Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
7.7 mg/m³
Most sensitive endpoint:
carcinogenicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - workers

According to the REACH “Guidance on information requirements and chemical safety assessment”, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

 

As the substance is a gas, oral and dermal routes of exposure are considered to be irrelevant for workers, therefore no DN(M)ELs were derived for these routes.

 

As the substance is not classified for acute toxicity, according to the REACH “Guidance on information requirements and chemical safety assessment” (R.8.4.3.1), no acute / short-term exposure DNEL needs to be derived.

In 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) it is noted that:

‘When an EU IOEL exists the registrant may, under conditions as described below, use the IOEL in place of developing a DNEL. A registrant is allowed to use an IOEL as a DNEL for the same exposure route and duration, unless new scientific information that he has obtained in fulfilling his obligations under REACH does not support the use of the IOEL for this purpose. This could be because the information obtained is more recent than the information that was used to support setting the IOEL at EU level and because it leads to another value being derived which requires different risk management measures (RMMs) and operational conditions (OCs)’.

The SCOEL has performed an assessment of human risk of carcinogenicity of vinyl chloride related to workplace conditions (SCOEL/SUM/109 final, December 2002). Toxicology and carcinogenicity of vinyl chloride 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. Vinyl chloride is classified as a human carcinogen by the European Union (EU) (category l) and the International Agency for Research on Cancer (IARC) (group l). Therefore, the SCOEL has been asked to provide a human carcinogenicity risk assessment as background of further regulatory action of the EU.

 

As a first step, available data were reviewed which indicated that a linear high dose – low dose extrapolation of tumour risk was the most appropriate way 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, by means of PBPK modelling. The different approaches resulted in final risk estimates which were basically consistent with each other. As a result, it was inferred from epidemiological studies that a continuous exposure for working life (estimated to be 14% of the total lifetime) to 3 ppm (7.7 mg/m3) vinyl chloride would be associated with a cancer risk for hepatic angiosarcoma of about 0.9 x 10-3.

This value agrees with the limit value of 3 ppm (7.7 mg/m3), measured or calculated in relation to a reference period of eight hours, for occupational exposure to vinyl chloride, established by the Directive 2004/37/EC.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
0.002 mg/m³
Most sensitive endpoint:
carcinogenicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
1.4 ng/kg bw/day
Most sensitive endpoint:
carcinogenicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

Many (inter)national bodies and groups have reviewed the available carcinogenicity data for vinyl chloride for deriving limit values.

Inhalation exposure

With regard to exposure via inhalation, some reported risk estimates are based on human data, while others based their risk estimates on animal data considering exposures in the available epidemiological settings as less well characterised. Using human data WHO (2000, 1987) arrived at an Air Quality Guideline of 1 µg/m3 associated with a 1 per million lifetime risk. US EPA (2000) used animal data to arrive at a remarkably similar unit risk estimate of 4.4 per million with this exposure level, using a kinetic model to calculate human equivalent concentrations. Both organisations warn for higher risks in case exposure starts at very early life [1]. The above named risk estimates are basically similar to values arrived at by others, i.e. ranging from 0.6 to 4 µg/m3 with a 1 per million lifetime risk, using either animal or human data and kinetic models (to account for non-linearity in metabolism and interspecies extrapolation) (Clewell et al., 1995; Reitz et al., 1996; Clewell et al., 2000).

The derivation procedures for calculating these exposure limits are in line with the approach for deriving a DMEL outlined under REACH [2], i.e. deriving a relevant dose descriptor using recent available information, applying allometric scaling (AS) for dose descriptors in case of animal data (here a kinetic model is used instead of the default AS factor), and applying linear low dose extrapolation while accommodating for demonstrated non-linearities (here again by using a kinetic model).

As there are no specific reasons to take one of these assessments as of higher quality – all have their uncertainties - a mean of 2 µg/m3 with a 1 per million lifetime risk is chosen for this assessment. It is noted that SCOEL also used this value for deriving their Occupational Exposure Limit (see above; SCOEL, 2002).

[1] For scenarios with early life exposure an extra assessment factor of 2 is proposed by the US EPA (2000).

[2] Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. May 2008. ECHA.

Oral exposure

With regard to the quantitative assessment of vinyl chloride associated cancer risks for the general population upon oral exposure, only animal data are available. Studies by Feron et al. (1981), Til et al. (1983, 1991), and by Maltoni et al (1981, 1984) were retrieved from literature. From these, US EPA concluded that the Feron study provided the most suitable dose response data for deriving a limit value. Using the Clewell (1995) PBPK model and extrapolating to low dose via the linearised multistage model, US EPA arrived at a daily dose of 1.4 ng/kg bw/day for a lifetime risk level of 10-6 lifetime exposed (US EPA, 2000).

Dermal exposure

As the substance is a gas, the dermal route of exposure is considered to be irrelevant, therefore no DN(M)EL was derived for this route.