Elsevier

The Lancet

Volume 368, Issue 9553, 16–22 December 2006, Pages 2167-2178
The Lancet

Review
Developmental neurotoxicity of industrial chemicals

https://doi.org/10.1016/S0140-6736(06)69665-7Get rights and content

Summary

Neurodevelopmental disorders such as autism, attention deficit disorder, mental retardation, and cerebral palsy are common, costly, and can cause lifelong disability. Their causes are mostly unknown. A few industrial chemicals (eg, lead, methylmercury, polychlorinated biphenyls [PCBs], arsenic, and toluene) are recognised causes of neurodevelopmental disorders and subclinical brain dysfunction. Exposure to these chemicals during early fetal development can cause brain injury at doses much lower than those affecting adult brain function. Recognition of these risks has led to evidence-based programmes of prevention, such as elimination of lead additives in petrol. Although these prevention campaigns are highly successful, most were initiated only after substantial delays. Another 200 chemicals are known to cause clinical neurotoxic effects in adults. Despite an absence of systematic testing, many additional chemicals have been shown to be neurotoxic in laboratory models. The toxic effects of such chemicals in the developing human brain are not known and they are not regulated to protect children. The two main impediments to prevention of neurodevelopmental deficits of chemical origin are the great gaps in testing chemicals for developmental neurotoxicity and the high level of proof required for regulation. New, precautionary approaches that recognise the unique vulnerability of the developing brain are needed for testing and control of chemicals.

Section snippets

Vulnerability of the developing brain

The developing human brain is inherently much more susceptible to injury caused by toxic agents than is the brain of an adult.12 This susceptibility stems from the fact that during the 9 months of prenatal life, the human brain must develop from a strip of cells along the dorsal ectoderm of the fetus into a complex organ consisting of billions of precisely located, highly interconnected, and specialised cells. Optimum brain development requires that neurons move along precise pathways from

Recognition of neurotoxicity

Developmental neurotoxicity in children exposed to industrial chemicals is often first identified through recognition of obvious functional abnormalities after high-dose exposure that clearly caused poisoning. Good quality research later documented the presence of less striking, but nonetheless serious adverse effects at low doses of exposure (figure 1). This sequence of discovery led to the recognition that environmental pollutants exert a range of adverse effects—some are clinically evident,

Identification

Studies in animals support the notion that a wide range of industrial chemicals can cause developmental neurotoxicity at low doses that are not harmful to mature organisms.26, 27 Such injury seems to result in permanent changes in brain function that might become detectable only when the animal reaches maturity. Because developmental neurotoxicity might not be apparent from routine toxicology tests,28 identification of neurotoxic chemicals often rests on clinical and epidemiological data.

To

Emerging neurotoxic substances

Documentation of developmental effects in human beings for the other compounds listed in the panel is poor. However, three obvious candidate substances deserve particular attention, including two that have not seemed to cause neurotoxicity in adults.

Effects of developmental neurotoxicity

The five substances recognised as causes of developmental neurotoxicity show similar patterns in the development of scientific documentation of their risks. This pattern of discovery started in each instance with recognition of adult neurotoxicity, typically in people with occupational exposure, and of episodes of acute, high-dose poisoning in children. The next stage was the accumulation of epidemiological evidence of neurobehavioural deficits in children with prenatal exposures at

Prevention

A pandemic of neurodevelopmental toxicity caused by industrial chemicals is, in theory, preventable. Testing of new chemicals before allowing them to be marketed is a highly efficient means to prevent toxicity, but has been required only in recent years. Of the thousands of chemicals used in commerce, fewer than half have been subjected to even token laboratory testing for toxicity testing.24 Nearly 3000 of these substances are produced in quantities of almost 500 000 kg every year, but for

Search strategy and selection criteria

We identified industrial chemicals that have caused neurotoxic effects in man from the hazardous substances data bank of the US National Library of Medicine, supplemented by fact sheets by the US Agency for Toxic Substances and Disease Registry, and the integrated risk information system of the US Environmental Protection Agency. We searched for the terms “neurotoxic”, “neurological”, and “neuro”. For all neurotoxic substances identified, we then used synonyms, commercial names, and CAS

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