Acrylaldehyde

Endpoint summary

Description of key information

"Acrolein is irritating and corrosive to skin and eyes in laboratory animals and humans."
"Several studies show that acrolein causes sensory irritation of the respiratory tract after inhalation."
"The RD50 of acrolein, the concentration causing 50% reduction in respiratory rate, amounted to 2.4 - 6.6 mg/m³ in mice and 9.2 and 21.7 mg/m³ in rats."  quotation from European Union Risk Assessment Report Acrylaldehyde (EU, 2001) 

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

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 skin and eye irritation/corrossion as well as on respiratory irritation of acrolein as stated are quotations taken from this EU Risk Assessment. The information on irritaing/corrosive activity of acrolein given in the EU Risk Assessment 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); United States Agency for Toxic Substances and Desease Registry, Toxicological Profile for Acrolein (US ATSDR, 2007); United States Environmental Protection Agency, Reregistration Eligibility Decision (RED) Document for Acrolein (US-EPA, 2008)). Supplementary information to EU, 2001 regarding a study on respiratory irritation (Morris et al., 2003 as quoted in US ATSDR, 2007) has been considered:

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

“Acrolein is irritating and corrosive to skin and eyes in laboratory animals and humans.

In humans threshold levels for various local effects of acrolein were as follows: slight eye irritation (subjectively reported) was apparent after exposure to 0.14 mg/m³ for 5 minutes, 0.48- 0.80 mg/m³ was the odour threshold, continuous exposure to 0.69 mg/m³ resulted in considerable eye and nose irritation after 10 - 20 minutes and a significantly decreased respiratory frequency after 40 minutes of exposure, and exposure to 1.9 mg/m³ for 10 minutes resulted in extreme irritation of all mucosal surfaces.” quotation from EU, 2001, p82

In Detail:

Animal studies:

“Exposure to acrolein vapour concentrations between 1.9 and 2.6 ppm for 4 hours caused slight irritation of the eyes in rabbits (Mettier, 1960). Exposure of rabbits to 0.6 ppm acrolein vapour (1.4 mg/m³), for 30 days, 4 hours/day, 5 days a week produced no eye irritation (Mettier et al., 1960).”

“Acrolein is stated to be corrosive to the skin and eyes of rabbits and 1 % solutions of acrolein give rise to serious eye and skin damage (Albin, 1975, no reports available).”

“Reduction of the ciliary movement in tracheas was observed in in vitro tests with tracheal preparations from rabbits, cattle and sheep (Guillerm et al., 1967; Kensler et al., 1963; Sisson et al., 1991), and in an in vitro/in vivo test with hens (Battista et al., 1970).

General appearance and behaviour of the rats exposed to atmospheres containing 0.25, 0.67 or 1.40 ppm acrolein in air (nature of the substance is unknown), 6 h/day for 1 or 3 days in a nose only inhalation chamber were essentially normal during and after exposure. No clinical signs of eye, nose or respiratory irritation were reported. Microscopic examination revealed, however, slight treatment-related histopathological changes in the respiratory/transitional but not in the olfactory epithelium of the nose of rats exposed to 0.25 or 0.67 ppm acrolein. The 1.40 ppm group was not examined histologically (Cassee et al., 1996).

Several studies show that acrolein causes sensory irritation of the respiratory tract after inhalation.

The RD₅₀ of acrolein, the concentration causing 50% reduction in respiratory rate, amounted to 2.4 - 6.6 mg/m³ in mice (nature of the substance is unknown) (IPCS, 1992). In rats RD₅₀ values of 9.2 and 13.7 mg/m³ are found (nature of the substance is unknown) (IPCS, 1992, Cassee et al., 1996).” quotations from EU, 2001, p58 and p60

Human Data:

Accidental Exposure

“A few cases of accidental exposure to acrolein and a suicidal attempt with acrolein ingested in orange juice were described. Effects were observed on the primary exposure sites and were characterised by signs of severe irritation, finally resulting in corrosion, of skin and eyes and of the mucosal layer of stomach and respiratory tract.” quotation from EU, 2001, p58

Volunteer Studies

“Several studies with volunteers were performed to establish threshold levels for odour perception and recognition, and for effects on eyes, nose and respiratory tract. It is noted that many of these studies are of older date and the analytical methods used are often unspecific or poorly described.” quotation from EU, 2001, p58

Irritant Effects, Dermal Exposure

“Patch tests were conducted with acrolein in ethanol at concentration of 0.01, 0.1, 1 and 10% on groups of 8, 10, 48 and 20 volunteers respectively (Lacroix et al., 1976). At 1% positive reactions were recorded in 6 out of 48 persons (12.5%), four cases of serious oedema with bullae and two with erythema. At 10% all subjects (n = 20) showed skin effects with bullae, necrosis, inflammatory cell infiltrate and papillary oedema. No reactions were observed at 0.01 (n = 8) or 0.1% (n = 10). These data cannot be used to establish a no-effect-level for human skin irritation, because the duration of exposure and the onset of symptoms were not reported. In addition, at lower concentrations the number of volunteers per group was too small.” quotation from EU, 2001, p60

