Styrene-7,8-Oxide Burden in Ventilated, Perfused Lungs of Mice and Rats Exposed to Vaporous Styrene

Hofmann, Christiana; Pütz, Christian; Semder, Brigitte; Faller, Thomas; Csanády, György A.; Filser, Johannes G.

doi:10.1093/toxsci/kfj056

Cited by 11 publications

(2 citation statements)

References 43 publications

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“…In ventilated, perfused lungs of mice and rats exposed to styrene vapours the concentration of styrene 7,8-oxide in the effluent perfusate was only 2-fold different, far too small to account for the species difference of susceptible versus resistant to the tumorigenicity of styrene (Hofmann et al 2006).…”

Section: Cyp Catalytic Activities (Table 3)mentioning

confidence: 97%

Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

2019

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The xenobiotic metabolism in the lung, an organ of first entry of xenobiotics into the organism, is crucial for inhaled compounds entering this organ intentionally (e.g. drugs) and unintentionally (e.g. work place and environmental compounds). Additionally, local metabolism by enzymes preferentially or exclusively occurring in the lung is important for favorable or toxic effects of xenobiotics entering the organism also by routes other than by inhalation. The data collected in this review show that generally activities of cytochromes P450 are low in the lung of all investigated species and in vitro models. Other oxidoreductases may turn out to be more important, but are largely not investigated. Phase II enzymes are generally much higher with the exception of UGT glucuronosyltransferases which are generally very low. Insofar as data are available the xenobiotic metabolism in the lung of monkeys comes closed to that in the human lung; however, very few data are available for this comparison. Second best rate the mouse and rat lung, followed by the rabbit. Of the human in vitro model primary cells in culture, such as alveolar macrophages and alveolar type II cells as well as the A549 cell line appear quite acceptable. However, (1) this generalization represents a temporary oversimplification born from the lack of more comparable data; (2) the relative suitability of individual species/models is different for different enzymes; (3) when more data become available, the conclusions derived from these comparisons quite possibly may change.

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Section: Cyp Catalytic Activities (Table 3)mentioning

confidence: 97%

Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

2019

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“…These findings indicate that the absence of lung tumors in rats exposed up to 1000 ppm styrene is not due a differential inability for in situ formation of SO in lungs. Hofmann et al 2006 Chronic oral dosing of SO did not increase lung tumors in mice (gavage 375 or 750 mg/kg, 3X/week, 2 years) or rats (gavage 275 and 550 mg/kg, 3X/week, 2 years). The carcinogenic response of SO in mice and rats was limited to site-of-contact carcinomas and papillomas of the non-glandular forestomach.…”

Section: Cruzan Et Al 2013mentioning

confidence: 89%

Evaluation of potential health effects associated with occupational and environmental exposure to styrene – an update

Banton

Bus

Collins

et al. 2019

Journal of Toxicology and Environmental Health, Part B

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The potential chronic health risks of occupational and environmental exposure to styrene were evaluated to update health hazard and exposure information developed since the Harvard Center for Risk Analysis risk assessment for styrene was performed in 2002. The updated hazard assessment of styrene's health effects indicates human cancers and ototoxicity remain potential concerns. However, mechanistic research on mouse lung tumors demonstrates these tumors are mouse-specific and of low relevance to human cancer risk. The updated toxicity database supports toxicity reference levels of 20 ppm (equates to 400 mg urinary metabolites mandelic acid + phenylglyoxylic acid/g creatinine) for worker inhalation exposure and 3.7 ppm and 2.5 mg/kg bw/day, respectively, for general population inhalation and oral exposure. No cancer risk value estimates are proposed given the established lack of relevance of mouse lung tumors and inconsistent epidemiology evidence. The updated exposure assessment supports inhalation and ingestion routes as important. The updated risk assessment found estimated risks within acceptable ranges for all age groups of the general population and workers with occupational exposures in non-fiber-reinforced polymer composites industries and fiber-reinforced polymer composites (FRP) workers using closedmold operations or open-mold operations with respiratory protection. Only FRP workers using open-mold operations not using respiratory protection have risk exceedances for styrene and should be considered for risk management measures. In addition, given the reported interaction of styrene exposure with noise, noise reduction to sustain levels below 85 dB(A) needs be in place.

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Epoxy Compounds—Olefin Oxides (Ethylene Oxide, Propylene Oxide, and Miscellaneous Oxides)

Klapacz

Doskey

2023

Patty's Toxicology

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This chapter discusses the chemistry, uses, health information, and industrial hygiene handling procedures of epoxides, that is, substances containing strained, three‐membered rings with two adjacent carbons and one oxygen atom. This functionality underlies epoxides' high reactivity, physicochemical properties, and toxicity. The majority of the content is dedicated to ethylene oxide and propylene oxide, but other epoxides are also of industrial interest and are described here; their databases have evolved over the last couple of decades and this new understanding is highlighted here. These are 1,2‐butylene oxide, 2,3‐epoxybutane, butadiene diepoxide, vinylcyclohexene monoxide, vinylcyclohexene dioxide, and styrene oxide.

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Styrene-7,8-Oxide Burden in Ventilated, Perfused Lungs of Mice and Rats Exposed to Vaporous Styrene

Cited by 11 publications

References 43 publications

Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

Evaluation of potential health effects associated with occupational and environmental exposure to styrene – an update

Epoxy Compounds—Olefin Oxides (Ethylene Oxide, Propylene Oxide, and Miscellaneous Oxides)

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