Abstract
The toxicity of pesticides on human reproduction is largely unknown--particularly how mixtures of pesticide products might affect fetal toxicity. The Ontario Farm Family Health Study collected data by questionnaire on the identity and timing of pesticide use on the farm, lifestyle factors, and a complete reproductive history from the farm operator and eligible couples living on the farm. A total of 2,110 women provided information on 3,936 pregnancies, including 395 spontaneous abortions. To explore critical windows of exposure and target sites for toxicity, we examined exposures separately for preconception (3 months before and up to month of conception) and postconception (first trimester) windows and for early (< 12 weeks) and late (12-19 weeks) spontaneous abortions. We observed moderate increases in risk of early abortions for preconception exposures to phenoxy acetic acid herbicides [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.1-2.1], triazines (OR = 1.4; 95% CI, 1.0-2.0), and any herbicide (OR = 1.4; 95% CI, 1.1-1.9). For late abortions, preconception exposure to glyphosate (OR = 1.7; 95% CI, 1.0-2.9), thiocarbamates (OR = 1.8; 95% CI, 1.1-3.0), and the miscellaneous class of pesticides (OR = 1.5; 95% CI, 1.0-2.4) was associated with elevated risks. Postconception exposures were generally associated with late spontaneous abortions. Older maternal age (> 34 years of age) was the strongest risk factor for spontaneous abortions, and we observed several interactions between pesticides in the older age group using Classification and Regression Tree analysis. This study shows that timing of exposure and restricting analyses to more homogeneous endpoints are important in characterizing the reproductive toxicity of pesticides.
Full Text
The Full Text of this article is available as a PDF (78.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arbuckle T. E., Savitz D. A., Mery L. S., Curtis K. M. Exposure to phenoxy herbicides and the risk of spontaneous abortion. Epidemiology. 1999 Nov;10(6):752–760. [PubMed] [Google Scholar]
- Arbuckle T. E., Schrader S. M., Cole D., Hall J. C., Bancej C. M., Turner L. A., Claman P. 2,4-Dichlorophenoxyacetic acid residues in semen of Ontario farmers. Reprod Toxicol. 1999 Nov-Dec;13(6):421–429. doi: 10.1016/s0890-6238(99)00057-x. [DOI] [PubMed] [Google Scholar]
- Arbuckle T. E., Sever L. E. Pesticide exposures and fetal death: a review of the epidemiologic literature. Crit Rev Toxicol. 1998 May;28(3):229–270. doi: 10.1080/10408449891344218. [DOI] [PubMed] [Google Scholar]
- Blakley P. M., Kim J. S., Firneisz G. D. Effects of paternal subacute exposure to Tordon 202c on fetal growth and development in CD-1 mice. Teratology. 1989 Mar;39(3):237–241. doi: 10.1002/tera.1420390305. [DOI] [PubMed] [Google Scholar]
- Burruel V. R., Raabe O. G., Overstreet J. W., Wilson B. W., Wiley L. M. Paternal effects from methamidophos administration in mice. Toxicol Appl Pharmacol. 2000 Jun 1;165(2):148–157. doi: 10.1006/taap.2000.8933. [DOI] [PubMed] [Google Scholar]
- Charles J. M., Cunny H. C., Wilson R. D., Ivett J. L., Murli H., Bus J. S., Gollapudi B. In vivo micronucleus assays on 2,4-dichlorophenoxyacetic acid and its derivatives. Mutat Res. 1999 Jul 21;444(1):227–234. doi: 10.1016/s1383-5718(99)00076-5. [DOI] [PubMed] [Google Scholar]
- Crichton N. J., Hinde J. P., Marchini J. Models for diagnosing chest pain: is CART helpful? Stat Med. 1997 Apr 15;16(7):717–727. doi: 10.1002/(sici)1097-0258(19970415)16:7<717::aid-sim504>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
- Cummings A. M., Rhodes B. E., Cooper R. L. Effect of atrazine on implantation and early pregnancy in 4 strains of rats. Toxicol Sci. 2000 Nov;58(1):135–143. doi: 10.1093/toxsci/58.1.135. [DOI] [PubMed] [Google Scholar]
