Hormesis: implications for public policy regarding toxicants.

Protecting workers and the public from toxic chemicals, particularly carcinogens, has been a principal goal of public policy. In the absence of knowing by what mechanism of action a toxicant harms people, regulatory toxicology assumes that even tiny doses can cause harm. Risk aversion has led to legislation and regulation that seek to ban toxic chemicals or lower exposure to trivial levels. Contradicting this policy, many studies show health benefits from low-level exposure to toxicants, including some carcinogens. This is known as hormesis. Thus, hormesis could lead to a fundamental change in the policy for regulating toxic substances. In particular, all toxicants that benefit health at low-level exposures should face similar change in regulations for low-dose exposure. The result would be the dissolving of the source of differences in policy for carcinogens and noncarcinogens at low doses. Two questions must be answered before hormesis can be incorporated into regulatory policy. (a) Are there sensitive individuals who would be harmed at doses that would help most people? (b) Is the hormetic effect toxicant specific or would exposure to just a few toxicants achieve the full benefit from hormesis?

Effect of the fine fraction of particulate matter versus the coarse mass and other pollutants on daily mortality in Santiago, Chile.

Daily counts of non-accidental deaths in Santiago, Chile, from 1988 to 1996 were regressed on six air pollutants--fine particles (PM2.5), coarse particles (PM10-2.5), CO, SO2, NO2, and O3. Controlling for seasonal and meteorological conditions was done using three different models--a generalized linear model, a generalized additive model, and a generalized additive model on previously filtered data. Single- and two-pollutant models were tested for lags of 1-5 days and the average of the previous 2-5 days. The increase in mortality associated with the mean levels of air pollution varied from 4 to 11%, depending on the pollutants and the way season of the year was considered. The results were not sensitive to the modeling approaches, but different effects for warmer and colder months were found. Fine particles were more important than coarse particles in the whole year and in winter, but not in summer. NO2 and CO were also significantly associated with daily mortality, as was O3 in the warmer months. No consistent effect was observed for SO2. Given particle composition in Santiago, these results suggest that combustion-generated pollutants, especially from motor vehicles, may be associated with increased mortality. Temperature was closely associated with mortality. High temperatures led to deaths on the same day, while low temperatures lead to deaths from 1 to 4 days later.

Hormesis: policy implications.

Protecting workers and the public from toxic chemicals, particularly carcinogens, has been a principal focus of public policy. Uncertainty regarding the toxicity of particular chemicals and their dose-response relationship has led to the use of the 'precautionary principle' in which regulators are willing to accept more costly regulation than necessary in order to prevent exposure and disease from these toxic chemicals. The Environmental Protection Agency's (EPA's) current policy of using 'mechanism of action' to set regulations means that hormesis could be used by the EPA without any change in policy if hormesis is accepted as scientifically valid. Hormesis could result in a qualitative change in regulatory policy. Because exposure to toxic chemicals conveys no health benefit in the current dose-response model, public risk aversion leads to a Delaney Clause-like 'no-risk' model for policy: ban toxic chemicals or lower exposure to trivial levels. Hormesis implies that individuals benefit from low exposure to toxicants. Although hormesis may not be relevant for individuals with compromised immune systems, it would be expected to help the vast majority of people. If so, permitting exposure levels that provided the greatest health benefit to most people would be balanced against these same levels hurting the most immune-compromised individuals. Public health routinely makes these trade-offs using a 'risk-risk' model. Thus, hormesis could transform the 'no-risk' approach into a 'risk-risk' approach that could tolerate much higher exposures to toxic chemicals than the current policy.

A life-cycle comparison of alternative automobile fuels.

We examine the life cycles of gasoline, diesel, compressed natural gas (CNG), and ethanol (C2H5OH)-fueled internal combustion engine (ICE) automobiles. Port and direct injection and spark and compression ignition engines are examined. We investigate diesel fuel from both petroleum and biosources as well as C2H5OH from corn, herbaceous bio-mass, and woody biomass. The baseline vehicle is a gasoline-fueled 1998 Ford Taurus. We optimize the other fuel/powertrain combinations for each specific fuel as a part of making the vehicles comparable to the baseline in terms of range, emissions level, and vehicle lifetime. Life-cycle calculations are done using the economic input-output life-cycle analysis (EIO-LCA) software; fuel cycles and vehicle end-of-life stages are based on published model results. We find that recent advances in gasoline vehicles, the low petroleum price, and the extensive gasoline infrastructure make it difficult for any alternative fuel to become commercially viable. The most attractive alternative fuel is compressed natural gas because it is less expensive than gasoline, has lower regulated pollutant and toxics emissions, produces less greenhouse gas (GHG) emissions, and is available in North America in large quantities. However, the bulk and weight of gas storage cylinders required for the vehicle to attain a range comparable to that of gasoline vehicles necessitates a redesign of the engine and chassis. Additional natural gas transportation and distribution infrastructure is required for large-scale use of natural gas for transportation. Diesel engines are extremely attractive in terms of energy efficiency, but expert judgment is divided on whether these engines will be able to meet strict emissions standards, even with reformulated fuel. The attractiveness of direct injection engines depends on their being able to meet strict emissions standards without losing their greater efficiency. Biofuels offer lower GHG emissions, are sustainable, and reduce the demand for imported fuels. Fuels from food sources, such as biodiesel from soybeans and C2H5OH from corn, can be attractive only if the co-products are in high demand and if the fuel production does not diminish the food supply. C2H5OH from herbaceous or woody biomass could replace the gasoline burned in the light-duty fleet while supplying electricity as a co-product. While it costs more than gasoline, bioethanol would be attractive if the price of gasoline doubled, if significant reductions in GHG emissions were required, or if fuel economy regulations for gasoline vehicles were tightened.

