Comparison of Oral and Inhalation Exposures to Toluene

Male Fisher-344 rats were exposed to [14C]toluene by either liquid gavage or vapor inhalation and blood toluene levels were measured by radiospectroscopy. Oral doses of 110, 336, 741, and 911 mg toluene/kg body weight were administered to 82 rats by gavage and blood toluene levels were followed for 6 h. For the inhalation group (120 rats), 3-h exposures to 99, 549, and 1,145 ppm were given and blood toluene levels were measured during this 3-h uptake phase and during a 4-h elimination period. The data for these two exposure methods were fitted to parametric kinetic models, and the resulting curves were then integrated. The blood toluene versus time profiles for oral and inhalation exposures were then compared and the equation: In(oral dosage, mg/kg) = -1.44 + 0.95 In(3-h inhalation exposure concentration, ppm) was derived (where In represents the natural logarithm). This equation describes the relation between toluene inhalation and oral exposure methods used in this study. This investigation demonstrates that oral toluene administration produces high blood toluene concentrations that can simulate the blood levels achieved after inhalation exposure to this solvent.

Glue Sniffing Deaths in Singapore — Volatile Aromatic Hydrocarbons in Post-Mortem Blood by Headspace Gas Chromatography

Over a period from 1983 to 1991, of a total of 19,000 post-mortems, 33 were found to have at least one aromatic hydrocarbon (benzene, toluene or xylenes) in the blood. Of the 33 deceased, 22 had a history of toluene or petrol abuse while most of the remaining 11 were suspected to be glue sniffers through evidence found at the scene. This number, which represented 0.17 per cent of all the unnatural deaths, is considered small for a nation having a glue sniffing epidemic. The low death rate, as compared to 2.1 per cent through drug and chemical poisoning during the same period, is attributed to the timely intervention by the Government who outlawed glue sniffing and the effectiveness of compulsory rehabilitation. The male gender predominates (81.8 per cent) among the 33 deceased with a mean age of 20.1 years (range 15 to 33). The mean age for the female gender is 17.7 years (range 16 to 20). The blood toluene levels were found to be in the range 0.2 to 92μg per ml blood. The causes of death are: 63.6 per cent due to falling or suicide by jumping; 18.2 per cent drowning; 6.1 per cent hanging; 6.1 per cent homicide; and 6.1 per cent acute toluene poisoning. The high proportion of traumatic deaths are discussed. Headspace gas chromatography with a suitable GC column was used for the analysis. Calibration blood standards were prepared in situ or in bulk stabilized by 10 per cent (v/v) methanol to overcome the hydrophobic and volatile nature of the aromatic hydrocarbons. Both methods of calibration gave analogous calibration factors, (slope for toluene: 0.092 to 0.095; slope for m-xylene: 0.070 to 0.071; and slope for o-xylene: 0.064 to 0.065), correlation coefficients of 0.9997 or better and standard deviation of 3.1 per cent or less. The consequences of different ways of blood standards preparations are discussed.

Influence of varions mixtures of inhaled toluene and xylene on the biological monitoring of exposure to these solvents in rats

The present study was undertaken to describe the influence of simultaneous exposure by inhalation to toluene and xylene on some aspects of their respective metabolic disposition. Adult male rats were exposed acutely (5 h) to 75, 150, and 225 ppm of toluene or xylene and to various mixtures of these solvents: toluene (75 ppm) and xylene (225 ppm), toluene (150 ppm) and xylene (150 ppm), toluene (225 ppm) and xylene (75 ppm). Compared with single exposure, simultaneous exposure resulted in lower amounts of excreted hippuric acid (20–30%) and methylhippuric acids (4–40%) in urine over a period of 24 h, even though significant differences were seen only with the toluene (150 ppm) and xylene (150 ppm) combination. In addition, increased concentrations of solvents in blood (toluene, 230%; xylene, 500%) and in brain (toluene, 230%; xylene, 320%) were found during the immediate post-exposure period. Simultaneous exposure also enhanced the pulmonary elimination of both solvents (toluene, 190–240%; xylene, 340–650%). Influence of repeated simultaneous exposure (9 days) was investigated for the toluene (150 ppm) and xylene (150 ppm) combination and the results compared with those of repeated exposure to each solvent administered singly. Under these conditions, repeated simultaneous exposure decreased the excretion of urinary metabolites, but only after the first exposure. On the other hand, simultaneous exposure resulted in significantly higher concentrations of toluene (210%) and xylene (240%) in blood throughout the entire 9-day exposure period. These results strongly suggest mutual metabolic interactions (inhibition) between toluene and xylene that affect the metabolic disposition of both solvents and ultimately the biological monitoring of data of exposure to a combination of solvents in rats.Key words: toluene, xylene, simultaneous exposure, biological monitoring, metabolic interaction, inhalation.

Diagnosis and Treatment of Acute Poisoning with Volatile Substances

1 The acute toxicity of many volatile compounds is similar, being more related to physical properties than to chemical structure. 2 Volatile substance abusers experiences euphoria and disinhibition but this may be followed by nausea and vomiting, dizziness, coughing and increased salivation; cardiac arrhythmias, convulsions, coma and death occur in severe cases. 3 Laboratory analysis of blood and urine samples collected up to 24 h post-exposure may be helpful if the diagnosis of volatile substance abuse is in doubt. 4 There is only a weak correlation between blood toluene and 1,1,1-trichloroethane concentrations and the clinical features of toxicity, possibly because of rapid initial tissue distribution and elimination. 5 Recovery normally occurs quickly once exposure has ceased but support for respiratory, renal or hepatic failure may be needed as well as treatment for cardiac arrhythmias. Therapy with intravenous acetylcysteine should be considered in cases of acute carbon tetrachloride poisoning.