- Curtis K. M., Savitz D. A., Weinberg C. R., Arbuckle T. E. The effect of pesticide exposure on time to pregnancy. Epidemiology. 1999 Mar;10(2):112–117. [PubMed] [Google Scholar]
- Davis J. R., Brownson R. C., Garcia R., Bentz B. J., Turner A. Family pesticide use and childhood brain cancer. Arch Environ Contam Toxicol. 1993 Jan;24(1):87–92. doi: 10.1007/BF01061094. [DOI] [PubMed] [Google Scholar]
- Greenland S. Modeling and variable selection in epidemiologic analysis. Am J Public Health. 1989 Mar;79(3):340–349. doi: 10.2105/ajph.79.3.340. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iyer P., Gammon D., Gee J., Pfeifer K. Characterization of maternal influence on teratogenicity: an assessment of developmental toxicity studies for the herbicide cyanazine. Regul Toxicol Pharmacol. 1999 Feb;29(1):88–95. doi: 10.1006/rtph.1998.1276. [DOI] [PubMed] [Google Scholar]
- Kligerman A. D., Doerr C. L., Tennant A. H., Zucker R. M. Cytogenetic studies of three triazine herbicides. I. In vitro studies. Mutat Res. 2000 Feb 16;465(1-2):53–59. doi: 10.1016/s1383-5718(99)00211-9. [DOI] [PubMed] [Google Scholar]
- Lemasters G. K., Perreault S. D., Hales B. F., Hatch M., Hirshfield A. N., Hughes C. L., Kimmel G. L., Lamb J. C., Pryor J. L., Rubin C. Workshop to identify critical windows of exposure for children's health: reproductive health in children and adolescents work group summary. Environ Health Perspect. 2000 Jun;108 (Suppl 3):505–509. doi: 10.1289/ehp.00108s3505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lerda D., Rizzi R. Study of reproductive function in persons occupationally exposed to 2,4-dichlorophenoxyacetic acid (2,4-D). Mutat Res. 1991 Jan;262(1):47–50. doi: 10.1016/0165-7992(91)90105-d. [DOI] [PubMed] [Google Scholar]
- Lieberman A. D., Craven M. R., Lewis H. A., Nemenzo J. H. Genotoxicity from domestic use of organophosphate pesticides. J Occup Environ Med. 1998 Nov;40(11):954–957. doi: 10.1097/00043764-199811000-00003. [DOI] [PubMed] [Google Scholar]
- Lioi M. B., Scarfi M. R., Santoro A., Barbieri R., Zeni O., Salvemini F., Di Berardino D., Ursini M. V. Cytogenetic damage and induction of pro-oxidant state in human lymphocytes exposed in vitro to gliphosate, vinclozolin, atrazine, and DPX-E9636. Environ Mol Mutagen. 1998;32(1):39–46. [PubMed] [Google Scholar]
- Lioi M. B., Scarfì M. R., Santoro A., Barbieri R., Zeni O., Di Berardino D., Ursini M. V. Genotoxicity and oxidative stress induced by pesticide exposure in bovine lymphocyte cultures in vitro. Mutat Res. 1998 Jul 17;403(1-2):13–20. doi: 10.1016/s0027-5107(98)00010-4. [DOI] [PubMed] [Google Scholar]
- Mathur A., Bhatnagar P. A teratogenic study of carbaryl in Swiss albino mice. Food Chem Toxicol. 1991 Sep;29(9):629–632. doi: 10.1016/0278-6915(91)90145-w. [DOI] [PubMed] [Google Scholar]
- Meisner L. F., Belluck D. A., Roloff B. D. Cytogenetic effects of alachlor and/or atrazine in vivo and in vitro. Environ Mol Mutagen. 1992;19(1):77–82. doi: 10.1002/em.2850190110. [DOI] [PubMed] [Google Scholar]
- Munger R., Isacson P., Hu S., Burns T., Hanson J., Lynch C. F., Cherryholmes K., Van Dorpe P., Hausler W. J., Jr Intrauterine growth retardation in Iowa communities with herbicide-contaminated drinking water supplies. Environ Health Perspect. 1997 Mar;105(3):308–314. doi: 10.1289/ehp.97105308. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nybo Andersen A. M., Wohlfahrt J., Christens P., Olsen J., Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ. 2000 Jun 24;320(7251):1708–1712. doi: 10.1136/bmj.320.7251.1708. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Osborn J. F., Cattaruzza M. S., Spinelli A. Risk of spontaneous abortion in Italy, 1978-1995, and the effect of maternal age, gravidity, marital status, and education. Am J Epidemiol. 2000 Jan 1;151(1):98–105. doi: 10.1093/oxfordjournals.aje.a010128. [DOI] [PubMed] [Google Scholar]
