Reviews
Mechanisms of Large Effects from Small Exposures
The issues surrounding dose response to environmental endocrine-disrupting
chemicals (EEDCs) are pivotal to exposure risk assessment and consequently to
regulatory considerations. Many EEDCs are biologically active at very low concentrations.
Welshons et al. (p. 994) review
the issues associated with the underestimation of true bioactivity when only
high doses are used in toxicologic studies. The major points considered include
low-dose biological activity not observed by traditional testing, nonlinear
dose extrapolation, complex receptor responses, and the effects of exogenous
exposure on an already active biological pathway.
Environmental Pollutants and Breast Cancer
Breast
cancer is the most common cancer in women and the leading cause of cancer death
among women 35 to 54 years of age. Although not now directly linked to environmental
exposure, a review of research in this area (Brody
and Rudel, p. 1007) reveals major knowledge gaps, difficult challenges
in research design, and contrasting bodies of evidence from toxicologic and
epidemiologic studies. Substantial work is needed in exposure assessment, toxicology,
and susceptibility before we can expect a pay-off from large epidemiologic studies
of breast cancer and environment.
Assessing Estrogenic Potency of Human Milk
No clinical
or epidemiologic evidence demonstrates that levels of estrogenic chemicals in
human milk or infant formulas cause adverse effects. Nonetheless, the question
is sufficiently important to warrant consideration of how best to evaluate estrogenic
risks. Borgert et al. (p. 1020) review
the data for measuring estrogenic potency and the methods for estimating health
risks from chemicals in infant nutrition sources and conclude that the science
is insufficiently developed to allow a credible risk assessment for infants.
Etiology and Pathology of Uterine Leiomyomas
Uterine
leiomyomas, or fibroids, represent a major public health problem. It is believed
that these tumors develop in the majority of American women and are the most
common cause of hysterectomy in the United States. Flake
et al. (p. 1037) summarize clues from what has been learned during the
past 20 years, including predisposing conditions such as age and ethnicity,
cytogenetic abnormalities, and hormonal factors involved in growth. The role
for environmental endocrine disruptors has only recently begun to be explored.
Genetic Polymorphisms in Environmental Health
Polymorphisms render some individuals or groups in the population more or less
likely to develop disease after exposure to environmental hazards (geneenvironment
interaction). Kelada et al. (p. 1055)
present examples of geneenvironment interaction that illustrate the major
theme of effect modification. Current data gaps illustrate limitations of past
research and the need for more robust methods in future research. The ability
to detect different levels of risk within the population, and greater understanding
of etiologic mechanisms offer opportunities for disease prevention.
Parkinson's Disease and Exposure to Infectious Agent and Pesticides
Despite
decades of intense research, the etiology of sporadic idiopathic Parkinson's
disease and the mechanism underlying the selective neuronal loss remain unknown.
The late-onset and slow-progressing nature of the disease have prompted the
consideration of environmental chemical exposure as a risk factor (Liu
et al., p. 1065). Some evidence suggests that early-life brain inflammation
may play a role. There may exist a self-propelling cycle of inflammatory processes
involving brain immune cells (microglia and astrocytes).
Particulate Matter Health Effects Research
In
recent years epidemiologic studies have linked increasing ambient particulate
matter (PM) concentrations with increasing annual mortality, cardiovascular
disease, hospital admissions, and a range of other adverse health effects. The
U.S. Environmental Protection Agency acknowledges that information about PM
exposures as causal factors in the human population is not fully consistent
with controlled animal and human studies. As a result, a multiyear research
initiative was established to thoroughly investigate the health effects of PM
through a series of research centers. Lippman
et al. (p. 1074) provide an overview of research progress and goals
related to a) biological mechanisms, b) acute effects, c) chronic effects, d)
dosimetry, and e) exposure assessment.
