Isopropenyl acetate

Endpoint summary

Description of key information

The No Observed Adverse Effect Concentration (NOAEC) for systemic toxicity under the condition of a 28 days inhalative  study was 2075 mg/m3 (500 ppm). The NOAEC for hyperplasia of nasal transitional and degeneration of olfactory epithelium was 830 mg/m3(200 ppm). A NOAEC for slight irritancy leading to nasal epithelial inflammatory cell infiltration in some ofthe animals could not be established.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

830 mg/m³

Additional information

Five male and five female Wistar rats per test group were whole body exposed to dynamic at-mospheres of 2-Acetoxypropene (Essigsaeureisopropenylester) vapours for 6 hours per working day for about 28 days (20 exposures). The target concentrations were 207.5, 830 and 2075 mg/m3 (about 50; 200 and 500 ppm. A concurrent control group was exposed to clean air. On exposure days clinical examination was performed before, during and after exposure. During preflow period and on post exposure day clinical findings were recorded once each working day. Additionally the general state of health was controlled twice on workdays and once on weekends or holidays. Body weight of the animals was determined weekly. Ophthalmology was carried out prior to and at the end of exposure period. Detailed clinical examinations (open field observa-tion; OFO) were performed before start of exposure period and three times during exposure pe-riod in about weekly intervals. Neurofunctional tests comprising functional observational battery and motor activity measurements were performed at the end of exposure period. Hematological and clinicochemical examination of numerous parameters as well as urinalysis was performed at the end of the study as required by the corresponding test guidelines. A complete necropsy in-cluding weighing of selected organs and gross pathological evaluation was performed. Several organs and tissues were examined histopathologically as required by the corresponding test guidelines (OECD - Guideline method 412 with scope of examinations according to OECD - Guideline 407 and parts of 413).

The following study means of concentrations were determined analytically using gravimetry: 209.1 ± 12.3 (50.4); 809.0 ± 22.4 (195); 2011 ± 65.3 (485) mg/m3 (ppm).

The following substance related effects were produced by inhalation of the test substance:

Test group 3 (2075 mg/m3 (500ppm)): Low arousal during exposure, (multi)focal hyperplasia of the transitional epithelium in level I of the nasal cavity, (multi)focal degeneration of the olfactory epithelium in levels II and III of the nasal cavity, (multi)focal inflammatory cell infiltration in levels I and II of the nasal cavity

Test group 2 (830 mg/m3 (200 ppm)): (multi)focal inflammatory cell infiltration in level I of the nasal cavity

Test group 1 (207.5 mg/m3 (50ppm)): (multi)focal inflammatory cell infiltration in level I of the nasal cavity

Inhalation exposure of Wistar rats to 2075 mg/m3 (500 ppm) of the test substance vapours re-sulted in clear upper respiratory tract irritation as demonstrated by the presence of epithelial hy-perplasia or degeneration. The finding of inflammatory cell infiltration in the mid and low con-centration are also interpreted as mild reaction to the irritant properties of the inhaled vapours. No signs of systemic toxicity occurred at any concentration.

Thus the No Observed Adverse Effect Concentration (NOAEC) for systemic toxicity under the condition of this study was 2075 mg/m3 (500 ppm). The NOAEC for hyperplasia of nasal transitional and degeneration of olfactory epithelium was 830 mg/m3 (200 ppm). A NOAEC for slight irritancy leading to nasal epithelial inflammatory cell infiltration in some of the animals could not be established [cited in a modified form from BG Chemie, Toxicological Evaluation No 262, Isopropenyl acetate, CAS No 108-22-5, Berufsgenossenschaft der chemischen Industrie, 2005].

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Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: other