Anne Spurgeon

Recent developments in low-level lead exposure and intellectual impairment in children.

In the last decade children’s blood lead levels have fallen significantly in a number of countries, and current mean levels in developed countries are in the region of 3 μg/dL. Despite this reduction, childhood lead poisoning continues to be a major public health problem for certain at-risk groups of children, and concerns remain over the effects of lead on intellectual development in infants and children. The evidence for lowered cognitive ability in children exposed to lead has come largely from prospective epidemiologic studies. The current World Health Organization/Centers for Disease Control and Prevention blood level of concern reflects this and stands at 10 μg/dL. However, a recent study on a cohort of children whose lifetime peak blood levels were consistently < 10 μg/dL has extended the association of blood lead and intellectual impairment to lower levels of lead exposure and suggests there is no safety margin at existing exposures. Because of the importance of this finding, we reviewed this study in detail along with other recent developments in the field of low-level lead exposure and children’s cognitive development. We conclude that these findings are important scientifically, and efforts should continue to reduce childhood exposure. However, from a public health perspective, exposure to lead should be seen within the many other risk factors impacting on normal childhood development, in particular the influence of the learning environment itself. Current lead exposure accounts for a very small amount of variance in cognitive ability (1–4%), whereas social and parenting factors account for 40% or more.

Neuropsychological effects of long-term exposure to organophosphates in sheep dip.

Organophosphate-based pesticides are widely used throughout the world. The acute effects of over-exposure to such compounds are well known. Concern has also been expressed that long-term exposure may result in damage to the nervous system. In a cross-sectional study, we compared neuropsychological performance in 146 sheep farmers who were exposed to organophosphates in the course of sheep dipping with 143 non-exposed quarry workers (controls). The farmers performed significantly worse than controls in tests to assess sustained attention and speed of information processing. These effects remained after adjustment for covariates. The farmers also showed greater vulnerability to psychiatric disorder than did the controls as measured by the General Health Questionnaire. There were no observed effects on short-term memory and learning. Repeated exposure to organophosphate-based pesticides appears to be associated with subtle changes in the nervous system. Measures should be taken to reduce exposure to organophosphates as far as possible during agricultural operations.

Abnormalities on neurological examination among sheep farmers exposed to organophosphorous pesticides

OBJECTIVES: Organophosphates are effective pesticides which are frequently used in several agricultural settings. Although their acute effects are well characterised, it remains unclear whether long term exposure can damage the human nervous system. This study sought to investigate their long term effects by comparing abnormalities on neurological examination between groups of workers exposed to organophosphates and an unexposed group. METHODS: 146 exposed sheep farmers and 143 unexposed quarry workers were recruited into a cross sectional study of symptoms and neuropsychological effects of long term exposure to organophosphates in sheep dip. From a symptom questionnaire given immediately after dipping the 10 most symptomatic and 10 least symptomatic farmers were selected. Several months later each of these, along with 10 of the unexposed quarry workers, underwent a standardised neurological examination similar to that which might be used in clinical practice, at at time as remote as possible from recent exposure to organophosphates so as to exclude any acute effects. RESULTS: All 30 selected subjects agreed to participate. The components of the examination which showed a significant difference were two point discrimination on the dorsum of the hand (symptomatic farmers 22 mm; asymptomatic farmers 13 mm; quarry workers 8 mm) and the dorsum of the foot (symptomatic farmers 34 mm; asymptomatic farmers 10 mm; quarry workers 11 mm), and mean calf circumference (symptomatic farmers 35.0 cm; asymptomatic farmers 36.3 cm; quarry workers 38.6 cm). Overall the prevalence of neurological abnormalities was low. CONCLUSIONS: The differences in neurological examination detected between groups were subtle and their clinical significance was unclear. However, they do suggest evidence of an adverse neurological effect from exposure to organophosphates. Further, larger scale studies will be required before it is possible to confirm or refute the differences detected.

Organophosphates: The relationship between chronic and acute exposure effects

The relationship between chronic (nonreversing) neuropsychological effects and acute exposure effects was investigated in 77 organophosphate exposed male sheep-dippers. Acute exposure effects were assessed prospectively using a purpose-constructed symptoms questionnaire administered pre-, and 24 h postexposure. Urine was analysed for dialkylphosphate levels to confirm recent exposure. Chronic effects were assessed in a cross-sectional neuropsychological study in the absence of recent exposure using computerised neuropsychological tests, the General Health Questionnaire, and the Subjective Memory Questionnaire. Simple correlation and multiple linear regression analyses (adjusting for confounders) were used to assess relationships between the change in total symptom reporting from baseline to 24 h after exposure and chronic effect outcomes. There was no evidence of any association between reported symptom levels and chronic neuropsychological effects. This suggests that chronic effects of OP exposure appear to occur independently of symptoms that might immediately follow acute OP exposure. This has implications for exposure control: individuals may experience chronic effects without the benefit of earlier warning signs of toxic effects during acute exposures.

Prenatal methylmercury exposure and developmental outcomes: review of the evidence and discussion of future directions.

