Emergency and Continuous Exposure Limits for Selected Airborne Contaminants: Volume 1 (1984)

Acrolein is used as a warning agent in methyl chloride refrigerant and (as Papite) was used as a lacrimatory agent in World War I (Grant, 1974). It is also used as an intermediate in the preparation of resins and pharmaceuticals and in organic syntheses. It has had some use as an aquatic herbicide. It is prepared industrially by passing glycerol vapors over magnesium sulfate heated to 330–340°C (Windholz et al., 1976). Acrolein is considered a potential submarine contaminant and atmospheric pollutant. Urban air is said to contain acrolein at an average concentration of 0.006 ppm (Community Air Quality Committee, 1968).

Early studies on acrolein examined effects of short-term exposures, from 5 sec to 5 min. In one study, Yant et al. (1930) subjected seven human volunteers to acrolein at 1 ppm. Slight nasal irritation was experienced within 1 min, and moderate nasal irritation and intolerable eye irritation with lacrimation within 5 min. According to a table published by the Shell Chemical Corporation, (1958), acrolein at 0.25 ppm produced moderate irritation of sensory organs in humans (number of subjects unstated). Darley et al. (1960) exposed human volunteers to acrolein for 5 min; 0.6 ppm caused slight eye irritation, 1.3–1.6 ppm caused mild irritation, and 2–2.3 ppm produced severe irritation. Sim and Pattle (1957) reported that a 10-min exposure at 8 ppm and a 5-min exposure at 1.2 ppm elicited extreme irritation in humans and described the response as “only just tolerable.” A series of studies conducted by Stephens et al. (1961) revealed that acrolein exposure at 0.5 ppm produced eye irritation within 5 min in 10–35% of subjects and within 12 min in 91% of subjects.

Weber-Tschopp et al. (1977) reported the acute effects of acrolein on human volunteers. Groups of healthy subjects were exposed to acrolein at 0–0.6 ppm under the following three sets of experimental conditions:

Irritation, discomfort, and eye blinking rate were measured during exposures; all increased with increasing acrolein concentration and duration of exposure. Respiratory frequency was also measured. For deriving 1-h EELs, the data derived from Group III are most appropriate. Those subjects experienced discomfort during the first 20–30 min, but the intensity of discomfort did not increase thereafter. Irritation of the throat was significant at 10 min. Acute (subjective) irritation was reported as “considerable” after 10–20 min at 0.3 ppm. In this same group, respiratory frequency decreased during the course of the experiment, and a 10% decrease in frequency was observed in 60% of exposed subjects within 20 min. A summary of the effects of continuous exposure at 0.3 ppm (Group III) is presented in Table 6.

The most extensive animal study of acrolein toxicity available is that reported by Lyon et al. (1970). The study featured both repeated and continuous exposures to acrolein under conditions relevant to the establishment of 90-d CELs for humans. There are other recently reported animal data which are reviewed here. These studies do not provide data useful for establishing CELs, but they do afford some insight into the mode of action of acrolein and suggest a possible treatment for intoxication.

Murphy et al. (1963) observed a significant decrease in respiratory frequency and a significant increase in total respiratory flow resistance and tidal volume in guinea pigs after exposure to acrolein at 0.4–1.0 ppm for 2 h. The authors postulated that acrolein primarily increases the respiratory resistance and that, as a compensatory mechanism, the tidal volume increases and the respiratory frequency decreases. The change in respiratory resistance was said to be caused by bronchoconstriction, inasmuch as this change was eliminated by treatment with bronchodilating substances, such as atropine and epinephrine.

Davis et al. (1967) observed an increase in respiratory resistance and tidal volume in guinea pigs after exposure at 17 ppm for 60 min. Decreases in respiratory frequency and minute volume and prolongation of the expiration cycle were also noted. The authors presumed that the receptors were stimulated by an irritant to trigger a reflex-like

safety mechanism in the upper respiratory tracts, which decreased further inhalation of the irritant by prolonging expiration, lowering respiratory frequency, and decreasing minute volume. The decrease in respiratory frequency and the increased expiration cycle, which Weber-Tschopp et al. (1977) noted in humans exposed to acrolein, indicated a close similarity between humans and guinea pigs with regard to the effects of this substance on respiratory function. Because of this, Weber-Tschopp et al. (1977) proposed that acrolein may cause bronchoconstriction in humans at the concentration at which the respiratory effects were recorded (0.3 ppm).