Benefit-cost analysis in public health.

This chapter gives an overview of benefit-cost analysis (BCA) and similar evaluation tools, such as cost-effectiveness analysis and technology-based standards, in the context of public health. We describe these evaluation tools, how they are used, their shortcomings, and how they should be interpreted. As with other powerful tools, they are subject to misuse and misinterpretation, even by professionals doing the analysis.

Predictions of rodent carcinogenicity testing results: interpretation in light of the Lave-Omenn value-of-information model.

The recent National Institute of Environmental Health Sciences/National Toxicology Program Carcinogen Prediction Challenge elicited a valuable array of predictions of the carcinogenicity of chemicals tested in the lifetime rodent bioassay. The data warrant additional analyses of the similarities and differences of the predictive methods. We provide here analyses of the sensitivity, specificity, and false-positive/false-negative tendencies of the different sets of predictions. Our value-of-information model provides guidance to testing agencies and regulatory agencies in determining the social value of additional information and setting up the framework for assessing the social consequences of different test strategies and nontest predictive methods. These considerations deserve attention in the second round of the Carcinogen Prediction Challenge.

Parent preferences and prenatal testing for neural tube defects.

Previous analyses of prenatal screening for neural tube defects have generally found benefits to exceed costs. The usual screening battery follows an elevated maternal serum alpha-fetoprotein level with high-resolution ultrasound and/or amniocentesis. Current thinking focuses on weighing the risk of a false-negative (an abnormality missed) against the risk of an amniocentesis-induced fetal loss. This thinking neglects the risk of a false-positive (an unaffected fetus labeled abnormal) and individual parents' preferences concerning a false-negative vs a fetal loss. With these risks included, we find that high-resolution ultrasound is appropriate for all women with elevated serum alpha-fetoprotein. Women with moderately elevated serum alpha-fetoprotein who have negative ultrasound scans need no further testing, nor do women with highly elevated serum alpha-fetoprotein and positive ultrasound scans. Further testing using amniocentesis to confirm the ultrasound result is appropriate for women with moderately elevated serum alpha-fetoprotein and positive ultrasound scans, and for women with highly elevated serum alpha-fetoprotein and negative ultrasound scans. The actual cutoffs defining normal, moderately elevated, and highly elevated serum alpha-fetoprotein depend on several parameters, particularly the underlying prevalence of neural tube defects and the parents' preferences.

The risks of licensing persons with diabetes to drive trucks.

The 1990 Americans with Disabilities Act forbids employers to bar disabled persons from jobs unless employers can show the disabled person cannot perform the tasks. The Federal Highway Administration will not license persons with diabetes mellitus to drive commercial motor vehicles in interstate commerce. These individuals may experience severe hypoglycemia, greatly increasing their risk of losing control of the truck. This prohibition is currently being reexamined. We describe the disease process leading to severe hypoglycemia and its physical manifestations. To quantify the risks of licensing persons with diabetes to use insulin, we first estimate the number of potential insulin-using drivers. We estimate that 1420 insulin-using persons would seek licenses in the United States if they were permitted to do so (920 noninsulin dependent and 500 insulin dependent). Next, we estimate the annual incidence of mild and severe hypoglycemia in these populations. The third step is to estimate the number of hypoglycemic episodes while driving. Estimating the likelihood of a crash due to a mild or severe hypoglycemic episode is the fourth step. We estimate that an additional 42 crashes each year would occur if insulin using persons were licensed to drive commercial motor vehicles in interstate commerce (20 from insulin dependent and 22 from non-insulin dependent drivers).

Should persons with diabetes be licensed to drive trucks?--Risk management.

