2-ethylhexyl methacrylate

Endpoint summary

Description of key information

2-ethylhexyl methacrylate is of low  toxicity by oral route (LD0/rat >= 2000 mg/kg). No reliable data are available on 2-ethylhexyl methacrylate for the dermal and inhalation routes. 
However, methyl- and n-butyl methacrylate, analogue substances  to 2-ethylhexyl methacrylate are of low  toxicity (LD0/rabbit >= 2000 mg/kg) by the dermal routes. As well, methyl-, ethyl- and n-butyl methacrylate are also of low  acute inhalation toxicity with 4-h LC50 in rats of 28.9, 55.0 and 29.0 mg/l, respectively. 
Due to the low  vapour pressure, inhalation is not considered as a relevant route of exposure for 2-ethylhexyl methacrylate.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

16 465 mg/kg bw

Additional information

Oral route

The Acute oral toxicity of 2-ethylhexyl methacrylate was evaluated in male and female Crj: CD(SD) rats according to OECD N°401 guideline and in compliance with principles of Good Laboratory Practices (Furuhashi et al., 1998). Animals were treated by gavage at the dose level of 2000 mg/kg and then observed for 14 days for mortality, clinical signs and effect on body weight. No mortality was recorded in the 14 day-observation period. Although soft faeces were observed in all treated groups, these effects were considered to be attributable to corn oil used as a vehicle. A tendency of the depression of body weight gain was observed on the second day in both sexes. No treatment related macroscopic abnormality was observed. Under these experimental conditions, the oral LD₀of 2-ethylhexyl methacrylate is higher than 2000 mg/kg in female/male rats.

The Acute oral toxicity of 2-ethylhexyl methacrylate was evaluated in male and female Wistar rats according to FDA (1959) guideline (Sterner, 1977). Animals were treated by gavage at the dose level of 10.0, 12.6, 15.9, and 20.0 ml/kg and then observed for 14 days for mortality, clinical signs and effect on body weight. Mortality was observed in 1/10, 1/10, 3/10 and 6/10 rats in the 14 day-observation period, respectively. Reduced activity, impairment of coordination, exophthalmos and piloerection were observed up to 24 hours after treatment. At the end of the observation period, the body weight of the animals was in a normal range. Reddening of mucous membranes was observed in the stomach and the intestine. Under these experimental conditions, the oral LD50 of 2-ethylhexyl methacrylate was 18.5 ml/kg bw (16465 mg/kg bw).

Inhalation route

No reliable data are available on 2-ethylhexyl methacrylate for the inhalation route. However, data are available on analogue substances: methyl-, ethyl- and n-butyl methacrylate. The respective LC50 values are in a range between 5000 and 11000 ppm indicating low inhalation toxicity.

At ambient temperature 2-EHMA has a saturated vapour density of 50-100 ppm (64 ppm at 20 °C) and, therefore, it is extremely unlikely that acutely toxic concentrations could ever be reached. Hence, the inhalation pathway is not considered a relevant route of exposure for 2-EHMA.

Dermal route

No reliable data are available on 2-ethylhexyl methacrylate for the dermal route. However, data are available on analogue substances: methyl- and n-butyl methacrylate.

There is one valid study available reporting a LD50 value in rabbits comparable to OECD guideline 402 (Rohm & Haas 1982). Unchangedmethyl methacrylatewas applied to the clipped skin of two New Zealand White rabbits per dose for 24 h under occlusive conditions. Even under these harsh conditions, no mortality, clinical signs or pathological findings were observed and the LD50 was therefore assessed to be >5000 mg/kg bw. Irritation effects were irreversible within 24 d if 2000 mg/kg bw or more were applied; effects were reversible after application of 200 mg/kg bw within 3 days.

In an OECD 402 and GLP study, a single dose ofn-butyl methacrylatewas applied to the shaved, intact skin of 5 male and 5 femaleNew Zealand White rabbits at a dosage of 2000 mg/kg of body weight (Sarver, 1993). The application site was occluded for 24 hours. The rabbits were observed for 14 days following application. No rabbits died within 14 days after dosing. No to severe erythema and no to severe edema were observed in the treated rabbits during the study. Superficial necrosis was observed in 1 rabbit on day 4 after application of the test substance and in most other rabbits by day 12 after application. Two rabbits also exhibited necrosis during the study. No target organ was identified at necropsy. Under the conditions of this test, the acute dermal LD0 for n-butyl methacrylate was greater than 2000 mg/kg of body weight.

Although no fully valid study is available for 2-EHMA, there is an early pre-guideline study available in guinea pigs that indicates low acute toxicity by the dermal route and data on the other two esters of the category (MMA and n-BMA) show low dermal toxicity. 

.Furthermore, a skin absorption study indicates that less than 10 % of the applied dose are absorbed through the skin within 30 h and, hence, bearing in mind the already low acute oral toxicity, toxic effects via the dermal route are unlikely. Thereis a trend of decreasing skin absorption with increasing chain-length of the alkyl moiety of the methacrylate esters indicating that the acute dermal toxicity will be equally low (cf section toxicokinetics). This is supported by the observation that the members are all of low acute oral toxicity and a survey of chemical registrations in the EU demonstrated that acute dermal toxicity was rarely greater than acute oral toxicity (Creton et al. 2010).

Taken as a whole there are sufficient data available for 2 -EHMA for assessment purposes so for the sake of animal welfare it is not proposed to repeat this study.

Justification for classification or non-classification

According to the available data and CLP criteria no classification is warranted for the acute oral, dermal and inhalation toxicity.