Article resulting from a research project financed by

Corporación Universitaria Minuto de Dios- UNIMINUTO

Fabian Jose Vera Vera

Master's Degree, Corporación Universitaria Minuto de

Dios, Bogota, Colombia, fabian.vera@uniminuto.edu

Master's Degree, Corporación Universitaria Minuto de

Glyphosate is a broad-spectrum herbicide that has been used primarily in the agricultural

sector for pest control and eradication of illicit crops in drug-trafficking countries such as

Colombia. According to the International Agency For Research On Cancer (IARC) this herbicide

is classified as probably carcinogenic to humans, however, the world literature on the effects

on human health presents a confusing and diverse picture. The objective of this review was

to identify the possible health effects of exposure to herbicides with active ingredient

glyphosate, following the recommendations of the Cochrane Collaboration for systematic

reviews and the PRISMA guidelines for reporting the results. A literature search was

performed in PubMed, MedLine, VHL Regional Portal, ProQuest, EBSCOhost databases,

among others, using DECS and MESH search engines, all existing articles in the time period

Keywords: glyphosate; Environmental Hazards Exposure; pesticides; toxicity; toxicity

RESUMEN

El glifosato es un herbicida de amplio espectro que ha sido usado principalmente en el sector

agrícola para el control de plagas y la erradicación de cultivos ilícitos en países que trafican

droga como Colombia. Según la International Agency For Research On Cancer (IARC) este

herbicida es clasificado como probablemente carcinogénico para humanos, sin embargo, la

literatura mundial sobre los efectos en la salud humana presenta un panorama confuso y

diverso. El objetivo de esta revisión fue identificar los posibles efectos en salud por exposición

a herbicidas con principio activo glifosato, se siguieron las recomendaciones de la

necrolisis epidérmica y daño renal, manifestaciones clínicas que no fueron documentadas en

los estudios con otro tipo zde metodología. Pero otras investigaciones presentan medidas

estadísticas que indican que la exposición a glifosato es un factor de riesgo para problemas

with Brazil being the main consumer of these products due to its model of agricultural

expansion and economic development (Ferreira F, et al., 2016). The use of these substances

is not only intended for pest control in crops, but is also used at the domestic level, in

gardening, forestry work and animal production, among others, exposing in different ways a

large number of people and generating potential risks to health and the environment (Karam

et al. 2005).

Among the most common uses of glyphosate are gardening, agriculture, illicit crop control

and weed control in forestry plantations, industrial complexes and railways. (Agencia EFE,

2016) and weed control in forestry plantations, in industrial complexes and railways, which

brings this chemical compound uncontrollably close to different population groups, children,

action is to inhibit the activity of 5-enolpyruvyl shikimate 3-phosphate synthetase in plants

and in several microorganisms, causing a reduction in the synthesis of proteins and other

molecules leading to premature cell death (Solange 2011), humans use a different mechanism

to perform protein synthesis, which in theory would not cause toxic effects, but several

scientific studies expose negative health effects.

In the literature there are systematic reviews on possible health effects in humans caused by

glyphosate such as the one conducted by Mink P and collaborators, this review found that

most studies did not observe statistically significant positive differences between glyphosate

and various outcomes studied, but for respiratory disease, asthma, bronchitis and wheezing,

the results were varied, finding significant association for rhinitis, concluding that

glyphosate and its formulations do not pose a risk of producing heritable mutations in

humans, but does not rule out that at high or toxic doses it causes effects on DNA (Kier and

Kirkland 2013), Niemann in (2015) analyzed the results of seven studies conducted in Europe

and the United States and concluded that although amounts of glyphosate are detected in

urine samples, the estimated exposure is below the Acceptable Daily Intake (ADI) or

Acceptable Operator Exposure Levels (AOELs), which shows that exposure is documented, but

not possible harm. Finally, a meta-analysis gathered 81 experimental studies on the

relationship between glyphosate exposure and micronuclei formation, concluding that

exposure to glyphosate and its formulations increases the frequency of micronuclei

formation, which is related to cancerous processes (Ghisi, Oliveira, and Prioli 2016).

