Phosgene: A possible role in the potentiation of carbon tetrachloride hepatotoxicity by 2-propanol

Harris, Richard N.; Anders, M.W.

doi:10.1016/0024-3205(81)90217-4

Cited by 12 publications

(2 citation statements)

References 19 publications

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“…Severe isopropanol poisoning results in CNS and respiratory depression, and circulatory collapse. Recent studies have shown that high-level isopropanol exposure can cause health hazards, such as liver toxicity [ 3 , 4 ], teratogenicity [ 5 ], and reproductive and developmental toxicity [ 6 – 8 ]. But low-level isopropanol exposure-caused potential health hazards are often ignored.…”

Section: Introductionmentioning

confidence: 99%

Telomere length in peripheral leukocytes is a sensitive marker for assessing genetic damage among workers exposed to isopropanol, lead and noise: the case of an electronics manufacturer

Liu

Zhao

et al. 2021

Genes and Environ

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Background Workers in electronics manufacturers may be exposed to various occupational hazards such as isopropanol, lead, and noise. Telomeres are special segments of cap-like DNA protein complex at end of liner chromosomes in eukaryotic cells. Telomere length is a potential marker of genetic damage. The aim of this study is to evaluate the effect of occupational hazards on the relative telomere length (rTL) of peripheral blood cells of workers in an electronics manufacturer, and to explore whether relative telomere length could be a biomarker for assessing genetic damage in the electronics manufacturing industry. Methods We investigated a large-scale electronics manufacturer in the Pearl River Delta Region. We ultimately collected 699 qualified workers (248 with isopropanol exposure, 182 with lead exposure, 157 with noise exposure, and 112 controls). During physical examination of the workers, we gave them questionnaires to understand their health statuses and living habits. We also collected peripheral blood samples from these workers to test exposure levels and rTL in the leucocytes. Results The concentrations of air isopropanol in all monitored workshops was 25.3 mg/m3 and air lead smoke was 0.020 mg/m3. The maximum equivalent continuous A sound level noise exposure position was 82.2dB (A). All were lower than those in the Occupational Exposure Limits in Workplaces in China. Urinary acetone in the isopropanol exposed group was 1.04 (0, 1.50) mg/L, and cumulative urinary acetone was 1.48 (0, 5.09) mg-years/L. Blood lead levels (BLLs) were 28.57 (22.77, 37.06) µg/dL, and cumulative blood lead levels (CBLLs) were 92.75 (55.47, 165.13) µg-years/dL. rTL was different between occupational exposed workers and controls: rTL was 0.140 units (95 % CI: 0.022, 0.259) shorter in lead exposed workers and 0.467 units (95 % CI: 0.276–0.658) shorter in noise exposed workers compared to the controls. There is no statistical difference in rTL between isopropanol exposure workers and the controls. In order to elucidate the relationship between rTL and occupational hazards exposure, we divided the isopropanol exposure workers into three groups (0, ~1.43 mg/L, and >1.43 mg/L). None of the rTL difference was statistically significant among exposed workers at different uroacetone levels (P>0.05). The groups with ≥100 µg/dL blood lead had shorter rTL than the group with blood lead below 100 µg/dL (F=4.422, P=0.013). We incorporated age, gender, birthplace, race, education level, smoking, and alcohol consumption into the linear regression equation. Only blood lead concentration (X) was entered into the regression equation, yielding a multivariate linear regression equation of Y=0.397-0.124X (F=8.091, P=0.005). Workers with different hearing loss also had statistically significant differences in rTL (F=5.731, P=0.004). rTL was a protective factor for the occurrence of noise-induced hearing loss (NIHL). The longer the rTL, the lower the risk of NIHL [OR=0.64 (0.42, 0.98)]. Conclusions rTL was shorter in lead exposed workers and noise exposed workers, and it was a protective factor for the occurrence of the noise-induced hearing loss. Thus, rTL of peripheral blood may be a sensitive marker of genetic damage among workers in environments with lead and noise exposure.

