Human bioassay

Animal and Human Toxicity. The acute toxicity of lindane depends on the age, sex, and animal species, and on the route of adrninistration. The oral LD q in mice, rats, and guinea pigs is 86, 125—230, and 100—127 mg/kg, respectively. In contrast, most of the other isomers were considerably more toxic (94,95). Some of the other toxic responses caused by lindane in laboratory animals include hepato- and nephotoxicity, reproductive and embryotoxicity, mutagenicity in some short-term in vitro bioassays, and carcinogenicity (80). The mechanism of the lindane-induced response is not known. Only minimal data are available on the mammalian toxicides of hexachlorocyclopentadiene. 

Several recent expert reviews and workshops have discussed the effects of endocrine disruption on wildlife and especially invertebrate species. These include the EU workshop on the impact of endocrine disrupters on human health and wildlife (Weybridge, 1996), the lEH workshop (Leicester, May 1997), the Environment Agency Consultative report (January 1998) and the Tyndall Forum at the Royal Institution (February 1998). They have concluded that endocrine disruption may have far-reaching adverse consequences for biodiversity and the sustainability of natural ecosystems. More comprehensive bioassay systems are required to identify and assess chemicals alleged to produce endocrine modulating effects. 

Methods. As discussed in the previous chapter, a number of approaches have been used to assess the presence of potentially toxic trace elements in water. The approaches used in this assessment include comparative media evaluation, a human health and aquatic life guidelines assessment, a mass balance evaluation, probability plots, and toxicity bioassays. Concentrations of trace elements were determined by atomic absorption spectrometry according to standard methods (21,22) by the Oregon State Department of Environmental Quality and the U.S. Geological Survey. 

No studies were located regarding cancer in humans after oral exposure to endosulfan. Carcinogenic effects of endosulfan were investigated in a number of chronic animal bioassays with rats and mice the available data provide no evidence that endosulfan is carcinogenic. 

Cancer. No reports of cancer in humans associated with exposure to endosulfan have been found. The carcinogenicity of endosulfan has been studied in chronic oral bioassays using rats (EMC 1959b ... 

NTP. 1983. National Toxicology Program—technical report series no. 232. Carcinogenesis bioassay of pentachloroethane in Fischer-344/N rats and B6C3Fj mice. Research Triangle Park, NC U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health. 

Bioassay of alternate molecular forms supports the view that the ORs are capable of resolving isomeric distinctions in neutral (non-biological) odourants. Stereochemical pairs of odours were tested for differential sensitivities in the blind subterranean mole rat (Spalax ehrenbergi). The subjects responded to one enantiomer, but not to its stereoisomer. Both sexes were attracted to the odour of R-(-)-carvone but unresponsive to S-(+)-carvone in contrast, males and females were repelled by the odour of (+)-citronellol, but not by (-)-citronellol (Heth et al., 1992). The lack of responsiveness by mole rats could be central due to lack of salience, or peripheral due to hyposmia/anosmia for one isomer. Both carvones have distinct odours for the human nose. 

Guilmette RA, Eidson AF. 1992. Using animal dosimetry models to interpret human bioassay data for actinide exposures. J Radioanal Nucl Chem 156(2) 425-449. 

National Toxicology Program. "Carcinogenesis Bioassay of di(2-ethylhexyl)-phthalate." (Draft Report) U.S. Dept, of Health and Human Services, DHAS Pub. No. 81-1773, 1980. 

Bioassays and in vitro human models can be used to characterize the toxicity of leachate integrating the biological effects of all its constituents, in contrast to chemical analyses ... 

The potential for a compound to induce carcinogenicity is a crucial consideration when establishing hazard and risk assessment of chemicals and pharmaceuticals in humans [53]. To date, the standard approach to assess carcinogenicity at a regulatory level is the 2-year bioassay in rodents. According to the recent REACH... 

A word of caution should be made with respect to estimating tenability for human exposures. Experimental LC values are determined using rat lethality as the bioassay. Judgement should be exercised for human tenability, with limits set considerably lower than FED summation at unity. An FED limit of, perhaps, 0.3 may be more appropriate for assessment of the potential escape of humans. 

Due to false positives, zinc may confound interpretation of the paralytic shellfish poisoning (PSP) mouse bioassay, one of the routine tests used to measure shellfish safety for human consumption. For example, mice injected intraperitoneally with extracts of healthy oyster tissues showed extreme weakness, a drop in body temperature, cyanosis, and some deaths (McCulloch et al. 1989). The threshold for a toxic PSP response corresponds to a drained tissue zinc level >900 mg/kg FW, and this overlaps the zinc concentration range of 230 to 1650 mg/kg FW (1900 to 9400 mg/kg DW) recorded in healthy oyster soft tissues (McCulloch et al. 1989). 

Cohen SM (2004) Human carcinogenic risk evaluation an alternative approach to the two-year rodent bioassay. Toxicol Sci 80 225-229... 

The single most important statistical consideration in the design of bioassays in the past was based on the point of view that what was being observed and evaluated was a simple quantal response (cancer occurred or it didn t), and that a sufficient number of animals needed to be used to have reasonable expectations of detecting such an effect. Though the single fact of whether or not the simple incidence of neoplastic tumors is increased due to an agent of concern is of interest, a much more complex model must now be considered. The time-to-tumor, patterns of tumor incidence, effects on survival rate, and age of first tumor all must now be captured in a bioassay and included in an evaluation of the relevant risk to humans. 

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