DDT (Analogs)

Introduction (1,2)

DDT and its analogs are part of the organochlorine compounds. DDT or p,p’-DDT has a full chemical name of 1,1,1-Trichloro-2,2-bis(4-chlorophenyl)ethane. O. Zeidler synthesized it in 1874, but 65 years later, Paul Miller would find its true purpose when he discovered its insecticidal properties.  DDT became known as the catch-all insecticide as it was useful against pests that decimated agriculture as well as vector based insects that carried deadly diseases. Below are DDT and a few of its many analogues, including DDE.

image

Image Source found here

In the mid-1900’s DDT gained an increase in production and was being used overseas to help allied troops stave off the threat of malaria, typhus and yellow fever during World War 2. After the war, DDT found an increased use in the agricultural sector. It wouldn’t be until the 1970’s that the negative effects of DDT were realized.

 

Image source found here

Mechanism of Action (1,2,9)

DDT acts on the sodium ion channels by keeping the channels open longer than usual. In turn there is a prolonged afterpotential which causes an increase in neuronal excitability as pictured below. In insects, a protein subunit of ATP synthesis might be the target for DDT. DDT also affects the ATPases of calcium which is responsible for keeping a stable external calcium balance. With inhibition of these ions the membrane becomes destabilized. DDT is also responsible for a decrease in potassium and sodium ions.

Image source found here

Toxicokinetics (1,6,7)

DDT is a lipid-soluble compound. It travels fast through the lymphatic system and bloodstream where it is dispersed in the organs lipid tissue content.  DDT is primarily excreted through urine as DDA (urinary metabolite), but can also be excreted through feces and breast milk. Due to the extremely slow metabolism, DDT can be stored in the fatty tissue for several years after exposure.

DDT can be absorbed through the following routes

  • Oral Exposure
    • Primary route of exposure in humans
  • Dermal Exposure
    • Low risk
  • Inhalation Exposure
    • DDT is a larger particle size and is usually trapped in the upper respiratory tract where it is ultimately swallowed

Toxicity in Rats (1,8)

  • Acute oral LD50 of 113-800 mg/kg
  • Acute dermal LD50 of 2500-3000 mg/kg

Symptomology (1,2,3)

The first symptoms of exposure in humans would include;

  • hyperesthesia of the lower part of the face
  • paranesthesia of the lower part of the face and tongue

In acute exposures, patients would experience;

  • Vomiting
  • Seizures
  • Tremors

In chronic exposures, a patients would experience;

  • Hepatic cell hypertrophy
  • Liver necrosis
  • Weight gain of the liver

In most cases, DDT is not significantly harmful to humans, but acute cases can lead to death through respiratory arrest.

DDT is a probable human carcinogen.

Genetic susceptibility or heritable traits (5,7)

A mother can pass DDT down to offspring through the placenta, maternal blood and breast milk.

Although studies have shown that DDT can easily be transmitted from parent to offspring, there is still debate as to how much of an effect DDT has on human reproduction.

A study conducted on vector-control workers in Africa on whether DDT exposure affects semen, fertility and sexual function found that DDT might have an effect on testis size as testis disposition was found to be 71%. The researchers concluded that there was no significant evidence that DDT lowered sperm count.

Historical or unique exposures (3,4,7)

DDT may be most famous for its impact on fish and wildlife species

  • Shown to have lethal and sublethal effects on phytoplankton, mollusks and arthropods
  • Can cause reproductive issues in fish
  • Has led to a decrease in egg thickness of eagles, ospreys and other piscivorous birds

Image source found here

Although DDT plays an important part as an insecticide, the benefits do not outweigh the risks. The United States banned its use 1972.

Biomarkers (6)

  • Biomarkers of effect
    • Liver
    • Nervous system
    • Reproductive system
  • Biomarkers of exposure
    • Serum
    • Blood
    • Breast milk

Treatments (1,2)

  • Diazepam
  • Phenobarbital
  • Decontamination

Biomarkers

Works Cited

  1. Smith. A. Chapter 93-Toxicity of DDT and Some Analogues. Hayes Handbook of  Pesticide Toxicology (Third Edition). Pages 1975-2032. https://www.sciencedirect.com/science/article/pii/B9780123743671000938
  2. Klaassen, C.D., Ed. (2013). Chapter 22: Toxic Effects of Pesticides. https://accesspharmacy-mhmedical-com.proxy.lib.ohio-state.edu/content.aspx?bookid=958&sectionid=53483747#1100089899

  3. Dichlorodiphenyltrichloroethane (DDT) Factsheet. National Biomonitoring Program. https://www.cdc.gov/biomonitoring/DDT_FactSheet.html

  4. DDT-A Brief History and Status. United States Environmental Protection Agency. https://www.epa.gov/ingredients-used-pesticide-products/ddt-brief-history-and-status

  5. The long-term effects of DDT exposure on semen, fertility, and sexual function of malaria vector-control workers in Limpopo Province, South Africa. Environmental Research. V. 96, Issue 1. (2004). https://www.sciencedirect.com/science/article/pii/S0013935103001750

  6. Chapter 3. Toxicokinetics, Susceptible populations, Biomarkers, Chemical Interactions. https://www.atsdr.cdc.gov/toxprofiles/tp35-c3.pdf

  7. DDT. Chemistry, Metabolism and Toxicity. United States Environmental Protection Agency. DDT (Technical Fact Sheet). National Pesticide Information Center. https://nepis.epa.gov/Exe/ZyNET.exe?User=ANONYMOUS&Password=anonymous&Client=EPA&SearchBack=ZyActionL&SortMethod=h&SortMethod=-&MaximumDocuments=15&Display=hpfr&ImageQuality=r85g16%2Fr85g16%2Fx150y150g16%2Fi500&DefSeekPage=x&ZyAction=ZyActionS&Toc=&TocEntry=&QField=&QFieldYear=&QFieldMonth=&QFieldDay=&UseQField=&Docs=&IntQFieldOp=0&ExtQFieldOp=0&File=&SeekPage=&Back=ZyActionL&BackDesc=Contents+page&MaximumPages=1&ZyEntry=0&TocRestrict=n&SearchMethod=2&Time=&ZyActionS=+Search+–%3E+&Query=DDT&FuzzyDegree=0&Index=2016+Thru+2020&Index=1991+Thru+1994&Index=2011+Thru+2015&Index=1986+Thru+1990&Index=2006+Thru+2010&Index=1981+Thru+1985&Index=2000+Thru+2005&Index=1976+Thru+1980&Index=1995+Thru+1999&Index=Prior+to+1976&Index=Hardcopy+Publications&IndexPresets=entry
  8. Younis H.M., Abo-El-Saad M.M., Abdel-Razik R.K., Abo-Seda S.A. Resolving the DDT target protein in insects as a subunit of the ATP. Biotechnology and Applied Chemistry, 35 (2002). https://www.scopus.com/record/display.uri?eid=2-s2.0-0036183493&origin=inward&txGid=5b6f71b53e5587d7cf635b1a26162bcf