How should a regulatory agency interpret a risk analysis that concludes there is a small increase in risk? The agency must decide on behalf of society whether the increased risk is large enough to justify banning the risky activity or taking some other step to lessen the risks. In a companion paper (Songer et al.), we conclude that licensing insulin using persons to drive commercial motor vehicles in interstate commerce would result in 42 additional crashes each year. Here we address risk management issues by interpreting the number of additional crashes and the relative risks of the prospective handicapped drivers. Are the number of additional crashes (42) significant? Is the increase in the annual crash risk (from 0.00785 to 0.032 for non-insulin dependent and 0.048 for insulin dependent persons) significant? Are the relative risks significant for all insulin using drivers (4.7)? For drivers with a history of severe hypoglycemic reactions (19.8)? How should society tradeoff risk increases for increases in opportunity for these handicapped persons? We review other social decisions concerning highway safety: Accepting the increasing risks of letting 16 year olds drive, allowing extremely light cars, allowing some unsafe highways, and allowing extremely unsafe driving conditions at some times of day. We conclude that the additional risks from insulin using persons are well within the current accepted range of risks.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology of insulin-using commercial motor vehicle drivers. Major variability of state licensing requirements in the U.S.

OBJECTIVE: Licensing agencies in many areas, including the U.S., prohibit insulin-using individuals from driving CMVs or large trucks. This study examined the debate over the risks of licensing insulin-using individuals to drive CMVs as an occupation, and the variations in regulations of different states. RESEARCH DESIGN AND METHODS: As part of an ongoing review of the regulations governing interstate commerce in the U.S., we surveyed all 50 states and Washington, D.C. to determine the regulations concerning intrastate driving. We received responses from 48 states and D.C., representing 95% of the U.S. population. RESULTS: Only 9 states reported preventing insulin users from acquiring a CMV license, whereas 39 states and D.C. permitted licensing within state boundaries. Of the states allowing insulin users to drive, 26 placed special requirements on CMV licensing. CONCLUSIONS: The results indicate that, despite a standardized U.S. federal law for driving across states, enormous variability exists in the policies for driving within states, ranging from no restrictions to a complete ban on CMV driving for insulin users.

Public perception of the risks of floods: implications for communication.

Floods in the U.S. kill an average of 162 people each year and cause $3.4 billion in property damage. Flood control programs have been successful in lowering, but not eliminating, the risks to lives and property. Since the late 1960s, the federal government has emphasized flood insurance as a primary tool for improving location and flood-proofing decisions, as well as for reimbursing flood losses. Since only 12.7% of houses in flood plain areas are covered by flood insurance, the program has been ineffective. We interviewed people living in three communities that had recently been flooded. Most people had little knowledge of the cause of floods or what could be done to prevent damage. People who work and who are better educated know more and are more likely to have flood insurance. Current government publications about flood risks are not likely to be understood by those at risk. There is little effective communication about the nature and magnitude of the risks and what individuals can do to protect their lives and property and lower their financial risks. The risk management program should both emphasize communication and enforcement of the current law requiring people at risk who hold federally funded loans to be insured.

Risk analysis and risk management.

During the past several decades, the public has given increasing attention to environmental problems and increased their demands that these problems be solved. During this period, the difficulty and costs of solving the problems have become apparent. Environmental abatement programs must be effective in achieving the desired goals and efficient in achieving them at low cost. Risk analysis is necessary to quantify the benefits of proposed solutions in order to make them effective and efficient. The necessity for performing risk assessment stems from a presidential executive order, from a Supreme Court Decision, and from the public's demand for information about the extent of possible danger from a hazard, rather than knowing simply that it is a hazard. The science of risk analysis is an an early stage and so there are many uncertainties concerning interpretation of the estimates. This approach has sharpened the scientific questions and hastened improvements in scientific understanding. Risk analysis is most helpful when the analysis reflects the science, without intrusion of the risk assessor's values or attempts to force a risk management outcome by skewing the risk analysis.

Value-of-information analysis of testing strategies: estimating the effect of uncertainty about the proportion of chemicals that are true human carcinogens.

Choosing a cost-effective strategy for classifying chemicals as human carcinogens and non-carcinogens depends upon the costs of false positives (carcinogens erroneously treated as non-carcinogenic) and false negatives (non-carcinogens erroneously treated as carcinogenic); upon the accuracy (sensitivity and specificity) of the classification strategy; and upon the underlying proportion of carcinogens in the population of chemicals to be classified. If these values are known, value-of-information analyses can indicate the most cost-effective among three strategies: classify as carcinogenic without testing, classify as non-carcinogenic without testing, or choose the most cost-effective test and classify on the basis of the test result. When some or all of the values are uncertain, the analysis becomes more complex, but still helps to guide decisions among the three classification strategies.