Ethyl acrylate

Endpoint summary

Description of key information

Ethyl acrylate is of moderate toxicity after a single ingestion and of pronounced toxicity after a short-term inhalation. EA is of low toxicity after a short-term skin contact.
Oral: LD50 = 1120 mg/kg bw (rat)
Dermal: LD50: 3049 mg/kg bw (rat, occluded)
Inhalation: LC50 = 9.0 mg/L (rat)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

1 120 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

9 000 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

3 049 mg/kg bw

Additional information

Oral exposure route:

For the key study evaluating the acute oral toxicity of ethyl acrylate in rats, the LD50 was 1120 mg/kg body weight (Rohm & Haas, 1984). In this study, groups of 10 male rats were administered ethyl acrylate at 0 (vehicle control) 710, 840, 1000, 1190, 1410, 1680, 2000 and 2380 mg/kg bw and the animals were observed for 14 days. The mortality was 0/10, 1/10, 1/10, 2/10, 6/10, 8/10, 10/10, 10/10 and 10/10, respectively. Deaths generally occurred within 1 day of dosing. Signs of central nervous system depression (passiveness, ataxia) and/or respiratory depression (cyanosis, abdominal breathing) were observed at lethal doses, possibly secondary to the severe gastrointestinal irritation evidenced at necropsy. Necropsy observations included stomachs enlarged 2-3 times normal size, filled with tan fluid, reddened stomach mucosa and intestines and thoracic cavity filled with clear or red fluid. There were no findings in the vehicle control group.

Additionally, there are several other studies of varied quality which all gave LD50 values in the range of 554 - 1020 mg/kg bw. In two older studies, conducted according to an internal method long before establishment of OECD guidelines, LD50 values of ca. 554 and 461 -731 mg/kg bw were determined depending on the used vehicle (aqueous emulsion in traganth and olive oil, respectively) (BASF AG 1958). These studies were of low to moderate quality with regard to method (only 5 animals/group, 5 doses, observation period of 7 days) and documentation of results as compared to the key study. Thus, these studies were used as supporting studies.

The LD50 values determined for rabbits were 280 - 420 mg/kg bw (Treon et al. 1949) and > 184 < 368 mg/kg bw (BASF AG 1960), respectively. NTP determined an LD50 in mice of 900 - 1800 mg/kg bw (1986) which is supported by an older study by Rohm & Haas (1950) comprising an LD50 value of 1800 mg/kg bw.

Dermal exposure route:

The acute dermal LD50 in rats was 3049 mg/kg body weight (Rohm and Haas, 1986). In this study, groups of six male rats received a single occluded application of undiluted ethyl acrylate for 24 hours at doses of 2000, 2514, 3162, 3976 and 5000 mg/kg bw. Animals in all dose groups exhibited red-stained eyes and muzzle. Passiveness, ataxia and tan-stained muzzle were observed in animals at doses as low as 2514 mg/kg bw. Salivation and yellow-stained anogenital area were observed in animals at doses as low as 3162 mg/kg bw and a single incident of prostration was observed at 3162 mg/kg bw. Scant droppings were observed in one animal at 5000 mg/kg bw and one animal each at 2000 and 5000 mg/kg bw had diarrhea. The animals in the 2000 mg/kg bw group and the surviving animals in the 2514 mg/kg bw group recovered from clinical signs by day 2 while surviving animals in the 3162, 3976 and 5000 mg/kg bw dose groups recovered by day 4. Skin irritation was noted in animals in all dose groups. Well defined to severe erythema and severe edema with pocketing were observed on day 1. Pocketing edema was no longer evident on day 4. Edema was no longer evident on day 11. Eschar and desiccation were observed on day 4 and persisted throughout the study. Possible scar formation was observed on day 13 and persisted throughout the study. Mortality was 0/6, 3/6, 3/6, 5/6 and 5/6 in the 2000, 2514, 3162, 3976 and 5000 mg/kg bw groups, respectively.

Other acute LD50 values ranging from approximately 1800 to > 5000 mg/kg bw (Reliability = 2) were reported. The description of severe irritation and necrosis of the dose site in the study cited with the lowest LD50 in rabbits makes this study less reliable for the purpose of defining an LD50 (Pozzani 1949). Based on these data, the rabbit appears to be somewhat more sensitive to the toxicity of ethyl acrylate. However, it is possible that this apparent toxicity may be due to rabbits responding more seriously to the irritant properties of ethyl acrylate.

Inhalation exposure route:

A weight of evidence approach was used for the acute inhalation endpoint based upon two quality studies with analytical confirmation of the administered dose concentration.

