Benzene

Source

Benzene is formed from both natural processes and human activities. Natural sources of benzene include volcanoes and forest fires. Benzene is also a natural part of crude oil, gasoline, and cigarette smoke.

Biotransformation

The above diagram shows how Benzene is transformed in the body.

Toxicokinetics

Carcinogenicity

Benzene is a known human carcinogen by regulatory agencies around the world. The IARC classifies benzene as a Group 1 carcinogen.

Mechanism of Action

Mechanism of action of benzene in hematotoxicity. Benzene suppresses the cell cycle by p53-mediated overexpression of p21, a cyclin-dependent kinase inhibitor, resulting not simply in suppression of hemopoiesis but rather in a dynamic change of hemopoiesis during and after benzene exposure.

Target organ

Bone marrow is the target organ for benzene and the liver is the main organ of metabolism for benzene.

Signs and symptoms of toxicity

Adverse effect of benzene is hematopoietic toxicity, which precedes leukemia. Chronic, high benzene exposure can lead to bone marrow damage, which may be manifest initially as anemia, leukopenia, thrombocytopenia, or a combination of these.

Genetic susceptibility or heritable traits

A study in mice either expressing the gene for NAD(P)H: quinone oxidoreductase-1 (NQO1) or lacking the gene found a 9 fold increase in micronucleated reticulocytes compared with a 3-fold increase in mice with the gene.

Historical or unique exposures

Because of benzene’s volatility and solvent properties, it was used in the printing industry in inks, ink solvents, and cleaning agents from the 1930s to the 1970s. Typical benzene air concentrations, considering both personal and area samples of various durations, were as high as 200 p.p.m. in the 1930s through the 1950s, 3-35 p.p.m. in the 1960s, 1.3-16 p.p.m. in the 1970s, 0.013-1 in the 1980s, and far less than 1 p.p.m. in the 1990s and 2000s.

Treatments

Benzene poisoning needs to be treated with medial care. There is not antidote for benzene poisoning and the best that can be done is to seek medical attention.

Biomarkers

Benzene in alveolar air, unmetabolized benzene, and ttMA in urine are potential biomarkers for occupational benzene exposure. The main marker here is the ttMA in urine. It is interesting to see that benzene itself is used to determine if exposure if significant.

References

https://www.youtube.com/results?search_query=toxicokinetics+of+benzene

Bruckner J.V., & Anand S, & Warren D (2013). Toxic effects of solvents and vapors. Klaassen C.D.(Ed.), Casarett and Doull’s Toxicology: The Basic Science of Poisons, Eighth Edition. McGraw-Hill. https://accesspharmacy-mhmedical-com.proxy.lib.ohio-state.edu/content.aspx?bookid=958&sectionid=53483749

https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.slideshare.net%2Fotrec%2Fair-quality-toxics-and-transportation&psig=AOvVaw0h2rRKOr6cNIIIKcYDmyoC&ust=1594254870540000&source=images&cd=vfe&ved=0CAIQjRxqFwoTCIjm95C3vOoCFQAAAAAdAAAAABAD

Yoon BI, Hirabayashi Y, Kawasaki Y, et al. Mechanism of action of benzene toxicity: cell cycle suppression in hemopoietic progenitor cells (CFU-GM). Exp Hematol. 2001;29(3):278-285. doi:10.1016/s0301-472x(00)00671-8

https://www.google.com/url?sa=i&url=https%3A%2F%2Fslideplayer.com%2Fslide%2F7736311%2F&psig=AOvVaw2iUkNjk4bOi5jgVW-ayXLw&ust=1594256517861000&source=images&cd=vfe&ved=0CAIQjRxqFwoTCJiXqsC6vOoCFQAAAAAdAAAAABAc

https://cancerres.aacrjournals.org/content/63/5/929