Sister-chromatid exchanges and chromosome aberrations in lymphocytes from monkeys exposed to ethylene oxide and propylene oxide by inhalation

Lynch, Dennis W.; Lewis, Trent R.; Moorman, William J.; Burg, JeAnne R.; Gulati, Dushyant K.; Kaur, Parvinder; Sabharwal, P. S.

doi:10.1016/0041-008x(84)90031-0

Cited by 58 publications

(16 citation statements)

References 27 publications

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“…Rather, the occurrence of these lesions indicates that EO may produce similar effects in other tissues where they may serve as initiating events. The findings for chromosomal aberrations in exposed humans are supported by the results of animal studies (Embree & Hine, 1975;Lynch et al, 1984b;Kligerman et al, 1983;van Sittert et al, 1985).…”

Section: Mode Of Actionmentioning

confidence: 57%

Addressing Nonlinearity in the Exposure‐Response Relationship for a Genotoxic Carcinogen: Cancer Potency Estimates for Ethylene Oxide

Kirman¹,

Sweeney²,

Teta³

et al. 2004

Risk Analysis

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Ethylene oxide (EO) has been identified as a carcinogen in laboratory animals. Although the precise mechanism of action is not known, tumors in animals exposed to EO are presumed to result from its genotoxicity. The overall weight of evidence for carcinogenicity from a large body of epidemiological data in the published literature remains limited. There is some evidence for an association between EO exposure and lympho/hematopoietic cancer mortality. Of these cancers, the evidence provided by two large cohorts with the longest follow-up is most consistent for leukemia. Together with what is known about human leukemia and EO at the molecular level, there is a body of evidence that supports a plausible mode of action for EO as a potential leukemogen. Based on a consideration of the mode of action, the events leading from EO exposure to the development of leukemia (and therefore risk) are expected to be proportional to the square of the dose. In support of this hypothesis, a quadratic dose-response model provided the best overall fit to the epidemiology data in the range of observation. Cancer dose-response assessments based on human and animal data are presented using three different assumptions for extrapolating to low doses: (1) risk is linearly proportionate to dose; (2) there is no appreciable risk at low doses (margin-of-exposure or reference dose approach); and (3) risk below the point of departure continues to be proportionate to the square of the dose. The weight of evidence for EO supports the use of a nonlinear assessment. Therefore, exposures to concentrations below 37 microg/m3 are not likely to pose an appreciable risk of leukemia in human populations. However, if quantitative estimates of risk at low doses are desired and the mode of action for EO is considered, these risks are best quantified using the quadratic estimates of cancer potency, which are approximately 3.2- to 32-fold lower, using alternative points of departure, than the linear estimates of cancer potency for EO. An approach is described for linking the selection of an appropriate point of departure to the confidence in the proposed mode of action. Despite high confidence in the proposed mode of action, a small linear component for the dose-response relationship at low concentrations cannot be ruled out conclusively. Accordingly, a unit risk value of 4.5 x 10(-8) (microg/m3)(-1) was derived for EO, with a range of unit risk values of 1.4 x 10(-8) to 1.4 x 10(-7) (microg/m3)(-1) reflecting the uncertainty associated with a theoretical linear term at low concentrations.

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Section: Mode Of Actionmentioning

confidence: 57%

Addressing Nonlinearity in the Exposure‐Response Relationship for a Genotoxic Carcinogen: Cancer Potency Estimates for Ethylene Oxide

Kirman¹,

Sweeney²,

Teta³

et al. 2004

Risk Analysis

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“…In our study we have assessed the clinical changes and health condition of these groups, besides genotoxicological and immunotoxicological alterations. Some cytostatic and sterilizing drugs are carcinogenic, mutagenic, or teratogenic, as it was well documented earlier in animal experiments 29–32 and some anesthetic gases were clastogenic in human studies 33,34 …”

