Toxicological Parameters

So far, we have discussed the basic concept of a dose-response relationship, how toxic effects are measured, and the types of toxic effects that can occur in a variety of organisms. This chapter introdnces mcmy of the core concepts of toxicology. We have seen that toxicity Ccm differ bcised on differences cunong species. The factors that result in these differences are farther discussed here. The majority of these factors affect toxicity across species in predictable ways. Children cmd the elderly are often considered most susceptible to toxic effects of chemicals the concepts presented here illustrate why this is so. 

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An overview of some basic mathematical techniques for data correlation is to be found herein together with background on several types of physical property correlating techniques and a road map for the use of selected methods. Methods are presented for the correlation of observed experimental data to physical properties such as critical properties, normal boiling point, molar volume, vapor pressure, heats of vaporization and fusion, heat capacity, surface tension, viscosity, thermal conductivity, acentric factor, flammability limits, enthalpy of formation, Gibbs energy, entropy, activity coefficients, Henry s constant, octanol—water partition coefficients, diffusion coefficients, virial coefficients, chemical reactivity, and toxicological parameters. 

Currently, there are many databases where the physicochemical, toxicological parameters required to perform a risk assessment can be obtained. It must be borne in mind that the existence of a quality control parameters included in the databases is of great importance. This quality control can be accomplished through periodic updating of the database, the inclusion of bibliographical references of the origin of each parameter, peer reviewed bibliography, etc. 

Despite the existence of several databases for certain substances, it is not possible to find physicochemical and/or toxicological parameters to assess the risk for all substances. The lack of data is one of the main problems in risk assessment. This is especially true for emerging pollutants. One solution to solve this problem is the use of QSAR or estimation tools. QSAR models correlate the structure of the substance with their activities (physicochemical properties, environmental fate, and/or toxicological properties). 

Kimmerle, G. 1974. Aspects and methodology for the evaluation of toxicological parameters during fire exposure. Combust. Toxicol. 1 4-51. 

These studies employed one dose level and toxicological parameters measured were limited. The inadequacies of these studies precluded derivation of a chronic oral MRL. No chronic-duration animal inhalation or dermal exposure studies were located. Well conducted chronic-duration inhalation. 

Are sufficient toxicity data available to derive a meaningful toxicological parameter, i.e., point of departure (POD), corresponding to the timescale of exposure and the route(s) of exposure as established in the exposure assessment ... 

Metabolism in the above equation is defined as either the rate of metabolism at non-saturating substrate concentrations, toxicological parameters such as the initial slope of a dose-response curve in a toxicity assay or the slope of a mutation dose-response curve, or the intrinsic clearance for the enzyme. The P450 form with the highest relative contribution is predicted to be the principal P450. 

The MRL is not a toxicological parameter, but rather a trading standard set by national and international authorities (e.g. Codex Alimentarius) to ensure that residues are controlled in world food trade. 

Each evaluation should conclude with a summary of the risk posed by a substance. The summary can consist of background information on the chemical and toxicological parameters of the agent human exposure information a summary of the male and female reproductive toxicity data and the developmental toxicity data a list of the quantitative values derived from the data a description of the default assumptions and UFs used in the process the data needs to reduce uncertainty and a reference section. 

The aim of the experimental studies is to determine a number of toxicological parameters that will serve as a basis in classifying a substance. The most important are ... 

Based on case studies, many countries have tried to develop similar indices where a number of toxicological parameters are integrated with the aim of quickly measuring the potential danger of the samples, particularly industrial effluents. The potential ecotoxic effects probe (PEEP) is one of the best known. It was developed in Canada as part of the St. Lawrence River Action Plan and was used to rank the impact of 50 industrial effluents discharged daily into the St. Lawrence River (Costan elal.. 1993). 

To assess the environmental impact of chemical processes, EATOS can take into consideration up to ten different substances ecotoxicological and human toxicological parameters, and each parameter can be given a different weight. Such substances parameters are then normalized (each parameter is made to vary from 1 to 10) and then combined to afford an environmental quotient (El) (much the same as Sheldon s Q). Thus, each different component of the waste can be assigned a quantitative potential environmental impact PEIout (much the same of Sheldon s environmental quotient EQ), defined as the product of its mass (relative to the product unit mass) with its El. 

Finally, for prediction of toxicological parameters, the OSIRIS Property Explorer available at http //www.chemex-per.com/tools/propertyExplorer/main.html (and listed above in the section Prediction and calculation of molecular properties ) has some interesting capabilities. 

Levin S, Semler D, Ruben Z. Effects of two weeks of feed restriction on some common toxicologic parameters in Sprague-Dawley rats. Toxicol Pathol 1993 21 1-14. 

Toxicological parameters (animal species) TCPE active substance Buvinol WP... 

Applicable target risk limits (TR) for health protection can be matched to levels specified by the environmental regulatory authority. Toxicological parameters for each contaminant can be determined from published references, such as the U S. EPA Integrated Risk Information System (IRIS). Exposure rates correspond to the chronic rate of contact or intake of the affected exposure medium (air, water, soil) by the receptor under anticipated land use conditions. As a conservative measure, these rates can be estimated based on standard exposure factors published by the regulatory authority or other source (e.g., American Industrial Health Council) for the anticipated land use at the site (e.g., residential, commercial, etc.). 

Characterize the carcinogenicity of PVC and present the toxicological parameters for these compounds. 

Discuss the toxicological parameters of PCBs in animal and human organisms and explain the differences in PCB metabolism in various living species. 

Levin, S., D. Semler, and Z. Ruben. 1993. Effects of two week feed restriction on some toxicological parameters in Sprague-Dawley rats. Toxicologic Pathology 21 1-14. 

Provided the test compound does not result in any residues exceeding 0.1 ppm on food crops, applicator exposxire is minimal, and the limited toxicity data indicate that the negligible daily intake (i.e. that dose below which intake, on a daily basis for a lifetime is considered to be toxicologically insignificant -usually a dose level of l/lOOOth of the "no observable effect level" on the most sensitive toxicological parameter examined, in the most sensitive species) will not be exceeded it is possible that registration would be recommended. The tendency is, however, to require considerably more data than the minimum acceptable package described above. 

Table 6.8 shows selected toxicological parameters for two sample compounds from earlier in the chapter aspirin and morphine. The pK values... 

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