Project Number: 9278278 Project Title: Methods for Assessing Male Reproductive Toxicity Division: DART Project Officer (PO): Steven Schrader PO Degree: Ph.D. PO Area of Expertise (scientific discipline): Andrology Project Start Date: 10/96 Project End Date: 09/04 Total Budget over the Project Period: $346,472 Goal/Sub-Goal: Chronic Effects of Pesticide Exposure/Health Outcomes Research Challenge/Issue: Data from wildlife and animal testing has shown that male reproductive system can be affected by the toxic nature of agricultural pesticides. Moving the research from animals to humans has been challenging considering the extensive number of pesticides used in agriculture and the need to make sure limited resources are being used to study the pesticides which may have the greatest health risk. Two approaches were studied. The first was to look at the most widely used pesticides that have animal data showing effects on the male reproductive system and determine if human exposures are getting into the body (body burden) and more specifically into the male reproductive system (e.g., 2,4-D in semen). Another approach was to study agricultural areas reporting excess adverse pregnancies (NW Minnesota) to determine which pesticide group (herbicides, insecticides, fungicides) may be associated with adverse effects on male reproductive health. Activities: Male reproductive hazards have been shown to attack at least one of four major sites (endocrine system, the testes, the accessory sex glands, and sexual function). The goal of this project as to implement new technologies and clinical methods for assessing these sites to measure toxic effects found in occupational field studies, including pesticide exposures. Field studies were conducted with partners to assess the reproductive health of men exposed to potential hazards. A study was conducted in partnership with Health Canada which evaluated body burden of 2,4-D exposure. The study was to determine if 2,4-D was entering the male reproductive system of pesticide applicators and then subsequently to determine if there was a negative effect on reproductive function in these workers. 2,4-D was found in the semen of approximately half of the study participants; however, the pesticide manufacturers blocked Health Canada from conducting any health outcome research related to this finding. A collaborative research study was conducted with the University of Minnesota to study pesticide applicators in northwest Minnesota. Previous research by this group had shown an increase in adverse pregnancy outcomes in agricultural areas compared to the metropolitan area. Semen and endocrine analyses were conducted in pesticide applicators (and unexposed controls) during herbicide spraying season and fungicide spraying season in an attempt to ascertain if a specific pesticide exposure to the male partner could have contributed to the observed adverse pregnancy outcomes. Outputs:
A method for collecting semen samples from married couples that would be useful for assessing toxicants in semen was established using plastic condoms. These condoms were manufactured to be non-spermicidal to for couples collecting sperm for fertility clinic procedures. Because the condoms had to be relatively inert for sperm survival it was found there was minimal effect of the pesticide of interest in semen stored frozen in the home freezer in the condom after being collected by the couple. This data was published as an abstract and subsequently presented as poster: Schrader, S.M., T. Arbuckle, L. Turner, and L. Ritter. 1997. The Use of Plastic Condoms in an Exposure Assessment Occupational Field Study. Journal of Andrology 17:P-31 The findings showing 2,4-D in the semen of men applying this pesticide appeared in the Reproductive Toxicology journal. Arbuckle, T.E., S.M. Schrader, D. Cole, J.C. Hall, C.M. Bancej, L.A. Turner, and P. Claman. 1999. 2,4-D Residues in Semen of Ontario Farmers. Reproductive Toxicology 13:421-429. The study of pesticide applicators in northwest Minnesota resulted in 4 abstracts followed by 3 poster presentations at the annual meeting of the American Society of Andrology and one platform presentation at an international workshop on endocrine disruptors in Japan. Schrader, S.M., T.W. Turner, P.B. Shaw, L.L. Erickson, S. Holland, and V.F. Garry. 2000. Semen Quality of Men Applying Pesticides in Northwest Minnesota. Journal of Andrology Suppl 21:50 Schrader, S.M., and V. F. Garry. 2001. Abnormal Sperm Morphology and Offspring Sex Ratio in Male Fungicide Applicators. International Workshop on Endocrine Disrupting Chemicals and Their Toxicological Evaluation. Presented in Tsukiba, Japan, February 2001 Holland, SE, V.F. Garry S.M. Schrader, J.S. Kesner, and E.A. Knecht. 2002. Testosterone Levels in Male Pesticide Applicators and the Sex of Their Children. Journal of Andrology Suppl page 39. Schrader, S.M., T.W. Turner, V.F. Garry, and S.E. Holland. 2002. Abnormal Sperm Morphology and Offspring Sex Ratio in Male Fungicide Applicators. Journal of Andrology Suppl page 40. Intermediate Outcomes: Results from the study conducted in partnership with Health Canada which evaluated body burden of 2,4-D exposure were published in the newsletter Farm Family Health which was distributed to all study participants. In addition, the study results were shared with a group of pesticide license educators so that this information would be transferred to new pesticide applicators so they were warned upfront of the potential hazards. The results of the 2,4-D study of the pesticide in the semen provided the rationale for analyzing the semen collected in the ongoing NIH/LIFE study for pesticides and other toxicants – see project 92700A1.
External Factors: The pesticide manufacturers in Canada blocked health studies in men who had 2,4-D in their semen. The project was eventually discontinued by our partner Health Canada. Future Directions: The NIH LIFE study, discussed in project 92700A1, assessing pesticides in blood, urine, and semen in couples trying to conceive is currently underway. A prioritization method is being established to determine which pesticides need human data based on relative toxicity from EPA toxicity data and number of people exposed.