Xylene: Its toxicity, measurement of exposure levels, absorption, metabolism and clearance

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Abstract

Xylene is an aromatic hydrocarbon widely used in industry and medical technology as a solvent. Health and safety authorities in most countries, including Australia, recommend a threshold limit value (TLV) of 100 ppm in the working environment. Recently, the amount of the major metabolite of xylene, methylhippuric acid (MHA), in urine has been recommended as a better indicator of exposure. The American Conference of Governmental Industrial Hygienists has recommended an upper limit for this indicator, called a biological exposure index (BEI), of 2.0 g MHA/L urine (SG 1.016).

Xylene vapour is absorbed rapidly from the lungs, and xylene liquid and vapour are absorbed slowly through the skin. Of the xylene absorbed, about 95% is metabolised in the liver to MHA and 70 to 80% of metabolites are excreted in the urine within 24 hours. However, the many variables which affect the absorption, metabolism and clearance of xylene include exercise, alcohol intake, cigarette smoking, co-exposure to other solvents, gender, and gastrointestinal, hepatic and renal pathology.

Xylene in high concentrations acts as a narcotic, inducing neuropsychological and neurophysiological dysfunction. Respiratory tract symptoms are also frequent. More chronic, occupational exposure has been associated with anemia, thrombocytopenia, leukopenia, chest pain with ECG abnormalities, dyspnea and cyanosis, in addition to CNS symptoms. Concomitant exposure to xylene and other solvents, including toluene, affected hematological parameters, liver size, liver enzymes, auditory memory, visual abstraction, and vibration threshold in the toes. Normal metabolic pathways were altered and significant increases in some serum bile acids may reflect early liver damage. Skin contact has caused burning, erythema and dermatitis. In experimental studies, xylene at about 100 ppm had a deleterious effect on equilibrium, reaction time and manual coordination in non-adapted subjects. At higher concentrations some neurophysiological parameters were altered, particularly when xylene concentration fluctuated. Exercise and alcohol consumption increased blood xylene levels, but altered the neurophysiological effects of xylene in an inconsistent manner. Two reports associating exposure to solvents, including xylene, and increased risk of carcinoma were inconclusive, as were studies on reproduction.

While animal studies fail to provide convincing evidence that xylene is carcinogenic or has significant genetic or reproductive effects, they do confirm that xylene has effects on many organ systems, including the CNS, liver, kidney, hemopoietic tissues and respiratory tract. However, there are factors which require animal studies to be interpreted cautiously. Differences are suspected between animal species, and between animals and humans, in the metabolism of, and sensitivity to, xylene. Conditions of exposure to xylene in animal experiments and human studies, both occupational and experimental, are also usually very different.

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