Metals and the Biodegradation of Organic Pollutants
Forty
percent of hazardous waste sites in the United States are co-contaminated with
organic and metal pollutants. Biodegradation of organic components can be reduced
by metal toxicity determined largely by metal bioavailability. Sandrin
and Maier (p. 1093) address a) the importance of the physicalchemical
state of metals in relation to metal bioavailability and microbial inhibition,
b) the impact of metals on biodegradation processes, and c) mitigation of metal
toxicity.
Recreational Water Quality and Gastrointestinal Illness
Wade
et al. (p. 1102) examined the association between microbial indicators
of recreational water quality and gastrointestinal (GI) illness. Results support
the use of enterococci in marine water at U.S. Environmental Protection Agency
guideline levels and Escherichia coli as a more consistent predictor
of GI illness than enterococci and other bacterial indicators in fresh water.
Indicators of viral contamination were strong predictors of GI illness in both
fresh water and marine environments. There was significant heterogeneity among
study designs. Future studies should focus on the ability of new more rapid
and specific microbial methods to predict health effects of recreational water
exposure among susceptible persons.
Potential Allergenicity of Genetically Modified Foods
The
general public and the scientific community are concerned about the potential
toxicity of genetically modified foods. The use of biotechnology to enhance
pest resistance or nutritional value has raised a number of questions including
the consequences of reporter gene insertion, spread of resistance genes, and
the use of suicide genes to prevent reuse of seed. Of particular interest is
the ability of proteins from genetically modified foods to elicit potentially
harmful immunologic responses, including allergic hypersensitivity (Melcalfe,
p. 1110).
Clinical Aspects of Food Allergy
Food allergy affects 6% of children and 1.52% of adults in the United
States. A number of expert committees have created decision trees based on assessment
of IgE-mediated food allergenicity; however, not all food allergy is mediated
by IgE. Difficulties include limited allergen-specific IgE antisera from allergic
persons as validated source material, the utility of specific IgE assays, limited
characterization of food proteins, cross-reactivity between food and other allergens,
and modifications of food proteins by processing. (Bernstein
et al., p. 1114).
Protein Digestion and Allergenicity
Digestion stability as a criterion for protein allergenicity assessment has
been widely adopted. However, a review of more recent work (Bannon
et al., p. 1122) with various known and unknown food allergens and various
other proteins, i.e., storage proteins, plant lectins, contractile proteins
and enzymes indicates food allergens may not necessarily be more resistant to
digestion than nonallergenic proteins.
Animal Models for Protein Allergenicity
Given the public concern over consumption of genetically modified foods, it
is critical to have appropriate methods for identification of potential hazards.
A view that animal studies will contribute important information about the allergenicity
of modified foods has given momentum to the development of suitable animal models.
Although considerable progress has been made, none has been evaluated rigorously
or validated formally (Kimber et al.,
p. 1125).
Issues in Assessing Allergenicity of Genetically Modified Foods
Participants in the workshop "Assessment of the Allergenic Potential of Genetically
Modified Foods" met in breakout groups to discuss general and specific questions
in the following areas: 1) use of human clinical data, 2) animal models to assess
food allergy, 3) biomarkers of exposure and effect, 4) sensitive populations,
5) doseresponse assessment, and 6) postmarket surveillance. Germolec
et al. (p. 1131) present a brief summary of the discussions of each
of the six breakout groups regarding our current state of knowledge and what
information is needed to advance the field.
Research Needs for Assessment of Genetically Modified Foods
The potential risks of allergenicity associated with genetically modified
foods will likely be manageable, provided appropriate information is available
to decision makers. In the breakout sessions presented by Germolec et al., participants
were asked to identify research needs to ensure the safety of foods derived
from biotechnology. Selgrade et al. (p. 1140)
present a summary of these research needs and identify critical data gaps in
our basic understanding of the mechanisms of food allergy and in the methods
that can be used for hazard identification. Significant coordination between
funding organizations combined with open and free exchange of information will
be required for meaningful progress.
[Table of Contents]
Last Updated: June 17, 2003
