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Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
Toxicokinetic Assessment
Type of information:
other: Based on available studies
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)

Data source

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
3,3,4,4,5,5,6,6,7,7,8,8-dodecafluorodeca-1,9-diene
EC Number:
217-288-0
EC Name:
3,3,4,4,5,5,6,6,7,7,8,8-dodecafluorodeca-1,9-diene
Cas Number:
1800-91-5
Molecular formula:
C10H6F12
IUPAC Name:
3,3,4,4,5,5,6,6,7,7,8,8-dodecafluorodeca-1,9-diene
Test material form:
liquid

Results and discussion

Any other information on results incl. tables

Toxicokinetic qualitative assessment

There are no standard toxicokinetics studies available in the dataset. The following assessment relies on available toxicological studies and physico-chemical properties (REACH guidance R.7.12, V 3.0, 2017).

ABSORPTION

 Oral /GI absorption

No toxicity was observed in the acute oral toxicity study at up to 2000 mg/kg. However, the adverse effects noted in the repeated dose toxicity study at the highest dose (limit dose of 1000 mg/kg/day) provide evidence that the substance can be absorbed by the oral route. The statistically significant increase in liver weight (absolute and relative) at the highest dose and some variations in the clinical biochemistry parameters in male rats following 29 days exposure at the highest dose indicate systemic exposure.

 

Molecular weight below 500 are favourable for gastro-intestinal absorption. Because of the fluorinated backbone, the molecule has lipophilic properties, as shown by the LogKow determination, which may limit dissolution in gastrointestinal fluids and the absorption by passive diffusion. In that case absorption may occur via micellular solubilisation.

 

In conclusion,1,6-Divinylperfluorohexane can be absorbed to some extent by the oral route. No sufficient data are available for estimating the absorption rate. The default absorption is set at 100% for the oral route.

 

Respiratory Absorption

The substance is quite volatile (vapour pressure of 1200 Pa at 20°C) therefore inhalation is a relevant route of exposure.

 

Based on the perfluorinated structure, LogKow and low water solubility the molecule has lipophilic properties which may limit dissolution and absorption along the respiratory tract, but the substance may reach deeper lung regions. Based on the relatively low molecular weight range (ca. 354), logKow and low water solubility, absorption may occur via micellar solubilisation.

Based on physical-chemical properties, a certain absorption of1,6-Divinylperfluorohexanevapours through the respiratory system can be expected. 

No sufficient data are available for estimating the absorption rate. There were no clinical signs, no mortality and no macroscopic findings at up to the maximum stable vapour concentrationachievable of 1761 ppm (25.5 mg/l).

 

In the absence of further information on the fraction absorbed by inhalation, the default absorption is set at 100% for the inhalation route.

 

 

Dermal absorption

The molecular weight below 500 is favourable to dermal uptake. The Log Kow value of 4.18 can favour the penetration into the stratum corneum, but further absorption into the dermis and systemic circulation might be slowed by the low hydrophilicity.

 

In addition absorption of volatile liquids across the skin may be limited by the rate at which the liquid evaporates off the skin surface and from the stratum corneum layer. This can be the case for substances with vapour pressures above 100-10,000 Pa.

As 1,6-Divinylperfluorohexane has a vapour pressure of 1200 Pa at 20°C, the volatilization rate is expected to prevent any significant absorption through the stratum corneum. Furthermore, in case a certain amount of substance has reached the stratum corneum, the distribution from the stratum corneum to the epidermis and systemic circulation may be too limited, due to both the low water solubility (1.61 mg/l) and volatility.

 

This is supported by skin absorption prediction modelled in IH SkinPerm which predicts an absorption rate below 1% when applied onto the skin, either using the instantaneous model (splash exposure) or continuous model (repeated or continuous exposure), while the vapor to skin model predicts negligible levels of substance reaching the epidermis.

 

In addition,1,6-Divinylperfluorohexane caused no skin irritation in vivo in the in vivo skin irritation or acute dermal toxicity tests, and no effects in the skin sensitization test following repeated topical applications. Therefore no enhanced absorption is expected in relation to potential skin damages.

 

In conclusion1,6-Divinylperfluorohexane is not expected to be significantly absorbed through the skin. The absorption potential is set at 10% as a reasonable worst case estimate.

 

 

DISTRIBUTION

 Substances that are absorbed from the gastrointestinal tract are distributed to the liver via the hepatic portal vein. In the combined repeated dose toxicity study and reproduction/developmental toxicity screening test, variations of clinical biochemistry parameters although not all statistically significant (increased ALAT, decreased bilirubin, triglycerides and bile acids), and statistically significant increased liver weight provide evidence of distribution at least to the liver. In females follicular hypertrophy observed at the mid- and high doses also indicate systemic distribution.

 

No sufficient data are available for estimating distribution rate and tissues affinity.

 

 

METABOLISM

No sufficient data are available to predict the metabolic changes and formation of potential metabolites. Considering the perfluorinated backbone, complete metabolic transformation of the chemical is unlikely. Profiling in the OECD QSAR toolbox predicts no metabolites formed using the various hydrolysis simulators, nor from the multiple metabolic transformation pathways included in both in vivo rat and in vitro rat liver S9 metabolism simulators, and skin metabolism simulator. Only the microbial metabolism simulator, more relevant to biodegradation catabolism by environmental microorganisms, predicts 13 possible metabolites derived from the end-terminal groups.

The increased liver weight can be a sign of increased metabolic activation following exposure triggered by the substance although not necessarily associated with its own metabolisation. Transient binding to proteins is not excluded.

 

 

EXCRETION

Characteristics favourable to urinary excretion are low molecular weight (below 300 in the rat), high water solubility, and ionisation of the molecule at the pH of urine.

Considering the physico-chemical properties of the substance (in particular low water solubility) urinary excretion of unchanged 1,6-Divinylperfluorohexane does not appear likely, but cannot be excluded in case of metabolic conjugation. Considering the fluorinated structure and the slight changes in some of the clinical biochemistry parameters, excretion via the bile is a more likely route.

A fraction of the volatile liquid may be also re-excreted as vapours in exhaled air.

Applicant's summary and conclusion

Conclusions:
There are no experimental toxicokinetic study available for 1,6-Divinylperfluorohexane. The toxicokinetic behaviour of the substance was estimated based on the available dataset.
Based on the available data, including physico-chemical properties and repeated dose toxicity study, there are evidences that the substance can be absorbed to some extent by the oral route and distributed systemically. Absorption by the dermal route is expected to be limited, and absorption by the inhalation route is possible. No sufficient data are available for predicting the metabolisation and excretion pattern.
The absorption is set at 100% for the oral and inhalation routes, and at 10% for the dermal route.

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