Toxicity tests shortcomings

Most aquatic toxicity studies are based on a single experimental design, the concentration/response aqueous toxicity test. The protocols are well defined and their interpretational limitations understood (Rand and Petrocelli 1985). The major shortcomings are succinctly outlined in Standard Methods (APHA 1980) ... 

Chemical characteristics and environmental conditions will influence the design of fleld studies to assess distributions of occurrence and exposure." Important chemical characteristics of the test substance include water solubility. Aloe, vapor pressure, degradation rate and potentially labile functional groups. These characteristics also need to be known for toxicologically important fiansformation products. One shortcoming in many fleld studies is a failure to address adequately exposure to toxic transformation products. 

During the 1970 s and early 1980 s a large number of test methods were developed to measure the toxic potency of the smoke produced from burning materials. The ones most widely used are in refs. 29-32. These tests differ in several respects the conditions under which the material is burnt, the characteristics of the air flow (i.e. static or dynamic), the type of method used to evaluate smoke toxicity (i.e. analytical or bioassay), the animal model used for bioassay tests, and the end point determined. As a consequence of all these differences the tests result in a tremendous variation of ranking for the smoke of various materials. A case in point was made in a study of the toxic potency of 14 materials by two methods [33]. It showed (Table I) that the material ranked most toxic by one of the protocols used was ranked least toxic by the other protocol Although neither of these protocols is in common use in the late 1980 s, it illustrates some of the shortcomings associated with small scale toxic potency of smoke tests. 

U.S. EPA (1991) derived a cancer inhalation unit risk for sulfur mustard based on the results of inhalation animal studies conducted by McNamara et al. (1975, see Section 3.7.2) however, it was emphasized in the EPA report that the studies of McNamara et al. (1975) contained deficiencies which made a quantitative analysis difficult. Conducted in 1970, the studies do not conform to the modem norms of acceptable experimental protocol, and it is likely that there was bias in the assignment of the animals to the test categories (U.S. EPA, 1991). In addition, many of the exposures were very brief, included only a few animals, and many of the animals were sacrificed (and some were replaced) before their capacity to develop late-appearing tumors was fully developed (U.S. EPA, 1991). Despite these shortcomings, it was noted by EPA that the McNamara et al. data are the best available for estimating the carcinogenic potency of sulfur mustard. The authors of the EPA report analyzed two sets of McNamara s data one from a toxicity study and one from a carcinogenicity study (see Section 3.7.2). 

Nontechnical Summary In this paper, the process of risk assessment with compounds which exhibit chronic but not acute toxicity is first reviewed. The remainder of the paper is spent on reviewing the procedure for quantifying absorption through the skin. The test animal used is the rhesus monkey since previously published work has shown this animal to yield data most similar to man. Data are presented on oryzalin for which dermal absorption was less than 2 percent of the applied dose. The problems and shortcomings of the procedure as well as its advantage (similarity to man) are also discussed. 

One of the primary shortcomings of the standard data package with regard to worker/bystander risk assessment as It exists today is the emphasis on the oral route of exposure. Others are the limited data on kinetics of the chemical, lack of attention to determining the effect of the route of exposure on toxicity and the Inability to test combinations of pesticides In a manner which would approximate the type of nilxed exposure that applicators receive. These Issues complicate the risk assessments for applicators, for whom the primary route of exposure Is dermal and generally Is Intermittent. 

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