HealthRisk strategies response. (Correspondence).

We appreciate the comments of Landrigan et al. and find that few of them are inconsistent with the conclusions presented in our paper (1). Indeed, many of their comments are mentioned in our paper. Nowhere in our paper, however, do we argue that child-protective safety factors should be subject to cost--benefit analysis, nor do we suggest "that a child-protective safety factor should not be added to risk assessment unless it can be directly shown to confer benefit," as Landrigan et al. state. Curiously, Landrigan et al. fail to acknowledge or to address the conclusions in our paper, which focus on dose--response assessment (the subject of our paper); they prefer instead to reiterate yet again the conclusions of their 1993 NAS report (2), with which we are certainly familiar.

For example, we agree with Landrigan et al.'s comment that children's exposures differ from those of adults. We acknowledge that difference in our paper (1) by pointing out that it can be accounted for as part of exposure assessment, but we also noted that for the purpose of our paper, we chose to focus on biological susceptibility, an aspect of children's risk that is the subject of much current research, including that of Landrigan et al. We also agree that cancer is not the only end point of interest, as we pointed out in our paper when we acknowledged that the age-dependence of other outcomes, such as neurotoxicity, is poorly characterized. We certainly agree that the paucity of toxicologic data for most environmental chemicals is a serious limitation. It is precisely that limitation that underlies the conclusions of our paper.

As we stated in our paper (1), our goal was to articulate some of the questions that must be addressed in the context of dose--response assessment to determine whether an extra 10x uncertainty factor is appropriate, necessary, or adequate to protect children from chemical carcinogens or other environmental chemicals. The NAS report (2) recommends that

   an uncertainty factor up to the 10-fold uncertainty factor traditionally
   used by EPA [the U.S. Environmental Protection Agency] and FDA [Food and
   Drug Administration] for fetal developmental toxicity should also be
   considered when there is evidence of postnatal developmental toxicity and
   when data from toxicity testing relative to children are incomplete.

Our paper thus articulated some of the questions the U.S. EPA might pose when considering the need to apply such an uncertainty factor and, as such, is quite consistent with the recommendations of the NAS report.

In our paper (1), we discussed, for example, the fact that age-related differences in susceptibility seen at high doses in laboratory experiments may not hold true at low doses. As a consequence, whether the use of uncertainty factors will be sufficiently (or overly) protective depends on the dose at which the measurement is made compared to the exposure of interest. We pointed out that evaluating the effectiveness of an uncertainty factor also depends on whether differences between adults' and children's susceptibilities, where they exist, can be accounted for by current risk assessment models, noting the limitations of such models. We commented on the regulatory use of statistical upper bounds on cancer risk estimates instead of maximum likelihood estimates and suggested that, even if a particular uncertainty factor were found to be consistent with the best estimate of the risk for children, there is no reason to assume that the upper-bound risks would have the same relationship as the best estimates. Finally, we concluded that determining whether additional regulatory stringency will demonstrably improve public health in general or children's health in particular is unknown and cannot be evaluated without far more information than is currently available. Such a conclusion should be interpreted as encouraging the generation of such information (and serves only to promote the interests of researchers such as Landrigan et al.) presuming, of course, that one is interested in whether environmental health regulation does, in fact, protect public health. As Landrigan points out frequently, use of a child-protective safety factor is policy based, not science based. As scientists, we are interested in the question of whether and to what extent additional science might improve public policy.

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.

Gail Charnley
HealthRisk Strategies
Washington, D.C.
E-mail: [e-mail]

Resha M. Putzrath
Georgetown Risk Group
Washington, D.C.