Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.05 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.05 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
15 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

The violent and instantaneous hydrolysis of VOCl3 was confirmed by industrial practice (see section 5.1.2. of the technical dossier). In contact with moist skin or mucous membranes (water), VOCl3 is quasi-instantaneously decomposed into V2O5 and HCl. VOCl3 appears then not available in the body due to its quasi-instantaneously degradation on contact with moist skin or mucous membranes.

 For these reasons, this approach was followed for the hazard characterization of VOCl3:

·        Short term toxicity and local toxicity endpoints were waived, based on corrosive potential and for animal welfare considerations,

·        Repeated toxicity, reprotoxicity and genotoxicity endpoints were based on degradation products; HCl and V2O5 (annex V of REACH regulation).

 

Threshold values

In this section, data from all end-points are examined and analysed in order to determine for which it is relevant and possible to establish a DNEL value. The method followed is that proposed in the guidance for the implementation of REACH (Chapter R.8: Characterisation of dose (concentration) -response for human health, November 2012).

 

1.   Oral toxicity

Not considered for workers

 

2.   Inhalation toxicity

a.   Acute exposure

Regarding the breakdown product, the threshold values chosen as relevant ones, are those of HCl released during the VOCl3 process when in contact with humidity of air. These values of concern were communicated by the HCl consortium and are European OELs:

·        Short Term Exposure Limit (STEL) (15 min): 10 ppm (15 mg/m3)  

·        Time Weighted Average (TWA) (8h): 5 ppm (8 mg/ m3) 

The STEL is then considered as threshold value to cover peak exposure of HCl during the manufacturing process or uses (short exposure duration tasks as cleaning, sampling or maintenance). This value of 15 mg/m3 is chosen for acute local effect risk characterization.

 

b.   Repeated exposure

For long term effect, the toxicity of VOCl3needs to be estimated by taking into account the indirect toxicity of its degradation products (V2O5 and HCl).

·        For HCl, as indicated below the TWA at 8 mg/m3 value and is then chosen to cover repeated exposure of HCl during manufacture or uses.

·        For V2O5, a DNEL for local effects was derived (2010 REACH dossier) but without the right to use this DNEL, it is necessary to collect breakdown data and determine DNEL.

Breakdown data

The principal data is the National Toxicology program publication (Toxicology and carcinogenesis of vanadium pentoxide (CAS No. 1314-62-1) In F344/N Rats and B6C3F1 Mice (Inhalation studies), NTP TR 507 - NIH Publication No. 03 -4441, 2002) where :

·        Groups of 50 male and 50 female rats were exposed to atmospheres containing aerosols of 0.5, 1, or 2 mg of vanadium pentoxide particles per cubic meter of air. Animals were exposed six hours per day, five days per week for two years.

·        Groups of 50 male and 50 female mice were exposed to atmospheres containing 1, 2, or 4 mg vanadium pentoxide per cubic meter. Animals were exposed six hours per day, five days per week for two years.

 The conclusions were:

·        The exposure to vanadium pentoxide caused a spectrum of no-neoplastic lesions in the respiratory tract (nose, larynx, and lung) including alveolar and bronchiolar epithelial hyperplasia, inflammation, fibrosis, and alveolar histiocytosis of the lung in male and female rats and an unusual squamous metaplasia of the lung in male and female rats. The lowest concentration tested (0.5 mg/m3) represents a LOAEC for effects in the respiratory tract.

·        The exposure to vanadium pentoxide caused a spectrum of no-neoplastic lesions in the respiratory tract (nose, larynx, and lung) including alveolar and bronchiolar epithelial hyperplasia, inflammation, fibrosis, and alveolar histiocytosis of the lung in male and female mice. Hyperplasia of the bronchial lymph node occurred in female mice. The lowest concentration tested (1 mg/m3) represents a LOAEC for effects in the respiratory tract.

Concerning the reproductive toxicity, different studies are available and indicate Fertility impairment in male and female rats and fetotoxicity in mice. The level of the reproductive dose is below the level of the carcinogenicity dose.  No information on the reproductive and developmental toxicity of V2O5 in humans was found in the literature.

 

DNEL

The relevant dose-descriptor for repeated-toxicity and carcinogenicity is a LOAEC for effects in the respiratory tract of 0.5 mg/m3. The origin of this LOAEC is a combined repeated dose and carcinogenicity (duration of exposure 104 weeks) in F344/N Rat.

The overall assessment factor was obtained as follows:

·        For interspecies: 1. Indeed the most of the experiments are performed on rodents and the physiology of human’s and rat’s respiratory system is different. For the same exposure concentration, rodents receive a higher toxic dose per unit of surface of the respiratory system or per unit of body weight than human does. It is therefore accepted that experimental data obtained by inhalation on animals applies directly to human without any uncertainty factor for a local site-limited effect.

·        For intraspecies: 5 for intraspecies differences for workers

·        For LOAEL/NOAEL extrapolation : 2.

The result of this elaboration (for long-term inhalation DNEL) was: 0.05 mg/m3.

This DNEL is more protective than the HCL DNEL. It is the final DNEL for long term inhalation.

 

3.   Dermal toxicity

No dose descriptor can be set for the corrosive / irritant effects (as VOCl3 and HCl are classified for corrosive effects).

A qualitative approach, based on the part E of the ECHA technical guidance document on chemical safety report (part E.3.4.2) is followed. The general approach when no DNEL for an endpoint is available aims at reducing/avoiding contact with the substance. However, implementation of risk management measures (RMMs) and operational conditions (OCs) needs to be proportional to the degree of concern for the health hazard presented by the substance. The purpose of this qualitative approach is to minimize the exposure considering the level of risk related to the hazard properties of the substance (indicated by R-phrases). 

According to this guidance document, VOCl3 and HCl, with the H-mention H314 (Causes severe skin burns and eye damage), which relates to strong corrosive effects, are allocated to the high hazard category on the basis that exposure to such corrosive substances should be strictly contained.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The general population; consumers as professionals, is not a relevant population for deriving DNEL as workers only, in industrial plants for manufacture or use of VOCl3 are potentially in contact with the substance or degradation products.