ASSESSMENT OF PYRETHROID-INDUCED PARESTHESIAS - COMPARISON OF ANIMAL-MODEL AND HUMAN DATA

The quantification of upper respiratory tract (URT) sensory irritation is considered to be important in rodent inhalation studies, since it may be also used as an endpoint mimicking trigeminal paraesthesias obs erved in humans. URT sensory irritation is known to be associated with rodent-specific secondary physiological effects such as depression of body temperature and changes in heart rate. In acutely exposed rats, these endpoints have been addressed by telemetrical measurements. The analysis of the ventilation pattern during acute inhalation studies of rats exposed to the cc-cyano-pyrethroid cyfluthrin demonstrates that concentration-dependent URT sensory irritation was associated with a h ypothermic response. The no-effect levels (NO(A)EL) based on the URT s ensory irritation endpoint following acute inhalation exposure for 1 h and following a repeated 4-week or 13-week inhalation exposure for 6 h/day on 5 days/week were virtually identical (approximate to 0.1 mg/m (3) air). An additional objective was to examine whether human volunte ers experience comparable signs when acutely exposed for I h to airbor ne concentrations slightly above or in the range of the NO(A)EL. In hu man volunteers there were no clinically significant or pyrethroid rela ted abnormalities in vital signs, ECG's or in any clinical laboratory tests after either exposure, although transient effects related to URT (sensory) irritation were reported. In conclusion, an initial actual exposure concentration of approximate to 0.1 mg cyfluthrin/m(3) air ap pears to be in the range of the sensory irritant threshold concentrati on for both rats and humans. Thus, with regard to physiological affere nt portal-of-entry effects, the interspecies response was consistent. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.