Role of human neurobehavioural tests in regulatory activity on chemicals.

Stephens, Richard; Barker, Penny

doi:10.1136/oem.55.3.210

Cited by 6 publications

(5 citation statements)

References 17 publications

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“…In the present study, motor performance varied as expected, with age, education and gender; the group was homogeneous with regard to culture. Cigarette smoking and alcohol consumption, factors that may potentially modify or confound the relationship between chemical substances and neurotoxic eects (Stephens and Barker 1998), aected performance on the Santa Ana motor dexterity test, as did reported arthritis. There was a high frequency of reported arthritis in this population, that was inversely associated with manual dexterity.…”

Section: Discussionmentioning

confidence: 94%

Methylmercury exposure affects motor performance of a riverine population of the Tapajós river, Brazilian Amazon

Dolbec¹,

Mergler²,

Passos

et al. 2000

International Archives of Occupational and Environmental Health

187

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Gold mining and deforestation in the Brazilian Amazon are increasing mercury pollution of the extensive water system, exposing riverine populations to organic mercury through fish-eating. The aim of the present study was to evaluate the effect of such exposure on motor performance. This cross-sectional study was carried out in May 1996, in a village located on the banks of the Tapajós river in the Amazonian Basin, Brazil. Information concerning sociodemographics, health, smoking habits, alcohol drinking, dietary habits and work history were collected using an interview-administered questionnaire. Mercury concentrations were measured by cold vapor atomic absorption in blood and hair of each participant, of whom those aged between 15 and 79 years were assessed for motor performance (n = 84). Psychomotor performance was evaluated using the Santa Ana manual dexterity test, the Grooved Pegboard Fine motor test and the fingertapping motor speed test. Motor strength was measured by dynamometry for grip and pinch strength. Following the exclusion of 16 persons for previous head injury, working with mercury in the goldmining sites, or for diabetes, the relationship between performance and bioindicators of mercury was examined using multivariate statistical analyses, taking into account covariables. All participants in the study reported eating fish, which comprised 61.8% of the total meals eaten during the preceding week. The median hair total mercury concentration was 9 microg/g. Organic mercury accounted for 94.4 = 1.9% of the total mercury levels. Multivariate analysis of variance indicated that hair mercury was inversely associated with overall performance on the psychomotor tests, while a tendency was observed with blood mercury. Semipartial regression analyses showed that hair total mercury accounted for 8% to 16% of the variance of psychomotor performance. Neither hair nor blood total mercury was associated with the results of the strength tests in women and men. Although dose-effect relationships were observed in this cross-sectional study, they may reflect higher exposure levels in the past. The findings of this study demonstrated neurobehavioral manifestations of subtle neurotoxic effects on motor functions, associated with low-level methylmercury exposure.

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Section: Discussionmentioning

confidence: 94%

Methylmercury exposure affects motor performance of a riverine population of the Tapajós river, Brazilian Amazon

Dolbec¹,

Mergler²,

Passos

et al. 2000

International Archives of Occupational and Environmental Health

187

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show abstract

“…In a meeting report from an international workshop organized by the United Kingdom Health and Safety Executive (Stephens & Barker, 1998), it was stated that "the difficulties encountered by regulators confronted with neurobehavioural studies seem to be twofold; some studies lack scientific rigor; other studies, although scientifically sound, are problematic because it is not clear what interpretation to place on the results" (p. 211).…”

Section: Cognitive and Sensory Effectsmentioning

confidence: 98%

“…This information is generally derived from human case studies, which may be problematic due to deficient exposure documentation or dose-response information; use of anecdotal reports; lack of causality; expectation bias; and the authors may not have considered alternative etiologies. In the United Kingdom (UK), there is concern that longterm exposure to pesticides, particularly OPs, may result in damage to the nervous system (Stephens et al, 1995;Stephens & Barker, 1998;Ray, 1998). In a cross-sectional study (Stephens et al, 1995), neuropsychological performance of 146 sheep farmers who were exposed to OPs in the course of sheep dipping were compared to 143 quarry workers (controls).…”

