Toxicity

Most cases of toluene poisoning are due to intentional abuse. However, acute poisoning from spillages at work (Reisin et al., 1975) and from the use of toluene containing products in poorly ventilated areas, has been reported (Brugnone et al., 1983; Meulenbelt et al., 1990; Knight et al., 1991; Shibata et al., 1994; Carder and Fuerst, 1997; Tan and Seow, 1997; Hobara et al., 2000). Deaths at work due to falls and drowning while under the influence of toluene have also occurred (Takeichi et al., 1986). Occasionally toluene abuse may occur following occupational exposure (Tarsh, 1979).

Much of the information concerning the toxicity of toluene derives from studies on individuals who have chronically abused this solvent. These individuals are exposed to very high concentrations but the dose is difficult, if not impossible, to determine. Workers are usually exposed to much lower concentrations of toluene and extrapolation of the clinical effects of toluene exposure between these two groups may not be appropriate (Harbison, 1998). Consequently, where it has been possible, a distinction has been made in this review between effects reported from occupational exposure and those reported with abuse of toluene.

At low concentrations or in a short exposure toluene is excitatory, whereas at higher concentrations or longer duration the effects are depressant (Benignus, 1981b). Toluene induced effects are reversible except for effects on the nervous system (Benignus, 1981b). Death from acute toluene poisoning is believed to be due to hypoxia during CNS depression or cardiac arrhythmia (Bakinson and Jones, 1985; Ikeda et al., 1990).

Toxicology of Solvents Absorption

The mean uptake of toluene is initially 75-80% (Astrand et al., 1972) and then falls to 40-60% of the quantity inhaled (Ovrum et al., 1978; Veulemans and Masschelein, 1978a; Carlsson, 1982; IPCS, 1985; Lof et al., 1993; Morata et al., 1995). Absorption is rapid; toluene can be detected in arterial blood after 10 seconds of inhalation exposure (Astrand et al., 1972). After the first 10-15 minutes the concentration of toluene increases more slowly and reaches a plateau concentration after about 25 minutes (Astrand et al., 1972).

There is a correlation between the toluene blood concentration and the alveolar air concentration (Astrand et al., 1972; Brugnone et al., 1976; Ovrum et al., 1978). Uptake of toluene appears to be independent of the amount of body fat (Veulemans and Masschelein, 1978a). However, some workers have found uptake to be influenced by body fat percentage (Carlsson, 1982). These differences may be due to other physiological differences between lean and obese individuals, e.g., respiration rate. Exercise increases the total uptake of toluene (Astrand et al., 1972; Astrand, 1975; Veulemans and Masschelein, 1978a,b; Carlsson, 1982) due to increased respiration and heart rate.

Dermal absorption of toluene is less than that of some other hydrocarbon solvents. After immersion of one hand in toluene for one minute, hardly any toluene was detected in the blood. After a 30 minute immersion the maximum blood concentration did not exceed a quarter of the concentration reached in a two hour inhalation exposure at 100 ppm (Sato and Nakajima, 1978). Washing of hands in toluene for five minutes did not contribute significantly to the total toluene exposure (Monster et al., 1993). Dermal absorption of toluene vapour is less than that for liquid toluene. The risk of systemic toxicity from dermal exposure is low, because any toluene absorbed through the skin rapidly diffuses out again after cessation of exposure (Cohr and Stokholm, 1979).

Toluene is absorbed from the gastrointestinal tract but more slowly than by inhalation (Pyykko et al., 1977). Distribution

Toluene is distributed widely throughout the body but it is highly lipophilic and tissues with a high lipid content act as reservoirs; therefore the higher the lipid content the more toluene the tissue will retain (Benignus, 1981a). The half-life of toluene in lipid-rich tissue is long at almost 80 hours (Cohr and Stokholm, 1979; Nise et al., 1989). The rate of rise in the tissue toluene concentration is proportional to the vascularisation and diffusion of toluene into tissue (Astrand, 1975). A study of exposed workers found a correlation between the air concentration of toluene and the concentration in the subcutaneous adipose tissue (Nise et al., 1989).

Death occurred 30 minutes after ingestion of 60 ml of toluene in a 51 year old male. Tissue distributions were highest in the stomach contents followed by the liver, pancreas, brain, heart, blood, fat and cerebrospinal fluid (Ameno et al., 1989).

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