Narcotics Council in Colombia took the decision to suspend spraying, at the request of the

Constitutional Court, for use on illicit crops. (El Espectador, 2015) .

The panorama in the country with respect to the use of glyphosate is diverse, it is used in

different productive processes in addition to having a leading role in the control of illicit crops,

from 1978 to 1982 it was used to fumigate marijuana crops in the Sierra Nevada, in 1984, the

government funded a study to evaluate the convenience of the use of glyphosate, the

conclusion was that it was not possible to establish the consequences. Despite this and in

comparison with other pesticides, it was decided to use the herbicide for national security

reasons, to spray poppy and cocaine crops, in 1994 began the struggle of people to avoid

spraying with glyphosate because they were exposed to a chemical that was used in an

pesticides, but glyphosate caused a great interest due to the particular use that has been

given to it in several regions of Colombia. The main objective of this review is to determine

the possible health effects of glyphosate exposure in order to identify research priorities and

followed for the reporting of results (flowchart 1).

The choice of articles was made taking into account the following inclusion and exclusion

criteria, in addition to the date of publication comprised between the years 2007 - 2017:

Methodological documents , articles in peer-reviewed journals.

Exclusion criteria:

-Summary , letters to the editor, comments, or editorials

Not available in full text

-Not published in English, Spanish or Portuguese language

Animal studies

standard format in Excel® 2010 that included the following variables: title, author, year,

country, type of study, number of persons included, population, outcomes, intervention or

comparator, observation time, study quality, financing or report of conflicts of interest.

descriptors.

Glyphosate "AND" Impacts of health

RESULTS

Twenty-three articles were selected (see Table 1) to be analyzed and included in the

systematic review, the vast majority of the references found did not meet the inclusion and

exclusion criteria, in addition to finding a large number of studies in vitro, in animals and in

plants.

The systematic review contains studies of methodological diversity, the most common

methodology used in the investigations was case studies (n=6), followed by case-control

studies and retrospective data investigations with participation of 5 for each, in addition to

analyzing descriptive studies and meta-analysis and a cohort study (Table 1).

developed in Thailand by Sribanditmongkol et al. where the patient was diagnosed with

erosion of tissues including mucous membranes and linings of the gastrointestinal and

respiratory tracts (2013). In Ireland they studied blood and urine samples from 13 cases of

glyphosate poisoning, clinical results confirmed high blood glyphosate concentrations with a

mean value of 61 mg / L (range 0.6-150 mg / L) and 4146 mg / L (range 690-7480 mg / L)

respectively in mild-moderate poisoning and fatal cases. Among the signs and symptoms of

the patients were oropharyngeal ulceration, nausea, vomiting, respiratory distress, cardiac

arrhythmia, hyperkalemia, impaired renal function, cardiovascular shock and multiple organ

failure (Zouaoui et al. 2013), a study that agrees with the one conducted in Korea by Han and

collaborators where similar symptomatology was documented (2016).

glyphosate corresponded to an intake of food with glyphosate in addition to an individual

susceptibility (2017).

Retrospective data studies were not conclusive to establish cause-effect relationship with the

use of glyphosate, a study conducted in the United States found no association between

reported cumulative days of glyphosate use and suffering from multiple myeloma, the study

does not attribute the use of the herbicide as a risk for the disease (Sorahan,T 2015), on the

other hand an investigation found how the exacerbation of asthma was inversely associated

with the use of glyphosate (OR CI = 0.5, 95% 0.3, 0.8) but presented apparently contradictory

results because it considers glyphosate as a substance that exacerbates asthma in patients

with a history of allergies (Henneberger et al. 2014). Another such study conducted in the

statistically significant relationship between current glyphosate use and the presence of

allergic wheezing (OR 1.56 CI 95% 1.19, 2.03), and non-allergic wheezing (OR 1.24 CI 1.07,

1.44), people who manifested prolonged use of the herbicides 2,4-D and Glyphosate showed

higher prevalence of allergic wheezing (Hoppin et al. 2017).

