Methylene chloride: an inhalation study to investigate toxicity in the mouse lung using morphological, biochemical and Clara cell culture techniques

Foster, John R.; Green, T.; Smith, Lewis L.; Tittensor, S.; Wyatt, I. J.

doi:10.1016/0300-483x(94)90011-6

Cited by 21 publications

(4 citation statements)

References 30 publications

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“…The mice were terminated with an overdose of halothane and exsanguinated, and the lungs were immediately excised, weighed, and infused and fixed via the trachea with 1.5-2.0 ml of 3% glutaraldehyde in phosphate buffer. The quantitation of cell replication was undertaken as described by Foster et al (1994).…”

Section: Methodsmentioning

confidence: 99%

Trichloroethylene-Induced Mouse Lung Tumors: Studies of the Mode of Action and Comparisons between Species

1997

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Section: Methodsmentioning

confidence: 99%

Trichloroethylene-Induced Mouse Lung Tumors: Studies of the Mode of Action and Comparisons between Species

1997

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“…Most Clara cell toxicants are activated by cytochromes P450 and, for example, CYP2F2, the isoform primarily responsible for the metabolism of naphthalene, also shows a quantitative distribution pattern between species which is very similar to that of CYP2E1 (52,54). Inhibition of cytochromes P450 has also been shown to prevent the development of this type of lesion (48). Ultimately, a gene knockout experiment could potentially prove the role of CYP2E1 in the development of pulmonary toxicity and cancer in mice exposed to TCE.…”

Section: Species Differences In the Pulmonary Metabolism Of Tcementioning

confidence: 87%

“…Acrylonitrile, bromobenzene, carbon tetrachloride, 1,1 -dichloroethylene, dichloromethane, 4-ipomeanol, naphthalene, 1-nitronaphthalene, 0,0S-trimethylphosphorothioate, styrene, and a number of other chemicals selectively target the Clara cells of the pulmonary airways; a number of these chemicals cause an increase in pulmonary tumors (39)(40)(41)(42)(43)(44)(45)(46)(47)(48). It seems improbable therefore that the observed acute effects in Clara cells are unrelated to the subsequent development of these tumors.…”

Section: Mechanisms Of Toxicitymentioning

confidence: 99%

Pulmonary toxicity and carcinogenicity of trichloroethylene: species differences and modes of action.

Green

2000

Environ Health Perspect

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Trichloroethylene (TCE) is both acutely toxic and carcinogenic to the mouse lung following exposure by inhalation. In contrast, it is not carcinogenic in the rat lung and is markedly less toxic following acute exposure. Toxicity to the mouse lung is confined almost exclusively to the nonciliated Clara cell and is characterized by vacuolation and increases in cell replication. Chloral, a metabolite of TCE that accumulates in Clara cells and has been shown to be the cause of the toxicity, also causes aneuploidy in some test systems. Cytotoxicity, increased cell division, and aneuploidy are known risk factors in the development of cancer and provide a plausible mode of action for TCE as a mouse lung carcinogen. All acute and chronic effects of TCE on the mouse lung are believed to be a direct consequence of high cytochrome P450 activity and impaired metabolism of chloral in Clara cells. Comparisons between species suggest that the ability of the human lung to metabolize TCE is approximately 600-fold less than that in the mouse. In addition, the human lung differs markedly from the mouse lung in the number and morphology of its Clara cells. Thus, the large quantitative differences between the metabolic capacity of the mouse lung and the human lung, together with the species differences in the number and morphology of lung Clara cells, suggest that the risks to humans are minimal and that other tumor sites should take precedent over the lung when assessing the potential risks to humans exposed to TCE. Key words: carcinogenicity, lung, mode of action, species comparisons, toxicity, TCE, trichloroethylene. - (1). Consequently, the pulmonary airways are exposed to this chemical irrespective of the route of administration, and at high dose levels both toxicity and cancer have been observed in laboratory animals. The effects are species specific; the mouse is far more sensitive to the acute toxicity of TCE than the rat and is also the only species in which an increased incidence of lung tumors has been seen. As a result of this difference in sensitivity between laboratory animals, a number of investigators have sought to explain the mechanistic basis of the both toxicity and carcinogenicity in mice and the relevance of these data to humans exposed to this chemical. In this article the effects of TCE on the lung are reviewed together with proposed modes of action for both acute toxicity and cancer. Lung Cancer in AnimalsIncreases in pulmonary adenomas and adenocarcinomas have been observed in two studies in which mice were exposed to TCE by inhalation. Fukuda et al. (2) reported an increase in both pulmonary adenomas and adenocarcinomas following exposure of female CD-1 mice (males were not tested) to 150 and 450 ppm TCE (6 hr/day, 5 days/week for 104 weeks) and, in a shorter study, Maltoni et al. (3,4) reported an increase in pulmonary adenomas in male Swiss and female B6C3F1 mice exposed to 600 ppm, 7 hr/day, 7 days/week for 78 weeks. In contrast to the inhalation studies, lung tumor incidences were not increased in B6...

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“…It is a potential human carcinogen which is the primary concern of it. The oral exposure to DCM can increase liver cancer [43][44][45][46][47][48][49].…”

Section: Fig 3 Two Pathway Of Chloroform Bio-activation [42]mentioning

confidence: 99%

An Overview on Common Organic Solvents and Their Toxicity

Joshi

Adhikari

2019

JPRI

384

156

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Organic solvents are known as carbon-based solvents and their general property is primarily based on their volatility, boiling point, the molecular weight and color. Having enormous hazards associated with the organic solvents, they are used for millions of purposes which alert us to think more on its toxicity points. Almost all of the solvents are hazardous to health, if swallowed or inhaled more than the limit quantity and on contact to the skin most of them cause irritation. Some of the common solvents are acetone, ethyl acetate, hexane, heptane, dichloromethane, methanol, ethanol, tetrahydrofuran, acetonitrile, dimethylformamide, toluene, dimethylsulfoxide etc. Researchers, scientists, workers in the chemical industry and research institutes use these solvents on regular basis leading them to be affected in major aspects. But also, the nearby persons are affected by the contamination to the soil, water, air etc. If constantly exposed with solvents, it will badly affect the function of CNS and other body parts. The level of impact, sign and symptoms will depend on concentration, time, duration, frequency and nature of solvents, leading to common effects like headache, dizziness, tiredness, blurred vision, behavioral changes, unconsciousness, and even(Zimmermann, Mayer et al. 1985) death. To overcome it, the green chemistry concept is growing rapidly, and the solvent selection guide is in practice in many big company and research institute. A researcher or chemical worker is the primary person who works with solvents and they need to consider throughout these things while performing their activities for their own good health and for the sake of the world. The purpose of this review is to provide needed basic knowledge about common organic solvents and their potential toxicities which will alert researchers to think twice and always think for their health as well as for the environment via safe and green practice.

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Methylene chloride: an inhalation study to investigate toxicity in the mouse lung using morphological, biochemical and Clara cell culture techniques

Cited by 21 publications

References 30 publications

Trichloroethylene-Induced Mouse Lung Tumors: Studies of the Mode of Action and Comparisons between Species

Trichloroethylene-Induced Mouse Lung Tumors: Studies of the Mode of Action and Comparisons between Species

Pulmonary toxicity and carcinogenicity of trichloroethylene: species differences and modes of action.

An Overview on Common Organic Solvents and Their Toxicity

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