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 (micrograms/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.