not available.

Dermal absorption

Dermal absorption is not a relevant route of exposure, as the substance 1,1,1,3,3,3-Hexafluoropropane is a gas.

Distribution/Metabolism:

The molecular weight (152 g/mol), water solubility (724 mg/L) and log P (1.12 at 20 °C) are favourable for wide distribution. However, the blood: gas co-efficient is expected to be low, so the fraction of the substance available in the blood for distribution will be low. There is no direct evidence to indicate if or how the substance is metabolised.

Excretion

The substance is expected to be excreted unchanged in exhaled air or in the urine due to its low molecular weight (<300) and good water solubility.