主题：【求助】PX的毒性 -- 燕人

Environmental Aspects. In Germany xylenes are assigned to water hazard class 2 (WGK 2) [55]. The solubility of xylenes in water is low (ca. 0.14 g/L). Because of the comparatively low vapor pressure (7 – 8 mbar at 20 °C), the danger of vapor emissions in air is relatively low. However, xylenes can react with other air pollutants to give environmentally damaging products. This applies particularly to the UV-catalyzed photooxidation of xylenes by nitrogen oxides. However, compared with some other hydrocarbons, the reactivity of xylenes is comparatively low, with a reaction rate of ca. 2×10–9 min–1 [55]. For example, disubstituted internal olefins have a reaction rate of ca. 50×10–9 min–1.

Toxicology. Exposure to xylene is possible through inhalation of vapors and resorption through the skin. The MAK value is 100 ppm (ca. 440 mg/m3) for all three isomers [54].

General Activity. Xylene exhibits acute prenarcotic and narcotic activity. Chronic exposure to xylene leads to disturbance of the CNS (e.g., headaches, sleep disturbance) [56] and damage to the blood picture (dyspepsia). Provided that there is no long-term chronic overexposure, these effects are reversible. Besides developing a certain tolerance, frequent exposure to xylene can also lead to habituation or even addiction (solvent abuse).

Acute Toxicity. The LD50, LC50, and TCLo values for oral administration and inhalation vary widely, depending on the animal investigated and the isomer composition. The following values give an indication of the toxicity of xylene isomer mixtures [54], [57]: LD50 (rat, oral) 4300 mg/kg, LDL0 (rat, i.p.) 2000 mg/kg, TCLo (humans, inhalation) 200 ppm.

A very high exposure to xylene of ca. 10 000 ppm caused by an accident led to lung edema and subsequent death in one person [58]. In other cases severe damage to the CNS, kidneys, and liver were observed.

Irritant Effects. On repeated application xylenes can cause irritation of the respiratory passages and mucous membranes of the eye. Frequent skin contact can lead to blister formation and dermatitis [57], [59-62].

Subchronic and Chronic Toxicity. At a concentration range of 100 to over 1000 ppm xylene in inhaled air, damage to the CNS with disturbance of balance or slowing of reactions is observed. Inhalation of xylene vapors can also cause nausea and headaches [63-65].

A change in the blood picture is also frequently observed. In ca. 10 % of persons who had been exposed to xylene vapors in concentrations of up to ca. 100 ppm for ca. 5 years, a leucocyte level of < 4500 mm–3 was established [66]. A decrease in the immunobiological activity has occasionally been observed [58].

Carcinogenicity, Mutagenicity, and Embryotoxicity. The assessment of the carcinogenicity of xylenes is not consistent [67-69]. While in one study no indications of carcinogenicity or cocarcinogenicity were found, another investigation indicated that xylenes act as tumor promoters for skin tumors in rats.

None of the three xylene isomers showed mutagenicity in the Ames test [70]. However, slight mutagenicity was detected in a recessive lethal test on drosophila [71].

In animal experiments long-term exposure through inhalation of xylenes causes small changes to fetuses [72].

Pharmacokinetics and Metabolism. All three xylene isomers are resorbed in the same way. Various investigations have shown that ca. 60 – 70 % of the xylene reaching the organism via the lungs is retained [73-76]. This percentage remains approximately constant over the whole exposure period. The ratio of the concentration in the air in the alveoli (mg/m3) and in the blood (mg/kg) changes with the degree of bodily activity. When the body is at rest the ratio is ca. 15 : 1 and when moving ca. 30 – 40 : 1 [77]. Xylene can be resorbed at a rate of ca. 2.5 (0.7 – 4.3) mg/m3 per minute through intact skin [78].

Xylenes are deposited rapidly in body fat (up to ca. 5 %) and remain there for hours after exposure. The half-life in fat deposits is ca. 0.5 – 1.0 h [78]. The metabolism of the individual xylene isomers is identical. The main biotransformation pathway initially involves oxidation to methylbenzoic acid, which forms the corresponding methylhippuric acid by conjugation with glycine (A) [74], [79-81]. The methylhippuric acid can be excreted rapidly via the kidneys. Another, less favored biotransformation pathway involves the hydroxylation of the xylene on the aromatic ring, forming xylenols (B) [73].