Mostafa A. Shirazi

An analysis of risk from exposure to aldicarb using immune response of nonuniform populations of mice

The immunomodulation response of mice to low levels of aldicarb in drinking water was investigated in four series of studies. The splenic plaque forming cell (PFC) response to red sheep cells were measured for treatment levels of 0.01 to 1,000 ppb (μg/kg). Based on their beginning and end body weights, the animal populations were uniform in all series of tests, but based on their net body weights and PFC counts they were highly nonuniform in the 30 and 60 day tests and uniform in the 90 and 180 day tests.The mean PFC counts for animals in each treatment were calculated and compared with the mean PFC counts for animals in the controls in all four series of tests. This approach ignores the variability and nonuniformity in the animal population. The outcomes using this approach were stimulatory for the 30 and 60 day tests and inhibitory for the 90 and 180 day tests.An alternative approach was developed based on the analysis of the distributions of the relative PFC counts of each animal in a treatment with each animal in a control, and specifically addresses the variability and nonuniformity in animal population as integral parts of the analysis. The distribution peaks were estimated by maximum likelihood and kernel/bootstrap procedures and were used to summarize the tests. The outcomes were consistently inhibitory, indicating immune suppression. The outcome of this approach converged to the outcome of the mean PFC approach for the 90 and 180 day tests where the animal populations were uniform.

Comparative toxicity based on similar asymptotic endpoints

Results of laboratory tests are used in assessing the environmental risk of exposure to industrial chemicals. The combined effects of doselevel exposure and time-duration exposure are tested in the laboratory, but only a single endpoint reflecting the dose-level exposure at the end of the test period is routinely reported and used. At times, this might be sufficient, or the data otherwise inappropriate for calculation of more than a single endpoint. Nevertheless, an approach that makes a more complete use of existing sufficient test information is needed. One method is presented in this paper, the focus of which is the evaluation of an LC50 endpoint at a calculated exposure time. This calculation determines a condition for the toxicity curve to become established along the time axis. We refer to this condition of the dose-response curve as an asymptotic state and the LC50 calculated from it as the asymptotic LC50. An analysis of 152 toxicity tests using fathead minnows show that the 96-hr LC50 is 25% more conservative than the asymptotic LC50. The calculation of LC50 under asymptotic conditions better enables comparing toxicities of different chemicals on the basis of comparable dose-level and time-duration exposures.

Developmental malformation of frog embryos an analysis of teratogenicity of chemical mixtures

Chemical compounds known to be teratogenic to frog embryos were tested singly and in binary mixtures and Weibull functions were used to model their concentration-response relationships. A separate Weibull function with an additive concentration variable modeled the mixtures using only single chemical test data. Seven chemicals in five binary mixtures at 3/1, 1/1, and 1/3 mixture proportions each were tested. The ratios of measured and calculated model parameters and median concentrations were estimated for comparing the results. The ratios ranged from 0.72 and 1.44 with an average at 0.99, an agreement that was qualitatively similar to modeling mixtures of narcotic chemicals which are known to produce additive concentration effects. The model reliability in determining mixture response classes and prediction of effects based on single chemical data was quantified. The model is useful for environmental risk assessment of chemical mixtures in hazardous waste sites and for the design of mixture experiments.

A probabilistic statement of the structure activity relationship for environmental risk analysis.

In this paper, we define a mode of biological response of an organism to a chemical in terms of a general mathematical model of the response surface. The model describes the combined effects of dose-level exposure and time-duration exposure using 570 96-hr toxicity tests with fathead minnows. The response surface along the dose and time axes for each chemical in these tests were completely defined by two scale factors, one for dose and one for time, and two form factors, one for dose and one for time. The scale factors for dose and time are proportional with the inverse of LC50 and Lt50, respectively. The form factors measure the relative response strategies with respect to dose and time exposures.Only the scale factor for the dose is correlated with the logarithm of the octanol water partition coefficient (log P) and molecular weight (Mw). Additional and independent observations beyond log P and Mw are needed to correlate various modes of chemical action with the form factors. It is shown that narcosis-producing chemicals can be distinguished from other classes of chemicals by the dominance of the response strategy with respect to the dose over time exposures.

A model of additive effects of mixtures of narcotic chemicals

Biological effects data with single chemicals are far more abundant than with mixtures. Yet, environmental exposures to chemical mixtures, for example near hazardous waste sites or non point sources, are very common and using test data from single chemicals to approximate effects of mixtures can be useful in environmental risk assessment. To facilitate the linkage, the Weibull function was used as a common model to link responses of single chemicals with the response of their mixtures. The present paper addresses the response of fish to mixtures of narcotic chemicals and a second paper addresses the developmental malformation of frog embryos when exposed to defined mixtures of teratogenic chemicals.Biological effects data with singly tested chemicals cannot be used directly to predict effects of mixtures. However, narcotic chemicals are known to produce an additive concentration effects in fish and the Weibull function with an additive concentration variable was used to model the effects of mixtures of these chemicals. The model produced good agreement with data over a wide range of chemicals and mixture ratios and provides a useful initial assessment of environmental effects of mixtures of narcotic chemicals.

