Until the early 1960s, pesticide use was perceived as a benefit to agriculture and public health, with few harmful consequences. This perception changed dramatically with the publication 50 years ago of Rachel Carson’s Silent Spring. The book was the start of a debate that continues to this day on the relative benefits and risks of not just pesticides but all synthetic chemicals. Pesticides are unquestionably beneficial for food production. but there is a grow ing awareness of the risks to human and ecological health associated with their use. Over the past decade, a growing literature.has examined how early life exposure to an array of chemical agents, found not only in pesticides but also in personal care products and plastics, can affect human health. The effects on endocrine signaling.have been observed in the exposed generation and in succeeding generations, but the conclusions are not without controversy. “It is ironic to think that man might determine his own future by something so seemingly trivial as the choice of an insect spray” wrote Carson in 1962. Although she had no mechanism to explain her observations, it is now well documented that expo sure early in embryonic development to commonly used chemicals alters gene expression patterns that can lead to altered health later in life.
But what dose is required to cause an effect?
A large literature in the fields of endocrinology and general physiology demonstrates strates not only that different effects can be induced at different doses but also that the mechanisms driving those effects can differ as well. A report from the Endocrine Society states that different effects should be expected when comparing high and low dose regimens of endocrine disruptors. Studies using acute high dose exposures may thus be of limited value for predicting what might occur following the chronic low dose exposures that almost every population on Earth is subjected to today, often at low but detectable concentrations. Early life exposure to chemicals with endocrine disruption potential has been shown to alter gene expression profiles that are linked to altered morphology and physiologyiology, such as compromised fertility and reproductive tract development, altered metabolism, obesity, and altered behavior.
The multigenerational relation ship between chemical exposure and health has been observed in laboratory models and wildlife. Given the heritable nature of some epigenetic modifications. , the results indicate that the classic “gene by environment” paradigm used to understand environmental impacts on health is incomplete: The parental genome is based on both the genome inherited from the parents.and the epigenetic modifications that occurred to that genome before fertiliza tion of the new offspring. Much has been made of the inability of some research groups to replicate the endocrine crine disruptive effects of some chemicals reported by other laboratories. For example, Hayes et al..reported effects on the development of frogs after exposure to environmentally relevant concentrations of atrazine, but other groups were unable to replicate these findings. However, differences in the design of these experi ments did exist, including the source of the animals used and the density at which they were housed. Disparate outcomes have also been reported in studies of bisphenol A in rodents that used different designs or methodologies.and in studies of human semen quality or genital development. Blount et al. have found that in men, per chlorate.showed no relationship with the concentrations of thyroid biomarkers. In contrast, in women, raised urinary iodine levels were associated with an influence of perchlorate on thyroid biomarker concentrations. Thus, dietary iodine, a key fac tor influencing urinary iodine output, influenced whether an effect was observed or not. How many studies examining potential effects of contaminants on thyroid function record the iodine concentration in the diet of their research animals? Other studies also illustrate the complexityity of the response to environmental endocrine disruptors.
Further, a physical factor such as hypoxia can down regulate the mixed function oxygenase enzyme.that metabolizes polycyclic aromatic hydrocarbons and polychlorinated biphenyls, thereby affecting the biotransformation of environmental contaminants, thus altering persistence or even the metabolites present. These complex genetic and environmental effects must be taken into account in studies assessing the health effects of environmental pollutants. Rachel Carson was right: Chemical con taminants play an important role in our health and the health of the environment. We must continue her legacy and focus on how exposure to environmental contaminants, stress, and diet interacts with the human germline genome and epigenome to establish predispositions for disease that are influenced by secondary exposures later in life. Understanding this complexity is essential to our understanding of the mul multiple tiple roles of the environment in promoting those factors that lead to health.