I conducted a review of the published literature to assess the strength of the evidence for an association between prenatal exposure to methylmercury (MeHg) and subsequent child development. I identified 12 studies on this subject published since 1980. Of these, 3 were longitudinal studies—2 conducted in the Seychelle Islands, and 1 in the Faroe Islands. Nine were cross-sectional studies conducted in different countries where seafood, a source of MeHg, constituted a major part of the diet. The ages of the children studied ranged from 2 weeks to 12 years. The results of the longitudinal studies were contradictory. Researchers in the Faroe Islands identified an association between MeHg exposure and developmental effects, whereas those in the Seychelle Islands identified no such association. This inconsistency was mirrored in the results of the cross-sectional studies where there were some positive and some negative findings. It was concluded that it was not possible from currently available data to determine whether there is an association between prenatal MeHg exposure and adverse developmental effects in children. In advance of future research, consideration should be given to resolving the uncertainties surrounding exposure assessment and outcome measurement, as both elements varied between studies. It was suggested that questions of exposure assessment would benefit from the application of an expert review process. Outcome assessment would benefit from the development of theoretically based measures of specific aspects of cognitive functioning to replace the relatively crude measures of attainment and IQ currently employed in most studies. This would assist in the development of classic longitudinal studies by allowing repeated assessment over the full age range and providing data that are more readily interpretable and comparable between studies.

Analysis of chlorpyrifos exposure and human health: Expert panel report

This report summarizes the deliberations of an eight-member panel of scientists convened by Dow AgroSciences in cooperation with the U.S. Environmental Protection Agency (EPA). The panel was charged with evaluating the scientific literature on the health effects potentially associated with exposure to the insecticide chlorpyrifos. Specifically, the panel was asked to (1) evaluate human experience data available and address the adequacy of the available current literature; (2) develop a list of recommendations for epidemiology studies, including appropriate endpoints and study populations, and strengths and weaknesses of each approach; and (3) draft a report to summarize its recommendations. The panel assessed the quality of the existing epidemiologic literature on chlorpyrifos and specific outcomes such as neuropathy (including organophosphate induced delayed neurotoxicity), behavior (cognition and affect), immunologic, and multiple complaints (also referred to as multiple chemical sensitivities). The majority of panel members (five members) agreed that the literature reviewed provided little or no scientific evidence that chlorpyrifos exposure causes harm to human health other than its known cholinergic effects associated with acute poisoning. Those panel members voting in the minority (three members) agreed that the studies reviewed provided inadequate evidence to preclude the possibility of adverse effects to human health from chlorpyrifos exposure at levels associated with its manufacture or professional application. Those voting in the minority suggested further investigation of cohort(s) of workers engaged in either the manufacture or the professional application of chlorpyrifos, or both. Compared to the general population, these groups have relatively high levels of exposure to chlorpyrifos. The primary health outcomes recommended for study were cognitive and affective disorders, with consideration of the assessment of peripheral neuropathy also suggested for at least a subset of the cohort.

Investigation of dose related neurobehavioural effects in paintmakers exposed to low levels of solvents.

A cross sectional study was carried out to compare 110 paintmakers exposed to solvents with 110 age matched controls for outcome measures designed to assess cognitive performance and mental health. Hygiene data available for the paintmakers allowed the development of individual indices of solvent exposure and the analyses of health effects in relation to both duration and intensity of exposure. No effects on cognitive functioning or mental health were found in the paintmakers. For most of their period of employment the exposure of the paintmakers had been below current occupational exposure limits. The results are therefore interpreted as providing support for the view that long term exposure at or below current compliance levels does not result in damage to the central nervous system.

The use of neurobehavioural test batteries for research, diagnosis and screening: methodological aspects

In recent years neurobehavioural tests have been used increasingly in occupational and environmental settings to identify changes in cognitive functioning associated with exposure to neurotoxicants. Applications in cross-sectional research studies, involving the comparison of the performance of exposed and control groups, are relatively well established. However, the use of such methods requires attention to a variety of methodological issues including aspects of study design such as sample size, the selection of appropriate controls, the separation of acute and chronic effects and control or adjustment for numerous potential influences on performance. Studies requiring repeated testing, such as longitudinal investigations or studies of acute effects require attention to learning and practice effects and diurnal rhythms. The validity of adapting existing test batteries for use as diagnostic or screening instruments is questionable. Well-developed techniques exist for diagnosis but this requires lengthy and skilled test administration and interpretation and cannot be accomplished using research batteries. Existing tests may, in the future, be used for screening, but a number of problems will need to be addressed before they can be successfully applied in this context.

Review : Occupational Lead Exposure Do Current Exposure Standards Protect Workers from Harm? A Review of Neurobehavioural Findings since 1978

During the last 20 years a number of studies have been carried out to investi gate the neurobehavioural effects of occupational exposure to lead. These studies suggest that subtle effects on intellectual functioning may occur at exposure levels below those currently considered in many countries to be suffi cient to protect workers from harm. This paper critically reviews the evidence from these studies and considers the case for reviewing the position on stan dards for exposure to lead in the workplace.

Is There an Adverse Effect on the Intellectual Development of Children Exposed to Low Levels of Lead

Lead has been recognised as a neurotoxicant for hundreds of years. Initial awareness of its potential to damage the nervous system occurred as far back as the Roman Empire when lead was used extensively, for example in plumbing, and as a paint pigment, cosmetic agent and a sweetener and preservative for wines and fruits juices. Intoxication resulted in a variety of systemic and neurological effects, including encephalopathy and the well-documented motor peripheral neuropathy ’wrist drop’. During the last 200 years, the more severe manifestations of lead intoxication have tended to occur amongst industrial workers engaged in such diverse operations as lead mining and smelting, battery making, recycling processes, lead shot manufacture, paint-making, glass-making and motor car repair. As a result a major part of research into the effects of lead exposure has been directed towards the occupational field in an attempt to establish safer working conditions. More recently, however, attention has focused on the possible effects on the general population, whose exposure derives largely from living in a modern industrial society where lead is used extensively in manufacturing processes, and hence is transmitted via numerous routes into the wider environ-