1. Methoxychlor Aquatic Toxicology Spring 2011 Karen Chow

2. Why Bees are gold?

3. Methoxychlor Compound structure Production history Uses and Application Physical Properties Chemical Properties Physical half-life Mode of entry to aquatic environment Biochemical metabolism Toxic effect Defense mechanisms for animals

4. Structure of Methoxychlor

5. Production History – Replacement for DDT DDT Methoxychlor

6. Production History Synthesized in 1893 1948: Registered as a pesticide Formulated as wettable powders, dusts, ready-to-use products, pressurized liquids Suspended in 2000 Methoxychlor is not eligible for re-registration  all registered technical source of methoxychlor were cancelled in 2003, all tolerances have been revoked. It is not necessary to assess the risks of methoxychlor products because there are no tolerances for methoxychlor

7. Uses and Application Used to kill cockroaches, mosquitoes, flies, arthropods Found on field crops, vegetables, fruits, ornamentals, stored grain, livestock, domestic pets.

8. Physical Property Melecular weight: 345.65 g/mol Color: pale yellow Odor: slightly fruity; musty; chlorine-like Physical state: Crystalline solid Melting point: 89 o C Density: 1.41g/cm 2

9. Chemical Properties Organic solvents: soluble in chlorinated aromatic solvents, ketonic solvents, ethanol, methylene chloride, methlated naphalene, carbon tetrachloride, chloroform, xylene, methanol, petroleum ether, benzene Chemical reactivity with water: soluable Solubility in water: Degree Celsius mg/L 150.02 250.045 350.095 450.185

10. Physical Half-life In soil: ~120 days Distilled water: 130days Natural water: 2-5 hours In atmosphere: 7 hours When degraded in water: 1 year Within some organisms: less than 2 weeks

11. Mode of Entry to Aquatic Environment Released to air  settles to the ground Sticks strongly to particles in soil Runoff from soil that contains methoxychlor Industrial sewage Leaks at storage and waste sites Can be released directly to surface water on farm as a pesticide Harp seals had detectable concentration of methoxychlor in various tissue. (Zitko 1998)

12. What happens when it enters the environment? Does not dissolve in water easily In water: Binds to sediments and settles to the bottom Breaks down slowly in air, water, soil by sunlight and microscopic organisms Harmful breakdown products of methoxychlor

13. Biochemical metabolism Breakdown in water and sediment: Methoxychlor degraded to dechlorinated, dehydrochlorinated, and demethylated products by chemical, photochemical, and biological processes. Rapidly metabolized to phenolic derivatives In animals: methoxychlor is rapidly metabolized and eliminated

14. Toxicity to aquatic life Toxic for aquatic animal by ingestion, contact with skin For freshwater invertebrate: 0.0005 mg/L For Marine birds: non toxic (LD 50 >2000 mg/kg)

15. Toxic effect Affect the hypothalamic-pituitary-gonadal axis Developmental effect Thyroid toxic effect Irritate skin, eyes, Affect human nervous system Group D carcinogen Group 3 carcinogen 1978: NCI concluded Insufficient evidence to classify as a carcinogen

16. Defense mechanism for organisms Antibodies is important to the defense strategy of the organisms. Integration in number of cells that produce antibody Methoxychlor undergoes oxidative metabolism by cytochromes P450, yielding 1,1,1-trichloro-2- (4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane (mono-OH-M) and 1,1,1-trichloro-2,2-bis(4- hydroxyphenyl)ethane (bis-OH-M) as main metabolites.

17. References ATSDR. 2002. Methoxychlor CAS #72-43-5. Toxicological Profile for Methoxychlor. U.S. Department of Health and Human Service, Public Health Service. ATSDR. 2009. Addendum to the toxicological profile for methoxychlor. U.S. Department of Health and Human Service, Public Health Service. EPA. 2000. Toxicological Reviewfor Chloral hydrate (CAS No. 302-17-0). U.S. Washington, DC: Environmental Protection Agency. Gray, L.E. Jr., J. Ostby, J. Ferrell et al. 1989. A dose- response analysis of methoxychlor-induced alterations of reproductive development and function in the rat. Fund. Appl. Toxicol. 12(1): 92- 108. Goldman, J.M., R.L. Cooper, G.L. Rehnberg, J.F. Hein, W.K. McElroy, and L.E. Gray Jr. 1986. Effects of low subchronic doses of methoxychlor on the rat hypothalamic-pituitary reproductive axis. Toxicol. Appl. Pharmacol. 86(3): 474-483.

18. References Kapoor IP, Metcalf RL, Nystrom RF, et al. 1970. Comparative metabolism of methoxychlor, methiochlor and DDT in mouse, insects, and in a model ecosystem. J Agric Food Chem 18:1145- 1152. Kupfer, D. and W.H. Bulger. 1987. Metabolic activation of pesticides with proestrogenic activity. Fed. Proc. 46(5): 1864-1869. 6. Ware, G.W. 1982. Fundamentals of Pesticides, Thompson Publications. Shea, D. Transport and fate of toxicants in the environment. New York: Academic Press, 1994 Stoltz RL, Pollock GA. 1982. Methoxychlor residues in treated irrigation canal water in Southcentral Idaho. Bull Environ Contam Toxicol 28:473–476. Zitko V, Stenson G, Hellou J. 1998. Levels of organochlorine and polycyclic aromatic compounds in harp seal beaters (Phoca groenlandica). Sci Total Environ 221:11-29.