Propyl acetate

Neurotoxicity

Description of key information

Propyl acetate
Rat, inhalation, motoneuronal EC37: ca. 27.5 mg/L (Frantik et al. 1994)
Mouse, inhalation, motoneuronal EC30: ca. 26 mg/L (Frantik et al. 1994)
Analogous substances
Butyl acetate
Rat, inhalation, NOAEL neurotoxicity: 14.10 mg/L (David et al. 1998)

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Effect on neurotoxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Effect on neurotoxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Propyl acetate

Groups of 4 male albino SPF-Wistar rats or 4 female H strain mice were exposed individually for 4 hours to a range of propyl acetate concentrations (analytically determined; Frantik et al. 1994). Measurement of any potential neurotoxic effect started within one minute after removal from exposure. A short electrical impulse (0.2 sec, 50 Hz, 180 V) was applied through ear electrodes. The duration of tonic extension of the hindlimbs in exposed and control rats was measured. All animals were given three control tests at weekly intervals prior to the first exposure. The concentration which resulted in a 37% (EC37) decrease in  rat hindlimb extension during electrically-induced seizure events was 6600 ppm (+/- 1200 ppm) or 27.522 mg/L (+/- 5.004 mg/L), while the concentration which resulted in a 30% (EC30) decrease in  mouse hindlimb extension during electrically-induced seizure events was 6200 ppm (+/- 830 ppm) or 25.854 mg/L (+/- 3.461 mg/L)

Analogous substance:

Butyl acetate

The study consisted of two sets of animals, male and female ad libitum fed Sprague-Dawley (SD) rats designated for functional observational battery, motor activity, and neuropathology endpoints (FOB/MA/NP) and male (SD) rats restricted to 12-14 g of feed per day and which were designated for schedule-controlled operant behavior (SCOB; David et al. 1998). Animals were distributed into four groups of 30 animals each. Ten males and 10 females from each treatment group were designated for FOB/MA/NP testing while another 10 males from each treatment group were utilized for SCOB testing. Control (0 ppm) and high-concentration groups contained an additional 10 animals (5 males and 5 females) for possible post-exposure/recovery evaluation. Exposures were conducted 6 hr/day, 5 days/wk for 65 exposures over 13 consecutive weeks for food-restricted animals assigned to the SCOB group. Ad-libitum-fed animals assigned to the FOB/MA/NP group were exposed for 65 exposures over 14 weeks; the extra week of exposures was required because animals were not exposed on days when the FOB and MA tests were conducted.

Animals exposed to 1500 or 3000 ppm (7.05 or 14.10 mg/L) had minimal to minor reduced activity levels only during exposure. At 3,000 ppm, increased motor activity using MA assessments was seen in some animals while decreased activity was observed in other animals. Although the mean was not significantly greater than controls, the standard deviation was significantly greater than in controls. However, there was no evidence of neurotoxicity observed using FOB testing, SCOB endpoints or neuropathological examinations. There was no evidence of a cumulative effect of exposure on the severity of reduced activity. There were no other apparent differences in the clinical condition of FOB/MA/NP and SCOB animals. Body weights and/or body weight gains were reduced in the 1500 and 3000 ppm (7.05 and 14.10 mg/L) male and female animals. No differences in body weight or rate of weight gain were noted in the 500 ppm (2.350 mg/L) exposure group animals when compared to control groups. Histopathological evaluations of animals from the control and 3000 ppm groups did not indicate any treatment related effects.

Read across justification to propan-1-ol and n-butyl acetate for filling data gaps of n-propyl acetate:

As indicated by toxicokinetic studies (see chapter on toxicokinetics, metabolism and distribution), n-propyl acetate is rapidly hydrolyzed to propan-1-ol and acetate (acetic acid). Available data on propan-1-ol is therefore suitable for filling data gaps of n-propyl acetate.

N-propyl acetate and n-butyl acetate differ structurally by only one –CH2 group and both substances have a similar toxicological profile. The available data for n-butyl acetate is therefore suitable for filling the data gaps of n-propyl acetate due to structural similarities. For a detailed justification of read-across, please refer to IUCLID section 13.

Justification for classification or non-classification

Taken together all available data for propyl acetate and analogous substances, there were no irreversible subchronic neurotoxic effects in doses without systemic toxicity. Therefore no classification is required.