Devra Lee Davis

Fundamental flaws of hormesis for public health decisions.

Hormesis (defined operationally as low-dose stimulation, high-dose inhibition) is often used to promote the notion that while high-level exposures to toxic chemicals could be detrimental to human health, low-level exposures would be beneficial. Some proponents claim hormesis is an adaptive, generalizable phenomenon and argue that the default assumption for risk assessments should be that toxic chemicals induce stimulatory (i.e., “beneficial”) effects at low exposures. In many cases, nonmonotonic dose–response curves are called hormetic responses even in the absence of any mechanistic characterization of that response. Use of the term “hormesis,” with its associated descriptors, distracts from the broader and more important questions regarding the frequency and interpretation of nonmonotonic dose responses in biological systems. A better understanding of the biological basis and consequences of nonmonotonic dose–response curves is warranted for evaluating human health risks. The assumption that hormesis is generally adaptive is an oversimplification of complex biological processes. Even if certain low-dose effects were sometimes considered beneficial, this should not influence regulatory decisions to allow increased environmental exposures to toxic and carcinogenic agents, given factors such as interindividual differences in susceptibility and multiplicity in exposures. In this commentary we evaluate the hormesis hypothesis and potential adverse consequences of incorporating low-dose beneficial effects into public health decisions.

Ancillary human health benefits of improved air quality resulting from climate change mitigation

BackgroundGreenhouse gas (GHG) mitigation policies can provide ancillary benefits in terms of short-term improvements in air quality and associated health benefits. Several studies have analyzed the ancillary impacts of GHG policies for a variety of locations, pollutants, and policies. In this paper we review the existing evidence on ancillary health benefits relating to air pollution from various GHG strategies and provide a framework for such analysis.MethodsWe evaluate techniques used in different stages of such research for estimation of: (1) changes in air pollutant concentrations; (2) avoided adverse health endpoints; and (3) economic valuation of health consequences. The limitations and merits of various methods are examined. Finally, we conclude with recommendations for ancillary benefits analysis and related research gaps in the relevant disciplines.ResultsWe found that to date most assessments have focused their analysis more heavily on one aspect of the framework (e.g., economic analysis). While a wide range of methods was applied to various policies and regions, results from multiple studies provide strong evidence that the short-term public health and economic benefits of ancillary benefits related to GHG mitigation strategies are substantial. Further, results of these analyses are likely to be underestimates because there are a number of important unquantified health and economic endpoints.ConclusionRemaining challenges include integrating the understanding of the relative toxicity of particulate matter by components or sources, developing better estimates of public health and environmental impacts on selected sub-populations, and devising new methods for evaluating heretofore unquantified and non-monetized benefits.

Exposure Limits: The underestimation of absorbed cell phone radiation, especially in children

The existing cell phone certification process uses a plastic model of the head called the Specific Anthropomorphic Mannequin (SAM), representing the top 10% of U.S. military recruits in 1989 and greatly underestimating the Specific Absorption Rate (SAR) for typical mobile phone users, especially children. A superior computer simulation certification process has been approved by the Federal Communications Commission (FCC) but is not employed to certify cell phones. In the United States, the FCC determines maximum allowed exposures. Many countries, especially European Union members, use the “guidelines” of International Commission on Non-Ionizing Radiation Protection (ICNIRP), a non governmental agency. Radiofrequency (RF) exposure to a head smaller than SAM will absorb a relatively higher SAR. Also, SAM uses a fluid having the average electrical properties of the head that cannot indicate differential absorption of specific brain tissue, nor absorption in children or smaller adults. The SAR for a 10-year old is up to 153% higher than the SAR for the SAM model. When electrical properties are considered, a childs heads absorption can be over two times greater, and absorption of the skulls bone marrow can be ten times greater than adults. Therefore, a new certification process is needed that incorporates different modes of use, head sizes, and tissue properties. Anatomically based models should be employed in revising safety standards for these ubiquitous modern devices and standards should be set by accountable, independent groups.

