Human exposure to Household Pesticides: Safety Concerns Including Endocrine

Disruption Effects By

Michael Hansen, Ph.D.

Consumers Union of U.S. For

Fringe Meeting at CI World Congress 2007 Endocrine Disrupting Chemical Safety Campaign

Sydney, Australia

October 29, 2007

Outline

• Endocrine disruption chemicals – what they are, how they work, pesticide examples,

potential health problems

• Household pesticides– Potential health problems (cancer, neurobehavioral

effects, etc.); permethrin– Exposure via diet, residential use, outdoor use– Evidence of ED effects of glyphosate/RoundUp

• Conclusion

Endocrine disrupting chemicals

• By definition, chemicals that disrupt the endocrine system

• Endocrine system—network of glands (pituitary, thyroid, adrenal, testes and ovary) and organs/tissues (intestines) that secrete hormones

• Hormones– chemical message secreted by one tissue into bloodstream that travels to other tissues to affect growth, metabolism, reproduction and other physiological functions in the body

EDC mode of action and concerns• EDC’s work by mimicking a hormone or blocking a

hormone. Fetal exposure is of most concern as normal development of fetus require certain amounts of hormones at precise times. A change in amount or timing can lead to problems in behavior, immune function, neurological development or gender development

• Concerns– New studies show adverse effects at very low levels– Ubiquitous exposure in environment– More hormonal systems involved, not just estrogen or

reproductive system– Many more compounds involved– Problem of fetal exposure having impact on adult health

Examples of EDC pesticides (57 total)

• Pyrethroids: Allethrin, Karate, Talstar, sumithrin, fenvalerate, d-trans allethrin, permethrin (Bifenthrin, Bioallethrin, Cyhalothrin, Cypermethrin, Deltamethrin, Esfenvalerate, Fenothrin, Fluvalinate, Resmethrin)

• Organophosphates: Malathion, Ethylmalathion, Methylmalathion,Chlorpyrifos (Acephate, Chlorfenvinphos, , Cyclophosphamide, Demefion, Demeton-s-methyl, Diazinon, Dichlorvos, Dimethoate, Elsan (=Dimephenthoate), Ethylparathion, Fenitrothion, Fenthion, Formothion, Glufosinate, Metalodemeton, Mevinphos (=Phosdrin), Omethoate, Parathion, Phosphamidon, Quinalphos, Ronnel, Trichlorfon)

• Dithiocarbamates: Mancozeb, Maneb, Thiram, Zineb, Ziram (Metam Natrium, Metiram, Nabam)

Adverse health effects—phthalates

• Swan, SH, KM Main, F Liu, SL Stewart, et al and The Study for Future Families Research Group 2005. Decrease in Anogenital Distance Among Male Infants with Prenatal Phthalate Exposure. Environmental Health Perspectives 113: 1056-1061.

• What they did. 346 mothers, 176 baby boys. Looked at 9 phthalate metabolites in mothers. Measured AGD (anogenital distance). AGD is twice as long in baby boys as baby girls and is a very sensitive measure of decreased androgen activity (e.g. demasculinization). Develop AGI (anogenital index) from AGD, which takes into account different ages of infants. Infants divided into 3 groups: AGI less than 25% percentile for their age, AGI between 25% percentile and 75% percentile, and those more than 75% percentile

• What they found. Significant inverse correlation between AGI and levels for 4 phthalate metabolites. Looking at these 4 metabolites together, was a huge increase in risk of low AGI (p = 0.001). Babies with highest exposure to these 4 metabolites were more than 90 times as likely to have a low AGI as babies in the lowest exposure group

• Effects on AGI seen at phthalate levels below those found in 25% of US women, based on CDC studies

Adverse health effects--DEHPAndrade, AJM, SW Grande, CE Talsness, K Grote and I Chahoud. 2006. A

dose–response study following in utero and lactational exposure to di-(2-ethylhexyl)-phthalate (DEHP): Non-monotonic dose–response and low

dose effects on rat brain aromatase activity. Toxicology 227: 185-192

• Major finding is that the dose response curve in non-monotonic, e.g. lower doses of the DEHP suppress the activity of a key enzyme for masculinization of the male brain of rats, aromatase, while higher doses increase the enzyme's activity.

Adverse health effects—DEHP Takano, H, R Yanagisawa, K-I Inoue, T Ichinose, K Sadakano, and T

Yoshikawa. 2006. Di-(2-ehylhexyl) Phthalate Enhances Atopic Dermatitis-

Like Skin Lesions in Mice. EHPerspectives 114: 1266-1269

• Exposure to low levels of DEHP exacerbates allergic reactions in mice to a dust mite allergen. The dose response cure is non-monotonic, whether looking at the severity of the clinical symptoms or at levels of white blood cells, which are indicative of an immune system response

Menegaux, F et al. 2006. Household exposure to pesticides and risk of childhood acute leukamia. Occupational and Environmental Medicine, 63: 131-134.

