Atherosclerotic risks from chemicals: part II. A RASH analysis of in vitro and in vivo bioassay data to evaluate 45 potentially hazardous compounds.
As reviewed in the Part I companion manuscript by Basavaraju and Jones (Arch Environ Contam Toxicol), atherosclerosis and carcinogenesis may share some common mechanisms of toxicological action. On that hypothesis, standardized test data taken from the Registry of Toxic Effects of Chemical Substances (RTECS) were used to compute relative potency factors for chemical compounds associated with increased risk of atherosclerosis to humans. Potencies of the different compounds were computed relative to each of six reference compounds comprised of benzo(a)pyrene, nicotine, cisplatin, adriamycin, estrogen, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Reference-specific potencies were all converted to a common numerical scale adjusted to unit potency for B(a)P. Because the list of compounds contained several antibiotics, amino acids, hormones, chemotherapeutic agents, polynuclear aromatics, alkaloids, metals, and vitamins, the standardized estimates of potency varied significantly depending on which of the six reference compounds are considered as standards of comparison. For the n - 1 other substances. Estimates of relative potency, risk coefficients, and generalized risk equations are estimated for cigarette smoke condensate, dietary cholesterol, ethanol, and carbon disulfide. From data on atherosclerosis as a result of cigarette smoking, a tentative risk was estimated as Increased Relative Risk = S (mg/kg-day)-1 x dose (mg/kg-day) x RP, where the dose is chronic intake per kilogram of body weight per day, RP is the potency of the compound of interest relative to that of benzo(a)pyrene, and S is 0.83, 0.25, 0.20, or 13 depending on whether cigarette smoke, cholesterol, ethanol, or carbon disulfide epidemiological data were used as a standard of comparison.
Jones
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Life Sciences Division, Oak Ridge National Laboratory, Building 4500-S, M.S. 6101, P.O. Box 2008, Oak Ridge, Tennessee 37831-6101, USA.
Morris
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MD
Basavaraju
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SR
D000818:Animals; D001161:Arteriosclerosis / Q000139:chemically induced* / Q000209:etiology; D001681:Biological Assay; D002246:Carbon Disulfide / Q000009:adverse effects; D002784:Cholesterol / Q000009:adverse effects; D003198:Computer Simulation; D000431:Ethanol / Q000009:adverse effects; D005347:Fibroblasts; D015386:Hazardous Substances / Q000009:adverse effects* / Q000592:standards; D051379:Mice; D009538:Nicotine / Q000009:adverse effects; D012016:Reference Values; D018570:Risk Assessment; D012867:Skin; D012907:Smoking / Q000009:adverse effects
D015386:Hazardous Substances; D000431:Ethanol; D009538:Nicotine; D002784:Cholesterol; D002246:Carbon Disulfide