THIRD WORLD NETWORK BIOSAFETY INFORMATION SERVICE
Dear Friends and Colleagues
High environmental exposure to glyphosate and reproductive health impacts in Argentina
In 1996, Argentina began to grow genetically modified (GM) crops, which currently cover 25 million hectares. These crops annually utilize high amounts of pesticides, as they are largely engineered to be herbicide resistant. In 2013, Argentina sprayed 240,000 tons of glyphosate.
A change in the profile of morbidity and mortality has been perceived by physicians in agricultural areas in the country; reproductive disorders and cancer seem to prevail. An ecological study set out to determine the concurrence of glyphosate exposure and reproductive disorders in the typical Argentine agricultural town of Monte Maíz where local doctors noted changes in disease profile since the introduction of GM crops and the massive use of glyphosate.
A total of 650 tons of glyphosate per year is concentrated in and around the town, which faces fields that are sprayed daily. Glyphosate was found in 100% of soil and husk dust samples, at concentrations 10 times higher than that of other pesticides. Concentrations found in the inner town were several times higher than in the soil in cultivated fields. Glyphosate was also high in grain dust. The environmental exposure to glyphosate per person was 79 kg per year.
Spontaneous abortion and congenital abnormalities rates in Monte Maíz were three and two times higher than the national average. Neither maternal age, toxic habits or poverty could explain the high rate of spontaneous abortions.
There seems to be an association between high environmental exposure to glyphosate and reproductive problems, although the study could not ascertain a cause and effect relationship. The researchers therefore recommend the application of precautionary measures to protect the population from this environmental exposure.
With best wishes,
ENVIRONMENTAL EXPOSURE TO GLYPHOSATE AND REPRODUCTIVE HEALTH IMPACTS IN AGRICULTURAL POPULATION OF ARGENTINA
Avila-Vazquez, M., Difilippo, F. S., Mac Lean, B., Maturano, E., & Etchegoyen, A. (2018)
Journal of Environmental Protection, 9 (03), 241
3 March 2018
Argentina annually utilizes 240,000 tones of glyphosate in industrial agriculture and a change in the profile of morbidity is perceived for physicians of agricultural areas; now reproductive disorders seem to prevail. The objective of this study is to determine concurrence of glyphosate exposure and reproductive disorders in a typical Argentine agricultural town (Monte Maíz). An ecological study was developed with an environmental analysis of pollution sources including measurements of glyphosate and other pesticides and a cross-sectional study of spontaneous abortions and congenital abnormalities prevalence. Glyphosate was detected in soil and grain dust and was found to be at an even higher concentration in the village soil than in the rural area; 650 tonnes of glyphosate are used annually in the region and manipulated inner town contaminating the soil and dust in suspension of the town creating an burden of environmental exposure to glyphosate of 79 kg per person per year. We do not find other relevant sources of pollution. The spontaneous abortion and congenital abnormalities rates are three and two times higher than the national average reported by the national health (10% vs. 3% and 3% - 4.3% vs 1.4% respectively). Our study verified high environmental exposure to glyphosate in association with increased frequencies of reproductive disorders (spontaneous abortion and congenital abnormalities) in Argentine agricultural village, but is unable to make assertions [of] cause-effect. Further studies are required with designs for such purposes.
Seeds that are genetically manipulated to contain a transgene have the ability to survive in saturated environments with glyphosate, an herbicide used to eradicate other plants. Glyphosate interferes with the vital metabolism of plants, but not with transgenic plants for which an alternative metabolic pathway was generated through bioengineering. Since 1996, when GM soy was introduced in Argentina, its use has continued to expand due to the high profit generated by its commercialization and easy harvest  as the extension of this crop increases, so does the use of glyphosate. Currently, Argentina is using 240,000 tons of glyphosate per year. This has increased year-on-year as a consequence of herbicide-resistant weeds requiring higher doses of glyphosate and the combined use of other herbicides as 2.4D, atrazine, etc. . This increase has resulted in 5 kg of glyphosate per person per year as potential exposure burden for all inhabitants of the country, greater in agricultural areas.
Monte Maíz shows the effects of this agricultural model, as is a production boom in the region, a high standard of living among its population, and the relocation of local farmers in the village; these farmers left rural areas and moved with their families work equipment and supplies. Deposits of agricultural equipment are multiplying inside the village (twenty-two in total), the largest deposits in town are in R15 and are five pesticide storage sites. A total of 650 tons of glyphosate per year is concentrated, manipulated and has surrounded the town, which now faces fields that are sprayed daily. Glyphosate was found in 100% of soil and husk dust samples, the concentration was 10 times higher than that of other pesticides, this demonstrates that, of all pesticides that pollute the environment, glyphosate is the most prevalent. Concentrations found in inner town are several times higher than in the soil in cultivated fields (see table 1), reaffirming the impression that the town is at the operational center of the sprayed area. Glyphosate is also high in grain dust, it is also accompanied by other pesticides their joint presence discards that glyphosate is high within the village due to its use in gardening.
