Acrylaldehyde

Immunotoxicity

Description of key information

“Acrolein has been found to impair pulmonary antibacterial defense mechanisms upon inhalation exposure in vivo and in vitro.” quotation from European Union Risk Assessment Report Acrylaldehyde (EU, 2001)
However, the studies on this subject “do not suggest that inhaled acrolein causes an immune system effect, but the reduction in removal of bacteria from the alveolar spaces may result from the destruction of functionality of alveolar macrophages present in the respiratory epithelium.” quotation from United States Agency for Toxic Substances and Desease Registry, Toxicological Profile for Acrolein (US ATSDR, 2007)

Additional information

Acrolein has been the subject of a risk assessment carried out under Community Regulation (EEC) No 793/93 (EU, 2001). The key information on neurotoxicity as stated correspond to the greatest extend to the conclusions on this topic in this assessment and to a further assessments carried out under other international and national programmes published after finalisation of the EU Risk Assessment Report 2001 (United States Agency for Toxic Substances and Desease Registry, Toxicological Profile for Acrolein (US ATSDR, 2007). The information on immuntoxicity of acrolein given in the EU Risk Assessment and the US ATSDR correspond to the greatest extend to further assessments carried out under other international and national programmes published after finalisation of the EU Risk Assessment Report 2001 (World Health Organization, International Programme on Chemical Safety (IPCS), Concise International Chemical Assessment Document of Acrolein, CICADS 43 (WHO, 2002); United States Environmental Protection Agency, Toxicological Review of Acrolein (US-EPA, 2003). In the United States Environmental Protection Agency,

HED Risk Assessment for Reregistration Eligibility Decision (RED) Document for Acrolein (US-EPA, 2008) (US-EPA, 2008), immuntoxicity is not discussed.:

1. European Union Risk Assessment Report of Acrolein (EU, 2001)

“Acrolein has been found to impair pulmonary antibacterial defense mechanisms upon inhalation exposure in vivo and in vitro.” quotation from EU, 2001 p83

“The induction of impairment of the pulmonary antibacterial defense by inhalation exposure to acrolein was observed in studies in mice (Astry and Jakab, 1983; Kawabata and White, 1977) and rats (Carl et al., 1939). Inhalation exposure to 3 or 6 ppm during 8 hours induced a dose dependent impairment of the pulmonary antibacterial defence against infection with Staphylococcus aureusin mice (Astry and Jakab, 1983). Higher concentrations caused increased sensory irritation, but no additional impairment of antibacterial resistance.”

“Suppression of bactericidal activity of pulmonary macrophages was observed in several in vitro studies. Because acrolein is a metabolite of cyclophosphamide, in vitro studies were performed to investigate whether the antitumor activity of cyclophosphamide was mediated by enhanced immune reactivity of acrolein. The results suggest that the immune response is enhanced by acrolein.” quotations from EU, 2001 p79

2. Agreement with further International Reports and Studies Published after Finalisation of the EU Risk Assessment Report 2001

Yes

3. Substantial Disagreements in Comparison to further International Reports to European Union Risk Assessment Report 2001

None

4. Additional Aspects in further International Reports

US ATSDR, 2007 discusses the immunological and lymphoreticular effects of acrolein in more detail: “Short-term exposures to acrolein reduced bactericidal activity of the respiratory tract in experimental animals. Aranyi et al. (1986) observed a significantly lower removal by alveolar macrophages of Klebsiella pneumoniae bacteria from a 3-hour aerosol infection following a 5-day exposure to 0.1 ppm acrolein in mice. No difference was observed in rats for this same exposure/infection protocol (Sherwood et al. 1986). Similarly, 8-hour exposures to 3 and 6 ppm acrolein in mice showed a concentration-related reduction in clearance of Staphylococcus aureus from an 8-hour pulmonary infection. However, exposures to 8–10 ppm did not significantly add to the impairment of bactericidal activity (Astry and Jakab 1983). Rats exposed to 0.55 ppm for 10–26 days had significantly lower numbers of alveolar macrophages, but rats exposed for 60–180 days showed no significant difference in macrophage levels (Bouley et al. 1975). No statistically significant differences in mortality were observed in rats intravenously exposed to Listeria monocytogenes following a 3-week exposure to up to 3 ppm acrolein (Leach et al. 1987). These studies do not suggest that inhaled acrolein causes an immune system effect, but the reduction in removal of bacteria from the alveolar spaces may result from the destruction of functionality of alveolar macrophages present in the respiratory epithelium.” quotation from US ATSDR, 2007, p 39

5. Additional Information in Newer Studies, not Included in the European Union Risk Assessment Report 2001 or further Cited International Reports

None

Justification for classification or non-classification

The available data do not indicate that specific immunotoxicity is an instrinsic activity of acrolein.

Thus, acrolein does not comply with the classification requirements regarding immunotoxicity outlined in regulation (EC) 1272/2008 or the former directive on classification and labelling 67/548/EWG.