Introduction
Benzidine (1,1′-biphenyl-4,4′-diamine) is an organic compound that has the formula of (C6H4NH2)2
Benzidine is not a naturally occurring substance. Instead, it is manufactured and used in the dying process of cloth and paper. It was also used to detect blood and in the production of plastic films (1). However, benzidine is no longer produced or used commercially in the US.
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Source
- Benzidine-based dyes in paper, cloth, leather (Major exposure)
- Contaminated water, air, soil near hazardous waste sites (Rare)
- Food dyes (Rare – benzidine may be available as a byproduct)
Biotransformation
Biotransformation of benzidine in the body is through N-acetylation, which is likely to be done by N-acetyltransferases (2). Benzidine generally requires P-450 cytochrome for metabolism and to manifest genotoxicity and carcinogenicity (2). However, the isozymes involved in the process have remained unknown.
Toxicokinetics
Absorption: there are data that show the absorption of benzidine through inhalation and oral ingestion. Significantly elevated benzidine levels were detected in the urine samples of workers who had been exposed to benzidine during the work shift. In addition, inhaled particles that are coughed up by the ciliary activity can also be swallowed back down, leading to an increase in oral ingestion (2). Benzidine can also be absorbed through the dermal route (2).
Distribution: there are very limited information on benzidine information. It is unclear whether or not benzidine can cross the placenta or enter breastmilk (2).
Metabolism: benzidine is potentially involved in multiple metabolic pathways in vivo
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Elimination: a small amount of benzidine is eliminated in the urine and feces. The elimination process can occur pretty quickly. In fact, benzidine and its metabolite can be detected as early as 1 hour after exposure (2). Without continuous exposure to benzidine, most of the absorbed amount can be eliminated in a week (3).
Carcinogenicity
Benzidine is categorized as carcinogenic. It has been known to increase the risk of developing bladder cancer. It has been hypothesized that the mechanism of its carcinogenicity involved the formation of reactive species from the biotransformative processes. These reactive species can produce DNA adducts and produce mutations as the result (3).
Target organ
- Skin
- Bladder (cancer)
- Stomach, kidney, brain, mouth, esophagus, liver, gallbladder, bile duct, and pancreas can also be affected
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Signs and symptoms of toxicity
Generally non-specific:
- Skin allergy
- Lung/eye irritation
- Nausea
- Vomiting
- Bladder cancer symptoms: frequent/painful urination, lower back pain, blood in the urine
Routes of exposures
Benzidine has been detected in the system after being exposed through:
- Inhalation
- Oral ingestion
- Dermal absorption
- Treatments
Biomarkers
A number of benzidine metabolites can be detected and serve as the biomarkers for benzidine exposure. These compounds are hydroxybenzidine, N-acetylbenzidine, and N,N’-diacetylbenzidine, and various glucuronic acid conjugates of these compounds (3).
References
- https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/benzidinev
- https://www.atsdr.cdc.gov/ToxProfiles/tp62.pdf
- https://www.atsdr.cdc.gov/phs/phs.asp?id=567&tid=105