Neurodevelopment and endocrine disruption

Environmental Health Perspectives, June 15, 2004 by Theo Colborn

In this article I explore the possibility that contaminants contribute to the increasing prevalence of attention deficit hyperactivity disorder, autism, and associated neurodevelopmental and behavioral problems in developed countries. I discuss the exquisite sensitivity of the embryo and fetus to thyroid disturbance and provide evidence of human in utero exposure to contaminants that can interfere with the thyroid. Because it may never be possible to link prenatal exposure to a specific chemical with neurodevelopmental damage in humans, I also present alternate models where associations have been made between exposure to specific chemicals or chemical classes and developmental difficulties in laboratory animals, wildlife, and humans. Key words: ADHD, autism, behavior, endocrine disruptor, environmental contaminants, neurologic effects, prenatal exposure, thyroid. Environ Health Perspect 112:944-949 (2004). doi:10.1289/ehp.6601 available via http://dx.doi.org/[Online 17 November 2003]

**********

Approximately 12 years ago the scientific community acknowledged that certain synthetic chemicals are capable of crossing the placental and brain barriers and interfering with development and function (Colborn and Clement 1992). The chemicals mimic or interfere with endogenous hormones and other signaling chemicals of the endocrine system. These chemicals, distinguished as endocrine disruptors, bridge many chemical classes and are an integral part of the world economy and commerce. To date no validated or standardized screens or assays have been developed to test chemicals for their possible endocrine-disrupting effects. Consequently, none of the thousands of chemicals used today have been tested systematically for these effects for regulatory purposes. Despite this, the list is growing of known endocrine disruptors having a wide range of mechanisms of action that can interfere with brain development (Brucker-Davis 1998; Howdeshel12002).

The production and use of industrial and agricultural chemicals have increased at an almost exponential rate for the past 50 years, with roughly 10 new chemicals currently being introduced each day. The U.S. Environmental Protection Agency (U.S. EPA) estimates that 87,000 chemicals are in use today. In the United States the plastics industry has grown at the rate of 6-12% per year since the mid-1940s, with annual production in the United States reaching 85 billion pounds (> 338 pounds per person per year) in 1996. In developing countries, plastics production is expanding at the rate of 40% per year (Society of the Plastics Industry 1997). Plastics are used in toys, cosmetics, perfumes, cleaning compounds, clothing, telecommunication equipment, computers, almost all household products, high-impact sporting equipment, and construction material from buildings to automobiles, airplanes, and aerospace vehicles.

Currently approximately 875 active ingredients registered as pesticides by the U.S. EPA have been formulated into 21,000 pesticide products, with many more new products entering the market each month (Short and Colborn 1999). In 1995 the United States produced 1.3 billion pounds of pesticide active ingredients, of which herbicides (weed killers) are the most widely used. It is estimated that herbicides cover > 14% of the land surface of the United States. This does net include nonfarm use for lawns, gardens, golf courses, parks, roadsides, railways, airports, forests, federal applications on government lands, and vast rights-of-way by states, counties, and municipalities. More than 60% of herbicides are documented endocrine disruptors (Short and Colborn 1999). Among the most widely used herbicides that interfere with the thyroid system are 2,4-dichlorophenoxyacetic acid (2,4-D), acetochlor, aminotriazole, amitrole, bromacil, bromoxynil, pendamethalin, and the thioureas (Brucker-Davis 1998; Howdeshell 2002; Short and Colborn 1999).

Historical Perspective of Exposure and Human Disorders

When data on the growth in synthetic chemical production are compared with the data on increasing prevalence of neurodevelopmental and other developmental disorders in humans, the data begin to merge around 1970. At approximately the same time, the first generation of humans exposed in the womb to synthetic chemicals on a large scale began to have children of their own (Table 1). For example, a plastic monomer, bisphenol A (BPA), was introduced in the early 1920s. Polychlorinated biphenyls (PCBs) were introduced in 1929. DDT became available for retail sale in 1938, and the large-scale, widespread commercial use of a vast number of synthetic chemicals commenced near the end of World War II (WWII) in the 1940s. Companies previously producing chemicals for warfare converted to making pesticides and plastics as the petroleum industry began to find more uses for its by-products from gasoline production. Although indivduals were being exposed to these chemicals since the early 1920s, it was not until the end of WWII that exposure increased to such an extent that vast numbers of adults exposed daily were accumulating significant amounts of these chemicals in their bodies. In terms of generation time, these individuals in the 1950s produced the first generation of offspring exposed to numerous synthetic chemicals in the womb and at increased levels. By 1970 these post-WWII babies were having children of their own. It was during the 1970s that what appeared to be increases in unusual, previously rare neurodevelopmental disorders began to catch the attention of health professionals.

Terms such as learning disabilities, autism, attention deficit hyperactivity disorder (ADHD), childhood cancers, juvenile diabetes, and juvenile delinquency became household words by the mid-1990s. Parental support groups emerged across the nation for each anomaly, and in response, health authorities began to acknowledge these increases. In 1995 the U.S. EPA established the Children's Environmental Health Program to develop preventive measures to protect children from exposure to environmental contaminants, and in 2000, a presidential initiative led to the establishment of children's health centers nationwide to develop treatments and cures for these problems.