1,3-Butadiene

What is 1,3-butadiene?

According to OSHA (Occupational Safety and Health Administration), 1,3-butadiene is produced through petroleum processing. It is mainly used in the production of synthetic rubber.¹

Image

 

Check out this helpful video discussing exposure risks. 

Biotransformation/Toxicokinetics/Mechanism of Action

1,3-butadiene is metabolized to reactive intermediates. 1,3-butadiene is oxidized primarily by CYP2E1 to the metabolite 1,2-epoxy-3-butene (EB). This metabolite is then further oxidized to the metabolite 1,2:3,4-diepoxybutane (DEB). EB can also be hydrolyzed to the metabolite 1,2-dihydroxy-3-butene (B-diol). Both  DEB and B-diol can be further converted by hydrolysis and oxidation respectively, producing the metabolite 1,2-dihydroxy-3,4-epoxybutane (EBD). If detoxification of these metabolites by glutathione conjugation does not occur, they can react with DNA.² See Figure 1 for a nice illustration of this process.

Mutagenic potency of each metabolite is as follows: DEB >> EB > EBD² 

 

Figure 1 Source

Signs and Symptoms of Toxicity^3,4

Image

• Acute (low doses)^3,4
  • Eye, nose, throat and lung irritation
  • Frostbite (dermal exposure)
• Acute (high doses)^3,4
  • Blurry vision
  • Tiredness
  • Vertigo
  • Headache
  • Nausea
  • Decreased blood pressure/pulse rate
  • Fainting
• Chronic^3,4
  • Increased risk of cancer and cardiovascular disease

Organ Systems Affected⁵

 

• CNS
• Dermal
• Respiratory
• Cardiovascular
• Ocular
• Gastrointestinal

Carcinogenicity 

Studies in workers have shown that 1,3-butadiene is a human carcinogen. It can cause an increased risk of cancers of the lymphatic system (lymphomas), blood and stomach.³

Rat and mice studies have shown that it is a carcinogen that can affect many organs.⁶

Classification Status:¹

Environmental Protection Agency (EPA) –  Known Human Carcinogen (based on human and animal studies)

American Conference of Governmental Industrial Hygienists (ACGIH) – A2 rating of suspected human carcinogen

 

Are there any treatments available for exposure to 1,3-butadiene?

There are no current treatments for 1,3-butadiene exposure. Supportive care should be initiated if needed.⁵

 

Are there any biomarkers utilized to know if someone has been exposed to 1,3-butadiene?

Currently, there are no known biomarkers utilized to determine 1,3-butadiene toxicity.³ 

However, in studies, surrogate biomarkers have been utilized to determine 1,3-butadiene exposure. The following biomarkers are protein adducts produced by EB, DEB and B-diol.⁷

• N-(2-hydroxy-3-buten-1-yl)-valine (HB-Val)
• N,N-(2,3-dihydroxy-1,4-butadiyl)-valine (pyr-Val)
• 1,2,3-trihydroxybutyl-valine (THB-Val)

Genetic Susceptibility

A study analyzing the genetic polymorphism of the XRCC1 gene concluded that these polymorphisms could contribute to chromosomal damage of those exposed to 1,3-butadiene.⁸

Image

References

1. Occupational Safety and Health Administration. 1,3-Butadiene. United States Department of Labor. Accesssed July 6, 2021. https://www.osha.gov/butadiene.
2. Kirman, CR, Albertini, RJ, Sweeney, LM et al. (2010). 1,3-Butadiene: I. Review of metabolism and the implications to human health risk assessment. Critical Reviews in Toxicology. 40(S1): 1–11.
3. Agency for Toxic Substances and Disease Registry. ToxFAQs™ for 1,3-Butadiene. U.S Department of Health and Human Services. Updated March 3, 2011. Accessed July 6, 2021. https://wwwn.cdc.gov/TSP/ToxFAQs/ToxFAQsDetails.aspx?faqid=458&toxid=81.
4. Occupational Safety and Health Administration. 1,3-Butadiene: Health Effects. United States Department of Labor. Accesssed July 6, 2021. https://www.osha.gov/butadiene/health-effects.
5. Agency for Toxic Substances and Disease Registry. Medical Management Guidelines for 1,3-Butadiene. U.S Department of Health and Human Services. Updated October 21, 2014. Accessed July 6, 2021. https://wwwn.cdc.gov/TSP/MMG/MMGDetails.aspx?mmgid=455&toxid=81.
6. Melnick, RL, Huff, J. 1,3-Butadiene: toxicity and carcinogenicity in laboratory animals and in humans. (1992). Rev Environ Contam Toxicol. 124:111-44. doi: 10.1007/978-1-4612-2864-6_5.
7. Swenberg, JA, Bordeerat, NK, Boysen, G, et al. (2011). 1,3-Butadiene: Biomarkers and Application to Risk Assessment. Chem Biol Interact. 192(1-2): 150–154. doi: 1016/j.cbi.2010.10.010.
8. Wang, Q, Wang, A-H, Tan, H-S, Feng, N-N, et al. (2010). Genetic polymorphisms of DNA repair genes and chromosomal damage in workers exposed to 1,3-butadiene. Carcinogenesis. 31(5): 858–863. doi:10.1093/carcin/bgq049.