A DERMATOLOGICAL EVALUATION OF SYNTHETIC PYRETHROID INSECTICIDES (PARESTHESIA, FENVALERATE, PERMETHRIN)

In this investigation, differences in parasthesia were detected by human participants between synthetic pyrethroids with a cyano group in the (S)-configuration of the 3-phenoxybenzyl alcohol of their molecular structure (fenvalerate) and those that do not (permethrin). A strong relationship was noted between insecticidal potency and degree of induced cutaneous sensation for the alpha-cyano and non-cyano pyrethroids, with a prominent difference between the two. A linear correlation between concentration and degree of induced dysesthesia was observed for both pyrethroids. Regressing the cutaneous sensation on the common logarithm of concentration resulted in a regression equation of Y = 84.0 + 31.0X(,1) for fenvalerate and Y = 27.5 + 15.8X(,1) for permethrin. An evaluation for dermal cytotoxicity in albino rabbits yielded a slight increase in cutaneous perfusion as indicated both visually and by laser Doppler velocimetry. However, no significant difference was detected in edema or thermal variation. Histopathological alterations were minimal after repeated daily applications with the majority of changes involving acanthosis. A highly efficacious therapeutic agent for pyrethroid exposure was noted to be dl-alpha tocopherol acetate. An impressive degree of inhibition of parasthesia resulted from the topical application of vitamin E acetate, with a therapeutic index of almost 100%. ^

RESPIRATORY COMPENSATION MECHANISMS IN THE UPPER AND LOWER RESPIRATORY TRACTS OF AN ANIMAL MODEL AFTER SUBCHRONIC INHALATION EXPOSURE TO FORMALDEHYDE: IMPLICATIONS FOR TOXICOLOGY RISK ASSESSMENT (DEPOSITION, DOSE RECEIVED, RESPONSE)

The potential for significant human populations to experience long-term inhalation of formaldehyde and reports of symptomatology due to this exposure has led to a considerable interest in the toxicologic assessment of risk from subchronic formaldehyde exposures using animal models. Since formaldehyde inhalation depresses certain respiratory parameters in addition to its other forms of toxicity, there is a potential for the alteration of the actual dose received by the exposed individual (and the resulting toxicity) due to this respiratory effect. The respiratory responses to formaldehyde inhalation and the subsequent pattern of deposition were therefore investigated in animals that had received subchronic exposure to the compound, and the potential for changes in the formaldehyde dose received due to long-term inhalation evaluated. Male Sprague-Dawley rats were exposed to either 0, 0.5, 3, or 15 ppm formaldehyde for 6 hours/day, 5 days/week for up to 6 months. The patterns of respiratory response, deposition and the compensation mechanisms involved were then determined in a series of formaldehyde test challenges to both the upper and to the lower respiratory tracts in separate groups of subchronically exposed animals and age-specific controls (four concentration groups, two time points). In both the control and pre-exposed animals, there was a characteristic recovery of respiratory parameters initially depressed by formaldehyde inhalation to at or approaching pre-exposure levels within 10 minutes of the initiation of exposure. Also, formaldehyde deposition was found to remain very high in the upper and lower tracts after long-term exposure. Therefore, there was probably little subsequent effect on the dose received by the exposed individual that was attributable to the repeated exposures. There was a diminished initial minute volume response in test challenges of both the upper and lower tracts of animals that had received at least 16 weeks of exposure to 15 ppm, with compensatory increases in tidal volume in the upper tract and respiratory rate in the lower tract. However, this dose-related effect was probably not relevant to human risk estimation because this formaldehyde dose is in excess of that experienced by human populations. ^