Short-term improvements in public health from global-climate policies on fossil-fuel combustion: an interim report

BACKGROUND Most public-health assessments of climate-control policies have focused on long-term impacts of global change. Our interdisciplinary working group assesses likely short-term impacts on public health. METHODS We combined models of energy consumption, carbon emissions, and associated atmospheric particulate-matter (PM) concentration under two different forecasts: business-as-usual (BAU); and a hypothetical climate-policy scenario, where developed and developing countries undertake significant reductions in carbon emissions. FINDINGS We predict that by 2020, 700,000 avoidable deaths (90% CI 385,000-1,034,000) will occur annually as a result of additional PM exposure under the BAU forecasts when compared with the climate-policy scenario. From 2000 to 2020, the cumulative impact on public health related to the difference in PM exposure could total 8 million deaths globally (90% CI 4.4-11.9 million). In the USA alone, the avoidable number of annual deaths from PM exposure in 2020 (without climate-change-control policy) would equal in magnitude deaths associated with human immunodeficiency diseases or all liver diseases in 1995. INTERPRETATION The mortality estimates are indicative of the magnitude of the likely health benefits of the climate-policy scenario examined and are not precise predictions of avoidable deaths. While characterized by considerable uncertainty, the short-term public-health impacts of reduced PM exposures associated with greenhouse-gas reductions are likely to be substantial even under the most conservative set of assumptions.

Declines in sex ratio at birth and fetal deaths in Japan, and in U.S. whites but not African Americans

Background The expected ratio of male to female births is generally believed to be 1.05, also described as the male proportion of 0.515. Objectives We describe trends in sex ratio at birth and in fetal deaths in the United States, in African Americans and in whites, and in Japan, two industrial countries with well-characterized health data infrastructures, and we speculate about possible explanations. Methods Public health records from national statistical agencies were assembled to create information on sex ratio at birth and in fetal deaths in the United States (1970–2002) and Japan (1970–1999), using SPSS. Results Sex ratio at birth has declined significantly in Japan and in U.S. whites, but not for African Americans, for whom sex ratio remains significantly lower than that of whites. The male proportion of fetal death has increased overall in Japan and in the United States. Conclusions Sex ratio declines are equivalent to a shift from male to female births of 135,000 white males in the United States and 127,000 males in Japan. Known and hypothesized risk factors for reduced sex ratio at birth and in fetal deaths cannot account fully for recent trends or racial or national differences. Whether avoidable environmental or other factors—such as widespread exposure to metalloestrogens or other known or suspected endocrine-disrupting materials, changes in parental age, obesity, assisted reproduction, or nutrition—may account for some of these patterns is a matter that merits serious concern.

An updated weight of evidence approach to the aquatic hazard assessment of Bisphenol A and the derivation a new predicted no effect concentration (Pnec) using a non-parametric methodology.

An aquatic hazard assessment establishes a derived predicted no effect concentration (PNEC) below which it is assumed that aquatic organisms will not suffer adverse effects from exposure to a chemical. An aquatic hazard assessment of the endocrine disruptor Bisphenol A [BPA; 2, 2-bis (4-hydroxyphenyl) propane] was conducted using a weight of evidence approach, using the ecotoxicological endpoints of survival, growth and development and reproduction. New evidence has emerged that suggests that the aquatic system may not be sufficiently protected from adverse effects of BPA exposure at the current PNEC value of 100 μg/L. It is with this background that; 1) An aquatic hazard assessment for BPA using a weight of evidence approach, was conducted, 2) A PNEC value was derived using a non parametric hazardous concentration for 5% of the specie (HC(5)) approach and, 3) The derived BPA hazard assessment values were compared to aquatic environmental concentrations for BPA to determine, sufficient protectiveness from BPA exposure for aquatic species. A total of 61 studies yielded 94 no observed effect concentration (NOEC) and a toxicity dataset, which suggests that the aquatic effects of mortality, growth and development and reproduction are most likely to occur between the concentrations of 0.0483 μg/L and 2280 μg/L. This finding is within the range for aquatic adverse estrogenic effects reported in the literature. A PNEC of 0.06 μg/L was calculated. The 95% confidence interval was found to be (0.02, 3.40) μg/L. Thus, using the weight of evidence approach based on repeated measurements of these endpoints, the results indicate that currently observed BPA concentrations in surface waters exceed this newly derived PNEC value of 0.06 μg/L. This indicates that some aquatic receptors may be at risk for adverse effects on survival, growth and development and reproduction from BPA exposure at environmentally relevant concentrations.

Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA)

The International Agency for Research on Cancer (IARC) Monographs Programme identifies chemicals, drugs, mixtures, occupational exposures, lifestyles and personal habits, and physical and biological agents that cause cancer in humans and has evaluated about 1000 agents since 1971. Monographs are written by ad hoc Working Groups (WGs) of international scientific experts over a period of about 12 months ending in an eight-day meeting. The WG evaluates all of the publicly available scientific information on each substance and, through a transparent and rigorous process,1 decides on the degree to which the scientific evidence supports that substances potential to cause or not cause cancer in humans. For Monograph 112,2 17 expert scientists evaluated the carcinogenic hazard for four insecticides and the herbicide glyphosate.3 The WG concluded that the data for glyphosate meet the criteria for classification as a probable human carcinogen . The European Food Safety Authority (EFSA) is the primary agency of the European Union for risk assessments regarding food safety. In October 2015, EFSA reported4 on their evaluation of the Renewal Assessment Report5 (RAR) for glyphosate that was prepared by the Rapporteur Member State, the German Federal Institute for Risk Assessment (BfR). EFSA concluded that ‘glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential’. Addendum 1 (the BfR Addendum) of the RAR5 discusses the scientific rationale for differing from the IARC WG conclusion. Serious flaws in the scientific evaluation in the RAR incorrectly characterise the potential for a carcinogenic hazard from exposure to glyphosate. Since the RAR is the basis for the European Food Safety Agency (EFSA) conclusion,4 it is critical that these shortcomings are corrected. EFSA concluded ‘that there is very limited evidence for an association between glyphosate-based formulations …

The Limits of Two-Year Bioassay Exposure Regimens for Identifying Chemical Carcinogens

Background Chemical carcinogenesis bioassays in animals have long been recognized and accepted as valid predictors of potential cancer hazards to humans. Most rodent bioassays begin several weeks after birth and expose animals to chemicals or other substances, including workplace and environmental pollutants, for 2 years. New findings indicate the need to extend the timing and duration of exposures used in the rodent bioassay. Objectives In this Commentary, we propose that the sensitivity of chemical carcinogenesis bio-assays would be enhanced by exposing rodents beginning in utero and continuing for 30 months (130 weeks) or until their natural deaths at up to about 3 years. Discussion Studies of three chemicals of different structures and uses—aspartame, cadmium, and toluene—suggest that exposing experimental animals in utero and continuing exposure for 30 months or until their natural deaths increase the sensitivity of bioassays, avoid false-negative results, and strengthen the value and validity of results for regulatory agencies. Conclusions Government agencies, drug companies, and the chemical industry should conduct and compare the results of 2-year bioassays of known carcinogens or chemicals for which there is equivocal evidence of carcinogenicity with longer-term studies, with and without in utero exposure. If studies longer than 2 years and/or with in utero exposure are found to better identify potential human carcinogens, then regulatory agencies should promptly revise their testing guidelines, which were established in the 1960s and early 1970s. Changing the timing and dosing of the animal bioassay would enhance protection of workers and consumers who are exposed to potentially dangerous workplace or home contaminants, pollutants, drugs, food additives, and other chemicals throughout their lives.

Mobile phone radiation causes brain tumors and should be classified as a probable human carcinogen (2A) (Review)

Quickly changing technologies and intensive uses of radiofrequency electromagnetic field (RF-EMF)‑emitting phones pose a challenge to public health. Mobile phone users and uses and exposures to other wireless transmitting devices (WTDs) have increased in the past few years. We consider that CERENAT, a French national study, provides an important addition to the literature evaluating the use of mobile phones and risk of brain tumors. The CERENAT finding of increased risk of glioma is consistent with studies that evaluated use of mobile phones for a decade or longer and corroborate those that have shown a risk of meningioma from mobile phone use. In CERENAT, exposure to RF‑EMF from digitally enhanced cordless telephones (DECTs), used by over half the population of France during the period of this study, was not evaluated. If exposures to DECT phones could have been taken into account, the risks of glioma from mobile phone use in CERENAT are likely to be higher than published. We conclude that radiofrequency fields should be classified as a Group 2A ̔probable̓ human carcinogen under the criteria used by the International Agency for Research on Cancer (Lyon, France). Additional data should be gathered on exposures to mobile and cordless phones, other WTDs, mobile phone base stations and Wi‑Fi routers to evaluate their impact on public health. We advise that the as low as reasonable achievable (ALARA) principle be adopted for uses of this technology, while a major cross‑disciplinary effort is generated to train researchers in bioelectromagnetics and provide monitoring of potential health impacts of RF‑EMF.

“Hormesis”—An Inappropriate Extrapolation from the Specific to the Universal

Abstract Although it is generally accepted that some chemicals may have beneficial effects af low doses, incorporating these effects into risk assessments generally ignores well-established factors related to exposure and human susceptibility. The authors argue against indiscriminate application of hormesis in assessments of chemical risks for regulatory purposes.