Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
No data available.
Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Exposure based adaptation of information requirements:

According to REGULATION (EC) No 1907/2006, Annex IX and Annex X, reproductive toxicity testing (section 8.7) 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 reproductive 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 further pre-natal Developmental Toxicity Study (OECD 414) in a second species as well as a Two-Generation Reproduction Toxicity Study (OECD 416) or an Extended One-Generation Reproductive Toxicity Study (OECD 443) was not performed since the criteria of exposure based adaptation of information requirements are met.

Short description of key information:
No study available (exposure based adaptation of information requirements).

Effects on developmental toxicity

Description of key information
In a developmental toxicity study with MVE according to OECD TG414  the LOAEC for maternal toxicity was 5000 ppm or 12 mg/L (lowest dose tested). The NOEC for developmental toxic effects was 5000 ppm and the NOAEC for teratogenic effects was 19500 ppm or 47 mg/L (highest dose tested).
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
12 000 mg/m³
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

In a developmental toxicity study with MVE (according to OECD TG414; Union Carbide 1994) 25 pregnant Sprague-Dawley rats were exposed (whole body) 6 h/day to 0, 5000, 10000, or 19500 ppm (12; 24; 47 mg/L) at gestation day 6 -15.

No mortality occurred during the study. The pregnancy rate was equivalent for all groups and ranged from 96 to 100 %. No females aborted or delivered early. At scheduled necropsy, one female each from the 5000 and 10000 ppm groups was not pregnant. There were no exposure-related clinical signs observed in any exposure group. Gestational body weight and body weight gains were reduced during the exposure period in all exposure groups. Food consumption was decreased in the 10000 and 19500 ppm groups during the exposure period. Food consumption was also reduced in the 5000 ppm group early in the exposure period (gd 6-9). The relative liver weight was increased in all exposure groups. There were no effects of exposure on gestational parameters including resorptions, pre- and post-implantation losses, percentages of live fetuses, and sex ratios. There was no effect of exposure on fetal body weights/litter. There were no effects of exposure on the incidence of visceral, skeletal, or external malformations. An increased incidence of one common external variation, ecchymosis in the trunk region, was noted in the 19500 ppm group. In addition, several skeletal variations involving various regions of the skeleton were observed for the 10000 and 19500 ppm groups. These included: unossified cervical centra #5 and #6, unossified and poorly ossified cervical centrum #7, reduced number of (ossifying) caudal segments, unossified anterior arch of the atlas, and poorly ossified sternebra #4. In the 5000 ppm group, the incidences of unossified anterior arch of the atlas and poorly ossified sternebra #4 were also increased. In addition, increased incidences of all unossified proximal phalanges (forelimb and hindlimb), and some unossified metatarsals (hindlimb) occurred only in the 19500 ppm group.

All variations characteristic of delayed ossification of the anterior arch of the atlas or sternebrae (e .g., unossified, poorly ossified and bilobed) were combined and statistically analyzed using the Censored Wilcoxon test (Dow, 2005). The combined analysis of unossified, poorly ossified and bilobed anterior arch of the atlas revealed a 100 % litter incidence in all groups, with fetal incidences of 95.2, 88.6, 95.8, and 97.0 % in the 0, 5000, 10000, and 19500 ppm groups, respectively. Similarly, combined analysis of variations characteristic of delayed sternebrae ossification showed respective litter incidences of 100, 100, 100, and 96.0 %, with fetal incidences of 83.0, 79.6, 82.1, and 84.5 %. None of these differences were statistically significant. Furthermore, the high incidence in controls indicates that these minor skeletal variations were not biologically significant.

Based on this re-analysis, 5000 ppm is considered to be the developmental toxicity NOEC for the study. Maternal toxicity was observed at all concentration levels used in this study. No embryolethality or teratogenic effects were observed. A concentration-dependent profile of delayed skeletal development was observed for mid and high dose groups, considered as transient effects secondary to maternal toxicity. In conclusion, the LOAEC for maternal toxicity was 5000 ppm or 12 mg/L (lowest dose tested). The NOEC for developmental toxic effects was 5000 ppm and the NOAEC for teratogenic effects was 19500 ppm or 47 mg/L (highest dose tested).

Exposure based adaptation of information requirements:

According to REGULATION (EC) No 1907/2006, Annex IX and Annex X, reproductive toxicity testing (section 8.7) 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 reproductive 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 availablein vitroandin vivotests 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 typereactor. 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 further pre-natal Developmental Toxicity Study (OECD 414) in a second species as well as a Two-Generation Reproduction Toxicity Study (OECD 416) or an Extended One-Generation Reproductive Toxicity Study (OECD 443) was not performed since the criteria of exposure based adaptation of information requirements are met.

Justification for classification or non-classification

In a developmental toxicity study with MVE (according to OECD TG 414; Union Carbide 1994), maternal toxicity was observed at all exposure levels and no embryolethality or teratogenic effects were observed. A concentration-dependent profile of delayed skeletal development was observed for mid and high dose groups, considered as transient effects secondary to maternal toxicity.

According to Annex I, chapter 3.7.2.4.3. of Regulation (EC) No. 1272/2008 (CLP), "Classification is not necessarily the outcome in the case of minor developmental changes, when there is only a small reduction in foetal/pup body weight or retardation of ossification when seen in association with maternal toxicity". Thus, classification for reproductive toxicity is not warranted according to the criteria of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.