Section: Discussionmentioning

confidence: 76%

Chemical Safety and Health Conditions among Hungarian Hospital Nurses

Tompa

Jakab²,

Bíró³

et al. 2006

Annals of the New York Academy of Sciences

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In the present study genotoxicological and immunotoxicological follow-up investigations were made on 811 donors including 94 unexposed controls and 717 nurses with various working conditions from different hospitals (The Hungarian Nurse Study). The nurses were exposed to different chemicals: cytostatic drugs, anesthetic, and sterilizing gases, such as ethylene oxide (ETO) and formaldehyde. The measured biomarkers were: clinical laboratory routine tests, completed with genotoxicological (chromosome aberrations [CA], sister chromatid exchange [SCE]), and immune-toxicological monitoring (ratio of lymphocyte subpopulations, lymphocyte activation markers, and leukocyte oxidative burst). The highest rate of genotoxicologically affected donors (25.4%) was found in the group of cytostatic drug-exposed nurses. Comparing geno- and immunotoxicological effect markers, we found that among genotoxicologically affected donors the frequency of helper T cell (Th) lymphocytes, the ratio of activated T and B cells increased, whereas the oxidative burst of leukocytes decreased. In hospitals with lack of protective measures increased CA yields were observed compared to those with ISO 9001 quality control or equivalent measures. Anemia, serum glucose level, thyroid dysfunctions, benign, and malignant tumors were more frequent in the exposed groups than in controls. The hygienic standard of the working environment is the basic risk factor for the vulnerability of nurses. On the basis of these results, it is suggested, that the used cytogenetic and immunological biomarkers are appropriate to detect early susceptibility to diseases. The Hungarian Nurse Study proved that the use of safety measures could protect against occupational exposure at work sites handling cytostatic drugs, anesthetic, and sterilizing gases.

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“…In rats, EtO was carcinogenic when administered by any of three differ-ent routes of exposure: intragastric, subcutaneous injection, and inhalation [Lynch et al, 1984a;Snellings et al, 19841. Mononuclear cell leukemia, peritoneal mesotheliomas, and primary brain tumors were found.…”

Section: Introductionmentioning

confidence: 98%

“…EtO has been found to be carcinogenic in rats and mice [for review see USEPA, 1985b;IARC, 19851. In rats, EtO was carcinogenic when administered by any of three differ-ent routes of exposure: intragastric, subcutaneous injection, and inhalation [Lynch et al, 1984a;Snellings et al, 19841. Mononuclear cell leukemia, peritoneal mesotheliomas, and primary brain tumors were found. In mice, inhalation exposure produced lung tumors, lymphomas, and uterine adenocarcinomas [NTP, 1986;Adkins et al, 19861.…”

Section: Introductionmentioning

confidence: 99%

Review of the mutagenicity of ethylene oxide

Dellarco

Generoso

Sega

et al. 1990

Environ and Mol Mutagen

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Ethylene oxide has been shown to be an effective mutagen in a variety of organisms ranging from bacteria to mammalian cells. There is also an association between ethylene oxide exposure and human somatic cell cytogenetic damage. Furthermore, ethylene oxide has been shown to alkylate protein and DNA at exposure levels that have been encountered occupationally. Ethylene oxide is not only effective at producing somatic cell mutations but also at inducing genetic damage in germ cells. While it is clear that ethylene oxide is a germ cell mutagen in whole mammals, the mechanism(s) by which it produces genetic lesions in germ cells is uncertain.

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Sister-chromatid exchanges and chromosome aberrations in lymphocytes from monkeys exposed to ethylene oxide and propylene oxide by inhalation

Cited by 58 publications

References 27 publications

Addressing Nonlinearity in the Exposure‐Response Relationship for a Genotoxic Carcinogen: Cancer Potency Estimates for Ethylene Oxide

Addressing Nonlinearity in the Exposure‐Response Relationship for a Genotoxic Carcinogen: Cancer Potency Estimates for Ethylene Oxide

Chemical Safety and Health Conditions among Hungarian Hospital Nurses

Review of the mutagenicity of ethylene oxide

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