Human response to controlled levels of toluene in six-hour exposures.

Andersen, Ib; Lundqvist, Gunnar; Mølhave, Lars; Pedersen, Ole F.; Proctor, Donald F.; Væth, Michael; Wyon, David Peter

doi:10.5271/sjweh.2393

Cited by 119 publications

(69 citation statements)

References 14 publications

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“…It should be pointed out, however, that inhalation exposure does produce highly variable BTC in animals exposed to the same concentrations over the same period of exposure (Rees et al, 1985). Moreover, toluene vapors are irritating to the eyes at concentrations as low as 100 ppm (Andersen et al, 1983). For these reasons i.p.…”

Section: Experimental Protocol and Blood Toluene Concentrations (Btc)mentioning

confidence: 99%

Toluene-Induced Locomotor Activity is Blocked by 6-Hydroxydopamine Lesions of the Nucleus Accumbens and the mGluR2/3 Agonist LY379268

Riegel

Ali

French

2003

Neuropsychopharmacol

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The abuse of volatile inhalants remains a prominent, yet poorly understood, form of substance abuse among youth. Nevertheless, the identification of a mechanism underlying the reinforcing properties of inhalants has been hampered by the lack of a clearly identifiable neural substrate upon which these chemicals act. One ingredient that is common to many abused inhalants is toluene, an organic solvent that is self-administered by nonhuman primates and rodents. Most drugs of abuse have been found to elicit forward locomotion in rats, an effect owing to the activation of mesoaccumbal dopamine (DA) pathways. Thus, the present study was undertaken using two different approaches to determine whether toluene-induced locomotor hyperactivity is also ultimately dependent upon DA neurotransmission in the mesolimbic nucleus accumbens (NAC). Here we report on the effects of 6-hydroxydopamine (6-OHDA) lesions of the NAC or pretreatment with the metabotropic mGlu2/3 receptor agonist LY379268 on toluene-induced locomotor activity. Both procedures, which are known to alter neurotransmission within the NAC, significantly attenuated toluene's locomotor stimulatory effects. These results provide strong support for a central mechanism of action of inhalants, which in the past has been more typically attributed to general nonspecific mechanisms throughout the brain. Moreover, as with other drugs of abuse, the NAC may be the final common pathway subserving toluene's abuse liability.

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Section: Experimental Protocol and Blood Toluene Concentrations (Btc)mentioning

confidence: 99%

Toluene-Induced Locomotor Activity is Blocked by 6-Hydroxydopamine Lesions of the Nucleus Accumbens and the mGluR2/3 Agonist LY379268

Riegel

Ali

French

2003

Neuropsychopharmacol

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“…Toluene is another common solvent widely present in both domestic and industrial settings, particularly in the printing industry 9 . It has also been the target of a variety of investigations focusing on long exposures (up to 7 hours for up to 3 consecutive days) in environmental chambers 8,[10][11][12][13] . The concentration of toluene used in these studies was as high as 100 ppm, and, in some experiments, it reached a peak of 300 ppm every 30 min.…”

Section: Introductionmentioning

confidence: 99%

Psychometric functions for the olfactory and trigeminal detectability of butyl acetate and toluene

Cometto‐Muñiz

Cain

Abraham

et al. 2002

J of Applied Toxicology

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We measured psychometric (i.e. concentration–response) functions for the detection of odor, nasal pungency and eye irritation from butyl acetate and toluene. Olfactory detection was measured in subjects with normal olfaction (i.e. normosmics) for whom nasal trigeminal detection does not interfere because it requires much higher concentrations. Nasal trigeminal detection, called nasal pungency, was measured only in subjects lacking olfaction (i.e. anosmics) in order to avoid odor interference. Ocular trigeminal detection, called eye irritation, was measured in both groups. The method employed entailed a two‐alternative, forced‐choice procedure with presentation of increasing concentrations. The outcome showed, for both chemicals, similar ocular trigeminal chemosensitivity in normosmics and anosmics and similar overall ocular and nasal trigeminal chemosensitivity. Olfactory sensitivity was much higher than both forms of trigeminal sensitivity by concentration differences of six and four orders of magnitude for butyl acetate and toluene, respectively. Detectability plots (i.e. detection performance vs log concentration) for the three sensory endpoints followed an S‐shaped function with a middle range section that showed a robust linear fit (r > 0.94) on graphs of z‐score vs log concentration. These detectability functions allow the calculation of olfactory and trigeminal thresholds at various levels of performance. At a point half‐way between random and perfect detection, trigeminal and olfactory threshold concentrations were, respectively, 0.67 (±0.32) and 2.28 (±1.77) log units lower than those measured by us in the past for the same chemicals using an analogous procedure but under just one, fixed, level of performance. The available data suggest that, although considerably laborious, detectability functions provide chemosensory thresholds of closer relevance to environmentally realistic conditions (e.g. whole‐body exposures). Copyright © 2002 John Wiley & Sons, Ltd.

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“…9 Studies have shown that subjects exposed to 100 ppm of toluene for six hours complained of eye and nose irritation, and in some cases, headache, dizziness, and a feeling of intoxication (narcosis). 10,11,12 No symptoms were noted below 100 ppm in these studies. There are a number of reports of neurological damage due to deliberate sniffing of toluene-based glues resulting in motor weakness, intention tremor, ataxia, as well as cerebellar and cerebral atrophy.…”

Section: Toluenementioning

confidence: 89%

HETA 2001-0059-2861, Boat America Corporation, Alexandria, Virginia.

2001

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Human response to controlled levels of toluene in six-hour exposures.

Cited by 119 publications

References 14 publications

Toluene-Induced Locomotor Activity is Blocked by 6-Hydroxydopamine Lesions of the Nucleus Accumbens and the mGluR2/3 Agonist LY379268

Toluene-Induced Locomotor Activity is Blocked by 6-Hydroxydopamine Lesions of the Nucleus Accumbens and the mGluR2/3 Agonist LY379268

Psychometric functions for the olfactory and trigeminal detectability of butyl acetate and toluene

HETA 2001-0059-2861, Boat America Corporation, Alexandria, Virginia.

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