Section: Cognitive and Sensory Effectsmentioning

confidence: 99%

Regulating and Assessing Risks of Cholinesterase-Inhibiting Pesticides: Divergent Approaches and Interpretations

Chen²,

Eb³

et al. 1999

Journal of Toxicology and Environmental Health, Part B

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This document presents a revised framework for conducting worker and dietary risk assessments for less-than-lifetime exposures to organophosphate or carbamate pesticides based on red blood cell (RBC) or brain acetylcholinesterase (AChE) inhibition or the presence of clinical signs and symptoms. The proposals for appropriate uncertainty factors are based on the biological significance of the cholinesterase (ChE) inhibition noted at the lowest-observed-effect level (LOEL) and the degree of uncertainty in the extrapolation between human and animal data. An extensive evaluation of industry data, not previously summarized, and the available literature indicate that the following risk assessment principles are supportable and protective of human health: Plasma ChE inhibition is not an adverse effect, and therefore should not be utilized in risk assessments. Red blood cell AChE is not associated with the nervous system and inhibition is not per se an adverse (neurotoxic) effect. When available, cholinergic effects or brain AChE inhibition data should take precedence over RBC AChE for determining no-observed-effect levels (NOELs). When available, human RBC AChE inhibition or cholinergic effects data should take precedence over animal data for determining NOELs. Due to the lack of adversity associated with inhibition of RBC AChE, the use of a 10-fold (10x) uncertainty factor from the NOEL is adequate when RBC AChE inhibition data from either animal or human studies are used to assess human risk. Due to greater potential for adversity, NOELs for brain AChE inhibition and cholinergic effects identified in animal studies should receive a default uncertainty factor of 100x; lower uncertainty factors may be used on a case-by-case basis. NOELs based on cholinergic effects noted in human studies should only require a 10x uncertainty factor, since an interspecies extrapolation factor from animals to humans is unnecessary. For RBC and brain AChE activity the threshold for defining a NOEL should be less than or equal to 20% difference from control activity in all species. For risk assessment purposes, duration and route of the study should reflect the expected duration and route of exposure for humans (i.e., a 21-d or 28-d dermal study for subchronic occupational dermal exposure assessment). When dermal data are not available, a subchronic oral toxicity study and an appropriate dermal penetration factor should be used. A general default of 10% absorption should be used, analogous to the United Kingdom and German exposure models that are widely used in Europe. The recommendations in this document are generally consistent with current risk assessment procedures used by Canada, the European Community (EC), and the United Kingdom (UK).

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“…However, improvements in interpretability and comparability are more complex issues likely to require a radical change of approach. In recent years a number of authors have pointed to the overemphasis on empiricism in this field and the lack of a strong theoretical underpinning for the assessment tools employed ( Stephens and Barker 1998 ; Stollery 1990 , 1996 ; Williamson 1990 ). The development of tests grounded in well-established cognitive theory would allow results to be discussed in terms of the specific aspects of cognitive processing under investigation rather than simply by reference to broad and largely uninformative categories of effect such as “memory” or “attention.” Modern approaches to the study of memory processes, for example, have long distinguished between several elements that contribute to the final outcome (initial registration of information, encoding, transfer to long-term store, loss of information by decay or interference, and use of cues for retrieval) ( Baddeley 1987 ).…”

Section: Discussionmentioning

confidence: 99%

Prenatal Methylmercury Exposure and Developmental Outcomes: Review of the Evidence and Discussion of Future Directions

Spurgeon

2006

Environ Health Perspect

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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.

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Role of human neurobehavioural tests in regulatory activity on chemicals.

Cited by 6 publications

References 17 publications

Methylmercury exposure affects motor performance of a riverine population of the Tapajós river, Brazilian Amazon

Methylmercury exposure affects motor performance of a riverine population of the Tapajós river, Brazilian Amazon

Regulating and Assessing Risks of Cholinesterase-Inhibiting Pesticides: Divergent Approaches and Interpretations

Prenatal Methylmercury Exposure and Developmental Outcomes: Review of the Evidence and Discussion of Future Directions

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