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Administrative data

Description of key information

No data are available on the oral or dermal route of exposure (studies technically not feasable).
In sub-acute inhalation studies with MVE the NOAEC for male rats was 1500 ppm (3.6 mg/L) and the LOAEC is 3500 ppm (8.4 mg/L) due to systemic effects. In female rats the NOAEC was 3500 ppm (8.4 mg/L) due to local effects on the olfactory epithelium, clinical signs and reduced body weight at 25000 ppm (60 mg/L).

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
3 600 mg/m³

Additional information

A sub-acute GLP guideline study in rats (BG Chemie 1989) was carried out with methyl vinyl ether. Four groups of 5 male and 5 female Wistar rats each, were exposed (whole body) to target concentrations of 0, 500, 3500, 25000 ppm (0, 1.2, 8.4, or 60 mg/L) for 6 hours a day, five days a week during a period of four weeks. Clinical signs, body weights, weekly food consumption, haematological and biochemical parameters, gross- and microscopic pathology were used to examine the toxicological potency of the test substance. No NOAEC was identified for male rats; e.g. increased prothrombin time and decrease in total protein was found in all treatment groups. Therefore a 2nd study in male rats was performed (see next study record). The NOAEC for females was 3500 ppm; at 25000 ppm local effects on the olfactory epithelium, clinical signs and reduced body weight were found.

Conclusion: The NOAEC was 3500 ppm for females, local effects on the olfactory epithelium, clinical signs and reduced body weight were detected at 25000 ppm. No NOAEC could be established for males because of the increased prothrombin time and the decreases in total protein in all male dose groups.

In the 2nd study (BG Chemie 1989) groups of 10 male rats each, were exposed to target concentrations of 0, 150, 500 or 1500 ppm (0, 0.36, 1.2, 3.6 mg/L) for 6 hours a day, five days a week during a period of four weeks. Clinical signs, body weights, weekly food consumption, haematological and biochemical parameters, gross- and microscopic pathology were used to examine the toxicological potency of the test substance. This independent 2nd study on male rats exposed to atmospheres containing methyl vinyl ether did not result in any significant change in the parameters followed in this study. The LOAEC in male rats is therefore 3500 ppm (8.4 mg/L) due to the effects described in the 1st study: reduced body weight in the 1st week of treatment, reduced white blood cell counts and decreased total protein at this dose level.

Conclusion: the NOAEC for male rats is 1500 ppm (3.6 mg/L) with regard to the results of the 2nd study and the LOAEC is 3500 ppm (8.4 mg/L) for male rats concerning the results in the 1st subacute study.

In a further sub-acute inhalation study (supporting data; Dow1993) comparable to OECD TG412 but short exposure duration (9 days) 10 male and 10 female rats per dose level were exposed (no data about exposure frequency) to 0, 5000, 10000, or 19500 ppm (i.e. 0, 12, 24, 47 mg/L). At the high dose level clinical signs and hematologic effects (toxicological relevance not clear for both) were found in males; reduced food consumption and increased water consumption was recorded in males and females.

Conclusion: NOAEC was 10000 ppm (24 mg/L) in a subacute inhalation toxicity test in rats, the LOAEC was 19500 ppm (47 mg/L).

Exposure based adaptation of information requirements:

According to REGULATION (EC) No 1907/2006, Annex IX and Annex X, repeated dose toxicity testing (section 8.6) may be omitted, if relevant human exposure can be excluded in accordance with Annex XI section 3. Furthermore and in accordance with section 3.2 (b) of Annex XI (as amended by Regulation 134/2009), testing for repeated dose toxicity can be omitted when the substance is not incorporated in an article and the manufacturer can demonstrate and document for all relevant scenarios that throughout the life cycle strictly controlled as well as rigorously contained conditions as set out in Article 18(4)(a) to (f) (Regulation 1907/2006) apply.

Classification:

Methyl vinyl ether (MVE) is not classified for any toxicological endpoint. At room temperature, MVE is an extremely flammable gas and may generate explosive atmospheres. The acute toxicity after inhalation is low (LC50 > 64.000 ppm). Rats tolerate repeated inhalation of 1.500 ppm without any symptoms or findings. The available in vitro and in vivo tests for genetic toxicity gave no hint on a mutagenic or clastogenic effect (up to 25.000 ppm).

Process description:

The industrial method used for the production of MVE is the reaction of acetylene with methanol in the presence of potassium hydroxide in the liquid phase (Reppe vinylation). Vigorous reaction with methanol occurs at 120 °C. The choice of operating pressure depends on the boiling point of the alcohol to be vinylated. The alcohol methanol is vinylated under a pressure of ~1.6 MPa as the boiling point is below the reaction temperature. Working under pressure affords the acetylene to be diluted with nitrogen to avoid uncontrolled decomposition (55 % maximum for MVE). Because of the applied reaction conditions and the handling of gaseous compounds the manufacturing facilities are designed as closed systems for higher pressures. The reaction is carried out in a stirred vessel type reactor. The alcohol/KOH-mixture is charged at the top, while the gaseous mixture of acetylene and nitrogen is fed in from below. The un-reacted acetylene is recycled to the reactor and supplemented with pure acetylene. MVE is produced in a continuously run process in a closed system. Transfers, buffer/storage tanks, reactors, processing equipment and feeds are operated in fully closed systems. MVE is used as a starting material for polymers/copolymers (coatings, adhesives), leather processing agents, biocides, construction material, and personal care products. During manufacture and processing of MVE, worker exposure is controlled by the use of closed systems, industrial hygiene controls, and personal protective equipment. Any risk of accumulation is minimized by natural ventilation, as the chemical is produced in closed systems installed in open air. At processing sites, the exposure of workers is minimized by vapor abstraction. Prior to repair and maintenance work, vessels, pipes and other equipment are purged to remove any residual MVE. Dedicated systems designed to handle MVE are used for loading and unloading purposes to prevent the formation of explosive atmospheres and to minimize exposure. The vent gases are either incinerated or cleaned by means of a scrubber. At the production and processing sites, workers wear personal protective equipment which includes gloves, face shields and safety goggles in view of the low pH during processing. During repair and maintenance operations, respiratory protective equipment is additionally used. Exposure to MVE via air is routinely controlled by personal air sampling. Additionally, only a small, well-defined and trained group of workers will perform occasionally sampling tasks for quality control under strictly control conditions.

Consumer exposure to residual MVE is considered to be negligible, since most of the marketed vinyl ether polymers and co-polymers are heat-treated and potentially existing residual MVE is expected to evaporate during this process.

 

Rigorous containment measures:

The substance is manufactured and used under strictly controlled conditions over the entire lifecycle. Exposure is limited to occasional sampling tasks for quality control. Transport, storage tanks, reactors, processing equipment, and feeds operate in fully closed systems.

 

Procedural and control technologies are used to minimise residual emissions/exposure as well as qualitative risk considerations:

Operational and technical conditions and measures affecting and controlling workers exposure, such as local exhaust ventilation as well as personal protective equipment, such as goggles, chemically resistant gloves, and respiratory protection where potential exposure may occur.

 

On the basis of the described process conditions, testing of MVE in a Sub-chronic Toxicity Study (OECD 413) as well as in a Chronic Toxicity Study (OECD 452) was not performed since the criteria of exposure based adaptation of information requirements are met.

Repeated dose toxicity: inhalation - systemic effects (target organ) other: all gross lesions and masses

Justification for classification or non-classification

Classification for repeated dose toxicity is not warranted according to the criteria of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.