An interpretation of toxicity response of bobwhite quail with respect to duration of exposure

Avian dietary toxicity tests were conducted with seven pesticides, two age groups (2 and 16 weeks old) of northern bobwhite (Colinus virginianus) and two durations (5 and 28 days) of exposure. Results were analyzed with an emphasis placed upon comparing mortalities on similar test conditions. An analysis that used the entire dose-time-response results led to the calculation of a common measure (asymptotic rate e) of temporal development of the response surface and served as a basis of comparison of diverse test results. The asymptotic median lethal concentrations were designated by ALC50 and the median lethal concentrations at the end of a test period by LC50.It was found that: (1) Young birds in 5- and 28-day tests were more sensitive to incremental increases in the duration of exposure than adults. (2) Young birds were less sensitive to incremental increases of dietary concentration than adults only in the 5-day test and displayed delayed response patterns in six of seven chemicals in those tests. (3) LC50 values of 5-day tests of young birds were greater than LC50 values of 28-day tests, but the corresponding ALC50s were smaller in 5-day tests than 28-day tests. (4) ALC50s for 28-day tests were lower for young birds than for adults.The analysis based on the whole response surface can be used in the design of experiments, in utilizing less than optimum test results due to difficulties encountered during the test in selecting optimum dietary concentration, in linking results of short term exposure with long-term exposure, and in interpreting results of variable exposure tests on a common basis.

An approach to environmental risk assessment using avian toxicity tests

Toxicity tests results are often condensed into a single endpoint (LC50) to facilitate their use in environmental management. The single number cannot distinguish between two tests with equal LC50s but dissimilar slopes at LC50 and it cannot describe the response at low and high dose levels. Some chemicals produce a flat response at low dose levels, others produce a steep response. The management of different chemicals requires different strategies and a more comprehensive approach to analysis of test data than use of a single endpoint. An alternative analysis of test data using Weibull survivor function produces information on the overall form of the dose-response curve and enables calculation of toxicity, the slope, and errors at arbitrary protection levels, including the conventional 50% level.

A method for scaling biological response of soil microcosms

Abstract An extensive series of laboratory experiments was conducted in soil microcosms to study the respiratory response of microorganisms to toxicant amendments within different types of soils. Our analysis of test results demonstrates that coupled biological and environmental factors within soil can be scaled (i.e., commensurably and analogously grouped) by means of two rate constants, one characterizing the diffusion of CO 2 in the soil matrix and another the biological production of CO 2 . The two rate constants were used to classify the impact of metal compounds on diverse soil types and to predict the loss or gain of total respiratory CO 2 of amended soils relative to intact soils. This method exemplifies a more general approach, potentially useful for scaling complex physical and biological interactions in environmental assessments.

Land classification used to select abandoned hazardous waste study sites

The biological effects of hazardous substances in the environment are influenced by climate, physiography, and biota. These factors interact to determine the transport and fate of chemicals, but are difficult to model accurately except for small areas with a large data base. The requirement for a large data base may be reduced locally if the regional influences of these factors were predetermined from existing data. Knowledge of the regional factors would also relax the restriction to considering only small areas. This paper advocates consideration of regional characteristics of the environment in the early stages of waste management strategy development. It presents as an example a procedure for selecting study sites from candidate-abandoned hazardous waste dumpsites in the southeastern United States. It uses small-scale maps of low resolution from the National Atlas to delineate the boundaries and to determine the environmental characteristics that prevail over units of land within the region. A computer map-overlay and graphic approach is used to facilitate the grouping of land types. Abandoned hazardous waste dumpsites found within land types that best represent the region are surveyed for selecting a study site. It is expected that environmental impact data obtained from a representative site would be useful for predicting impact potentials in similar remotely located areas within the same general region.

Quantitative Soil Descriptions for Ecoregions of the United States

Researchers have defined and mapped ecological regions of the United States based on similar patterns of ecosystems such as deserts, forests, and croplands. These studies are useful in regional research, monitoring, and environmental management because data can be more readily extrapolated within the same ecoregion and to regions with similar characteristics. The description of ecoregions is largely holistic and qualitative. Conversely, quantitative information for soil are abundant and soil is an important ecosystem component related to many ecoregion properties. We used the nationwide State Soil Geographic database (STATSGO) to describe the soils of 84 Level III ecoregions in the United States. Among the 24 soil characteristics studied were texture, rock fragments, available water capacity, bulk density, and organic matter content. For each ecoregion we developed ranks to describe (i) its similarity to the U.S. average soil characteristics, (ii) the accuracy of predicting those characteristics, (iii) how well the soil map unit boundaries fit within ecoregion boundaries, (iv) the spatial relationship of soils across neighboring ecoregion boundaries, and (v) the homogeneity of texture-rock patterns. We present a national map of soil texture and rock fragments and five soil ranks for each ecoregion, and examine relationships between soils and other ecological components for selected ecoregions. Because soils relate to other ecosystem components such as vegetation, geology, and land use, the soil ranks complement and enrich the qualitative ecoregion descriptions. Similar analyses of physical or biological components of ecoregions will expand the understanding of the ecosystem patterns.