- Padungtod C., Hassold T. J., Millie E., Ryan L. M., Savitz D. A., Christiani D. C., Xu X. Sperm aneuploidy among Chinese pesticide factory workers: scoring by the FISH method. Am J Ind Med. 1999 Aug;36(2):230–238. doi: 10.1002/(sici)1097-0274(199908)36:2<230::aid-ajim2>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
- Pastore L. M., Hertz-Picciotto I., Beaumont J. J. Risk of stillbirth from occupational and residential exposures. Occup Environ Med. 1997 Jul;54(7):511–518. doi: 10.1136/oem.54.7.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pryor J. L., Hughes C., Foster W., Hales B. F., Robaire B. Critical windows of exposure for children's health: the reproductive system in animals and humans. Environ Health Perspect. 2000 Jun;108 (Suppl 3):491–503. doi: 10.1289/ehp.00108s3491. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rank J., Jensen A. G., Skov B., Pedersen L. H., Jensen K. Genotoxicity testing of the herbicide Roundup and its active ingredient glyphosate isopropylamine using the mouse bone marrow micronucleus test, Salmonella mutagenicity test, and Allium anaphase-telophase test. Mutat Res. 1993 Jun;300(1):29–36. doi: 10.1016/0165-1218(93)90136-2. [DOI] [PubMed] [Google Scholar]
- Restrepo M., Muñoz N., Day N. E., Parra J. E., de Romero L., Nguyen-Dinh X. Prevalence of adverse reproductive outcomes in a population occupationally exposed to pesticides in Colombia. Scand J Work Environ Health. 1990 Aug;16(4):232–238. doi: 10.5271/sjweh.1790. [DOI] [PubMed] [Google Scholar]
- Ribas G., Surrallés J., Carbonell E., Creus A., Xamena N., Marcos R. Lack of genotoxicity of the herbicide atrazine in cultured human lymphocytes. Mutat Res. 1998 Aug 7;416(1-2):93–99. doi: 10.1016/s1383-5718(98)00081-3. [DOI] [PubMed] [Google Scholar]
- Savitz D. A., Arbuckle T., Kaczor D., Curtis K. M. Male pesticide exposure and pregnancy outcome. Am J Epidemiol. 1997 Dec 15;146(12):1025–1036. doi: 10.1093/oxfordjournals.aje.a009231. [DOI] [PubMed] [Google Scholar]
- Selevan S. G., Kimmel C. A., Mendola P. Identifying critical windows of exposure for children's health. Environ Health Perspect. 2000 Jun;108 (Suppl 3):451–455. doi: 10.1289/ehp.00108s3451. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stein Z., Susser M. The risks of having children in later life. Social advantage may make up for biological disadvantage. BMJ. 2000 Jun 24;320(7251):1681–1682. doi: 10.1136/bmj.320.7251.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swan G. E., Carmelli D., LaRue A. Performance on the digit symbol substitution test and 5-year mortality in the Western Collaborative Group Study. Am J Epidemiol. 1995 Jan 1;141(1):32–40. doi: 10.1093/oxfordjournals.aje.a117342. [DOI] [PubMed] [Google Scholar]
- Taets C., Aref S., Rayburn A. L. The clastogenic potential of triazine herbicide combinations found in potable water supplies. Environ Health Perspect. 1998 Apr;106(4):197–201. doi: 10.1289/ehp.98106197. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taha T. E., Gray R. H. Agricultural pesticide exposure and perinatal mortality in central Sudan. Bull World Health Organ. 1993;71(3-4):317–321. [PMC free article] [PubMed] [Google Scholar]
- Weinberg C. R. Toward a clearer definition of confounding. Am J Epidemiol. 1993 Jan 1;137(1):1–8. doi: 10.1093/oxfordjournals.aje.a116591. [DOI] [PubMed] [Google Scholar]
- Zhang H., Bracken M. B. Tree-based risk factor analysis of preterm delivery and small-for-gestational-age birth. Am J Epidemiol. 1995 Jan 1;141(1):70–78. doi: 10.1093/oxfordjournals.aje.a117347. [DOI] [PubMed] [Google Scholar]
- Zhang H., Bracken M. B. Tree-based, two-stage risk factor analysis for spontaneous abortion. Am J Epidemiol. 1996 Nov 15;144(10):989–996. doi: 10.1093/oxfordjournals.aje.a008869. [DOI] [PubMed] [Google Scholar]