In metalwork factories, no significant pollution was found; the density per km2 of the source of electromagnetic radiation such as cell site, high voltage power lines, and electrical voltage transformers is low compared with source electromagnetic radiation density in big cities, which minimizes the value of this pollution; for example Nueva Cordoba, a neighborhood of Cordoba city, which is located on the same surface as Monte Maíz with a larger population, has nine cell sites, while there are only two towers in Monte Maíz , although, a weakness of the study is the lack of electromagnetic radiation direct measurements.
Moreover, household garbage management, sewage, and contaminant-free water (for 16 years now) remove these contaminating factors from the observed pathologies. Thus, pollution with glyphosate and to a lesser extent with other pesticides is the predominant factor in the environmental contamination analysis of Monte Maíz.
The rate of spontaneous abortions in five years (10%) in Monte Maíz was three times higher than that reported in a national analysis conducted in 2005 for the National Health Ministry (0.6% per year) , and also higher than that of a social-health survey recently conducted (2016) by our team in a neighbourhood of Cordoba where the prevalence of spontaneous abortions was 3.7% in 5 years . The spatial distribution of abortions shows a backlog of cases in the sector (R16 and R17) that is most contaminated with glyphosate-impregnated grain husk, although the association is not significant. This increased prevalence is consistent with the findings of Aiassa et al. that detected a spontaneous abortions rate of 19% between 166 households in the farming village of Las Vertientes (Cordoba, 180 km from Monte Maiz) . The “Ontario Farm Family Health Study” refers 18.7% of spontaneous abortions rate in farm families with a significant risk for preconception exposure to glyphosate . In our population young mothers were linked to this perinatal outcome and not the other way round; smoking was not linked to abortion either. The population is not inbred (it is a large town made up of farmers and steelworkers) and its social structure shows an excellent socioeconomic status measured in rate of unmet basic needs. Neither maternal age, toxic habits or poverty may explain the high rate of spontaneous abortions in Monte Maiz.
There seems to be a clear link between exposure to pesticides, including glyphosate, and pregnancy loss, similar to the observations made by Settini in Italy  , or the systematic reviews of evidence-based medicine of Sanborn et al. in MacMaster University, Canada, in 2007  and updated in 2012  .
On the other hand, the National Registry of Congenital Abnormalities of Argentina (RENAC) in 2014 Report that between 281.249 newborns a total of 4.120 major structural congenital abnormalities were recorded, with a prevalence of 1.4% ; in Monte Maiz the prevalence (3%) was twice that of the national prevalence. It is worth mentioning that our data does not include malformed children who died, which is why the difference could surely be even greater. The types of congenital anomalies do not differ significantly from those reported by the RENAC for the entire Province . The national rate of anomalies is generated from monthly reports issued by the neonatology services, there may be under reporting of cases. By contrast, our data may be biased due to the fact that they are self-referenced, and while this is a limiting factor for any study of disease through surveys, it is unlikely in some less prevalent pathology where, on the contrary, the most common error is type II. Data collected differently may reflect discrepancies, thus generating an information bias. In any case, the higher frequency of children born with congenital abnormalities in populations exposed to agrochemicals is described for records from maternity hospitals , case control  , american ecological studies  , and Canadian systematic reviews , among others.
In 2010 Paganelli demonstrates as glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling  and in recent years information on glyphosate genotoxicity in experimental models was published, information that was previously unknown, using test for chromosomal aberrations, micronuclei and comet assay the damage to DNA strands was verified   even in human cells  . More recently, these same studies were conducted in people environmentally and occupationally exposed to pesticides in general and glyphosate in particular, which reported rates of genetic damage well above those found in populations not exposed to pesticides used as reference or control groups   .
The Monograph Working Group of IARC-WHO in Evaluation of Carcinogenic Risks to Humans in 2015 reviews 1000 studies on glyphosate and chooses 200 relevant paper to conclude that there is strong evidence that exposure to glyphosate or glyphosate-based formulations is genotoxic based on studies in humans in vitro and studies in experimental animals , the occurrence of damage to the DNA strands that when not repaired nor the cell removed can lead to germ cell mutations with impact on reproductive health. Near Monte Maíz, in Marcos Juarez City, published studies showed twice frequency of chromosomal aberrations and micronuclei in environmentally exposed people to glyphosate or other pesticides  and genotoxicity in children exposed to pesticides comparing to not expose .
