2-hydroxyethyl acrylate

Neurotoxicity

Description of key information

Subchronic intraperitoneal administration of HEA over 90 days affected body weight gain and some behavioural measures in rats, but it did not produce distal axonopathy and neurobehavioural signs similar to those of acrylamide.The neurotoxic potential of test substance appears to be minimal.

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 study available

Effect on neurotoxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Neurotoxicity

In the key subchronic neurotoxicity study (Moser et al. 1992) the test substance in saline was injected intraperitoneally into Long-Evans rats (10/sex/group) at dosages of 0, 3, 20 and 60 mg/kg body weight/day, 5 days a week for 13 weeks. Two vehicle control groups were also included. As a positive control for detecting central-peripheral distal axonopathy, three dose levels of acrylamide (ACR) were also included. A functional observational battery (FOB) which included home-cage and open-field observations and interactive tests of sensory, neuromuscular, and autonomic function, was used to test all rats before dosing, at approximately 30 and 60 days of dosing, and on the day after the last dose. Subsets of rats (6/sex/dose level) were then perfused for neuropathlogical evaluation, and specific sites within the central and peripheral nervous system (tissues from the brain, spinal cord, and peripheral nerve) were evaluated by light microscopy. HEA treatment resulted in a statistically significant decrease in body weight gain for male rats in the 60 mg/kg body weight dose group. The authors observed abdominal bloating as a result of the intraperitoneal (i.p.) injection of HEA which was sometimes extreme. Bloating which was observed in HEA-treated rats and which was described as extreme, was likely responsible for some of the changes in the functional observational battery (FOB) that were described. Irritation of the peritoneum due to the i.p. injection of HEA at all dosages is consistent with “extreme” bloating, however gross and histological examination of the peritoneum found no evidence of overt peritonitis or other abnormalities. Histologic examination of the liver, kidneys, bladder, diaphragm and brain, spinal cord and peripheral nerve following fixation of tissues by perfusion revealed no treatment-related effects. Male (not female) rats had a transiently decreased hindlimb grip at the higher dosage at 90 days. The FOB showed increased reactivity to handling and to external stimuli, likely due to bloating of the abdominal area with tenderness (that could have interfered with behavioral measurements), as well as mild hypothermia; however, no information was given about dose-response relationship or magnitude of these effects. Righting reflex was significantly impaired in males at 90 days, but the effect was slight and there was no dose-response relationship. Gait was affected, but the authors indicated that the HEA treated rats did not show a clear dose-response relationship in the gait score. In fact, examination of the data showed that the baseline differences could account for most of the differences seen among dose groups. HEA produced no changes in foot splay. Body weights in male rats showed an effect in the high-dosage group, but no effect was seen in females.Neuropathological evaluation included evaluation of 6 brain sections, dorsal and ventral roots and ganglia, sciatic (2 locations), tibial and sural peripheral nerves. No neuropathological changes were detected either in the central, or in the peripheral nervous systems. Timecourse and dose-related changes in gait, splay and neuropathology were demonstrated for the positive control acrylamide and were consistent with the literature. Female gait score data were also presented, but failed to show a convincing effect (abnormal control data points may account for statistical significance). The authors did not comment about how bloating (pear-shaped belly) could have eventually affected gait scores.

Behavioural effects observed after i.p. administration of HEA were neither dose- nor time-related. They were not consistent in both sexes and were generally transient and only slight effects as compared to behavioural effects caused by the positive control acrylamide. Based on the reported results, the authors came to the conclusion that intraperitoneal administration of HEA affected weight gain and some behavioural measures, it did not produce distal axonopathy and neurobehavioural signs similar to those of acrylamide. The neurotoxic potential of HEA appears to be minimal. The NOAEL (males) for general toxicity was 20 mg/kg bw/day based on changes in body weight gain. The NOAEL (male/female) for neurobehaviour and neuropathology was equivalent to the highest dose tested of 60 mg/kg bw/day.

Justification for classification or non-classification

Based on the available data, the test substance in not classification as a neurotoxic substance according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.