Testing the Neural Sensitization and Kindling Hypothesis for Illness from Low Levels of Environmental Chemicals

Bell, Iris R.; Rossi, John; Gilbert, Mary E.; Kobal, Gerd; Morrow, Lisa A.; Newlin, David B.; Sorg, Barbara A.; Wood, Ronald W.

doi:10.2307/3433366

Cited by 12 publications

(14 citation statements)

References 54 publications

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“…Robinson and Becker (1986) concluded that behavioral sensitization or kindling is not unique to the psychopharmacology of stimulant drugs, but may be produced by many environmental stimuli that directly or indirectly activate brain catecholamine systems. A number of studies (Sorg et al, 1994;Bell et al, 1997a) have hypothesized that several human syndromes with poor medical diagnosis, including IEI and SBS, may involve chronic sensitization of catecholamine receptor systems resulting from repeated, low-level exposure to environmental chemical toxicants and stressors.…”

Section: Exposure Of Rats To Jp-4 Vapor 491mentioning

confidence: 98%

Repeated Exposure of Rats to Jp-4 Vapor Induces Changes in Neurobehavioral Capacity and 5-Ht/5-Hiaa Levels

Nordholm

Rossi²,

Ritchie³

et al. 1999

Journal of Toxicology and Environmental Health, Part A

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Thirty-two Sprague-Dawley rats were exposed for 6 h/d for 14 consecutive days to JP-4 jet fuel vapor (2 mg/L) or room air control conditions. Following a 14- or 60-d recovery period, rats completed a battery of 8 tests selected from the Navy Neurobehavioral Toxicity Assessment Battery (NTAB) to evaluate changes in performance capacity. Exposure to JP-4 vapor resulted in significant changes in neurobehavioral capacity on several tests that varied as a function of the duration of the recovery period. Rats were evaluated for major neurotransmitter and metabolite levels in five brain regions and in the blood serum. Levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were shown to be significantly elevated in several brain regions as well as in the blood serum in the vapor-exposed groups. Results of the rat study are compared to previously reported neurobehavioral evaluations of European manufacturing personnel exposed chronically to jet fuel vapor.

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Section: Exposure Of Rats To Jp-4 Vapor 491mentioning

confidence: 98%

Repeated Exposure of Rats to Jp-4 Vapor Induces Changes in Neurobehavioral Capacity and 5-Ht/5-Hiaa Levels

Nordholm

Rossi²,

Ritchie³

et al. 1999

Journal of Toxicology and Environmental Health, Part A

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“…It has been hypothesized (Bell et al, 1997a(Bell et al, , 1997b) that exposure to potent chemical odors may result in a "kindling-like" phenomenon by which inhaled chemicals can induce persisting changes in the excitabilit y of neuronal units in the olfactory bulbs and possibly in regions receiving secondary and tertiary inputs. The mechanism has been hypothesized as a possible basis for the development of such syndromes as IEI, through which a single high-dose exposure to an occupational or environmental chemical can ultimately result in widespread sensitivi ty to chemicals (foods, perfumes, ethanol, etc.)…”

Section: Olfactory Pathway Exposuresmentioning

confidence: 99%

“…There is mounting evidence that repeated exposure to low levels of certain volatile organic chemicals (VOCs), as are found as constituents of all hydrocarbon fuel formulations, may be involved in the etiology of such poorly defined diagnostic conditions as idiopathic environmental intolerance (IEI), chronic fatigue syndrome (CFS), sick building syndrome (SBS), tight building syndrome (TBS), fibromyalgia syndrome (FM), and Persian Gulf illnesses (PGI) (Bell et al, 1997a(Bell et al, , 1997bAshford & Miller, 1998). It is unknown whether repeated hydrocarbon fuel exposures, specifically those including exposure to low levels of multiple, potentially neurotoxic constituents, are sufficient to induce those syndromes commonly attributed to a single high-level exposure to one or more constituents.…”

