API

Event: 846

Key Event Title

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Accumulation, Highly carboxylated porphyrins

Short name

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Accumulation, Highly carboxylated porphyrins

Key Event Component

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Process Object Action
porphyrins increased

Key Event Overview


AOPs Including This Key Event

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AOP Name Role of event in AOP
Aryl hydrocarbon receptor activation leading to uroporphyria KeyEvent

Stressors

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Level of Biological Organization

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Biological Organization
Organ


Organ term

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Taxonomic Applicability

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Term Scientific Term Evidence Link
rat Rattus norvegicus Strong NCBI
mouse Mus musculus Strong NCBI
human Homo sapiens Strong NCBI
chicken Gallus gallus Strong NCBI
Japanese quail Coturnix japonica Strong NCBI
herring gull Larus argentatus Strong NCBI

Life Stage Applicability

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Life stage Evidence
Juvenile Strong
Adults Strong

Sex Applicability

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Term Evidence
Unspecific Moderate

How This Key Event Works

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Under normal conditions, the heme biosynthesis pathway is tightly regulated and porphyrins (other than protoporphyrin) are only present in trace amounts[1]. However, when the regulatory process is disturbed, a variety of porphyrin precursors of heme accumulate in various organs including the liver and urinary and fecal excretion is elevated[2]). The pattern of porphyrin accumulation in chicken and rodents is similar following exposure to a variety of chemicals, and can be used to identify which enzyme in the heme pathway is predominately affected[1].


How It Is Measured or Detected

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Methods that have been previously reviewed and approved by a recognized authority should be included in the Overview section above. All other methods, including those well established in the published literature, should be described here. Consider the following criteria when describing each method: 1. Is the assay fit for purpose? 2. Is the assay directly or indirectly (i.e. a surrogate) related to a key event relevant to the final adverse effect in question? 3. Is the assay repeatable? 4. Is the assay reproducible?

The hepatic and urinary/fecal porphyrin patters can be determined using a high-performance liquid chromatograph equipped with a fluorescence detector. Kennedy et al.[3] describe the method for tissue extraction and porphyrin quantification in detail, which is rapid and highly sensitive.


Evidence Supporting Taxonomic Applicability

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Elevated porphyrins have been reported in mouse[4], rat[5], Japanese quil and chicken liver[6] and in clinical diognosis of humans[2].  Elevated HCPs have been measured in Herring gulls from highly contaminated Great Lakes collinies[7].


References

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  1. 1.0 1.1 Marks, G. S., Powles, J., Lyon, M., McCluskey, S., Sutherland, E., and Zelt, D. (1987). Patterns of porphyrin accumulation in response to xenobiotics. Parallels between results in chick embryo and rodents. Ann. N. Y. Acad. Sci. 514, 113-127.
  2. Frank, J., and Poblete-Gutierrez, P. (2010) Porphyria cutanea tarda--when skin meets liver. Best. Pract. Res. Clin Gastroenterol. 24(5), 735-745.
  3. Kennedy, S. W., Wigfield, D. C., and Fox, G. A. (1986). Tissue porphyrin pattern determination by high-speed high-performance liquid chromatography. Anal. Biochem. 157 (1), 1-7.
  4. Hahn, M. E., Gasiewicz, T. A., Linko, P., and Goldstein, J. A. (1988). The role of the Ah locus in hexachlorobenzene-induced porphyria. Studies in congenic C57BL/6J mice. Biochem. J. 254(1), 245-254.

  5. Goldstein, J. A., Linko, P., and Bergman, H. (1982). Induction of porphyria in the rat by chronic versus acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochem. Pharmacol. 31(8), 1607-1613.

  6. Miranda, C. L., Wang, J. L., Henderson, M. C., Carpenter, H. M., Nakaue, H. S., and Buhler, D. R. (1983). Studies on the porphyrinogenic action of 1,2,4-trichlorobenzene in birds. Toxicology 28(1-2), 83-92.

  7. Kennedy, S. W., and Fox, G. A. (1990). Highly carboxylated porphyrins as a biomarker of polyhalogenated aromatic hydrocarbon exposure in wildlife: Confirmation of their presence in Great Lakes herring gull chicks in the early 1970s and important methodological details. Chemosphere 21(3), 407-415.