Diethylbenzene‐induced sensorimotor neuropathy in rats

Gagnaire, François; Marignac, B.; Céaurriz, J. de

doi:10.1002/jat.2550100208

Cited by 36 publications

(21 citation statements)

References 6 publications

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“…As Rhomberg pointed out, the choice of mode of action is directly related to human relevance as humans…"have insufficient metabolic activation to the naphthalene epoxide to deplete GSH or to create sufficient levels of reactive metabolites so as to produce cytotoxicity, genotoxicity, or both, and without such toxicity, no carcinogenic risk is induced" (Rhomberg et al 2010). Gagnaire et al (1990Gagnaire et al ( , 1991Gagnaire et al ( , 1992 reported that 1,2-diethylbenzene (1,2-DEB) produced a characteristic neurological effect in mice, whereas the other two diethylbenzene isomers (1,3-DEB, 1,4-DEB) were not neurotoxic. In subsequent studies, 1,2,4-triethylbenzene (1,2,4-TEB) was found to be neurotoxic, but the 1,3,5 isomer was not (Gagnaire et al 1993, Tshala-Katumbay et al 2006.…”

Section: Naphthalenementioning

confidence: 99%

Characterization of the toxicological hazards of hydrocarbon solvents

McKee

Adenuga

Carrillo

2015

Critical Reviews in Toxicology

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Hydrocarbon solvents are liquid hydrocarbon fractions derived from petroleum processing streams, containing only carbon and hydrogen atoms, with carbon numbers ranging from approximately C5-C20 and boiling between approximately 35-370°C. Many of the hydrocarbon solvents have complex and variable compositions with constituents of 4 types, alkanes (normal paraffins, isoparaffins, and cycloparaffins) and aromatics (primarily alkylated one-and tworing species). Because of the compositional complexity, hydrocarbon solvents are now identified by a nomenclature ("the naming convention") that describes them in terms of physical/ chemical properties and compositional elements. Despite the compositional complexity, most hydrocarbon solvent constituents have similar toxicological properties, and the overall toxicological hazards can be characterized in generic terms. To facilitate hazard characterization, the solvents were divided into 9 groups (categories) of substances with similar physical and chemical properties. Hydrocarbon solvents can cause chemical pneumonitis if aspirated into the lung, and those that are volatile can cause acute CNS effects and/or ocular and respiratory irritation at exposure levels exceeding occupational recommendations. Otherwise, there are few toxicologically important effects. The exceptions, n-hexane and naphthalene, have unique toxicological properties, and those solvents containing constituents for which classification is required under the Globally Harmonized System (GHS) are differentiated by the substance names. Toxicological information from studies of representative substances was used to fulfill REACH registration requirements and to satisfy the needs of the OECD High Production Volume (HPV) initiative. As shown in the examples provided, the hazard characterization data can be used for hazard classification and for occupational exposure limit recommendations. Introduction Scope and purpose of the documentThe present document summarizes information on the physical/ chemical properties and toxicological hazards of hydrocarbon solvents and provides examples of the ways in which the information on hazard characterization can be used for hazard classification and to set occupational exposure limits. Many of the toxicological studies were published separately, but the results are summarized herein and referenced in the appendices.Hydrocarbon solvents are liquid hydrocarbon fractions that are primarily produced by the distillation of petroleum feed stocks or their synthetic analogs (e.g., Fischer-Tropsch derived materials), sometimes followed by additional processing steps such as solvent extraction, hydrodesulfurization, or hydrogenation. 1 Most hydrocarbon solvents are complex substances with variable compositions and are best described as UVCB 2 (unknown and variable composition) substances, but some are single constituent (mono-constituent) substances. The complex and variable nature of these solvents is the consequence of their manufacturing processes. In short, most hydroca...