To conclude in one study, an association was found between having rheumatoid arthritis and

having reported long-term use of any pesticide, analyses for specific pesticides show a

sensitivity of diagnosed cases between rheumatoid arthritis and glyphosate use (OR = 1.4;

95% CI: 1.0, 2.1), in sensitivity analyses of cases diagnosed after the first 2 years of follow-up

(n = 96), associations of rheumatoid arthritis with any specific pesticide use were confirmed

(OR = 1.6; 95% CI: 1.0, 2.4) (Parks et al. 2016).

risk of cutaneous melanoma (OR 2.58, 95% CI, 1.18 - 5.65), simultaneous exposure to both

pesticides and sunlight, increased the statistical relationship (OR 4.68 95% CI 1.29-17.0)

and glyphosate in urine is higher in patients with the disease and in controls from SAN

endemic areas, the Kruskal-Wallis test showed significant difference in unadjusted creatinine

excretion for heavy metals and glyphosate except for Al, As, Cu, Mo, Ti and Zn between the

groups of people living in endemic area without the disease and in people from the non-

endemic area, urinary excretion of heavy metals and glyphosate is remarkably high in people

living in endemic areas compared to those living in non-endemic areas, the data support the

toxicological origin of FNS being present in people from specific geographical areas

(Jayasumana, Gunatilake, and Siribaddana 2015), in that country another research conducted

by Channa et al. looked for factors associated with chronic kidney disease of unknown

etiology (CKDu) and among them drinking safe drinking water (OR 2.52, 95% CI: 1.12-5.70),

respect to glyphosate exposure reported by 29 cases and 18 controls (OR 2.02, 95% CI 1.10

to 3.71), the above defined for an exposure period of less than 10 years and for a longer

latency period, the association increased to (OR 2.26, 95% CI 1.16 to 3.71).02, 95% CI 1.10-

3.71) the above defined for an exposure period of less than 10 years and for a longer latency

period, the association increased to (OR 2.26, 95% CI 1.16-4.40) (Eriksson et al. 2008).

Meta-analyses allow to know in a summarized way what is the great part of evidence that

exists on a given topic, one of the meta-analyses included was concerned with looking for the

risk between the use of glyphosate and the suffering of lymphohematopoietic cancer, the

results are presented in relative meta risks finding positive but marginal associations, for

Hodgkin's lymphoma (meta-RR = 1.3, 95% CI 1.0-1.6, based on six studies) and for multiple

and environment of the participants. This was found in the review conducted by Mink et al.,

2012 where it is concluded that the literature used does not present a pattern of associations

that indicate a causal relationship between any disease and exposure to glyphosate, arguing

that most associations are weak (Mink et al. 2011). Rome 2017, determine that the lack of

quantitative assessments of exposure and the design of studies to determine dose-response

relationships were common weaknesses in epidemiological investigations of health risks

posed by exposure to glyphosate (Paumgartten 2017), being a deficiency found in the present

Within the studies analyzed, there are results of statistical measures that indicate that

exposure to glyphosate is a risk factor for health problems such as multiple myeloma,

potential of glyphosate to cause harm. In the reviews, the authors recommend that research

health and the environment.

The history of the use of glyphosate in Colombia is broad, complex and somewhat

complicated, because the use of the herbicide has become an important point in the political

landscape of the country, due to the importance it has had in the eradication of illicit crops,

but at the same time, because of the consequences on populations and the environment that

are attributed to its use, This is why it is considered pertinent to continue with the creation

of scientific evidence that objectively guides decisions regarding the use not only of

glyphosate but also of other chemical substances, in order not to cause harm to people who

in different ways are exposed to contact with the chemical.

contact with it does not cause health effects. In the case reports, it is shown how these

presented health problems with different degrees of severity after having some type of

exposure to glyphosate, it is clear that, when ingesting the substance with the intention of

self-injury, intoxication is experienced by the oral intake of high doses of the chemical, but in

the other cases it is not clear which factors of the individual played an important role in the

development of the effects already described. The vast majority of the research included in

the study used surveys as a method of collecting information, based on clinical manifestations

referred by the persons included in the studies, leaving aside the importance of diagnostic

tests to search for the causal relationship. Respiratory system diseases such as asthma and

respiratory symptoms such as wheezing were the health effects that presented the most

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