Carcinogenesis, Vol 18, 531-537, Copyright © 1997 by Oxford University Press
S De Flora, A Camoirano, M Bagnasco, C Bennicelli, GE Corbett and BD Kerger
Estimates of the overall reducing capacity of hexavalent chromium(VI) in
some human body compartments were made by relating the specific reducing
activity of body fluids, cell populations or organs to their average
volume, number, or weight. Although these data do not have absolute
precision or universal applicability, they provide a rationale for
predicting and interpreting the health effects of chromium(VI). The
available evidence strongly indicates that chromium(VI) reduction in body
fluids and long-lived non-target cells is expected to greatly attenuate its
potential toxicity and genotoxicity, to imprint a threshold character to
the carcinogenesis process, and to restrict the possible targets of its
activity. For example, the chromium(VI) sequestering capacity of whole
blood (187-234 mg per individual) and the reducing capacity of red blood
cells (at least 93-128 mg) explain why this metal is not a systemic
toxicant, except at very high doses, and also explain its lack of
carcinogenicity at a distance from the portal of entry into the organism.
Reduction by fluids in the digestive tract, e.g. by saliva (0.7-2.1 mg/day)
and gastric juice (at least 84- 88 mg/day), and sequestration by intestinal
bacteria (11-24 mg eliminated daily with feces) account for the poor
intestinal absorption of chromium(VI). The chromium(VI) escaping reduction
in the digestive tract will be detoxified in the blood of the portal vein
system and then in the liver, having an overall reducing capacity of 3300
mg. These processes give reasons for the poor oral toxicity of chromium(VI)
and its lack of carcinogenicity when introduced by the oral route or
swallowed following reflux from the respiratory tract. In terminal airways
chromium(VI) is reduced in the epithelial lining fluid (0.9-1.8 mg) and in
pulmonary alveolar macrophages (136 mg). The peripheral lung parenchyma has
an overall reducing capacity of 260 mg chromium(VI), with a slightly higher
specific activity as compared to the bronchial tree. Therefore, even in the
respiratory tract, which is the only consistent target of chromium(VI)
carcinogenicity in humans (lung and sinonasal cavities), there are barriers
hampering its carcinogenicity. These hurdles could be only overwhelmed
under conditions of massive exposure by inhalation, as it occurred in
certain work environments prior to the implementation of suitable
industrial hygiene measures.
ARTICLES
Estimates of the chromium(VI) reducing capacity in human body compartments as a mechanism for attenuating its potential toxicity and carcinogenicity
Institute of Hygiene and Preventive Medicine, University of Genoa, Italy. sdf@unige.it
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