Conclusion: The results reported herein support the hypothesis that various types of insecticide exposure may be a risk factor for childhood acute leukemia. The observed association with insecticidal shampoo treatment of pediculosis . . . requires further study.Home pesticide use during pregnancy or childhood was associated with childhood acute leukemia in the six studies which investigated that exposure

Rauh, VA, Garfinkel, R, Perera, FP, Andrews, HF, Hoepner, L, Barr, DB, Whitehead, R, Tang, D and RW Whyatt. 2006. Impact of Prenatal Chlorpyrifos Exposure on Neurodevelopment in the First 3 Years of Life Among Inner-City Children. Pediatrics, 118(6): e1845-e1859

“detectable levels of chlorpyrifos were found in 99.7% of personal air samples and 100% of indoor air samples . . . Chlorpyrifos was also detected in 64% to 70% of blood samples collected from mothers and newborns at delivery. . . . Experimental work showed links between chlorpyrifos exposure and neurocognitive development in rats.”

Permethrin report. July 2007. TEDX (The Endocrine Disruptor Exchange).

At: http://www.endocrinedisruption.com/files/permethrin_report_9-07.pdf

Looked at 108 scientific journal articles on potential health effects of permethrin

One study suggested that the products permethrin breaks down into may be 100 times more potent with regards to endocrine disruption than permethrin itself. . . In 2006 the EPA also classified permethrin as “likely to be carcinogenic in humans”, based on mouse studies showing evidence of lung and liver tumors related to permethrin.

The toxicity of permethrin was shown to be greatly enhanced when used in combination with DEET. Given this, we recommend that serious consideration be given to risks and benefits of using DEET as an insect repellent in areas where permethrin is used.

Lu, C, Toepel, K, Irish, R, Fenske, RA, Barr, DB, and R Bravo. 2006. Organic diets significantly lower children’s dietary exposure to organophosphorus pesticides. Environmental Health Perspectives, 114(2): 260-263.

“In conclusion, we were able to demonstrate that an organic diet provides a dramatic and immediate protective effect against exposures to organophosphorus pesticides that are commonly used in agricultural production.”

Figure 1. Box plots of daily volume-weighted average of malathion dicarboxylic acid (MDA) concentrations in 23 children ages 3-11 for 15 consecutive days in which conventional and organic diets were consumed.

Lu, C, Toepel, K, Irish, R, Fenske, RA, Barr, DB, and R Bravo. 2006. Organic diets significantly lower children’s dietary exposure to

organophosphorus pesticides. Environmental Health Perspectives, 114(2): 260-263.

Figure 2. Box plots of daily volume-weighted average of 3,5,6-trichloro-2-pyridinol (TCPY; a chlorpyrifos metabolite) concentrations in 23 children ages 3-11 for 15 consecutive days inwhich conventional and organic diets were consumed.

Lu, C, Barr, DB, Pearson, M, Bartelli, S and R Bravo. 2006. A longitudinal approach to assessing urban and suburban

children’s exposure to pyrethroid pesticides. Environmental Health Perspectives, 114(9): 1419-1423.

Study found association between parents reported use of pyrethroids in the residential environment and elevated pyrethroid metabolite levels in

their children’s urine. Diet and age of child also had an affect on metabolite levels in urine, but affect not as strong as for residential use.

Richard, S, Moslemi, S, Sipahutar, H, Benachour, N and G-E Seralini. 2005. Differential effects of glyphosate and Roundup on Human Placental Cells

and Aromatase. Environmental Health Perspectives, 113(6): 716-720

Conclusion: Our studies show that glyphosate acts as a disruptor of mammalian cytochrome P450 aromatase activity from concentrations 100 times lower than the recommended use in agriculture. . . The dilution of glyphosate in Roundup formulation may multiply its endocrine effect. Roundup may be thus considered as a potential endocrine disruptor. Moreover, at a higher doses still

below the classical agricultural dilutions, its toxicity on placental cells could induce some reproduction problems.

Conclusion

• Pesticides, may be endocrine disrupting compounds and can cause a range of health problems, including cancer, immune system affects, reproductive effects, behavioral problems, and adverse effects newborns, etc.

• Household exposures may be more important and have greater effect than outdoor exposure or dietary exposure

• Action needs to be taken to dramatically reduce exposure to household pesticides, particularly those shown to be EDCs