This association is consistent with respect to abortions and malformations, the biological plausibility is very rational for reproductive problems in their causal link with 600,000 kg of glyphosate polluting the environment of Monte Maiz, although recognize that the ecological fallacy cannot be discarded from this analysis and the design of this study is limited for causality. The change in time sequence could not be stated in this cross-sectional study, but local doctors noted changes in the disease profile since the introduction of GM seeds and the massive use of glyphosate. Although the methodological limitations of this exploration suggest that we acknowledge its limited scope, it highlights the association at an evidence level and should be considered with caution given the small size of the population, the self-referenced nature of the survey and the descriptive modality of the study. The results of this study are also important because they describe a health problem in the environment where the people are living.
This research detected an urban environment severely polluted by glyphosate and other pesticides with high environmental exposure to glyphosate in the villagers and identified elevated frequencies of congenital abnormalities and spontaneous abortion, suggesting a link between environmental exposure to glyphosate and reproductive problems, although this was an exploratory and observational design unable to make direct causal assertions. However, from the point of view of collective health, this link requires recommending the precautionary application of measures to protect the population from this environmental exposure.
 RENAC—REPORTE ANNUAL. (2014) Análisis epidemiológico sobre anomalías congénitas en recién nacidos, registradas en 2013. Ministerio de Salud. http://www.msal.gov.ar/congenitas/renac-reporte-anual-2014/
 Aizen, M.A., Garibaldi, L.A. and Dondo, M. (2009) Expansión de la soja y diversidad de la agricultura argentina. Austral Ecology , 19, 45-54.
 REDUAS (2013) The Use of Toxic Agrochemicals in Argentina Is Continuously Increasing; Analysis of Data from the Pesticide Market in Argentina. http://www.reduas.com.ar/the-use-of-toxic-agrochemicals-in-argentina-is-continuo usly-increasing/
 Open Signal (2014) Towers Identifier and Cell Coverage Map. http://opensignal.com
 Centro de Estudios de Estado y Sociedad (CEDES) y Centro de Estudios de Población (CENEP) (2007) Morbilidad materna severa en la Argentina, Estimación de la magnitud del aborto inducido. http://www.despenalizacion.org.ar/pdf/evidencia/estudios/estimacion_aborto_indu cido.pdf  Avila-Vazquez, M., Maturano, E., Etchegoyen, A., Difilippo, F.S. and Maclean, B. (2016) Informe Estudio de Salud Ambiental de Barrio San Antonio y Residencial San Antonio, 2016. Red Universitaria de Ambiente y Salud. http://reduas.com.ar/informe-estudio-de-salud-ambiental-de-barrio-san-antonio-yresidencial-san-antonio-2016/
 Aiassa, D. (2010) Exposición a Plaguicidas. Monitoreo de daño genético en poblaciones humanas. 1 st National Meeting of Physicians in the Crop Spr ayed Towns , Cordoba, 10 August 2010, 18-20. http://www.reduas.com.ar/wp-content/uploads/2011/04/primer-informe.pdf
 Arbuckle, T.E., Lin, Z. and Mery, L.S. (2001) An Exploratory Analysis of the Effect of Pesticide Exposure on the Risk of Spontaneous Abortion in an Ontario Farm Population . Environmental Health Perspectives , 109, 851-857. https://doi.org/10.1289/ehp.01109851
 Settimi, L., Spinelli, A., Lauria, L., Miceli, G., Pupp, N., Angotzi, G., et al . (2008) Spontaneous Abortion and Maternal Work in Greenhouses. American Journal of Industrial Medicine , 51, 290-295. https://doi.org/10.1002/ajim.20556
 Sanborn, M., Kerr, K.J., Sanin, L.H., Cole, D.C., Bassil, K.L. and Vakil, C. (2007) Non-Cancer Health Effects of Pesticides: Systematic Review and Implications for Family Doctors. Canadian Family Physician , 53, 1712-1720.
 Sanborn, M., Bassil, K., Vakil, C. and Kerr, K. (2012) Systematic Review of Pesticide Health Effects. Department of Family Medicine, McMaster University, Ontario College of Family Physicians, Toronto. http://ocfp.on.ca/docs/pesticides-paper/2012-systematic-review-of-pesticide.pdf
 Trombotto, G.L. (2009) Tendencia de las Malformaciones Congénitas Mayores en el Hospital Universitario de Maternidad y Neonatología de la Ciudad de Córdoba en los años 1972-2003. Un Problema Emergente en Salud Pública (tesis). Universidad Nacional, Córdoba.
