methyl acrylate; methyl propenoate

Endpoint summary

Description of key information

In a subchronic study in Sprague-Dawley rats following vapour inhalation for 12-weeks, the NOAEC was 82 mg/m3. The respective LOAEC based on reduced body weight and reduced organ weights was 440 mg/m3. Following chronic exposure by the inhalation route (5 d/w, 6 h/d), the LOAEC for local effects (nasal and ocular) in rats was 58 mg/m3. The systemic NOAEC was >= 519 mg/m3. Following a 90-day oral administration of MA in the drinking water, the NOAEL was 5 mg/kg bw/d for CDF Fischer 344 rats. The LOAEL was 20 mg/kg bw/day based on changes in kidney weights.

Additional information

Repeated dose toxicity: Inhalation:

Ten Sprague Dawley rats/sex/group were exposed to 23, 124, 242 and 626 ppm; (0.082, 0.44, 0.86 and 2.24 mg/L) for 12 weeks, 5 day a week, 6 hours per day. The No Observed Adverse Effect Concentration (NOAEC) was 23 ppm (0.082 mg/L) (no clinical/chemical/haematological effect, no effect on body weight, organ weight and histology) and the Lowest Observed Adverse Effect Concentration (LOAEC) was 124 ppm (0.44 mg/L) (reduced body weight, reduced organ weights). At 242 ppm (0.860 mg/L), methyl acrylate caused transient respiratory and eye irritation at the beginning of exposure. At 626 ppm (2.24 mg/L), the animals exhibited laboured breathing, irritation of the mucosa, and hemorrhagic discharge from the eyes and nose that became increasingly severe. All animals of this dose group died during the first half of the study due to strong irritation (hyperemia in the trachea and lungs along with bronchopneumonia). Reduced body weight gain was seen to be treatment related in the 124-626 ppm groups (0.440 –2.24 mg/L). Increased relative lung and relative liver weights were observed in the 242 ppm group, and in the females of the 124 ppm group without detectable microscopic changes in these organs. Absolute organ weights of heart, liver, kidney and spleen were decreased in males of the 242 ppm dose group, absolute spleen weight of males was also reduced in the 124 ppm group. Keratinisation of the transition epithelium between respiratory and olfactory epithelium was observed, as well as degeneration and vacuolization of the olfactory epithelium at the histological examination of the 242 ppm and 626 ppm groups, but not in the 124 ppm group. No changes in blood chemistry were found, apart from a rise in sodium values and a drop in potassium values in the 242 ppm group (the 626 ppm group was not evaluated for blood chemistry due to lethality) (BASF AG 1978, 1980).

 

In a 2 year inhalation study rats were exposed 5 days/week, 6 hours/day to concentrations of 0, 5, 15, 45 ppm (0, 0.019, 0.058, 0.173 mg/L) during the first 13 weeks; followed by 0, 15, 45, 135 ppm (0, 0.058, 0.173, 0.519 mg/L) until the end of the study. Irritative changes, atrophy and basal cell hyperplasia in the nasal passage, accompanied by loss of olfactory and ciliated cells of the nasal turbinates, were observed when rats were exposed up to 135 ppm (0.519 mg/L) for 2 years (BASF AG 1985, Reininghaus 1991). Histological changes in the nasal mucosa were dose dependent; and were described as slight degeneration of the olfactory epithelium at 15 ppm, and partial loss of the columar cell layer and stratified reserve-cell hyperplasia at 45 and 135 ppm. Males and females were affected in the same manner. No changes were detected in the posterior nasal cavity, and no irritative effects on the larynx, trachea or lungs were seen. Opacification and vascularisation of the cornea were observed in all exposed animals. The only systemic changes observed were a slight and reversible delay in body weight gains along with changes in organ weights without histological correlation (mainly in the highest dose group.) There were no treatment related increases in benign or malignant tumours. The Lowest Observed Adverse Effect Concentration (LOAEC) for contact effects (nasal and ocular) was 15 ppm (0.058 mg/L). (For more details see Section Carcinogenicity)

Repeated dose toxicity: Oral:

Following a 3-month oral administration of methyl acrylate to the F344 rat in drinking water (0; 1, 5 and 20 mg/kg bw/d) slight decreases in body weight gain and water consumption were noted in both sexes receiving the highest dose. Also observed in the female rats at the highest dose was an increase in urinary specific gravity, probably as a result of decreased water intake and a slight but statistically significant increase in the mean relative kidney weight. All alterations seen in histology were typical of those occurring spontaneously in rats of this age and strain. The kidneys of male rats at the highest dose showed an increase in severity of a spontaneous renal disease normally seen in F344 rats. This alteration characterized by dilated renal tubules and eosinophilic cast formation, was observed in six of 10 males examined from the 20 mg/kg bw/day dose and in two of 10 male controls.

This observation was also noted in 2 of 10 females at the highest dose and in none of the female controls. The increase in relative organ weights and the histopathological observations indicate that the highest dose may have had a slight effect on the kidneys. No other histopathological effects were seen, including the sex organs. The No Observed Adverse Effect Level (NOAEL) based on the effects seen at 20 mg/kg bw/day in this study was determined to be 5 mg/kg bw/day for male and female CDF Fischer 344 rats and the Lowest Observed Adverse Effect Level was 20 mg/kg bw/day (Dow 1981).

Repeated dose toxicity: Dermal:

No subacute or subchronic repeated dose studies with dermal application are available for Methyl acrylate.

Justification for classification or non-classification

EU classification according to Regulation (EC) No. 1272/2008:

- Specific Target Organ Toxicity: Repeated Exposure: no classification required