[PDF] Toxicology vs Epidemiology Problems in Toxicological Modeling





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[PDF] Toxicology vs Epidemiology

Toxicology vs Epidemiology Toxicology: • Uses lab experiments, typically on animals and with control groups • Role in risk analysis: identify dose- 




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[PDF] Toxicology vs Epidemiology Problems in Toxicological Modeling

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[PDF] Toxicology vs Epidemiology Problems in Toxicological Modeling 76823_7ToxvsEpidem.pdf

Toxicology vs Epidemiology

Toxicology:

•Uses lab experiments, typically on animals and with control groups. •Role in risk analysis: identify dose-response relationship.

Epidemiology:

•Usually gathers and analyzes data from the real world.

Problems in Toxicological

Modeling

•High to low dose extrapolation •Species-to-species comparisons •Exposure route comparisons (stomach, lungs, skin). •Interactions among multiple toxins

High to Low Dose Extrapolation:

Carcinogenesis

•High dose effects may produce carcinogenic mechanisms not found at low doses ~> overestimation of risk. •Early, low-dose tumors are not identified as such ~> underestimate of risk. •Tumors might have appeared after sacrifice ~> underestimate of risk •Cumulative and sporadic doses may have different effects. •Model selection may produce over or under estimation of risk.

Model Choice Affects Low to

High Dose Extrapolation

•Threshold or not? •Two-hit model? (production of oncogenes plus disabling of tumor suppressor gene - order of mutations not important) •Multistage? e.g., initiation (reversible; oncogene or tumor suppressor disabling), promotion (proliferation), progression (spread to other locations). •Different models may fit different types of cancer.

Species to Species Comparison

•Different body weights have different metabolisms, which may affect processing of toxins. •Mechanisms and target organs or tissues may not be analogous. •Use of homogeneous and highly susceptible test animals is necessary to obtain a detectable response and produce health-conservative risk estimates, but this may inflate cancer rates.

Reasons for High-Dose

Toxicological Assessments

•Modeling provides information about possibilities. (e.g., if cost estimates for remediation vary by several orders of magnitude, but all are low, the choice of action is clear.) •Modeling provides information about which assumptions are most important and highlights where more research can be most useful. •Can address causality by using control groups. •Experiments with small doses need large numbers of animals, which is prohibitively expensive. (High dose studies may cost $1 - 5 million.) •Experiments with humans are unethical.

Problems with Epidemiological

Studies

1.Can not address cause and effect

•No control group •Confounding variables (appropriate analysis helps somewhat)

2. Measurement error

•Self-report may be necessary •Estimates, averages, or surrogates may be necessary.

Problems with Epidemiological

Studies, Continued

3. Extrapolation

•Population studied may have higher exposure than general population •Population studied may not be representative of general population (health, age, etc.)

4. Interpreting small effects (e.g., RR < 2)


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