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Description of key information

Isobutyl acrylate has not been tested in repeated dose studies. However, toxicity is expected to be very similar to that associated with the analogue n-butyl acrylate, i.e. irritating effects to nasal and respiratory mucosa, as well as to the eyes. At non-irritating concentrations/doses, systemic effects are not expected to occur.

Key value for chemical safety assessment

Additional information

No experimental data on isobutyl acrylate are available. Data on the structural analogue, n-butyl acrylate, which has been extensively studied in animal tests are included.

Repeated dose toxicity: Inhalation:

Sprague Dawley rats (20 animals per sex and dose) were exposed by inhalation to measured concentrations of 0, 21, 108, 211 and 546 ppm (corresponding to approx. 0, 0.11, 0.57, 1.11, 2.86 mg/L) for 6 hours per day, 5 days/week for 13 weeks (BASF AG 1978, 1980). Clinical, clinico-chemical, haematological, gross-pathological, and histopathological examinations revealed no substance-related effects in the 21 and 108 ppm dose groups. At 211 ppm, the test substance caused eye irritation and irritation of the nasal mucosa. Significant reductions in body weight changes (13.3 %) were observed. In clinico-chemical examinations of females, decreased potassium values and an increase in alkaline phosphatase activity were observed. In the 546 ppm dose group, 31 of 40 animals (77 %) died. Hemorrhagic discharge from eyes and noses and severe dyspnoea were observed, which became constantly more severe. Many clinico-chemical and haematological parameters were affected in animals of this dose group. The animals died during exposure due to strong irritation of the respiratory tract. Metaplasia of the respiratory epithelium as far as the terminal bronchioles and proliferation of the bronchoalveolar epithelium could be detected in histopathological examinations.

The NOAEC for this study is 108 ppm (0.57 mg/L/day) and the LOAEC is 211 ppm (1.11 mg/L/day) based on body weight decrease, clinico-chemical changes, and changed organ weights. The NOAEC for local effects (histological changes in the nasal mucosa and olfactory epithelium) is 21 ppm (0.11 mg/L/day) and the LOAEC is 108 ppm (0.57 mg/L/day).

In a 2-year inhalation study, Sprague-Dawley rats were exposed by whole body exposure 6 hours per day, 5 days a week to 0, 15, 45 or 135 ppm (0, 0.086, 0.258, 0.773 mg/L n-butyl acrylate. During the first 13 weeks of the study, the concentrations were lower: 0, 5, 15 or 45 ppm . The post observation period was 6 months (BASF AG 1985). There were no compound-related effects on general behaviour or appearance (no overt signs of toxicity and no effects on mortality). Body weight gain was normal in all groups, with only a slight decrease in food consumption in treated males and females. No compound-related effects were detected in haematological measurements or urinalysis. Organ weights were generally unaffected by treatment, except for slightly lower relative heart, kidney, liver and thyroid weights in the highest dose. Ophthalmological examinations demonstrated localized or diffuse stippling of the corneal epithelium, cloudiness of the cornea, and various degrees of vascularisation that increased with dose and duration of exposure. These effects were only significant in the highest dose group (compared with the controls), thus the NOAEC for effects on the eye is 45 ppm (0.258 mg/L).

Histological changes in the nasal mucosa were dose-dependent and described as slight atrophy of the neurogenic part of the olfactory epithelium at 15 ppm, and partial loss of the columnar cell layer and stratified reserve-cell hyperplasia at 45 and 135 ppm . The frequency of reserve-cell hyperplasia in nasal mucosa was 0, 8/169, 41/170, and 105/170 (for males and females combined) at 0, 15, 45, and 135 ppm, respectively. Males and females were affected in the same manner. No changes were detected in the posterior nasal cavity, and no irritation effects were detected on the larynx, trachea or lungs. The changes in the nasal mucosa and cornea proved to be reversible up to a point during the follow-up period. For these histological changes of the nasal mucosa no NOAEC could be derived. The LOAEC is 15 ppm (0.086 mg/L).

Examinations of tissues for neoplastic changes did not reveal any compound related increases or dose dependent effects.

Repeated dose toxicity: Oral:

In a 13 week-study, F344-rats (15 animals per sex and dose) received n-butyl acrylate via drinking water in concentrations of 0, 0.015, 0.09 and 0.15 % (0, 12, 73, 84 mg/kg body weight per day for males and 0, 15, 91, 111 mg/kg body weight per day for females). A satellite group (5 male and 5 female rats) was given 150 mg/kg bw n-butyl acrylate (in corn oil) via gavage 5 days a week for 13 weeks (Dow Chemical 1980). The only effects reported were a slight reduction in water consumption, which occurred in all dose groups, and a decrease in weight gain for male rats in the highest dose group. No abnormal haematology, clinical chemistry, urinalysis, or histopathology findings were reported. In the gavage satellite group, the only effect observed was a slight increase in relative liver weight. The highest level administered in drinking water approaches the maximum solubility limit of butyl acrylate in water and thus was the highest concentration that could be reasonably given.

The NOAEL for the drinking water study is 84 (male) and 111 (female) mg/kg body weight per day and the LOAEL for the gavage study is 150 mg/kg bw per day (male and female).

Repeated dose toxicity: Dermal:

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

A lifetime dermal carcinogenesis study was conducted in mice with the structural analogue n-Butyl acrylate. The dermal carcinogenic potential of n-butyl acrylate was assessed by applying 25 µL of a 1% (v/v) dilution in acetone (corresponding to approx. 8 mg/kg bw) to the backs of 40 male C3H/HeJ mice. n-Butyl acrylate was not carcinogenic when applied to the skin of C3H/HeJ mice throughout their lifetime.

Conclusion:

Isobutyl acrylate has not been tested in repeated dose studies. However, toxicity is expected to be very similar to that associated with the analogue n-butyl acrylate, i.e. irritating effects to nasal and respiratory mucosa, as well as to the eyes. At non-irritating concentrations/doses, systemic effects are not expected to occur.

Justification for classification or non-classification

EU classification according to Annex VI of Directive 67/548/EEC: no classification required

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

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