2016: The end of Endosulfan

 As an undergraduate I did a lot of research on immunotoxicology. I looked at the effects of the insecticide Endosulfan-a on certain macrophage cells and their inflammatory response. The usage of Endosulfan in agriculture is coming to an end in the United States in the year 2016. http://www.epa.gov/pesticides/reregistration/endosulfan/endosulfan-agreement.html

Endosulfan is an organochlorine insecticide used in agriculture.  It is typically manufactured as a mixture of endosulfan-a and endosulfan-b.  Although it has been banned from use in more than fifty countries, it is still manufactured, and it is still used in the United States, India, Brazil, and Australia.  

 Acute exposures in humans and animals have been shown to cause neurological toxicity.  Studies suggest that subacute and/or chronic exposures can cause endocrine disruption, altered immune function, altered development, altered liver metabolism, and other toxicities [1-3]. 

 A recent study [4] showed that endosulfan exposure in mouse macrophages caused deregulation of production of nitric oxide (NO). Dysregulation of inflammatory cytokines and NO may play a role in the pathogenesis of some human diseases.  Because the a and b isoforms of endosulfan have differential biological activity, I examined the effects of endosulfan-a on a macrophage cell line (RAW 264.7) in culture.

 NF-KB is a protein complex that controls the transcription of DNA. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress,cytokines, free radicals, ultraviolet irradiation,  oxidized low density lipoproteins, and bacterial or viral antigens. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development [5].  NF-kappaB triggers nitric oxide synthase II transcription when it translocates from the cytoplasm to the nucleus when inhibition factors are degraded, where it interacts with kappaB elements in the NOS2 5' flanking region.  [5].

Endosulfan is a very dangerous insecticide, especially for the agriculture workers who are in contact with the crops every day. Phasing out the insecticide in the United States was decided by the EPA, and phasing it out world wide was also proposed in 2011. http://www.epa.gov/pesticides/reregistration/endosulfan/endosulfan-agreement.html

1.  De Hond E, Schoeters G. Int J Androl. 2009 29:264.

2.  Teather K, Jardine C, Gormley K. Environ Toxicol. 2005 20: 110.

3. ATSDR. 2000. Toxicological profile for Endosulfan. Atlanta, GA: U.S. DHHS, PHS.

4. Benitez Kruidenier, S. Endosulfan-α Does Not Enhance LPS-Stimulated Cytokine Production

in RAW 264.7 Cells. 2010.[Abstract].

5. Davis RL et al. Effects of mechanistically distinct NF-kappaB inhibitors on glial inducible nitric-oxide synthase expression. Nitric Oxide. 2005 12(4):200-9.