Comparative chronic toxicity, including tumorigenicity, of gallium arsenide and arsenic trioxide intratracheally instilled into hamsters

Ohyama, Shiro; Ishinishi, Noburu; Hisanaga, Akira; Yamamoto, Akito

doi:10.1002/aoc.590020409

Cited by 26 publications

(5 citation statements)

References 15 publications

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“…p > 0.05). A study using IT instillation of gallium arsenide in hamsters has critical design flaws, including short duration, small group sizes, etc., and shows no indication of tumors (Ohyama et al, 1988). Therefore, the conclusions that can be drawn about the IT carcinogenicity of arsenic from these particular studies must be considered limited.…”

Section: Intratracheal Instillationsmentioning

confidence: 99%

Cancer in experimental animals exposed to arsenic and arsenic compounds

Tokar¹,

Benbrahim‐Tallaa

Ward

et al. 2010

Critical Reviews in Toxicology

122

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Inorganic arsenic is a ubiquitous environmental contaminant that has long been considered a human carcinogen. Recent studies raise further concern about the metalloid as a major, naturally occurring carcinogen in the environment. However, during this same period it has proven difficult to provide experimental evidence of the carcinogenicity of inorganic arsenic in laboratory animals and, until recently, there was considered to be a lack of clear evidence for carcinogenicity of any arsenical in animals. More recent work with arsenical methylation metabolites and early life exposures to inorganic arsenic has now provided evidence of carcinogenicity in rodents. Given that tens of millions of people worldwide are exposed to potentially unhealthy levels of environmental arsenic, in vivo rodent models of arsenic carcinogenesis are a clear necessity for resolving critical issues, like mechanisms of action, target tissue specificity, and sensitive subpopulations, and in developing strategies to reduce cancers in exposed human populations. This work reviews the available rodent studies considered relevant to carcinogenic assessment of arsenicals, taking advantage of the most recent review by the International Agency for Research on Cancer (IARC) that has not yet appeared as a full monograph but has been summarized (IARC 2009). Many valid studies show that arsenic can interact with other carcinogens/agents to enhance oncogenesis, and help elucidate mechanisms, and these too are summarized in this review. Finally, this body of rodent work is discussed in light of its impact on mechanisms and in the context of the persistent argument that arsenic is not carcinogenic in animals.

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Section: Intratracheal Instillationsmentioning

confidence: 99%

Cancer in experimental animals exposed to arsenic and arsenic compounds

Tokar¹,

Benbrahim‐Tallaa

Ward

et al. 2010

Critical Reviews in Toxicology

122

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“…Pulmonary tumours developed in animals treated with calcium arsenate, but not in those treated with arsenic trisulphide. Recently, Ohyama et al (1988) reported that neither arsenic trioxide nor gallium arsenide caused tumours when administered by intratracheal instillation to Syrian golden hamsters once a week for 15 weeks. Osswald and Goerttler (1971) reported a study in which pregnant Swiss mice received subcutaneous injections of 0.005% sodium arsenate (0.5 mg As kg -1) for 20 days.…”

Section: Tntratracheal Instillationmentioning

confidence: 99%

Inorganic arsenic compounds: are they carcinogenic, mutagenic, teratogenic?

Goldman

Dacre

1991

Environ Geochem Health

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This review examines and evaluates the literature on the ability of inorganic arsenic compounds to cause cancer in humans and laboratory animals. The epidemiological data that supports the position that inorganic arsenical derivatives are carcinogenic in humans is convincing and difficult to deny because of their consistency. These data are from studies of different occupational exposures such as smelter and pesticide workers, as well as from studies of drinking water, wines and medicinal tonics that contained or were contaminated with inorganic compounds of arsenic. Indeed, positive dose-response relationships between cancer incidence or mortality with many inorganic arsenical substances have been shown. Despite the presence of data which confuse the interpretation and evaluation of epidemiological data, associated neoplasms of the lungs, skin and gastrointestinal systems have been observed as a result of exposure to inorganic arsenic compounds.The mechanism of carcinogenicity of inorganic arsenical substances in humans is unknown. Inorganic arsenic compounds are not carcinogenic in laboratory animals by most routes of administration. However, further studies (subchronic, chronic, carcinogenic) using intratracheal and other conventional routes in other animal species would appear to be warranted. Moreso, especially since there is no evidence that organic arsenic compounds are carcinogenic in numerous mammalian species. Inorganic derivatives of arsenic are not mutagenic but may be teraiogenic. This latter conclusion is dependent on the method of administration and size of the dose, as well as on the species of animal used for the study.

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“…Intratracheal instillation of GaAs particles (particle characteristics not specified) into Syrian golden hamsters (1.5 mg/kg bw) once per week for 15 weeks caused severe and long-lasting pulmonary toxicity characterized by alveolar cell hyperplasia, congestion with hemorrhage, and pneumonia (Ohyama et al, 1988). In this study severe lung toxicity was observed at clearly lower dose levels as compared to those applied by Omura et al (1996b).…”

Section: Study With Intratracheal Administration To Hamstersmentioning

confidence: 61%