(E)-1,2-difluoroethylene

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

assessment of toxicokinetic behaviour

Type of information:

other: In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behavior has been conducted to the extent that can be derived from the relevant available information.

Adequacy of study:

key study

Study period:

The assessment was made in August 2022

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Relevant studies were reviewed with a view to fulfilling the requirements of Annex VIII (8.8).

Justification for type of information:

Relevant studies (reliability 1) were reviewed with a view to fulfilling the requirements of Annex VIII (8.8).

Data source

Reference

Title:

Unnamed

Year:

2022

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behaviour has been conducted to the extent that can be derived from the relevant available information. The assessment is based on the Guidance on information requirements and chemical safety assessment R.7c: Endpoint specific guidance (ECHA, June 2017)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

(E)-1,2-difluoroethylene

EC Number:

216-629-0

EC Name:

(E)-1,2-difluoroethylene

Cas Number:

1630-78-0

Molecular formula:

C2H2F2

IUPAC Name:

(E)-1,2-difluoroethene

Test material form:

gas

Results and discussion

Any other information on results incl. tables

Toxicokientic assessment:

The substance is a (liquified) gas with a molecular weight of 64.

The substance is classified as a flammable gas.

Inhalation is considered the most likely route of exposure.

The substance has a water solubility of 2.0 g/L and a relatively low log octanol/water partition coefficient (log Kow = 0.9).

There were no significant signs of toxicity observed in an acute inhalation toxicity study.

In repeated dose inhalation toxicity studies (28-day OECD 412 and 90-day OECD 413) there were no test-item related adverse effects indicative of systemic toxicity (including no test-item adverse effects on mortality, clinical observations, body weights, hematology, clinical chemistry, macroscopic necropsy observations and organ weights).

The main findings in the repeated inhalation studies was with neuronal cell degeneration in the vomeronasal organ. The vomeronasal organ is a sensory organ involved in detecting reproductive pheromones. It is well developed in rats and mice but poorly developed or absent in humans and its functionality has not been definitively established. The significance of this finding to humans is not established. This finding may also be considered as a local effect (effect at site of exposure).

In a screening test for reproductive/developmental effects (OECD 421) no effects on reproductive/developmental performance were observed.

The substance was positive (mutagenic) in bacteria (Ames study), negative in in-vitro chromosome aberration and micronucleus tests. The substance was negative in a in-vivo micronucleus test but a Comet assay showed evidence of causing an increase in DNA strand breaks in the bladder, lung, kidney and liver of male Crl:CD (SD) rats when administered via inhalation.

 

ABSORPTION:

Inhalation is considered the most likely route of exposure and therefore respiratory absorption is considered the most likely route of absorption.

The molecular weight of the substance supports the potential for respiratory absorption. The substances moderate  log Kow (between -1 and 4) is favourable for absorption across the respiratory tract epithelium by passive diffusion. The water solubility of the substance is unlikely to preclude respiratory absorption.

Respiratory absorption following inhalation exposure is therefore considered likely to occur.

The results of inhalation toxicity testing (including acute inhalation toxicity and repeated dose toxicity studies) do not provide evidence of significant systemic toxicity (to confirm absorption occurred) but absorption cannot be ruled out based on these results.

 

Dermal absorption can also be considered as gases can potentially be taken up across the skin.

The molecular weight (less than 100) favours dermal uptake. The water solubility and log Kow may also support some dermal uptake. No skin irritation or dermal toxicity studies are available to assess if damage to skin surface could enhance penetration or if absorption has occurred (i.e. signs of systemic toxicity).

 

DISTRIBUTION:

The molecular weight of the substance and its high water solubility indicates that any absorbed substance may be readily distributed in the water fraction of circulatory fluids.

No firm conclusion on skin sensitisation could be made based on modelling predictions and no study data is available, so it cannot be concluded if the substance has potential to bind to carrier/circulatory proteins in blood.

The relatively low Log Kow (0.9) suggests the substance is not sufficiently lipophilic to make it likely that it will accumulate within fatty/adipose tissues or deposit in the lungs.

 

METABOLISM:

The results of repeated dose inhalation toxicity studies did not show evidence to indicate any substance influenced hepatic metabolism.

Although the results of genotoxicity assays showed both positive and negative results, genotoxicity was neither enhanced nor diminished in the presence of S9 metabolising system in the studies.

The water solubility and molecular weight of the substance suggest that metabolism may not be necessary to facilitate excretion.

 

EXCRETION:

There is no evidence to indicate the route of excretion of the substance.

Gases are likely to be excreted in exhaled air.

Excretion via urine could also be favourable based on the substances molecular weight and water solubility.

 

 

 

Applicant's summary and conclusion

Conclusions:

The available information on the substance suggests that respiratory absorption may occur following inhalation exposure. Absorbed substance may be available for systemic distribution. There is no evidence to indicate the substance will be metabolized and excretion is likely to be a mixture of exhaled air and urine.