4-(vinyloxy)butan-1-ol

Endpoint summary

Description of key information

In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422) in Wistar rats the NOAEL for general, systemic toxicity of the test substance was 150 mg/kg body weight/day for the F0 parental animals based on adverse clinical findings (males + females) and decreased body weight gain (males) at 450 mg/kg body weight/day.

Additional information

In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422; BASF SE 2010) 4 -(vinyloxy)butan-1 -ol was administered orally via gavage to groups of 10 male and 10 female Wistar rats (F0 animals) at doses of 50, 150, and 450 mg/kg body weight/day. Control animals were dosed daily with the vehicle (Olive oil Ph. Eur./DAB). The duration of treatment covered a 2-week pre-mating and mating period in both sexes, approximately 1 week postmating in males, and the entire gestation period as well as 4 days of lactation in females. No adverse effects on fertility of the F0 parental animals of both sexes at dose levels of 50, 150 and 450 mg/kg bw/d were observed. The test substance caused also no impairments of the reproductive performance. Mating behaviour, conception, gestation, parturition, as well as sexual organ weights and gross and histopathological findings of these organs were not influenced. Slight general systemic toxicity was noted in the F0 parents at 450 mg/kg bw/d. Some males and females showed abdominal position exclusively when they were treated with the test substance for the first time. Furthermore, motor activity was slightly decreased in the high-dose males. Although no other effects were noted in daily cageside, detailed clinical examinations in an open field and detailed observations in a functional observational battery (FOB) these findings might indicate a minimal sedative potential of Hydroxybutylvinylether. They are considered as treatment-related. An additional clinical finding was a decreased body weight gain in high-dose males. Concerning clinical pathology no treatment-related, adverse effects were observed up to a dose of 450 mg/kg bw/d. Regarding pathology there were no substance-related organ weight changes, gross lesions, or microscopic findings. Under the conditions of this study the NOAEL for reproductive performance, fertility and for developmental toxicity is 450 mg/kg body weight/day, the highest dose tested. The NOAEL for general, systemic toxicity of the test substance is 150 mg/kg body weight/day for the F0 parental animals based on adverse clinical findings (males + females) and decreased body weight gain (males) at 450 mg/kg body weight/day.

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 / toxicological profile:

4-(vinyloxy)butan-1-ol (HBVE) is classified for acute oral toxicity (cat. 4) and eye irritation (cat. 2A) according to UN GHS. The acute toxicity in rats after inhalation of saturated vapour is low. No signs of toxicity were found in rats after dermal treatment with 2000 mg/kg bw. HBVE is not sensitizing and not irritant to skin. The availablein vitrotests for genetic toxicity gave no hint on a mutagenic or clastogenic effect.

Repeated dose and reproductive toxicity was investigated in rats by the oral route (OECD 422). The NOAEL for general, systemic toxicity of the test substance was 150 mg/kg body weight/day for the parental animals based on adverse clinical findings (males + females) and decreased body weight gain (males) at 450 mg/kg body weight/day. The NOAEL for reproductive performance, fertility and for developmental toxicity was 450 mg/kg body weight/day (highest dose tested).

 

Process description:

At room temperature, HBVE is a liquid with low vapor pressure. The industrial method used for the production of HBVE is the reaction of acetylene with 1,4-butanediol in the presence of potassium hydroxide in the liquid phase (Reppe vinylation) under pressure and increased temperature. Working under pressure affords the acetylene to be diluted with nitrogen to avoid uncontrolled decomposition. 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. Thus, HBVE is produced in a closed system.

Because of the significant health hazards during production (high pressure, high temperature, strong alkalinity, use of acetylene as starting material), transportation and storage (flammability, explosion, strong alkalinity), most stringent safety instructions and explosion protection measures must be adhered. Transfers, buffer/storage tanks, reactors, processing equipment and feeds are operated in fully closed systems. HBVE is practically exclusively used as an industrial intermediate for the manufacture of vinyl ether polymers and co-polymers. During manufacture and processing of HBVE, 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 HBVE. Dedicated systems designed to handle HBVE 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. Additionally, only a small, well-defined and trained group of workers will perform occasionally sampling tasks for quality control under strictly controlled conditions.

Consumer exposure to residual HBVE is considered to be negligible, since most of the marketed vinyl ether polymers and co-polymers are heat-treated and potentially existing residual HBVE 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 HBVE in a Sub-chronic Toxicity Study (OECD 408) 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.

Justification for classification or non-classification

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