Sensory irritation to mixtures of formaldehyde, acrolein, and acetaldehyde in rats.
Sensory irritation of formaldehyde (FRM), acrolein (ACR) and acetaldehyde (ACE) as measured by the decrease in breathing frequency (DBF) was studied in male Wistar rats using nose-only exposure. Groups of four rats were exposed to each of the single compounds separately or to mixtures of FRM, ACR and/or ACE. Exposure concentrations of the mixtures were chosen in such a way that summation of the effects of each chemical would be expected not to exceed 80% reduction of the breathing frequency. FRM, ACR and ACE appeared to act as sensory irritants as defined by Alarie (1966, 1973). With FRM and ACR desensitization occurred, whereas with ACE the breathing frequency gradually decreased with increasing exposure time (up to 30 min). For mixtures, the observed DBF was more pronounced than the DBF for each compound separately, but was less than the sum of the DBFs for the single compounds. A model for three compounds competing for the same receptor was applied to predict the DBF of mixtures of FRM, ACE and ACR. The results also showed that with mixtures no desensitization occurred; in fact, the breathing frequency further decreased in the last 15 min of exposure. These observations were similar to those found for ACE alone, and might have been caused by effects on the upper respiratory tract. The results of the present study allow the conclusion that sensory irritation in rats exposed to mixtures of irritant aldehydes is more pronounced than that caused by each of the aldehydes separately, and that the DBF as a result of exposure to a mixture could well be predicted using a model for competitive agonism, thus providing evidence that the combined effect of these aldehydes is basically a result of competition for a common receptor (trigeminal nerve).
Cassee
F R
FR
Toxicology Division, TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
Arts
J H
JH
Groten
J P
JP
Feron
V J
VJ
D000079:Acetaldehyde / Q000633:toxicity*; D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D004338:Drug Combinations; D005557:Formaldehyde / Q000633:toxicity*; D007509:Irritants / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects
D004338:Drug Combinations; D007509:Irritants; D005557:Formaldehyde; D000171:Acrolein; D000079:Acetaldehyde