Regional brain distribution of toluene in rats and in a human autopsy

Abstract

Toluene concentrations in 9 brain regions of acutely exposed rats and that in 11 brain regions of a human case who inhaled toluene prior to death are described. After exposure to toluene by inhalation (2000 or 10,000 ppm) for 0.5 h or by oral dosing (400 mg/kg), rats were killed by decapitation 0.5 and 4 h after onset of inhalation and 2 and 10 h after oral ingestion. After each experimental condition the highest range of brain region/blood toluene concentration ratio (BBCR) was in the brain stem regions (2.85-3.22) such as the pons and medulla oblongata, the middle range (1.77-2.12) in the midbrain, thalamus, caudate-putamen, hypothalamus and cerebellum, and the lowest range (1.22-1.64) in the hippocampus and cerebral cortex. These distribution patterns were quite constant. Toluene concentration in various brain regions were unevenly distributed and directly related blood levels. In a human case who had inhaled toluene vapor, the distribution among brain regions was relatively similar to that in rats, the highest concentration ratios being in the corpus callosum (BBCR: 2.66) and the lowest in the hippocampus (BBCR: 1.47).

Maternal and fetal blood and organ toluene levels in rats following acute and repeated binge inhalation exposure☆

“…While there is no comparable study assessing blood or tissue toluene levels in pregnant rats after repeated binge exposure(s) to high concentrations of inhaled ambient toluene, there are two inhalation studies of perhaps limited relevance in 42-day-old male rats using different patterns of exposure. One study assessed BTLs in Fisher-344 rats during and after exposure accompanying 3 hours of restraint to 99 ppm, 549 ppm, or 1145 ppm of toluene [23] and another assessed BTLs in Wistar rats after a single 30-min inhalation of 2,000 ppm or 10,000 ppm of toluene [2]. Blood or serum toluene levels were assayed in separate rats at different times during the 3-hr exposure [23], or from the same rats (via femoral catheters; [2]), for the next 4 to 10 hours.…”

“…One study assessed BTLs in Fisher-344 rats during and after exposure accompanying 3 hours of restraint to 99 ppm, 549 ppm, or 1145 ppm of toluene [23] and another assessed BTLs in Wistar rats after a single 30-min inhalation of 2,000 ppm or 10,000 ppm of toluene [2]. Blood or serum toluene levels were assayed in separate rats at different times during the 3-hr exposure [23], or from the same rats (via femoral catheters; [2]), for the next 4 to 10 hours. Gospe and Al-Bayati [23] showed that serum toluene levels asymptoted at ∼15 ppm between 1 hr and 2 hrs into the exposure period, similar to the ∼14.4 ppm level achieved after 2,000 ppm by Ameno, et al [2], and also comparable to the asymptotic levels at 30 min to 45 min in the current study.…”

“…Blood or serum toluene levels were assayed in separate rats at different times during the 3-hr exposure [23], or from the same rats (via femoral catheters; [2]), for the next 4 to 10 hours. Gospe and Al-Bayati [23] showed that serum toluene levels asymptoted at ∼15 ppm between 1 hr and 2 hrs into the exposure period, similar to the ∼14.4 ppm level achieved after 2,000 ppm by Ameno, et al [2], and also comparable to the asymptotic levels at 30 min to 45 min in the current study.…”

“…Since volatile toluene is cleared within one hour [16,20], the persistent levels of toluene in blood or serum [2,23] four to ten hours after removal from the toluene vapor also suggest transfer from other pools. There were also clear concentrationdependent differences in toluene levels [2,23] not seen in the current study, suggesting that it will be important to include lower concentration exposures in future studies to aid in interpretation of the impact of the much higher concentrations. In particular, the highest toluene level of ∼200 ppm, measured 30 mins after the 10,000-ppm exposure reported by the Ameno et al study [2] was substantially higher in blood and brain than even after two 45-min exposures at 12,000 ppm in the current study.…”

Changes in markers of oxidative status in brain, liver and kidney of young and aged rats following exposure to aromatic white spirit

“…These have been suspected to be especially toxI~, and therefore dearomatization is widely used, despite the fact that no firm evidence of a distinctive aromatic solvent-related neurotoxicity has emerged from human studies. However, using animal models, both pure aromatics such as xylene and toluene and aromatic mixtures have been implicated as distinctly neur~toxic (LeBel and Schatz 1988;Ameno et al 1992;Mattia et al 1993a,b). These studies have involved relatively high level dosing for rather short times.…”