 Benitez Leite, S., Macchi, M.L. and Acosta, M. (2007) Malformaciones congénitas asociadas a agrotóxicos. Pediatría ( Asunción ), 34, 111-121.
 Silva, S.R., Martins, J.L., Seixas, S., Silva, D.C., Lemos, S.P. and Lemos, P.V. (2011) Congenital Defects and Exposure to Pesticides in São Francisco Valley. Revista Br asileira De Ginecologia E Obstetricia , 33, 20-26.
 Winchester, P.D., Huskins, J. and Ying, J. (2009) Agrichemicals in Surface Water and Birth Defects in the United States. Acta Paediatrica , 98, 664-669. https://doi.org/10.1111/j.1651-2227.2008.01207.x
 Schreinemachers, D.M. (2003) Birth Malformations and Other Adverse Perinatal Outcomes in Four U.S. Wheat-Producing States. Environmental Health Perspe ctives , 111, 1259-1264. https://doi.org/10.1289/ehp.5830
 Paganelli, A., Gnazzo, V., Acosta, H., López, S.L. and Carrasco, A.E. (2010) Glyphosate-Based Herbicides Produce Teratogenic Effects on Vertebrates by Impairing Retinoic Acid Signaling. Chemical Research in Toxicology , 23, 1586-1595. https://doi.org/10.1021/tx1001749
 Dallegrave, E., Mantese, F.D., Coelho, R.S., Pereira, J.D., Dalsenter, P.R. and Langeloh, A. (2003) The Teratogenic Potential of the Herbicide Glyphosate-Roundup in Wistar Rats. Toxicology Letters , 142, 45-52. https://doi.org/10.1016/S0378-4274(02)00483-6
 Cava, T. and Könen, S. (2007) Detection of Cytogenetic and DNA Damage in Peripheral Erythrocytes of Goldfish ( Carassius auratus ) Exposed to a Glyphosate Formulation using the Micronucleus Test and the Comet Assay . Mutagenesis , 22, 263-268. https://doi.org/10.1093/mutage/gem012
 Mañas, F., Peralta, L., Raviolo, J., García Ovando, H. and Garcia-Schuler, H. (2009) Genotoxicity and Oxidative Stress of Glyphosate: In Vivo and in Vitro Testing. E nvironmental Toxicology and Pharmacology , 28, 37-41.
 Alvarez-Moya, C., Silva, M.R., Ramírez, C.V., Gallardo, D.G., Sánchez, R.L., Aguirre, A.C. and Velasco, A.F. (2014) Comparison of the in Vivo and in Vitro Genotoxicity of Glyphosate Isopropylamine Salt in Three Different Organisms . G enetics and Molecular Biology , 37, 105-110. https://doi.org/10.1590/S1415-47572014000100016
 Simoniello, M.F., Kleinsorge, E.C. and Carballo, M.A. (2010) Evaluación bioquímica de trabajadores rurales expuestos a pesticidas. Medicina ( B . Aires ), 70, 489-498.
 Paz-y-Miño, C., Sánchez, M.E., Arévalo, M., Muñoz, M.J., Witte, T., De-la-Carrera, G.O. and Leone, P.E. (2007) Evaluation of DNA Damage in an Ecuadorian Population Exposed to Glyphosate. Genetics and Molecular Biology , 30, 456-460. https://doi.org/10.1590/S1415-47572007000300026
 Guyton, K.Z., Loomis, D., Grosse, Y., El-Ghissassi, F., Benbrahim-Tallaa, L., Guha, N., et al . (2015) Carcinogenicity of Tetrachlorvinphos, Parathion, Malathion, Diazinon, and Glyphosate. The Lancet Oncology , 16, 490-491. http://monographs.iarc.fr/ENG/Monographs/vol112/mono112-09.pdf https://doi.org/10.1016/S1470-2045(15)70134-8
 Peralta, L., Mañas, F., Gentile, N., Bosch, B., Mnedez, A. and Aiassa, D. (2011) Evaluación del daño genético en pobladores de Marcos Juárez expuestos a plaguicidas: Estudio de un caso en Córdoba, Argentina. DiáLogos , 2, 7-26. http://gemalab.com.ar/wp-content/uploads/2016/11/2011-Marcos-Juarez.pdf
 Bernardi, N., Gentile, N., Mañas, F., Méndez, A., Gorla, N. and Aiassa, D. (2015) Assessment of the Level of Damage to the Genetic Material of Children Exposed to Pesticides in the Province of Córdoba. Archivos Argentinos De Pediatria , 113, 126-132.