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Administrative data

Description of key information

The oral LD50 of vinyl acetate in rats is 3500 mg/kg. A dermal LD50 value of 7440 mg/kg was determined in a study with rabbits. LC50 values of 15810 mg/m3/4 hours and 14084 mg/m3/4 hours were reported for inhalation exposure to rats. (The conversion of ppm to mg/m³ is based on Rm of 86.09, 25 °C, 1 atmosphere.)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
3 500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
15 810 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
7 440 mg/kg bw

Additional information

Non-human information

Oral

Although there are no current guideline studies available for vinyl acetate, in accordance with Section 1 of REACH Annex XI, no study needs to be conducted since there is a sufficient weight of evidence to conclude on the acute toxicity of vinyl acetate by the oral route of exposure.

Similar oral LD50 values in rats (3500 mg/kg and 3470 mg/kg) were derived from two studies (BASF AG, 1967 and Mellon Institute, 1969 respectively). The oral LD50 value of 3500 mg/kg (3.76 mL/kg) for rats was determined from the testing of 2% and 20% vinyl acetate emulsions with tragacanth. Clinical signs included dyspnoea, tremors, apathy and diarrhoea. No gross pathological changes were detected. The similar oral LD50 value of 3470 mg/kg (3.73mL/kg) was reported for rats in a study using vinyl acetate liquid of unknown purity. Doses were administered by stomach intubation to 5 rats per dose (8mL/kg, 4mL/kg and 2mL/kg). At the highest dose all animals died within 24 hours (clinial signs included sluggishness), whereas at the lowest dose no mortalities were observed. At the intermediate dose 3/5 rats died within 24 hours. Gross pathology detected congestion of the lungs and the abdominal viscera and, the liver was reported as ‘mottled’.

In a compilation of previously reported LD50 values for several substances, an oral LD50 value of 2500mg/kg was used for vinyl acetate (Kennedy and Graepel, 1991). The purpose of this publication was to investigate the relationship between the acute oral and acute inhalation data for 108 chemicals. The acute toxicity data were obtained from the Registry of Toxic Effecting Chemical Substances (NIOSH, 1986).

In the absence of the original experimental data leading to the quoted oral LD50 of 2500 mg/kg described by Kennedy & Graepel, 1991, the weight of evidence indicates that the rat oral LD50 is 3500mg/kg based on the striking similarity of the LD50 values derived by two independent laboratories (Mellon Institute, 1969; BASF AG, 1967).

INHALATION

Note: The conversion of ppm to mg/m3 is based on Rm of 86.09, 25 deg C, 1 atmosphere.

Similarly for inhalation exposure and in accordance with Section 1 of REACH Annex XI, a study does not need to be conducted since there is a sufficient weight of evidence to conclude on the acute toxicity of vinyl acetate by this route of exposure.

An acute inhalation study with rats (Mellon Institute 1969) reported a 4 hour LC50 value of 4490 ppm (15810 mg/m³). The rats were exposed to vinyl acetate vapour at 2000, 4000 or 8000 ppm (not analytically measured) in glass exposure chambers. All rats exposed to 8000 ppm died during the exposure period. Two male and two female rats died during exposure to 4000 ppm. Clinical signs ranged from redness of extremities and irritation at the lowest dose, to laboured breathing and convulsions at both higher doses. Gross pathology detected haemorrhages in lungs and tracheae in those rats that died at the higher dose levels, whilst there were no remarkable effects at the lowest dose level.

Similar results have been reported elsewhere (Carpenter et al., 1949). The 4 hour LC50 in rats was reported as 4000 ppm (14084 mg/m³). In this study, 4000 ppm vinyl acetate was reported to have killed 2 to 4 out of a total of 6 rats within an exposure time of 4 hours.

In a compilation of previously reported LD50 values for several substances, a 4 hour inhalation LD50 value of 4000 ppm was used for vinyl acetate (Kennedy and Graepel, 1991).The purpose of this publication was to investigate the relationship between the acute oral and acute inhalation data for 108 chemicals. The acute toxicity data were obtained from the Registry of Toxic Effecting Chemical Substances (NIOSH, 1986).

In an acute inhalation study of saturated vinyl acetate vapour (approx 400,000 mg/m3), 10/12 rats died within 3 minutes of exposure (BASF AG, 1967). Severe irritation of mucous membranes, laboured breathing and narcosis were observed prior to death. No gross changes were detected at necropsy. The LC100 was 10 minutes.

In summary, the 4 hour LC50 values for vinyl acetate in rats are 14084 and 15810 mg/m³.

DERMAL

Although there is only one non-guideline study available for dermal exposure, it is considered a scientifically acceptable study. In the study three dose levels, spaced appropriately to produce test groups with a range of toxic effects and mortality rates, were used. Although the study protocol used higher dose levels than might be used in current tests, nevertheless the data was sufficient to produce a dose-response curve and permit an acceptable determination of the LD50. The study is considered sufficient to conclude (key study) on the dermal toxicity of vinyl acetate (LD50 = 7440 mg/kg) and hence in accordance with Section 1 of REACH Annex XI, a study does not need to be conducted since there is a sufficient evidence to conclude on the acute toxicity of vinyl acetate by the dermal route of exposure.

In the dermal study, an LD50 value of 7440 mg/kg was determined for liquid vinyl acetate of unknown purity. Rabbits were administered 4, 8 or 16 mL/kg body weight). They were immobilised during a 24 hour contact period and prevented from inhaling the vapour. After occluded application of 16 mL/kg all animals died within 25-70 minutes. Clinical signs included convulsions within 15-30 minutes, vocalisation (reported as "crying") and upward-turned pupils. With 8 mL/kg, 2/4 animals died within 2 days. The skin showed signs of erythema, oedema and necrosis. With 4 mL/kg there were no mortalities and no clinical signs although congestion of the lungs and liver, mottled spleen and kidney and prominent changes to the liver were reported (Mellon Institute, 1969).

Human data on the acute toxicity of vinyl acetate are not available.

Justification for classification or non-classification

In two separate tests using rats, the oral LD50 values obtained were 3470 mg/kg and 3500 mg/kg.

A dermal LD50 value of 7440 mg/kg was determined in a study using rabbits.

Vinyl acetate does not warrant labelling according to EU criteria with respect to acute oral and acute dermal toxicity.

Inhalation toxicity testing in rats for 4 hours determined LC50 values of 15810 mg/m³ and 14084 mg/m³ therefore classification as Cat 4, H332 Harmful if inhaled according to Regulation (EC) No 1272/2008.