Acrylaldehyde

Specific investigations: other studies

Description of key information

The toxicodynamic of acrolein originates in its highly reactive nature. Acrolein can bind rapidly (both enzymatically and non-enzymatically) with cellular components. Many of the toxicological effects of acrolein may be due to the saturation of protective cellular mechanisms (most notably glutathione) and subsequent reaction with sulfhydryl groups in proteins and peptides. 

Additional information

Acrolein has been the subject of a risk assessment carried out under Community Regulation (EEC) No 793/93 (EU, 2001). However, Specific Investigations: Other Studies is no specific chapter in the EU Risk Assessment. The key information on the toxicodynamic of acrolein subsumed under this heading Specific Investigations: Other Studies as stated correspond to the greatest extend to a 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) and a recently published review (Stevens and Maier 2008):

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

There is no specific chapter on specific investigations: other studies in the EU Risk assessment.

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

Not applicable.

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

Not applicable.

4. Additional Aspects in further International Reports

In WHO 2002 the toxicodynamic of acrolein in relation to the endogenous detoxification of acrolein is discussed: “Due to its highly reactive nature, acrolein can bind rapidly (both enzymatically and non-enzymatically) with cellular components. Many of the toxicological effects of acrolein may be due to the saturation of protective cellular mechanisms (most notably glutathione) and subsequent reaction with critical sulfhydryl groups in proteins and peptides (Gurtoo et al., 1981; Marinello et al., 1984). In rats, inhalation of acrolein at levels ranging from 0.2 to 39 mg/m³ (0.1 to 17 ppm) produces a concentration-dependent reduction in non-protein sulfhydryl groups in the respiratory tract, but not in the liver (McNulty et al., 1984; Lam et al., 1985; Heck et al., 1986; Walk & Haussmann, 1989). Some studies have revealed that pretreatment with compounds containing free sulfhydryl groups (e.g., cysteine) is protective against the acute lethality of acrolein (Sprince et al., 1979; Gurtoo et al., 1981). Similarly, the studies of Eisenbrand et al. (1995) suggest that intracellular glutathione (or other free sulfhydryl groups) may protect against the DNA-damaging effects of acrolein. Although there have been some suggestions that the toxic effects of acrolein may be mediated, at least in part, through mechanisms involving acrolein–glutathione conjugates (Mitchell & Petersen, 1989; Horvath et al., 1992; Ramu et al., 1996), available data remain inconclusive. In one study, acrolein and its glutathione adduct, glutathionylpropionaldehyde, induced oxygen radical formation (Adams & Klaidman, 1993). “ quotation from WHO, 2002, p27-28

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

Stevens and Maier 2008: Humans may be exposed to this compound by industrial sources. However, this is not the only source humans by be exposed to this compound. Acrolein is ubiquitously present in (cooked) foods and in the environment. It is formed from carbohydrates, vegetable oils, animal fats and amino acids during heating of foods, and by combustion of petroleum fuels and biodiesel.” “Smoking of tobacco products equals or exceeds the total human exposure to acrolein from all other sources. Though there are not only exogenously sources but also endogenous sources, e.g. myeloperoxidase-mediated degradation of threonine and amine oxidase-mediated degradation of spermine and spermidine, which may constitute a significant source of acrolein in situations of oxidative stress and inflammation. The biological effects of acrolein are a consequence of its reactivity towards biological nucleophiles such as guanine in DNA and cysteine, lysine, histidine, and arginine residues in critical regions of nuclear factors, proteases, and other proteins. The interaction of acrolein with biomolecular targets is the research topic in a lot of different fields of medical, biological and toxicological research. Remark: An overview on a lot of these topics gives the recently published review of Stevens and Maier, 2008: Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease.