3.GLYPHOSATE: A DANGEROUS MOLECULE?
THE EFFECTS OF GLYPHOSATE (SHORT, MEDIUM OR LONG TERM), BOTH ON THE ENVIRONMENT AND ON ECOSYSTEMS AND HUMAN HEALTH, ARE MULTIPLE AND SOMETIMES INTERDEPENDENT. WHAT’S MORE, EVALUATING THESE EFFECTS IS STILL PROBLEMATIC DUE TO TWO MORE “TECHNICAL” ASPECTS. THE FIRST IS LINKED TO THE DIFFICULTY OF DETECTING AND ANALYTICALLY QUANTIFYING GLYPHOSATE IN THE ENVIRONMENT, FOOD OR THE HUMAN BODY. THE SECOND IS LINKED TO THE PLETHORA OF PUBLICATIONS AND STUDIES ON THE TOXICITY AND CARCINOGENICITY EFFECTS OF GLYPHOSATE. SINCE ITS FIRST USES IN THE 1970S, THE SCIENTIFIC COMMUNITY HAS FACED A MAJOR PROBLEM: DETECTING THE PRESENCE OF GLYPHOSATE IN NATURAL ENVIRONMENTS, MONITORING ITS EVOLUTION AND EVALUATING ITS TOXICITY BOTH ON FAUNA, FLORA AND MAN. EVEN IN 2020, RESEARCH TEAMS ARE STILL INVESTING IN THE DEVELOPMENT OF MORE EFFICIENT ANALYTICAL METHODS ADAPTED TO THE DETERMINATION OF GLYPHOSATE-BASED HERBICIDE RESIDUES. THE PROBLEM IS TO BE CORRELATED WITH TWO INTRINSIC DIFFICULTIES. THE FIRST IS LINKED TO THE MOLECULAR DIVERSITY OF GLYPHOSATE: WE HAVE IN FACT MENTIONED THAT IT IS RATHER GLYPHOSATE SALTS WHICH ARE USED IN COMMERCIAL FORMULATIONS. WHAT'S MORE, GLYPHOSATE EXISTS IN DIFFERENT IONIC FORMS DEPENDING ON PH CONDITIONS. GLYPHOSATE IS THEREFORE NOT EASY TO DETECT WHEN IT COMES TO MOLECULES THAT ARE SOMETIMES DIFFERENT, PARTICULARLY IN TERMS OF MASS OR FORMAL CHARGE. THE SECOND COMPLEXITY IN QUANTIFYING GLYPHOSATE IN THE ENVIRONMENT IS THAT THIS MOLECULE DECOMPOSES (IN THE PRESENCE OF CERTAIN MICROORGANISMS) TO GENERATE AMPA (AMINOMETHYLPHOSPHONIC ACID). BOTH GLYPHOSATE AND AMPA ARE THEREFORE FOUND IN SOIL, WATER, PLANTS, ETC. AND THESE TWO MOLECULES PRESENT “SIMILAR TOXICITY”. IT IS THEREFORE NOT SO MUCH THE QUANTITY AND EFFECT OF GLYPHOSATE THAT MUST BE ESTIMATED, IT IS ALSO THE QUANTITY AND EFFECT OF ITS DECOMPOSITION PRODUCTS, AS WELL AS THEIR RE-ASSIMILATION BY GROWING ORGANISMS AND THEIR POSSIBLE INTERACTION WITH ESSENTIAL NUTRIENTS.
2 MODE OF ACTION AND AGRONOMIC USE
IN AN EXTREMELY SIMPLIFIED MANNER, WE CAN SAY THAT GLYPHOSATE INTERFERES, BY BLOCKING A SPECIFIC ENZYME, WITH THE SHIKIMATE PATHWAY, A METABOLIC PATHWAY WHICH PRODUCES CERTAIN SPECIFIC AMINO ACIDS, PARTICULARLY IN PLANTS. BY INHIBITING THIS ENZYME, SHIKIMATE ACCUMULATES IN PLANT TISSUES, DISRUPTS ENERGY AND NUTRIENT SUPPLIES AND LEADS TO SHORT-TERM DESTRUCTION OF THE PLANT.
GLYPHOSATE THUS DEMONSTRATES AN INTEREST IN AGRICULTURE AS WELL AS IN HORTICULTURE, VITICULTURE, FORESTRY AND IN THE MAINTENANCE OF GARDENS AND GREEN SPACES. GLYPHOSATE IS NOT USED IN ITS PURE FORM. IT IS RATHER OFFERED, IN DILUTED AQUEOUS DISPERSION, IN THE FORM OF A SALT (AMMONIUM, ISOPROPYLAMINE, ETC.) IN COMBINATION MOST OFTEN WITH A SURFACTANT. THE EXACT COMPOSITION OF THE COMMERCIAL PRODUCT IS NOT OFTEN COMMUNICATED, BEING PART OF THE INDUSTRIAL SECRET. ONLY GLYPHOSATE, REFERRED TO AS THE “ACTIVE INGREDIENT”, MUST BE MENTIONED ON THE PRODUCT LABEL. THIS MEANS IT IS DIFFICULT TO KNOW EXACTLY WHAT IS IN THE GLYPHOSATE-CONTAINING HERBICIDES SOLD AROUND THE WORLD.
GLYPHOSATE IS THUS USED IN AGRICULTURE, ON ANNUAL CROPS, IN PARTICULAR TO FIGHT AGAINST WEEDS BEFORE SOWING OR TO STOP PREVIOUS CROPS. GLYPHOSATE IS ALSO SPRAYED ON CROPS 1 TO 2 WEEKS AFTER HARVEST TO DRY THEM OUT OR TO MAKE HARVESTING EASIER. THIS PRACTICE IS CALLED DESICCATION AND IS USED, AMONG OTHERS, ON CEREALS, RAPESEED, SUNFLOWER. GLYPHOSATE IS ALSO USED IN VINEYARDS, ORCHARDS AND OLIVE GROVES.
IN 2017, GLYPHOSATE REPRESENTED NEARLY 27% OF THE HERBICIDES USED IN BELGIUM, WHICH IS EQUIVALENT TO NEARLY 2,334 TONNES OF “PURE” GLYPHOSATE USED ANNUALLY ON THE NATIONAL TERRITORY. IN 2017, THIS REPRESENTED MORE THAN 17% OF THE TOTAL AREA CULTIVATED WITH WINTER WHEAT AND MORE THAN 92% OF ORCHARDS WHICH WERE TREATED WITH GLYPHOSATE WITH AN ANNUAL DOSE OF ACTIVE INGREDIENT SET BETWEEN 0.72 AND 1.08 KG/HECTARE. .
SINCE GLYPHOSATE IS A NON-SELECTIVE HERBICIDE, SOME CROPS HAVE HAD TO BE GENETICALLY MODIFIED TO BECOME TOLERANT TO IT. MONSANTO THUS DEVELOPED THE FIRST “GLYPHOSATE-TOLERANT” GMO PLANTS (ALSO CALLED “ROUNDUP READY”) IN THE MID-1990S.[10] THESE GENETICALLY MODIFIED CROPS (INCLUDING SOYA, CORN, COTTON, ETC.) HAVE OPENED A NEW MARKET FOR THE HERBICIDE, THEREBY BOOSTING ITS SALES. IN 2012, MORE THAN HALF OF THE CULTIVATED LAND IN THE UNITED STATES, OR 65 MILLION HECTARES, WAS OCCUPIED BY MONSANTO’S “ROUNDUP READY” CROPS.
IT WAS IN 1950 THAT GLYPHOSATE WAS SYNTHESIZED FOR THE FIRST TIME BY A SWISS CHEMIST (DR HENRI MARTIN) EMPLOYED BY THE COMPANY CILAG AG, CURRENTLY A SUBSIDIARY OF THE AMERICAN PHARMACEUTICAL GIANT JOHNSON & JOHNSON. AS NO PHARMACEUTICAL APPLICATIONS WERE IDENTIFIED, THE MOLECULE WAS SOLD TO OTHER COMPANIES AND SAMPLES WERE TESTED FOR A NUMBER OF POSSIBLE END USES. IT WAS THUS DISCOVERED, AT THE END OF THE 1950S, THE ABILITY OF GLYPHOSATE TO CHELATE ELEMENTS SUCH AS CALCIUM AND MAGNESIUM, AND GLYPHOSATE WAS THEN MARKETED AS A DESCALING AGENT FOR PIPES. IT WAS IN 1970, A LITTLE LESS THAN TWENTY YEARS LATER, THAT JOHN FRANZ, A CHEMIST EMPLOYED BY MONSANTO, IDENTIFIED THE HERBICIDAL ACTIVITY OF GLYPHOSATE AND A FORMULATION OF THE FINAL PRODUCT WAS MARKETED IN 1974.
FOR MORE THAN TWO DECADES, GLYPHOSATE REMAINED ONE OF THE MOST WIDELY USED HERBICIDES IN THE WORLD. IT IS CLASSIFIED AS A SYSTEMIC, NON-SELECTIVE, POST-EMERGENT HERBICIDE CAPABLE OF KILLING WEEDS THAT HAVE GREEN FOLIAGE. USE ON HERBICIDE-TOLERANT CROPS, IN NO-TILL APPLICATIONS, AND USE ON PERENNIAL CROPS CONSTITUTE THE PRIMARY AGRICULTURAL APPLICATIONS OF THE HERBICIDE, WHILE IT IS ALSO USED IN NON-AGRICULTURAL OPERATIONS SUCH AS HOME, INDUSTRIAL OR MUNICIPAL WEEDING.
3.B. REGULATORY ASPECTS !!!!
VARIOUS STUDIES HAVE THEREFORE BEEN CARRIED OUT ON GLYPHOSATE AND ITS BREAKDOWN PRODUCTS AND HAVE SUBSEQUENTLY BEEN REVIEWED BY SEPARATE ORGANIZATIONS INCLUDING THE EPA IN THE UNITED STATES, ECHA AND EFSA IN EUROPE AND THE IARC FOR THE WHO. WHILE THE EPA (ENVIRONMENTAL PROTECTION AGENCY), ECHA (EUROPEAN CHEMICALS AGENCY) AND EFSA (EUROPEAN FOOD SAFETY AUTHORITY) HAVE NOT CONSIDERED GLYPHOSATE TO BE CARCINOGENIC TO HUMANS WHEN IT IS USED CORRECTLY, THE IARC (INTERNATIONAL AGENCY FOR RESEARCH ON CANCER) DECLARED IN 2015 THAT GLYPHOSATE WAS “PROBABLY CARCINOGENIC TO HUMANS” BASED ON THE RESULTS OF ANIMAL EXPERIMENTS AND IN VITRO BIOCHEMICAL RESEARCH. [15] BASED ON MECHANISTIC DATA AND IN VITRO AND IN VIVO OBSERVATIONS, IT SEEMS LIKELY THAT GLYPHOSATE IS A WEAK CARCINOGEN, ALSO FOR HUMANS. THE RISK OF GLYPHOSATE CAUSING CANCER IN HUMANS IS PROBABLY VERY LOW, ALTHOUGH IT IS DIFFICULT TO MAKE A DECISION BASED ON CURRENT INFORMATION.
THIS LACK OF CONSENSUS AND THIS DIVERGENCE OF CONCLUSIONS LED TO THE START OF CONTROVERSIES AROUND GLYPHOSATE AND ASSOCIATED PUBLIC DEBATES. CURRENTLY, GLYPHOSATE IS APPROVED IN THE EU UNTIL DECEMBER 15, 2022.[16] THIS IMPLIES THAT GLYPHOSATE CAN BE USED AS AN ACTIVE INGREDIENT IN PHYTOPHARMACEUTICAL FORMULATIONS UNTIL THIS DATE. ALTHOUGH THE EU HAS APPROVED THE USE OF GLYPHOSATE, MEMBER STATES CAN DECIDE WHETHER THESE FORMULATIONS CAN BE USED ON THEIR TERRITORY. AS OF DECEMBER 31, 2018, BELGIUM BANNED THE SALE OF PHYTOSANITARY PRODUCTS BASED ON GLYPHOSATE (MOSTLY ROUNDUP
) AND THEIR NON-PROFESSIONAL USE ONLY.[17]
IN MAY 2019, THE EUROPEAN COMMISSION DESIGNATED 4 MEMBER STATES (FRANCE, HUNGARY, THE NETHERLANDS AND SWEDEN), UNITED UNDER THE NAME OF THE ASSESSMENT GROUP ON GLYPHOSATE (AGG), AS “RAPPORTEURS” FOR THE NEXT EVALUATION OF GLYPHOSATE. IN DECEMBER 2019, THE EUROPEAN GLYPHOSATE RENEWAL GROUP (GRG), MADE UP OF INDUSTRIALISTS AIMING TO OBTAIN THE RENEWAL OF THE APPROVAL OF GLYPHOSATE WITHIN THE EU, SUBMITTED A RENEWAL REQUEST TO THE AGG, TO THE STATES MEMBERS OF THE EU, EFSA AND THE EUROPEAN COMMISSION. THIS APPLICATION OFFICIALLY LAUNCHES THE RENEWAL PROCESS IN THE EU, AS PROVIDED FOR IN REGULATION (EC) NO 1107/2009.
HAVING BEEN SINGLED OUT FOR MORE THAN 10 YEARS FROM BOTH A TOXICOLOGICAL AND ENVIRONMENTAL POINT OF VIEW, GLYPHOSATE REMAINS A PRODUCT OF CHOICE WITH A MARKET THAT CONTINUES TO GROW. FOR THE FORECAST PERIOD 2019-2024, THE GLOBAL GLYPHOSATE MARKET IS EXPECTED TO REACH $12.54 BILLION BY 2024, GROWING AT A CAGR OF +6.8%. THE GLYPHOSATE MARKET IS THEREFORE NOT SLOWING DOWN, IN PARTICULAR DUE TO THE LACK OF AVAILABILITY OF EFFECTIVE ALTERNATIVES TO GLYPHOSATE. [5] BETWEEN 2019 AND 2024, THE MARKET GROWTH IS EXPECTED TO BE THE FASTEST IN NORTH AMERICA. THE LARGEST MARKET FOR GLYPHOSATE IS EXPECTED IN THE ASIA PACIFIC REGION. EUROPE REMAINS A WEAK MARKET FOR GLYPHOSATE WITH SALES (TO THE AGRICULTURAL SECTOR ONLY) REPRESENTING ONLY 7% OF GLOBAL PRODUCTION IN 2014.
IN 2017, GLOBAL GLYPHOSATE PRODUCTION CAPACITY WAS CONCENTRATED, IN PART, IN CHINA (AND INDIA). WORLD PRODUCTION THUS REACHED 1,065,000 TONNES, INCLUDING 380,000 TONNES FROM MONSANTO AND 685,000 TONNES FROM COMPANIES LOCATED IN CHINA.[6] IN 2019, THERE WERE FIVE MAJOR PLAYERS IN THE GLYPHOSATE-BASED HERBICIDE FORMULATION MARKET, NAMELY BAYER CROPSCIENCE AG, ADAMA AGRICULTURAL SOLUTIONS LTD, NUFARM LIMITED, EXCEL CROP CARE LIMITED AND UPL LIMITED. BAYER CROPSCIENCE AG, WHICH IS A MEMBER OF THE EUROPEAN GLYPHOSATE RENEWAL GROUP (GRG), THUS SUBMITTED TO THE AUTHORITIES IN JUNE 2020 THE RE-REGISTRATION FILE FOR THE AUTHORIZATION OF GLYPHOSATE IN THE EUROPEAN UNION (ASSESSMENT GROUP ON GLYPHOSATE). THE CURRENT AUTHORIZATION IS EFFECTIVE UNTIL 2032.
THE USE OF GLYPHOSATE FOR THE AGRICULTURAL SECTOR HAS INCREASED SUBSTANTIALLY SINCE 1974. IT IS ESTIMATED THAT IN THE UNITED STATES ALONE, MORE THAN 1.6 BILLION KILOGRAMS OF ACTIVE GLYPHOSATE HAVE BEEN APPLIED, OR 19% OF USE. ESTIMATED GLOBAL AMOUNT OF GLYPHOSATE (8.6 BILLION KILOGRAMS). GLOBALLY, THE USE OF GLYPHOSATE HAS INCREASED NEARLY 10-FOLD SINCE THE MID-1990S, FROM NEARLY 56,296 TONNES OF ACTIVE INGREDIENT IN 1994 TO MORE THAN 578,124 TONNES IN 2010.[8] TWO-THIRDS OF THE TOTAL VOLUME OF GLYPHOSATE APPLIED IN THE UNITED STATES BETWEEN 1974 AND 2014 WAS SPRAYED IN JUST THE LAST TEN YEARS. THE CORRESPONDING SHARE GLOBALLY IS 72%. IN 2014, FARMERS SPRAYED ENOUGH GLYPHOSATE TO APPLY ~1.0 KG/HA TO EVERY HECTARE OF CROPLAND IN THE UNITED STATES AND ALMOST 0.53 KG/HA TO ALL CROPLAND WORLDWIDE. ALTHOUGH QUANTITATIVE DATA IS AVAILABLE, PARTICULARLY IN THE UNITED STATES, NO ASSESSMENT OF THE VOLUMES OF GLYPHOSATE SOLD IN EUROPE HAS BEEN CARRIED OUT OVER THE LAST 30 YEARS.
3.C. HEALTH AND ENVIRONMENTAL ASPECTS
DUE TO THE MASSIVE (SOMETIMES POORLY CONTROLLED) USE OF GLYPHOSATE, CERTAIN PLANTS ARE NOW SHOWING INCREASING RESISTANCE TO GLYPHOSATE. TO GET AROUND THIS PROBLEM, THIS MEANS THAT OTHER PESTICIDES ARE SOMETIMES APPLIED IN COMBINATION WITH GLYPHOSATE. IF THE EFFECTS OF THE LATTER ARE ALREADY POORLY UNDERSTOOD AND STILL UNDER STUDY, IT IS IMPERATIVE TO MENTION THAT THE COMBINATION OF GLYPHOSATE WITH OTHER PHYTOSANITARY MOLECULES COULD LEAD TO SYNERGISTIC EFFECTS AND INCREASED TOXICITY. FURTHERMORE, THIS SYNERGY OF GLYPHOSATE WITH OTHER PHYTOSANITARY MOLECULES COULD MODIFY THE DECOMPOSITION OF GLYPHOSATE INTO AMPA AND GENERATE ADDITIONAL SECONDARY PRODUCTS WHOSE EFFECTS ON THE ENVIRONMENT AND HEALTH MUST BE EVALUATED ON A CASE-BY-CASE BASIS.
IF THESE REGULATORY ASPECTS ARE LINKED TO EUROPEAN POLICY, IT SHOULD BE MENTIONED THAT OTHER REGIONS IN THE WORLD HAVE NOT CAST DOUBT ON THE EFFECTS OF GLYPHOSATE ON BOTH HUMANS AND THE ENVIRONMENT, AND THAT, PARTICULARLY FOR REASONS OF EFFECTIVENESS AND ECONOMIC BENEFITS, GLYPHOSATE REMAINS WIDELY APPLIED, WITHOUT ANY RESTRICTION.
ALTHOUGH THE CARCINOGENICITY OF GLYPHOSATE IS AT THE HEART OF THE DEBATE, OTHER TYPES OF TOXICITY ARE KNOWN AND COULD EVEN SEEM MORE IMPORTANT. IT IS THUS PROVEN THAT GLYPHOSATE HAD A SIGNIFICANT IMPACT ON BIOLOGICAL SYSTEMS, IN PARTICULAR ON THE MICROBIOME AND THE ENTERIC SYSTEM. FURTHERMORE, A SIGNIFICANT PROPORTION OF PEOPLE AND LIVESTOCK WITH GLYPHOSATE IN THEIR URINE HAVE BEEN CONSIDERED OF CONCERN, EVEN IF THE CONCENTRATIONS DETECTED ARE QUITE LOW.[18] ALTHOUGH THE ACUTE TOXICITY EFFECTS OF GLYPHOSATE ON MAMMALS AND FISH ARE CONSIDERED LOW, COMMERCIALLY FORMULATED PRODUCTS ARE OFTEN MORE TOXIC THAN GLYPHOSATE ITSELF. CONCERNS HAVE THEREFORE ARISEN ABOUT THE CHRONIC EFFECTS OF THE FORMULATED PRODUCTS AND THE EMERGENCE OF VARIOUS FORMS OF CANCER AND MENTAL HEALTH DISORDERS.[19] IN ADDITION TO EXPOSURE TO HIGH CONCENTRATIONS OF GLYPHOSATE, AND THE FREQUENCY OF EXPOSURE, EXTERNAL PARAMETERS SUCH AS EXPOSURE TO SUNLIGHT APPEAR TO PLAY A ROLE IN THE TOXIC EFFECTS OF GLYPHOSATE-BASED FORMULATIONS ON HUMANS AND AQUATIC ANIMALS. AND TERRESTRIAL.