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confidence: 99%

A Review of the Neurotoxicity Risk of Selected Hydrocarbon Fuels

Ritchie¹

2001

Journal of Toxicology and Environmental Health, Part B

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Over 1.3 million civilian and military personnel are occupationally exposed to hydrocarbon fuels, emphasizing gasoline, jet fuel, diesel fuel, or kerosene. These exposures may occur acutely or chronically to raw fuel, vapor, aerosol, or fuel combustion exhaust by dermal, respiratory inhalation, or oral ingestion routes, and commonly occur concurrently with exposure to other chemicals and stressors. Hydrocarbon fuels are complex mixtures of 150-260+ aliphatic and aromatic hydrocarbon compounds containing varying concentrations of potential neurotoxicants including benzene, n-hexane, toluene, xylenes, naphthalene, and certain n-C9-C12 fractions (n-propylbenzene, trimethylbenzene isomers). Due to their natural petroleum base, the chemical composition of different hydrocarbon fuels is not defined, and the fuels are classified according to broad performance criteria such as flash and boiling points, complicating toxicological comparisons. While hydrocarbon fuel exposures occur typically at concentrations below permissible exposure limits for their constituent chemicals, it is unknown whether additive or synergistic interactions may result in unpredicted neurotoxicity. The inclusion of up to six performance additives in existing fuel formulations presents additional neurotoxicity challenge. Additionally, exposures to hydrocarbon fuels, typically with minimal respiratory or dermal protection, range from weekly fueling of personal automobiles to waist-deep immersion of personnel in raw fuel during maintenance of aircraft fuel tanks. Occupational exposures may occur on a near daily basis for from several months to over 20 yr. A number of published studies have reported acute or persisting neurotoxic effects from acute, subchronic, or chronic exposure of humans or animals to hydrocarbon fuels, or to certain constituent chemicals of these fuels. This review summarizes human and animal studies of hydrocarbon fuel-induced neurotoxicity and neurobehavioral consequences. It is hoped that this review will support ongoing attempts to review and possibly revise exposure standards for hydrocarbon fuels.

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“…Sensitization is defined in the neuroscientific and pharmacologic literature as a progressive increase in the response to a set stimulus over time (3). Many traditional toxicologists and occupational health physicians argue that there is a lack of biological and toxicologic plausi-~ -bility for the notion that nontoxic levels of chemicals would result in symptoms characteristic of MCS.…”

mentioning

confidence: 99%

Model development and research vision for the future of multiple chemical sensitivity

Arnetz¹

1999

Scand J Work Environ Health

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Arnetz BB. Model development and research vision for the future of multiple chemical sensitivity. Scand J Work Environ Health 1999;25 (6, special issue):569-573.Multiple chemical sensitivity (MCS) is characterized by heightened self-reported sensitivity to extremely low concentrations of chemicals. It has numerous symptoms in common with the sick building syndrome, the Gulf War syndrome, and chronic fatigue. Despite much research, reproducible objective findings are lacking for MCS, as is a sound model to explain it. This paper proposes a 2-step model combining the needed epidemiologic terminology with that of psychophysiological activation and sensitization. It is suggested that different environmental stressors act as initiators. After initiation, the limbic system and other parts of the brain become sensitized and hyperrreactive to environmental triggers. Odor acts as one important trigger. Future research should use more biological assessments in combination with environmental and psychosocial data and involve patient groups with similar symptoms, although diagnosed as suffering from different entities. The similarities and differences of patients with such entities need to be understood before the entities themselves can be understood, diagnosed, treated, and prevented.

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Testing the Neural Sensitization and Kindling Hypothesis for Illness from Low Levels of Environmental Chemicals

Abstract: 539-547 (1997)

Cited by 12 publications

References 54 publications

Repeated Exposure of Rats to Jp-4 Vapor Induces Changes in Neurobehavioral Capacity and 5-Ht/5-Hiaa Levels

Repeated Exposure of Rats to Jp-4 Vapor Induces Changes in Neurobehavioral Capacity and 5-Ht/5-Hiaa Levels

A Review of the Neurotoxicity Risk of Selected Hydrocarbon Fuels

Model development and research vision for the future of multiple chemical sensitivity

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