Comments on "children's health, susceptibility, and regulatory approaches to reducing risk from chemical carcinogens." (Correspondence).

In their recent commentary, "Children's Health, Susceptibility, and Regulatory Approaches to Reducing Risk from Chemical Carcinogens," Charnley and Putzrath (1) noted the seminal importance of the National Academy of Sciences (NAS) report Pesticides in the Diets of Infants and Children (2) in having catalyzed current concern about risks to children's health from environmental chemicals. As members of the NAS committee who wrote that report, we thank Charnley and Putzrath (1) for their acknowledgement. We are concerned, however, that their suggestion that child-protective safety factors be subjected to cost--benefit analysis would undercut a major recommendation of the NAS committee as well as a central provision of the Food Quality Protection Act (FQPA) (3). Specifically, the FQPA, motivated in part by our committee's report, calls for the application in risk assessment of an additional margin of safety to protect children's health in two circumstances: a) in the absence of data demonstrating assurance of safety, and b) in the presence of data showing children to be at greater risk to a particular chemical than adults.

Child-protective safety factors would not be a necessary default in risk assessment if good data were available on children's exposure and sensitivity to each of the many chemicals that they encounter. That, however, is not the case. Quantitative data on the exposures of fetuses, infants, and children to most chemicals are limited, as are data on the toxicity of most chemicals. A recent analysis by the U.S. Environmental Protection Agency (4) indicates that even minimal toxicologic data exist for only 43% of the 15,000 chemicals produced each year in quantities of over 10,000 pounds; data on developmental toxicity, the sort of data that would permit direct comparison of child versus adult sensitivities, are available for only about 20% of these high-production volume chemicals.

To address these large gaps in data, the NAS Committee on Pesticides in the Diets of Infants and Children (2) recommended that "there should be a presumption of greater toxicity to infants and children." The committee suggested that

   an uncertainty factor up to ten-fold ... be considered ... when data from
   toxicity testing relative to children are incomplete.

The committee coupled this recommendation with a call for expanded research that would enhance the "current limited database on relative sensitivity." It was the NAS committee's clear intent that the presumption of greater toxicity and the imposition of an additional safety factor would catalyze expansion of the database on developmental toxicology.

Charnley and Putzrath (1) questioned the wisdom of incorporating child-protective safety factors in risk assessment. They asked whether the cost is worth the benefit. The principal basis for their question lies in a comparison they presented of the relative sensitivities of children and adults to a series of carcinogenic chemicals. Drawing upon the work of our NAS committee, they found that adult animals are more susceptible to 53% of carcinogens, that young animals are more susceptible to 37%, and that there is no age-related difference in 10%.

We agree with those findings because they come mainly from our report (2). However, Charnley and Putzrath (1) presented their argument in a vacuum, and they manifested little apparent cognizance of the enormous voids in knowledge that surround it. The limitations in their analysis are threefold.

First, Charnley and Putzrath (1) mentioned only in passing the great differences in exposure that exist between adults and children. The NAS committee found, however, that differences in exposure are often orders of magnitude greater than differences in susceptibility. We noted in our report that children drink more water, eat more food, and breathe more air per pound of body weight than adults and thus are disproportionately exposed to any toxic chemicals contained in those media (2). Additionally, children's behavior--their play close to the ground and their oral exploratory activity--increase further their opportunities for intake of chemicals. Because children's risk of injury from toxic chemicals is determined by both exposure and susceptibility, we have difficulty in seeing how Charnley and Putzrath (1) can draw major conclusions about children's risks without considering both of these factors.

Lack of toxicologic data is a second important limitation underlying the analysis of Charnley and Putzrath (1). Their tables on relative sensitivity to chemical carcinogens, the tables that provide the central foundation of their analysis, are based on only about 30 chemicals. These chemicals represent fewer than 0.2% of the 15,000 high-production volume chemicals in commerce. There is no way to know whether these findings pertain to the broader chemical universe or whether they are representative of that universe. And in the absence of toxicologic testing data, there is no way to know which are the chemicals to which children are especially sensitive.

A third limitation of Charnley and Putzrath's analysis (1) is that it considers only cancer. Cancer, while clearly a health outcome of great concern, may turn out not to be the outcome with greatest age-related differences in risk. It is conceivable that differences in susceptibility to neurotoxins or to reproductive toxins could vary much more sharply across age groups than differences in susceptibility to carcinogens.

In summary, by arguing that a child-protective safety factor should not be added to risk assessment unless it can be directly shown to confer benefit, Charnley and Putzrath (1) assume that children are no more sensitive to chemicals than adults and that the consequences of toxicity are no greater. Charnley and Putzrath thus offer an analysis whose conclusions and recommendations are diametrically at odds with those of the NAS Committee on Pesticides in the Diets of Infants and Children. Their risk assessment strategy, if adopted, would remove the stimulus to expanded toxicologic testing that was recommended by the NAS committee and that is embodied in the FQPA. It would result in perpetuation of the current unhappy situation in which the overwhelming majority of the chemicals to which children are at risk of exposure have never been tested for their developmental toxicity.

REFERENCES AND NOTES

(1.) Charnley G, Putzrath RM. Children's Health, Susceptibility, and Regulatory Approaches to Reducing Risks from Chemical Carcinogens, Environ Health Perspect 109:187-192 (2001).

(2.) National Research Council. Pesticides in the Diets of Infants and Children. Washington, DC: National Academy Press, 1993.

(3.) Food Quality Protection Act of 1996. Public Law 104-170, 1996.

(4.) Goldman LR, Kuduru S. Chemicals in the environment and developmental toxicity to children: a public health and policy perspective. Environ Health Perspect 108(suppl 3):443-448 (2000).

Philip J. Landrigan
Mount Sinai School of Medicine
New York, New York
E-mail: [e-mail]

Donald R. Mattison
The March of Dimes Foundation
White Plains, New York

Barbara Boardman
Kaiser Permanente
Falls Church, Virginia

James V. Bruckner
University of Georgia
Athens, Georgia

Richard J. Jackson
Atlanta, Georgia

Meryl H. Karol
University of Pittsburgh
Pittsburgh, Pennsylvania

Daniel Krewski
University of Ottawa
Ottawa, Ontario, Canada

William B. Weil
Michigan State University
East Lansing, Michigan