THERE ARE ALSO NUMEROUS QUESTIONS FROM THE SCIENTIFIC COMMUNITY ON THE MODIFICATIONS (GENERATED BOTH BY GLYPHOSATE AND BY ITS DECOMPOSITION PRODUCTS) OF MICROBIAL COMMUNITIES IN SOILS, PLANTS, WATER OR THE INTESTINES (OF HUMANS, AQUATIC AND TERRESTRIAL ANIMALS) AND ON THE ASSOCIATION WITH SPECIFIC PLANT AND ANIMAL PATHOGENS.15,[20]
CHANGES IN MICROBIOMES RESULTING FROM THE INTENSIVE USE OF GLYPHOSATE CAN AFFECT RESISTANCE AND DEFENSE MECHANISMS AND ULTIMATELY HAVE SERIOUS REPERCUSSIONS ON THE HEALTH OF PLANTS, ANIMALS AND HUMANS. THESE COMPLEX AND INDIRECT EFFECTS OF GLYPHOSATE MUST BE CONSIDERED BY REGULATORY AGENCIES.
REGARDING THE PERSISTENCE AND MOBILITY OF GLYPHOSATE IN TERRESTRIAL AND AQUATIC ECOSYSTEMS, THE DATA PROVIDED BY THE SCIENTIFIC COMMUNITY REMAIN INCOMPLETE.HOWEVER, WE KNOW THAT GLYPHOSATE QUICKLY ATTACHES TO THE SOIL AFTER SPRAYING AND IS RELEASED RELATIVELY SLOWLY. THE SPEED AND RATE OF GLYPHOSATE RELEASE DEPEND NOT ONLY ON SOIL COMPOSITION, BUT ALSO ON PRECIPITATION RATES, WATER, AND AGRICULTURAL PRACTICES (TYPE OF TILLAGE).[23] DEPENDING ON SOIL COMPOSITION, FIXATION HALF-LIVES CAN VARY BETWEEN 0.8 AND 151 DAYS UNDER AEROBIC CONDITIONS (FOR THE ACID FORM OF GLYPHOSATE) TO SEVERAL MONTHS UNDER ANAEROBIC CONDITIONS.22 ENVIRONMENTAL DEGRADATION OCCURS MAINLY THROUGH THE ACTION OF SOIL MICROORGANISMS. THE MAIN DECOMPOSITION PRODUCTS ARE AMINOMETHYLPHOSPHONIC ACID (AMPA) AND CARBON DIOXIDE. LIKE GLYPHOSATE, AMPA BINDS TIGHTLY TO SOIL AND IS SLOWLY DEGRADED, ULTIMATELY BREAKING DOWN INTO PHOSPHATE, AMMONIA, AND CARBON DIOXIDE. AMPA IS WEAKLY PERSISTENT IN SOILS UNDER AEROBIC CONDITIONS WITH A HALF-LIFE OF 2.1 TO 151 DAYS.
AS GLYPHOSATE AND AMPA ARE POLAR MOLECULES, THEY DISSOLVE EASILY IN WATER AND IN HIGH CONCENTRATIONS. THESE TWO MOLECULES CAN THUS PENETRATE AQUATIC SYSTEMS. IN RIVERS AND PONDS, THE HALF-LIFE OF THESE MOLECULES VARIES DEPENDING ON THE COMPOSITION OF THE WATER AND THE PH, AS WELL AS THE COMPOSITION OF THE BOTTOM SEDIMENTS WHICH CAN CONSTITUTE AN IMPORTANT "SINK", ESPECIALLY IF THE SEDIMENTS CONTAIN METAL IONS. A 2010 STUDY ESTIMATED THAT THIS HALF-LIFE RANGED FROM A FEW DAYS TO MORE THAN 3 MONTHS. !!!!
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