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Section: Naphthalenementioning

confidence: 99%

Characterization of the toxicological hazards of hydrocarbon solvents

McKee

Adenuga

Carrillo

2015

Critical Reviews in Toxicology

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“…Animal models of neuropathy mediated by chemical toxicants are broadly relevant to the area of neurotoxicology. Motor nerve conduction velocity (MCV) testing is frequently used in experimental models of neurotoxicity caused by exposure to aromatic compounds [8] and pesticides [5] or associated with metabolic disorders (e.g., diabetes) neuropathies [7]. In human electro-diagnostic medicine, the testing of motor axons allows one to reliably detect conduction block associated with multifocal demyelination [9].…”

Section: Introductionmentioning

confidence: 99%

“…In the present study, we sought to determine if a chronic exposure to rotenone, resulting in dopaminergic loss, could also lead to peripheral neuronal damage related to motor dysfunction. Adult male Sprague-Dawley rats (n = 14) were treated with rotenone (1 or 2 mg/kg, s.c., once daily) on days 1, 3,6,8,10,13, 15, 17, 21, 22, and 27 to minimize mortality. Control rats received vehicle (DMSO) injections.…”

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confidence: 99%

Chronic exposure to rotenone, a dopaminergic toxin, results in peripheral neuropathy associated with dopaminergic damage

Binienda

Sarkar

Mohammed-Saeed

et al. 2013

Neuroscience Letters

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“…White spirit is such a mixture, associated with CNS effects in man. The effects on CNS of solvent mixtures may be induced by a small number of more potent components present in the organic solvent mixtures (Gagnaire et al 1990).…”

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confidence: 99%

Four Weeks' Inhalation Exposure of Long Evans Rats to 4‐tert‐Butyltoluene: Effect on Evoked Potentials, Behaviour, and Brain Neurochemistry

Lam

Ladefoged

Østergaard

et al. 2000

Pharmacology & Toxicology

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Long-lasting central nervous system (CNS) neurotoxicity of 4-tert-butyltoluene (TBT) has been investigated using electrophysiology, behaviour, and neurochemistry in Long Evans rats exposed by inhalation to 0, 20, or 40 p.p.m. TBT 6 hr/day, 7 days/week for 4 weeks. Flash evoked potentials and somatosensory evoked potentials were not affected by TBT. In Auditory Brain Stem Response there was no shift in hearing threshold, but the amplitude of the first wave was increased in both exposed groups at high stimulus levels. Three to four months after the end of exposure, behavioural studies in Morris water maze and eight-arm maze failed to demonstrate any TBT induced effects. Exposure was followed by a 5 months exposure-free period prior to gross regional and subcellular (synaptosomal) neurochemical investigations of the brain. TBT reduced the NA concentration in whole brain minus cerebellum. Synaptosomal choline acetyltransferase activity increased and acetylcholinesterase activity was unchanged suggesting increased synaptosomal ability for acetylcholine synthesis. The relative and total yield of synaptosomal protein was reduced suggesting reduced density and total number of synapses in situ, respectively. We hypothesise that a reduced yield of synaptosomal protein reflects a more general effect of organic solvent exposure on the software of the brain. The synaptosomal concentration per mg synaptosomal protein and the total amount of 5-hydroxytryptamine were not affected whereas the total amount of synaptosomal noradrenaline decreased. The concentration and the total amount of synaptosomal dopamine decreased. The noradrenergic and dopaminergic parts of CNS may be more vulnerable to TBT than the serotonergic, and these long-lasting effects may cause or reflect TBT-compromised CNS function.

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Diethylbenzene‐induced sensorimotor neuropathy in rats

Cited by 36 publications

References 6 publications

Characterization of the toxicological hazards of hydrocarbon solvents

Characterization of the toxicological hazards of hydrocarbon solvents

Chronic exposure to rotenone, a dopaminergic toxin, results in peripheral neuropathy associated with dopaminergic damage

Four Weeks' Inhalation Exposure of Long Evans Rats to 4‐tert‐Butyltoluene: Effect on Evoked Potentials, Behaviour, and Brain Neurochemistry

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