The Toxicology of ATRAZINE

1
The Toxicology of ATRAZINE

• Clair Morris
• ENVS 531 11-11-02

2
Atrazine Triazine Herbicide

• First synthesized in 1955
• Widely used for over 40 years
• 70 million pounds used per year

• 2-chloro-4-ethylamino-6-isopropylamino-s-triazine
• Systemic broad leaf herbicide
• Disrupts photosynthesis
• Used pre-emergence and post-emergence

3
Chemical Physical Properties

• Atrazine herbicides take several forms
• Powder, liquid or granular
• Atrazine
• Soluble in water
• No odor
• Low to medium volatility
• Kow 322 prefers organic phase

4
Atrazine Exposure Potential

• Environmental samples
• Found in rivers, wells, soil air samples
• Low atrazine residues found on food
• Half life
• Water gt Soil gt Air
• Groups with highest exposure potential
• Factory workers, farm workers herbicide
  applicators

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Acute Toxicity

• Low acute toxicity
• LD50 in rats 672 1471 mg/kg
• Dermal exposure
• Mild irritation to skin
• More severe irritation to eyes

6
Sub-Acute Sub-Chronic Toxicity

• Liver damage in sub-acute tests
• Pigs most sensitive to atrazine liver damage
• Other species showed liver damage
• Sub Chronic
• Low concentration ingestion of atrazine in mice
  for 7 weeks
• ? no effects

7
Chronic Toxicity

• Studies in several species, effects include
• Decreases in body weight organ weight
• Loss of appetite
• Depression anemia
• Liver damage
• Kidney epithelium
• Contact dermatitis
• Decreased glucose triglyceride levels
• Bone marrow, mammary gland prostate effects

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Carcinogenicity

• Classified by International Agency for Research
  on Cancer (IARC) as not classifiable as to its
  carcinogenicity to humans
• Mammary tumors found in 2 strains of female rats
• Debate by scientists about relevance to humans

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Reproductive Toxicity

• Female reproductive system primary target of
  atrazine
• Disrupts estrus cycle
• Canadian survey study of farm couples
• Increase in pre-term delivery miscarriage
• Embryonic fetal effects
• Increased embryo deaths in rat studies
• No teratogenic effects found

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Targets Antidotes

• Atrazine targets
• Female reproductive system
• Liver
• Kidney (lesser extent)
• Antidotes
• No known antidotes
• Doctors try to prevent absorption in case of
  poisoning

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Mechanism of Action

• Atrazine ? estrogenic activity
• In rats atrazine acts on CNS
• Interferes with GABAA receptor
• Hypothalamus control of pituitary disrupted
• Low levels of luteinizing hormone (LH)
• Constant high levels of estrogen
• Result accelerates senescence
• Humans have a different mechanism to control
  estrogen levels

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Metabolism Bioaccumulation

• Atrazine is readily metabolized
• Humans excrete in 24 hours
• Route of metabolism
• Dealkylation phase I oxidation
• Gluathione conjugation phase II
• Excreted as mercapturic acids
• Bioaccumulation is unlikely
• Low bioaccumulation factors found

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Atrazine Regulatory Status

• Registered pesticide under FIFRA
• Currently under review for reregistration
• Triazine herbicides under special review by EPA
• Current debate and research
• Effects of atrazine on amphibians other water
  dwelling animals
• May effect future regulatory action

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Conclusion

• Atrazine is an important herbicide for current
  agricultural use
• Data gaps
• Regulatory review provides opportunity to
  evaluate new research

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References, part 1

• 1)      http//www.syngentacropprotection-us.com/p
  rod/herbicide/Atrazine/ - website for the
  herbicide Aatrex produced by Syngenta. November
  2nd, 2002.
• 2)      MSDS for Aatrex, Atrazine herbicide
  produced by Syngenta. (Link to Syngenta MSDS
  database at http//www.syngentacropprotection-us.
  com/labels/ )
• 3)      IARC monographs database on carcinogenic
  risks to humans. (monographs.iarc.fr/)
• 4)      Verschueren, Karel (Ed.), (2001) Handbook
  of Environmental Data on Organic Chemicals. (4th
  Edn.) J. Wiley Sons, New York, NY.
• 5)      Montgomery, John H. (Ed.), (1997)
  Agrochemicals Desk Reference. (2nd Edn.) CRC /
  Lewis Publ., Boca Raton, FL.
• 6)      Liu, David and Bela Liptak (Eds.), (1997)
  Environmental Engineers Handbook (2nd Edn.) Lewis
  Publ., Boca Raton, FL.
• 7)      Meyers, Robert A. (Ed.), (1999) The Wiley
  Encyclopedia of Environmental Pollution and
  Cleanup. Vol.s 1 2. J. Wiley Sons, New York,
  NY.
• 8)      Pohanish, Richard P. (Ed.), (2002)
  Sittigs Handbook of Toxic and Hazardous
  Chemicals and Carcinogens. Vol. 1. (4th Edn.)
  Noyes Publications, Norwich, NY.

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References, part 2

• 9)      Bingham, Eula et. al. (Eds.), (2001)
  Pattys Toxicology. Vol.s 1,4 8. (5th Edn.) J.
  Wiley Sons, New York, NY.
• 10)  Gangolli, Sharat (Ed.), (1999) The
  Dictionary of Substances and their Effects. Vol.
  1. (2nd Edn.) Royal Soc. of Chemistry, Cambridge,
  UK.
• 11)  Eiden, Catherine Health Effects Division
  of EPA, (Jan. 19th 2001) Revised Preliminary
  Human Health Risk Assessment Atrazine (for the
  Reregistration Eligibility Decision.)
  Reregistration Branch 3, Health Effects Division,
  Office of Pesticide Programs, US Environmental
  Protection Agency. http//www.epa.gov/oppsrrd1/re
  registration/atrazine/revsd_pra.pdf
• 12)  Klaasen, Curtis D.(Ed.), (2001) Casarett
  Doulls Toxicology The Basic Science of Poisons.
  (6th Edn.) McGraw Hill, New York, NY.
• 13)  Taylor, Linda L. Health Effects Division
  of EPA (Apr. 11th 2002) Atrazine Toxicology
  Disciplinary Chapter( for the Reregistration
  Eligibility Decision Document.) Health Effects
  Division, Office of Pesticide Programs, US
  Environmental Protection Agency.
  http//www.epa.gov/oppsrrd1/reregistration/atrazi
  ne/hed_toxchap_11apr02.pdf
• 14)  Department of Health Human Services,
  Agency for Toxic Substances Disease Registry
  (ATSDR). (Sept. 2001) Toxicological Profile for
  Atrazine (Draft for Public Comment).