Tuesday, August 1, 2023

Hemoglobin Adducts and Other Biomarkers for Assessing Chemical Exposure

Hemoglobin adducts have long been a focus of study in the field of environmental exposure, with growing research revealing their importance as biomarkers for internal exposure to chemicals. 

Hemoglobin (Hb) adducts are formed when specific chemicals react with hemoglobin or other proteins, leading to compounds known as adducts. These adducts can be measured, making them invaluable for understanding whether a person has been exposed to particular chemicals, such as glycidol, acrylamide, and glucose.

Exposure to chemicals that bond with the N-terminal valine of Hb, like glycidol, acrylamide, can affect the formation of individual Hb adducts. This has been analyzed using in vitro and in vivo systems, showing that simultaneous exposure, factors such as glucose, serum albumin, and other chemicals could alter adduct formation. 

Hemoglobin adducts of substances like butadiene, ethylene oxide, acrylamide, and acrylonitrile have significant advantages, and in some cases, they are more useful than other types of biomarkers. Hemoglobin adducts from acrylamide, for example, have been associated with a higher risk of mortality and cardiovascular diseases in humans.

In certain industries, like the production of surfactants for the textile industry, the levels of specific adducts can provide valuable insights into occupational exposure.

Lifestyle choices also pay a role. A study revealed correlations between smoking habits and adduct levels, showing how personal choices might impact the formation of these adducts. Yet, while there was a strong correlation with the number of cigarettes smoked daily, high levels of Hb adducts in nonsmoking workers suggested potential exposure from other sources such as food and drinks. 

While hemoglobin adducts offer a promising way to assess exposure to various chemicals, other methods like measuring volatile organic compounds (VOCs) in exhaled breath or measuring urinary byproducts of metabolism also exist. 

Urinary metabolites, like 2-HPMA for propylene oxide exposure, reflect a shorter window of exposure. These metabolites are excreted in the urine, and their concentration can provide insight into exposure over a time frame that generally spans up to 24 hours. The exact window may vary depending on the specific compound, metabolism, and excretion rates. Factors like testing methodology, exposure level and duration, diet and hydration, age, gender, kidney function, and overall health can influence how quickly substances are metabolized and excreted.

While Hemoglobin Adducts provide integrated exposure information over several months (reflecting exposure over the life span of red blood cells, typically 120 days) and are suitable for assessing exposure to a wide range of chemicals, not only those in the air, VOCs offer real-time exposure information and are less complicated by the simultaneous exposure to other chemicals - although cumulative effects play a role too. 


REFERENCES

Schettgen T, Broding HC, Angerer J, Drexler H. Hemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile and acrylamide–biomarkers in occupational and environmental medicine. Toxicology letters. 2002 Aug 5;134(1-3):65-70.

Schettgen T, Müller J, Fromme H, Angerer J. Simultaneous quantification of haemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile, acrylamide and glycidamide in human blood by isotope-dilution GC/NCI-MS/MS. Journal of Chromatography B. 2010 Oct 1;878(27):2467-73.

Schettgen T, Müller J, Ferstl C, Angerer J, Göen T, Hartwig A, MAK Commission. Haemoglobin adducts of ethylene oxide (N-(2-hydroxyethyl)valine), propylene oxide (N-(2-hydroxypropyl)valine), acrylonitrile (N-(2-cyanoethyl)valine), acrylamide (N-(2-carbonamide ethyl)valine) and glycidamide (N-(2-hydroxy-2-carbonamide ethyl)valine) [Biomonitoring Methods, 2015] The MAK-Collection for Occupational Health and Safety 2017, 1 (1) (2016), pp. 473-506, 10.1002/3527600418.bi7521e2115

Shimamura Y, Okuda A, Ichikawa K, Inagaki R, Ito S, Honda H, Masuda S. Factors influencing the formation of chemical–hemoglobin adducts. Toxics. 2021 Dec 21;10(1):2.

Zhao FC, Li X, Wang YX, Zhou SJ, Lu Y. Relationship between acrylamide and glycidamide hemoglobin adduct levels and osteoarthritis: a NHANES analysis. Environmental Science and Pollution Research. 2023 May 22:1-1.

Dos Santos LD, de Souza TL, da Silva GI, de Mello MF, de Oliveira JM, Romano MA, Romano RM. Prepubertal oral exposure to relevant doses of acrylamide impairs the testicular antioxidant system in adulthood, increasing protein carbonylation and lipid peroxidation. Environmental Pollution. 2023 Jul 4:122132.

Project: OSF | Biological Factors that Influence Individual Responses to Environmental Epoxides DOI 10.17605/OSF.IO/W7682