In 1970, Philippin et al. reported the results of a study of the effects of acute (6 h) and extended (6 h/d for 2 wk) exposures of mice to acrolein. These investigators examined effects on swimming performance and body weight and analyzed the lungs histologically. The acute LC₅₀ was 66 ppm. In extended exposure, 6 ppm produced significant reductions in body weight; histologic examination of the lungs revealed atelectasis, inflammatory responses with edema and, in 2 of 15 cases, dilatation of alveoli and bronchioles.

Sinkuvene (1970) studied the effects of continuous acrolein exposure on albino rats. The experiments were performed on 80 male rats divided into four groups. Each group consisted of 10 healthy animals and 10 with chronic pulmonary insufficiency (experimental silicosis). One group served as a control and the others were exposed to acrolein at about 0.3, 0.056, and 0.011 ppm for 16 d. At the highest concentration, weight gain was significantly reduced by the sixth week in the healthy animals and by the fifth week in the animals with silicosis; there was a change in the chronaxy of antagonistic muscles in both healthy and silicotic animals and a sharp change (not specified) in blood cholinesterase activity. The author reported that “changes” were observed in the healthy animals at 0.056 ppm, but did not specify them; the “silicotic” animals displayed statistically significant changes in the chronaxy of antagonistic muscles and in vitamin C content. After 61 d at 0.011 ppm, no effects were observed in either healthy or silicotic animals; this result is in accord with that projected from the data of Lyon et al. (1970), as described below.

The most telling animal data are those from the work of Lyon et al. (1970), which included both repeated and continuous exposures. Rats, guinea pigs, monkeys, and dogs were exposed to acrolein repeatedly at 0.7 or 3.7 ppm 8 h/d, 5 d/wk, for 6 wk or continuously at 0.21, 0.23, 1.0, or 1.8 ppm 24 h/d for 90 d. The results were as follows:

In 1976, the Committee on Threshold Limit Values of the ACGIH established a TLV of 0.1 ppm; this limit was considered sufficiently low to minimize, but not entirely prevent, irritation in all exposed persons. This information and a 0.1-ppm TLV for acrolein were in the 1980 documentation (ACGIH, 1980).

In 1969, the Committee on Toxicology made the following tentative recommendations for EELs and CEL for acrolein:

The Committee considered the limiting factor for acrolein to be irritation of the eyes and respiratory tract. The data on which these recommendations were based were somewhat limited, and the Committee considered it desirable that additional long-term exposure data be obtained on guinea pigs, primates, and human volunteers.

The animal data available when the Committee on Toxicology made its tentative recommendations were derived from short-term, high-concentration exposures, and it appears that they were not considered useful for purposes of recommending EELs or CELs.

On the basis of the human data given earlier, which represent the most extensive human experience available, the Committee’s previous tentative recommendation of a 0.2 ppm limit for a 1-h exposure is insufficiently protective. Discomfort, irritation, and respiratory effects were observed at 0.09–0.3 ppm in exposures well short of 1 h. It is not possible to assign, on the basis of these data, a definitive EEL for acrolein, and another tentative recommendation seems appropriate, considering the lack of data for 1-h exposures to lower concentrations of acrolein. Such data are necessary for more definitive exposure limits to be derived. The Committee suggests that an EEL of 0.05 ppm for a 1-h exposure may be sufficient to protect most people from anything except discomfort, although irritation and decreased respiratory frequency will probably still occur in some.

No human data are available that can be used directly to assign an EEL for a 24-h exposure. The Committee proposes that a 5-fold margin of safety be applied to compensate for the absence of information regarding the effects of 24-h exposures and tentatively recommends a value of 0.01 ppm for 24-h exposures to acrolein.

