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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
0.063 mg/m³
Most sensitive endpoint:
carcinogenicity
DNEL related information
Overall assessment factor (AF):
1
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

The DMEL worker long-term inhalation exposure is derived as follows:

 

This is a volatile substance and potential worker population exposure would likely occur via the inhalation route. VF is considered to be a likely non-threshold genotoxic carcinogen in humans. No local effects were observed in acute or repeated exposure studies; therefore no DNEL for local effects was derived.

 

Discussion:

 

Per Appendix R.8-13 of the Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health (May 2008, ECHA), an EU IOEL may used in place of developing a DNEL (DMEL). In this case, the substance, vinyl fluoride (VF), is biotransformed by the same metabolic pathway as an extensively studied known human carcinogen, vinyl chloride (VC). The biotransformation proceeds via the cytochrome P450 (CYP) 2E1 pathway, and is followed by interaction with DNA. VC is associated with a very rare angiosarcoma cancer type in humans and cancer in laboratory animals. VF is likewise associated with cancer in laboratory animals. The production of cancer is related to the VC and VF biotransformation products. The biotransformation pathway becomes saturated at concentrations above 75 ppm VF and 250 ppm VC. While VC is biotransformed at a faster rate and to a greater extent than VF, the close structural and chemical similarity as well as behaviour in biological systems allows for the use of VC (human data and analysis) as a conservative read-across substance in the assessment of VF carcinogenicity. See additional supporting documentation (analogue reporting format) attached in IUCLID5. 

 

The SCOEL has performed an assessment of human risk of carcinogenicity of VC related to workplace conditions (SCOEL, 2002). Toxicology and carcinogenicity of VC have been widely studied during the last 25 years, and a number of assessments of carcinogenic risk have been carried out, based on both occupational epidemiology and animal experimental data. The established carcinogenicity is the main toxicological effect of the substance. VC is classified as a human carcinogen by the European Union (EU) (category l) and the International Agency for Research on Cancer (IARC) (group l). As a first step, available data were reviewed which indicated that a linear high dose – low dose extrapolation of tumour risk was appropriate in this case. On this basis, the available quantitative risk assessments were reviewed, including those based on human epidemiological data, and those based on extrapolation from animal data via PBPK modelling. The different approaches resulted in final risk estimates which were reasonably consistent with each other. Based on the robust VC dataset, it was concluded that continuous exposure throughout a working life to 1 ppm VC would be associated with a cancer risk for hepatic angiosarcoma of 0.3E-3. The derivation procedures for calculating these risk estimates are in line with the approach for deriving a DMEL outlined under REACH. The highly conservative nature of the linear extrapolation approach mitigates the need for additional application of assessment factors for intra- or interspecies differences.

A credible case could be made that based on kinetic information. VF has about 3 times less carcinogenic potential than VC. However, to provide an extra margin of safety, the SCOEL VC risk estimate was directly applied to VF. 

 

Using the risk estimate slope for VC and converting to mg/m3, the long-term worker inhalation DMEL is 0.063 mg/m3.

 

As a point of reference, the DMEL is considerably lower than safe worker numbers established via other organizations. Multiple countries, including, Canada, United States, and Ireland, have a safe workplace exposure guidance value of 1 ppm 8-hour TWA to protect workers from adverse VF effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
0.005 mg/m³
Most sensitive endpoint:
carcinogenicity
DNEL related information
Overall assessment factor (AF):
2
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The DMEL general population long-term inhalation exposure is derived as follows:

 

This is a volatile substance and potential general population exposure would likely occur via the inhalation route. VF is considered to be a likely non-threshold genotoxic carcinogen in humans. No local effects were observed in acute or repeated exposure studies; therefore no DNEL for local effects was derived.

 

Discussion:

 

Per Appendix R.8-13 of the Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health (May 2008, ECHA), an EU IOEL may used in place of developing a DNEL (DMEL). In this case, the substance, vinyl fluoride (VF), is biotransformed by the same metabolic pathway as an extensively studied known human carcinogen, vinyl chloride (VC). The biotransformation proceeds via the cytochrome P450 (CYP) 2E1 pathway, and is followed by interaction with DNA. VC is associated with a very rare angiosarcoma cancer type in humans and cancer in laboratory animals. VF is likewise associated with cancer in laboratory animals. The production of cancer is related to the VC and VF biotransformation products. The biotransformation pathway becomes saturated at concentrations above 75 ppm VF and 250 ppm VC. While VC is biotransformed at a faster rate and to a greater extent than VF, the close structural and chemical similarity as well as behaviour in biological systems allows for the use of VC (human data and analysis) as a conservative read-across substance in the assessment of VF carcinogenicity. See additional supporting documentation (analogue reporting format) attached in IUCLID5.

 

The SCOEL has performed an assessment of human risk of carcinogenicity of VC related to workplace conditions (SCOEL, 2002). Toxicology and carcinogenicity of VC have been widely studied during the last 25 years, and a number of assessments of carcinogenic risk have been carried out, based on both occupational epidemiology and animal experimental data. The established carcinogenicity is the main toxicological effect of the substance. VC is classified as a human carcinogen by the European Union (EU) (category l) and the International Agency for Research on Cancer (IARC) (group l). As a first step, available data were reviewed which indicated that a linear high dose – low dose extrapolation of tumour risk was appropriate in this case. On this basis, the available quantitative risk assessments were reviewed, including those based on human epidemiological data, and those based on extrapolation from animal data via PBPK modelling. The different approaches resulted in final risk estimates which were reasonably consistent with each other. Based on the robust VC dataset, it was concluded that continuous exposure throughout a working life to 1 ppm VC would be associated with a cancer risk for hepatic angiosarcoma of 0.3E-3 . The derivation procedures for calculating these risk estimates are in line with the approach for deriving a DMEL outlined under REACH, The highly conservative nature of the linear extrapolation approach mitigates the need for additional application of assessment factors for intra or interspecies differences in the worker population. However a couple of assessment factors are appropriate for the general population. The human risk assessments were done in worker populations, therefore, per REACH guidance, an assessment factor of 2 should be applied to account for greater susceptibility in the general population. Further, for the purposes of the DMEL, the general population is assumed to have a continuous lifetime exposure. As a result, an assessment factor of 7 should be applied to adjust from a working lifetime to a whole lifetime, as described in the SCOEL document.

 

Using the risk estimate slope for VC and converting to mg/m3, the long-term inhalation general population DMEL is 0.005 mg/m3.

 

0.063 mg/m3/ 2 / 7 = 0.0045 mg/m3 (rounded to 0.005 mg/m3)