From chemosensory thresholds to whole body exposures-experimental approaches evaluating chemosensory effects of chemicals.

OBJECTIVES: To ensure safety and health the avoidance of adverse chemosensory effects is essential at workplaces where volatile chemicals are used. The present study describes psychophysical approaches that provide information for the evaluation of such effects. METHODS: By means of a modified staircase procedure the odor (OT) and irritation thresholds (IT) of 15 irritants were determined. These basic chemosensory properties, confining the chemosensory effect range, were investigated in a random sample of 144 persons stratified for gender and age. Those irritants exhibiting high chemosensory potency were selected for the second psychophysical part of the study. Forty-eight persons, again stratified for gender and age, rated the intensity of 13 trigeminal and olfactory perceptions elicited by nine ascending concentrations of the irritants, ranging from the odor to the irritation threshold of the respective substances. RESULTS: Across the investigated chemicals the transition from concentrations eliciting pure olfactory stimulation (OT) to trigeminal stimulation (IT) differed markedly. The carboxylic acids yielded narrow ranges from odor to irritation thresholds, while for the amines (cyclohexylamine, dimethylamine, and trimethylamine) and the esters (ethyl formate and ethyl acetate) these ranges were somewhat wider. The two chemosensory thresholds of ethyl acrylate and ammonia were farthest from each other. Gender and age had only weak impact on the chemosensory thresholds. At present, the results of the intensity ratings could be given for six substances. Among them, the rated pungency for cyclohexylamine, formic acid, and ethyl acetate increased strongest across the nine applied concentrations. CONCLUSIONS: By means of these psychophysical approaches a diverse class of chemicals can be described and compared with respect to their chemosensory potency. This information can be used twofold (a) for the evaluation of existing studies reporting sensory irritations and (b) for the design of experimental exposure studies.

Renal toxicity after chronic inhalation exposure of rats to trichloroethylene.

Male Long-Evans rats were exposed to 0 (controls) or 500 ppm trichloroethylene (TRI) for 6 months, 6 h daily, and 5 days a week. The TRI metabolites trichloroethanol (TCE) in blood and trichloroacetic acid (TCA) in urine were measured. Specific parameters related to the renal damage were determined in urine [biomarker for glomerular damage: high molecular weight proteins (HMW), albumin (ALB); for proximal tubular damage: N-acetyl-beta-D-glucosaminidase (NAG), low-molecular-weight-proteins (LMW)]. Significantly increased concentrations of NAG and LMW in urine of exposed rats were detected. No DNA-strand breaks in kidney cells could be detected using the comet assay, and histological examinations were performed. Histological alterations were observed in glomeruli and tubuli of exposed rats. The release of biomarkers for nephrotoxicity suggested alterations preferably in the proximal tubules of the exposed rats.