Irritant Effects, Inhalation Exposure

“Several experiments were performed to examine the irritant effects of acrolein vapour on eyes, nose and respiratory tract. In a study of Weber-Tschopp et al. (1977) three experiments were conducted”:

“A. continuous exposure during 35 minutes to a gradually increasing concentrations from 0 to 0.6 ppm, followed by a constant exposure to 0.6 ppm for 5 minutes (n = 54)

B. exposure during 60 minutes to a constant concentration of 0.3 ppm (n = 46)

C. four exposures (1.5 minutes) to increasing concentrations of 0.15, 0.3, 0.45 and 0.6 ppm with 8 minutes recovery time between the exposures (n = 42)

In experiment A subjective irritation of eyes and nose, annoyance and eye blinking rate increased, and the respiratory rate decreased with increasing acrolein vapour concentration. At the following concentration the effects were statistically significant: eye irritation at 0.09 ppm (0.21 mg/m³), nose irritation at 0.15 ppm (0.34 mg/m³), increase of eye blinking rate at 0.26 ppm (0.59 mg/m³) and decrease of respiratory rate at 0.6 ppm (1.3 mg/m³). In experiment B considerable eye and nose irritation was recorded after 10 to 20 minutes, and a significant decrease in the respiratory frequency after 40 minutes exposure to a constant acrolein vapour concentration of 0.3 ppm (0.69 mg/m³). Comparing the effects caused by discontinuous exposure (experiment C) with continuous exposure (experiment A) it is concluded that irritation to the eyes and nose is significantly more severe at continuous exposure, indicating that the effects were dependent on the exposure time.”

“Volunteers exposed to acrolein vapour for 5 min recorded the eye irritation degree on a scale of 0 to 2 (0 = none, 1 = medium, 2 = severe). The irritation indices amounted to 0.471 at 0.06 ppm (0.14 mg/m³), 1.2 at 1.3 - 1.6 ppm and 1.5 at 2.0 - 2.3 ppm (Darley et al., 1960).

Sim and Pattle (1957) examined the irritant effects of acrolein in volunteers exposed to atmospheres containing acrolein concentrations of 0.83 ppm for 10 min and 1.2 ppm for 5 min. Acrolein was extremely irritating to all exposed mucosal surfaces. At 0.83 ppm lacrimation occurred within 20 seconds, at 1.2 ppm already after 5 seconds.” quotations from EU, 2001, p55, p60

Odour Threshold

“Leonardos (1969) found an odour threshold, defined as the first concentration at which all persons (n = 4) recognised the odour, of 0.21 ppm (0.48 mg/m³). Plotnikova reported an odour threshold for acrolein of 0.35 ppm (0.8 mg/m³) (Plotnikova 1957, abstract, no details).” quotations from EU, 2001, p58

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

No substantial deviations in characterisation of these intrinsic properties in the EU Risk Assessment Report 2001 to WHO, 2002; US-EPA, 2003, US ATSDR, 2007 and US-EPA, 2008.

Due to the large number of studies on the irritating properties of acrolein available and a slightly deviating selection of studies referred in the individual international reports, the reported range of RD₅₀values slightly deviate between the reports, e.g. RD₅₀ for rats of 10.5 to 21.7 mg/m³ reported in US-EPA, 2003 whereas values of 9.2 and 13.7 mg/m³ are referred in the EU Risk Assessment Report 2001. Furthermore, the focus of the different international reports are non-identically. Therefore, the way of data preparation and elaborateness are different, especially in US-EPA, 2003, US ATSDR, 2007 and US-EPA, 2008 in comparison to the EU Risk Assessment Report 2001. However, within the individual reports the judgement on irritation/corrosion activity of acrolein does not substantially deviate.

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: “Significantly decreased respiratory rates were observed in allergic airway-diseased mice compared to non diseased mice exposed to 0.3 ppm acrolein for 10 minutes (Morris et al. 2003).” Quotation from US ATSDR, 2007, p35

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

None substantial

The following information is taken into account for hazard / risk assessment:

Acrolein is irritating and corrosive to skin and eyes in laboratory animals and humans.

Several studies show that acrolein causes sensory irritation of the respiratory tract after inhalation.

The RD50 of acrolein, the concentration causing 50% reduction in respiratory rate, amounted to 2.4 - 6.6 mg/m³ in mice and 9.2 and 21.7 mg/m³ in rats.

Justification for selection of skin irritation / corrosion endpoint:
see European Union Risk Assessment Report of Acrolein (EU, 2001)

Justification for selection of eye irritation endpoint:
see European Union Risk Assessment Report of Acrolein (EU, 2001)

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: highly irritating

Justification for classification or non-classification

Legally binding harmonised classification as given in REGULATION (EC) No 1272/2008 Annex VI

Table 3.1 (CLP): Skin Corr.1B      H314

Table 3.2 (Annex I of Directive 67/548/EEC): C; R34

 

In addition to classification for inhalation toxicity, according to Annex I No. 3.1.2.3.3 (CLP) the test substance acrolein should be classified as:

EUH071      Corrosive to the respiratory tract