Human data are now available to permit a recommendation regarding a 10-min EEL. None of the effects reported by Weber-Tschopp et al. (1977) at 0.3 ppm for 10-min appears to be incapacitating; however, some effects such as decrease in respiratory frequency occurred in more than 47% of exposed people (see Table 5). In contrast, exposure to 0.09 ppm resulted in only discomfort and eye irritation; for this reason, it appears that 0.1 ppm for a 10-min period should adequately satisfy the requirements of an EEL. This recommendation is consistent with the other short-term human exposure data cited above.

The studies of repeated and continuous exposures of experimental animals to acrolein conducted by Lyon et al. (1970) appear to be the most extensive of their type available. For most of the effects measured, dogs and monkeys are more sensitive to exposure than rodents. Assuming that humans are as sensitive as dogs and monkeys, it appears that the earlier tentative recommendation of 0.1 ppm for continuous 90-d exposure to acrolein provides little, if any, margin of safety. Downward adjustment by a factor of 10 is recommended. This leads to 0.01 ppm, which is in agreement with the community air-quality guide recommended by the Community Air Quality Committee (1968) for 90-d continuous exposures.

To summarize, the following EELs and CEL are suggested:

American Conference of Governmental Industrial Hygienists. 1976. Threshold Limit Values for Chemical Substances and Physical Agents in the Workroom Environment with Intended Changes for 1976. Cincinnati, Ohio: American Conference of Governmental Industrial Hygienists. [94 p.]

American Conference of Governmental Industrial Hygienists. 1980. Documentation of the Threshold Limit Values. 4th ed. Cincinnati, Ohio: American Conference of Governmental Industrial Hygienists. p. 8.

Community Air Quality Committee. 1968. Community air quality guides: Aldehydes. Am. Ind. Hyg. Assoc. J. 29:505–512.

Darley, E.F., Middleton, J.T., and Garber, M.J. 1960. Plant damage and eye irritation from ozone-hydrocarbon reactions. J. Agr. Food Chem. 8:483–485.

Davis, T.R.A., Battista, S.P., and Kensler, C.G. 1967. Mechanism of respiratory effects during exposure of guinea pigs to irritants. Arch. Environ. Health 15:412–419.

Grant, W.M. 1974. Toxicology of the Eye. 2nd ed. Springfield, Ill. C.C.Thomas. [1201 p.]

Lyon, J.P., Jenkins, L.J., Jr., Jones, R.A., Coon, R.A., and Siegel, J. 1970. Repeated and continuous exposure of laboratory animals to acrolein. Toxicol. Appl. Pharmacol. 17:726–732.

Murphy, S.D., Klinghirn, D.A., and Ulrich, E.E. 1963. Respiratory response of guinea pigs during acrolein inhalation and its modification by drugs. J. Pharmacol. Exp. Ther. 141:79–83.

Philippin, C., Gilgen, A., and Grandjean, E. 1970. Toxicological and physiological investigation on acrolein inhalation in the mouse. Int. Arch. Arbeitsmed. 26:281–305.

Shell Chemical Corporation. 1958. Toxicity Data Sheet: Acrolein. SC: 57–76. Ind. Hyg. Bull. [4 p.]

Sim, V.M., and Pattle, R.E. 1957. Effect of possible smog irritants on human subjects. J. Am. Med. Assoc. 165:1908–1913.

Sinkuvene, D.S. 1970. Hygienic evaluation of acrolein as an air pollutant. Hyg. Sanit. (USSR) 35:325–329.

Stephens, E.R., Darley, E.F., Taylor, O.C., and Scott, W.E. 1961. Photochemical reaction products in air pollution. J. Air Pollut. 4:79–100.

Weber-Tschopp, A, Fischer, T., Gierer, R., and Grandjean, E. 1977. Experimentally induced irritating effects of acrolein on men. Int. Arch. Occup. Environ. Health 40:117–130.

Windholz, M., Budavari, S., Stroumtsos, L.Y., and Fertig, M.N. 1976. The Merck Index: An Encyclopedia of Chemicals and Drugs. 9th ed. Rahway, NJ: Merck & Co. Inc. p. 117.

Yant, W.P., Schrenk, H.H., Patty, F.A., and Sayers, R.R. 1930. Acrolein as a warning agent for detecting leakage of methyl chloride from refrigerators. Bureau of Mines Report of Investigations 2027. Pittsburgh: U.S. Bureau of Mines. [11 p.]