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Section: Introductionmentioning

confidence: 99%

Telomere length in peripheral leukocytes is a sensitive marker for assessing genetic damage among workers exposed to isopropanol, lead and noise: the case of an electronics manufacturer

Liu

Zhao

et al. 2021

Genes and Environ

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“…37 At high oxygen tension, such radicals can be oxidized by oxygen to form phosgene (COCl 2 ), which then undergoes hydrolysis to carbon dioxide. [37][38][39] Under insufficient oxygen or anaerobic conditions, this radical may abstract a hydrogen atom from its immediate environment to form chloroform, 23,37,40 and may covalently bind to the lipids and proteins of cells to initiate cell damage. 41,42 Alternatively, it may undergo further reduction by P450 producing another active metabolite, dichlorocarbene (:CCl 2 ), 13,26,43 which was firstly suggested by Wolf et al 44 The formation of :CCl 2 has been successively confirmed by the carbene trapping experiment of Pohl et al 26 and by the spectral experiment of Manno et al 13 This active species will then interact with the reduced haem iron leading to reversible inhibition of P450 or undergo hydrolysis to CO, which can bind to the reduced P450 haem as well, again resulting in P450 inhibition.…”

Section: Introductionmentioning

confidence: 99%

Theoretical insights into the reductive metabolism of CCl₄ by cytochrome P450 enzymes and the CCl₄-dependent suicidal inactivation of P450

Zheng

Wang

et al. 2014

Dalton Trans.

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The anaerobic metabolism of CCl4 by P450 enzymes was investigated using quantum chemical calculations. It was found that under anaerobic conditions, the substrate CCl4 might undergo one or two subsequent one-electron reductions to generate different reactive metabolites, trichloromethyl radical (˙CCl3) and dichlorocarbene (:CCl2) respectively. Meanwhile, it was the reduced ferrous haem complex rather than the unreduced ferric haem complex that could directly achieve such reductions. Based on the formation of the former reactive metabolite, a further one-electron reduction could take place with the assistance of a proton to yield the latter reactive species, i.e., a further reductive dechloridation of ˙CCl3 could take place via a novel SE3 mechanism. In addition, the ˙CCl3 species was capable of binding covalently to the meso-carbon atom of the prosthetic group, leading to the suicidal destruction of P450 enzymes. Whereas the :CCl2 species was involved in the CCl4-dependent reversible P450 inhibition as its hydrolysis product, CO, but was not significantly involved in the CCl4-dependent irreversible P450 destruction. It is obvious that the reductive metabolism of CCl4 to reactive intermediates by P450 enzymes is an essential prerequisite for its toxicity.

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Pathobiochemical mechanisms of hepatocellular damage following lipid peroxidation

Ungemach

1987

Chemistry and Physics of Lipids

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Phosgene: A possible role in the potentiation of carbon tetrachloride hepatotoxicity by 2-propanol

Cited by 12 publications

References 19 publications

Telomere length in peripheral leukocytes is a sensitive marker for assessing genetic damage among workers exposed to isopropanol, lead and noise: the case of an electronics manufacturer

Telomere length in peripheral leukocytes is a sensitive marker for assessing genetic damage among workers exposed to isopropanol, lead and noise: the case of an electronics manufacturer

Theoretical insights into the reductive metabolism of CCl₄ by cytochrome P450 enzymes and the CCl₄-dependent suicidal inactivation of P450

Pathobiochemical mechanisms of hepatocellular damage following lipid peroxidation

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Phosgene: A possible role in the potentiation of carbon tetrachloride hepatotoxicity by 2-propanol

Cited by 12 publications

References 19 publications

Telomere length in peripheral leukocytes is a sensitive marker for assessing genetic damage among workers exposed to isopropanol, lead and noise: the case of an electronics manufacturer

Telomere length in peripheral leukocytes is a sensitive marker for assessing genetic damage among workers exposed to isopropanol, lead and noise: the case of an electronics manufacturer

Theoretical insights into the reductive metabolism of CCl4 by cytochrome P450 enzymes and the CCl4-dependent suicidal inactivation of P450

Pathobiochemical mechanisms of hepatocellular damage following lipid peroxidation

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Theoretical insights into the reductive metabolism of CCl₄ by cytochrome P450 enzymes and the CCl₄-dependent suicidal inactivation of P450