Preclinic effects

No information is available concerning the effects of 2,3-benzofuran in humans. Acute oral exposure to 2,3-benzofuran has been shown to alter levels of enzyme activity in the livers of female mice (Heine et al. 1986), but much more work would need to be done to determine whether there is a pattern of enzyme alteration specific to 2,3-benzofuran exposure. Other effects found in animals following oral exposure to 2,3-benzofuran are kidney and liver damage and kidney, lung, liver, and stomach cancer (see Section 2.2.2). Such generalized responses do not suggest the basis for any specific biomarker of clinical or preclinical effects caused by 2,3-benzofuran. 

Biotransformation and generation of reactive intermediate metabolites are associated with a variety of toxicities and idiosyncratic reactions.37 Toxicologists should always consider how drug disposition and fate contribute to toxicity, as target organ dosimetry, biotransformation, and detoxification reactions can be important determinants of toxicity. In all cases, understanding how biotransformation may differ across species, with emphasis on human metabolism, is an important component in determining whether preclinical effects are predictive of and relevant for human safety evaluation. 

Recent improvements in neurological measures of performance (especially cognitive and behavior tests) as well as immunological assays have also improved the ability to resolve more subtle or preclinical effects. In this context, DHHS (1993) and other summary reports on the health risks from the use of mercury amalgam generally support the need for further investigations. 

Journal of Industrial Hygiene and Toxicology 18 571-577, 1936 Echeverria D, White RF, Sampaio C A behavioral evaluation of PCE exposure in patients and dry cleaners a possible relationship between clinical and preclinical effects. Occup Environ Med 37 667-680, 1995 Endo M, Sata T, Umaki I, et al Ethylene oxide withdrawal delirium. Biol Psychiatry 19 1731-1734, 1984... 

Here are described corneal opacities due to an exacerbation of spontaneous comeal deposits in rats receiving L-680,833, a Polymorphonuclear Elastase Inhibitor (PMNEI), a class of compounds for which some preclinical effects were reported (to date especially digestive effects (6)) but no ocular. Relation with spontaneous opacities observed in our rat population and with comeal changes observed in other species of laboratory animals is also presented. 

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