An epidemiologist hypothesizes that exposure to a chemical is associated with a
ID: 191917 • Letter: A
Question
An epidemiologist hypothesizes that exposure to a chemical is associated with a neurological disease. To study whether there is an association, the epidemiologist designs and conducts a prospective cohort research study. First, she recruits and enrolls into her study 5,000 people who do not have the neurological disease. During a 4-year follow-up period, the researcher observes the study population to assess exposure and finds that 1,000 participants work in industries where this chemical is used and the other 4,000 participants work in industries where this chemical is not used. She assumes that those who work with the chemical are exposed, and those who do not work with the chemical are unexposed. At the end of the follow-up period, there are 250 cases of the disease in her study population. Of those 250 participants, 50 worked in industries where the chemical was used during the study period, and 200 did not. Based on these results, please answer
the following questions, clearly showing how you arrived at your answers.
(20 points total) Methyl parathion is an insecticide. The current US EPA reference dose (RfD) for methyl parathion is 2.5 x 104 (0.00025) mg/kg/day. A toxicologist has conducted an experiment (hypothetical) in which six groups of laboratory mice were orally administered different doses of methyl parathion in their diet over a period of 24 months. At the end of the experiment each animal's hematocrit (percentage of blood by volume that is composed of red blood cells) was assessed. The following table shows the doses of methyl parathion administered to each group and the difference in average hematocrit for that group relative to the average among the control mice. (NOTE: you can assume that a decrease in hematocrit is an adverse effect). Please review the table, then answer four questions % Difference in Average Hematocrit From Control Grou Dose Administered Dose Group (mg/kg /day) 1 (control) 1x 104 (0.0001) 2.5 x 104 (0.00025 x 104 (0.0005) 1 x 103 (0.001) 0% 0% -10% ** -19% ** -32% ** 4 6 5 x 10-3 (0.005) **Statistically significant difference from the control group. A. (4 points) What is the NOAEL for methyl parathion in this experiment? B. (4 points) What is the LOAEL for methyl parathion in this experiment? C. (6 points) Based only on the results of this experiment do you think the RfD should be changed? Why or why not? D. (3 points) What is the best source of information to determine if methyl parathion is carcinogenic? E. (3 points) Based on that source of information, is methyl parathion carcinogenic?Explanation / Answer
The largest dose at which no effects are observed is called No Observed Adverse Effect Level. In this experiment, 2.5 X 10-4 mg/kg/day is clearly the largest dose with no effects observed compared to the control.
Smallest dose at which adverse effect was observed is the LOAEL or lowest observed adverse effect level.Here it is 5 X 10-4 mg/kg/day.
RfD is the maximum acceptable oral dose for a toxicant. RfD of methy parathion is 2.5 X 10-4 mg/kg/day which is determined from animal studies. But while calculating RfD for humans, they have added a 10 fold uncertainity factor - The intraspecies uncertainty factor, to account for the hypersensitive individuals. So even though more than 2.5 X 10-4 mg/kg/day of methy parathion is quite harmless up to 5 X 10-4 mg/kg/day it is always kept at a lower RfD to account for the variable sensitivity of the individuals in the population, to this substance.
Anermia occurs in majority of cancers. Here huge drop in hematocrit shows increase in anemic condition which is an indication of cancer.