The acute LC50 for rats following four hours of inhalation exposure was 2180 ppm (9.0 mg/L) (Oberly andTansy, 1985).In this study, groups of 10 male rats were exposed (whole-body) to vapour concentrations of 1538, 1991, 2417, 2791 and 3001 ppm for 4 hours.Test atmosphere concentrations were verified analytically.Mortality was 1/10, 6/10, 7/10, 7/10 and 9/10, respectively, during the 24-hour post-exposure observation period. Clinical signs of toxicity suggested irritation of the eyes, nose and respiratory tract. Deaths were caused by generalized cardiopulmonary collapse. No gross abnormalities were noted in major organs at necropsy.

The second acute inhalation study used for the weight of evidence was an acute vapor toxicity study conducted according to OECD 403 in 2012, in which the LC50 was determined to be less than 9.137 mg/L in rats. In addition, an acute vapour inhalation toxicity test in rats was conducted by Bushy Run Research Center (BAMM, 1989). Three groups, each containing five male and five female Sprague-Dawley albino rats, were exposed once for one hour to ethyl acrylate vapour at nominal concentrations of 10048, 8335, and 6143 ppm. Animals were observed for 14 days post exposure and the LC50 value was determined. Mean measured concentrations (± SD) of ethyl acrylate for the three exposures were 8882 (± 331), 7421 (± 273), and 5843 (± 657) ppm corresponding to approximately 35.3, 29.5, and 23.2 mg/L. On the day of exposure, clinical signs were observed for all groups and included blepharospasm, lacrimation, perinasal and perioral wetness, and a slow surface-righting reflex. Additional signs observed for the 8882 and 7421 ppm groups on the day of exposure included abdominal and/or mouth breathing, audible respiration, tremors, and distended stomachs. During the postexposure period, signs were observed primarily on days 1 and 2 and included ataxia (8882 ppm group only), decreased respiration rate, and decreased motor activity. Additional signs observed during the postexposure period included audible respiration, periocular, perinasal, and perioral encrustation, and unkempt fur. No clinical signs of toxicity were observed for the 7421 ppm group on postexposure days 10 through 14, or for the 5843 ppm group on postexposure days 6 through 14. Macroscopic lesions observed in animals that died included a dark red or mottled discoloration of lungs, liver and kidneys, and clear fluid in trachea and thoracic cavity, and gas filled stomachs. No macroscopic lesions were observed in animals sacrificed at the end of the 2-week postexposure period.

The 1-hr LC 50 (with 95% confidence limits) for the combined sexes was 6493 (5474 to 7702) ppm corresponding to 25.8 mg/L. For classification purposes, this value has to be converted to a 4-hour equivalent by dividing the 1-hour value by a factor of 2 (GHS 2nd revised edition, UN 2007). The resulting 4-hr LC50 is approx. 12.9 mg/L.

In another study published by Silver and Murphy (1981) an LC50 greater than 6.1 mg/L was determined in rats after a 4h exposure (whole body) to ethyl acrylate vapours. Pretreatment with Triorthotolyl Phosphate enhanced the toxicity of Ethyl acrylate. In an older study without analytical monitoring the LC50 in rats after exposure to Ethyl acrylate vapours for 4 hrs was found to be > 4.1 - < 8.2 mg/L (Pozzani 1949). In an Inhalation Hazard Test conducted by BASF AG (1958) exposure to an atmosphere saturated with vapors of the volatile components of Ethyl acrylate at 20 °C lead to the death of 3/3 animals within 15 min.

In addition, Battelle conducted a single dose inhalation toxicity study in Cynomolgus monkeys in compliance with the EPA guidelines (40 CFR Part 792) (Rohm & Haas Co., 1995). Five groups of primates, three animals each, were exposed via head-only inhalation exposure to a common target vapor concentration (75 ppm) of the test substance or filtered air (control). Each animal received a single exposure of either three or six hour duration. The achieved mean test substance vapour concentration values were all within eight percent of the target concentration and the percent relative standard deviations were all less than 10 percent. The inhaled dose was calculated for each animal based on its body weight, mean test substance concentration value and total inhaled volume. The individual animal inhaled doses for Ethyl Acrylate ranged from 13.9 mg/kg bw (animal #202) to 36.9 mg/kg bw (animal #302). All animals survived the exposures in good condition. No clinical signs of toxicity were observed and no treatment related findings were observed during the gross pathological examination.

Taking all the presented data into consideration, Ethyl acrylate was concluded to be harmful if swallowed or in contact with skin and toxic by inhalation.

Justification for classification or non-classification

EU classification according to Annex I of Directive 67/548/EEC: Xn, R20/21/22

GHS classification (GHS UN rev.3, 2009):

- Oral route: Acute Category 4

- Dermal route: Acute Category 4

- Inhalation route (vapour): Acute Category 3