Pilot survey of urinary porphyrins from persons transiently exposed to a pcb transformer fire

Osterloh, John; Cone, James E.; Harrison, Robert J.; Wade, Richard L.; Becker, Charles E.

doi:10.3109/15563658608995392

Cited by 9 publications

(4 citation statements)

References 10 publications

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“…Brewster (9) has reviewed the usefulness ofmeasuring total urine porphyrins to detect xenobiotic exposures to heavy metals, hormones, drugs, and halogenated aromatic hydrocarbons. These chemicals induce chronic disturbances in hepatic synthesis ofporphyrins (Tible 4) and thus lead to excess porphyrin excretion and skin symptoms in the final stage (107)(108)(109)(110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123)(124).…”

Section: Porphyrinsmentioning

confidence: 99%

The potential of exposure biomarkers in epidemiologic studies of reproductive health.

Hogue¹,

Brewster²

1991

Environ Health Perspect

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To further the development and application of exposure markers in field investigations in reproductive epidemiology, we have synthesized recent examinations of the issues surrounding exposure measurements in reproductive epidemiology. The specific goals of this paper are to define exposure biomarkers and explore their potential uses, particularly as screening tools. The tests for glucaric acid, thioethers, mutagenicity, and porphyrin patterns meet the general criteria for useful exposure screens. For certain xenobiotic agents, these tests accurately differentiate exposure levels, as demonstrated in occupational and environmental epidemiologic studies. As urinary screens, they are noninvasive and applicable on a large scale with current laboratory techniques. For short-term exposure, glucaric acid, thioethers, and mutagenicity tests are useful. Porphyrin patterns may measure cumulative effects as well as current exposure levels. The usefulness of these tests in epidemiologic studies of environmental effects on reproductive health has yet to be studied. To do so, the battery must be standardized for pregnant women, and test results must be correlated with measured adverse reproductive outcomes, such as gestational length and birthweight. This correlation is particularly important because maternal exposure rather than fetal exposure is being measured. The extent to which xenobiotic chemicals cross the placental barrier may vary greatly depending on the type of exposures, timing in pregnancy, and maternal detoxification capability. Without better exposure measures, epidemiologic studies of reproductive health probably will not successfully identify xenobiotic fetotoxic agents in the environment. However, with an adequate battery of nonspecific exposure biomarkers, prospective studies of environmental effects on pregnancy outcomes might be possible.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Porphyrinsmentioning

confidence: 99%

The potential of exposure biomarkers in epidemiologic studies of reproductive health.

Hogue¹,

Brewster²

1991

Environ Health Perspect

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“…Similar results have been noted by Stark et a1.28 in their study of men exposed to PCBs from a transformer explosion in Syracuse, N.Y. Seppalainen et al" have found slight and reversible impairment of the peripheral nerves among workers in a Finnish cardboard plant after a capacitor explosion. Osterloh et al 30 have examined urinary porphyrins in 90 persons transiently exposed to a PCB transformer fire, and concluded that excretion levels were unaltered and that they were insensitive measures of exposure.…”

Section: Discussionmentioning

confidence: 97%

Health Effects Three Years after Potential Exposure to the Toxic Contaminants of an Electrical Transformer Fire

Fitzgerald¹,

Weinstein²,

Youngblood³

et al. 1989

Archives of Environmental Health: An International Journal

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A medical surveillance program has been established for 482 persons who were potentially exposed to polychlorinated biphenyls (PCBs), dibenzo-p-dioxins, and dibenzofurans from an electrical transformer fire in a Binghamton, NY office building in 1981. Vital Record and Cancer Registry data, medical records, and mail questionnaires were used to assess mortality, symptomatology, cancer incidence, and reproductive events through 1984. The numbers of deaths, cancers, fetal deaths, and infants with low birth weight or congenital malformations were similar to those expected on the basis of age- and sex-specific rates for upstate New York and other comparison populations. Two suicides were observed compared with 0.31 expected, but the difference was not statistically significant. After adjustment for possible confounders, persons with the greatest degree of potential exposure were significantly more likely than those with less exposure to report unexplained weight loss (relative risk [RR] = 12.80), muscle pain (RR = 5.07), frequent coughing (RR = 4.14), skin color changes (RR = 3.49), and nervousness or sleep problems (RR = 3.19). The possibility of recall bias and the intervening effects of stress, however, weaken the conclusion that toxic chemicals caused the symptomatology. Exposure-related systemic disorders, e.g., chloracne or peripheral neuropathy, were not diagnosed by personal physicians; however, some persons refused to release their medical records because of ongoing litigation. The findings are consistent with those of our earlier assessment.

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“…In contrast, uroporphyria developed after the same oil mixture was administered to mice . Likewise, among people poisoned by polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs), disturbances of porphyrin metabolism have been detected by levels and patterns of the porphyrins excreted in urine, but clinical porphyria manifested by cutaneous symptoms of PCT is rare ,,− .…”

Section: Chemical-induced Uroporphyriamentioning

confidence: 99%

Complex Gene−Chemical Interactions: Hepatic Uroporphyria As a Paradigm

Smith

Elder

2010

Chem. Res. Toxicol.

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Many toxicological disorders, in common with numerous human diseases, are probably the consequence of multigene interactions with a variety of chemical and physiological factors. The importance of genetic factors may not be obvious initially from association studies because of their complexity and variable penetrance. The human disease, porphyria cutanea tarda (PCT), is a skin disease caused by the photosensitizing action of porphyrins arising secondary to the decreased activity of an enzyme of heme biosynthesis, uroporphyrinogen decarboxylase (UROD), in the liver. It is triggered by idiosyncratic hepatic interaction between genetic factors and chemicals such as alcohol, estrogenic drugs, and polyhalogenated aromatics. PCT and its animal models are known collectively as the hepatic uroporphyrias. There is strong evidence for the participation of iron in the pathogenesis of these conditions. Mouse models have been used to explore the relative importance of a variety of agents such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), alcohol, and iron in the development of uroporphyria and to elucidate the mechanism of the depression of hepatic UROD activity. Mutations of the UROD and hemochromatosis (HFE) genes are genetic factors in some PCT patients which can be mimicked in mice heterozygous for the Hfe and Urod null genes. Association studies of uroporphyria induced by TCDD or hexachlorobenzene with DNA markers in mouse intercrosses have shown the participation of other, unknown, genetic factors in addition to the strong influence of the Ahr gene. The pathogenesis of hepatic uroporphyrias exemplifies the complexity of the interactions between chemical and genetic factors that can contribute to the hepatotoxicity of chemicals.

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Pilot survey of urinary porphyrins from persons transiently exposed to a pcb transformer fire

Cited by 9 publications

References 10 publications

The potential of exposure biomarkers in epidemiologic studies of reproductive health.

The potential of exposure biomarkers in epidemiologic studies of reproductive health.

Health Effects Three Years after Potential Exposure to the Toxic Contaminants of an Electrical Transformer Fire

Complex Gene−Chemical Interactions: Hepatic Uroporphyria As a Paradigm

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