Critical body residue studies

CRITICAL BODY RESIDUE STUDIES AND LINKS TO (SUB)LETHAL TOXICITY RESPONSES... 

Mathematical models have been developed and used to extrapolate toxicity under pulsed exposure conditions (for an overview, see Boxall et al. 2002 Reinert et al. 2002 Ashauer et al. 2006 Jager et al. 2006). Some models consider concentration x time (Meyer et al. 1995) others, uptake and depuration (Mancini 1983) or damage and repair (Breck 1988). Several models are based on the concept of critical body residues, which integrates toxicokinetics and the effects of exposure time on toxicity (McCarty and Mackay 1993 Barron et al. 2002). This approach is promising because several studies showed that toxicity from pulse exposures is largely... 

EPA bases its procedures for estimating RfD on several assumptions, the most basic of which is that a threshold exists in the dose-response relationship for the critical response. If the dose is above the threshold (not the same as RfD) and is of sufficient duration, EPA considers that the chemical will cause the response in some segment of the exposed population. The U.S. Food and Drug Administration uses a similar approach to identify safe levels of exposure to food additives and certain residues. Studies on many substances have shown that before toxicity occurs, the chemical must deplete a physiological reserve or overcome the various repair capacities in the human body (Klaassen et al., 1996). 

The lipid content of the organism is a critical controlling factor of body residues of organic chemicals. Bio concentration studies often provide lipid-corrected results to compensate for this. Therefore, the lipid content of organisms used in bioassays should be reported routinely in all aquatic bioassays, such as bio concentration, bio accumulation, biomagnification, and toxicity studies with organic chemicals. 

Nervous system The residual effects of gaboxadol 10 mg and flurazepam 30 mg on the day after bedtime administration have been compared in a crossover, double-blind, randomized, placebo-controUed study in 25 healthy elderly subjects [16. Flurazepam significantly impaired choice reaction time, the threshold for critical flicker fusion, digit symbol substitution, and speed of compensatory tracking, but did not alter immediate or delayed word recall or the eyes-closed endpoint of the body sway test. Gaboxadol had no deleterious effects. 

---