Opposing glufosinate as a defoliant for adzuki beans: The toxicological review ignores reproductive toxicity risks
Text / Zeng Deci (Professor Emeritus, Department of Plant Pathology, National Chung Hsing University; author of the book "Pesticide Pharmacology and Application")
Regarding the controversy over expanding the registration of glufosinate for use as a defoliant on adzuki beans, although the competent authority followed established procedures and administered according to law, and held two rounds of expert meetings for communication and consultation, it still struggled to gain the acceptance of farmers and the general public. The Bureau of Animal and Plant Health Inspection and Quarantine recently made a special trip south to hold a symposium; however, the directors-general of five farmers' associations in the main adzuki bean production areas and most speakers expressed doubts about the risks and control of glufosinate, urging the government not to open it up hastily.
After nearly two months of turmoil, it is said that the Council of Agriculture will use public opinion from the "Public Policy Participation Platform" as the basis for policy, and will soon announce the policy direction. Based on my long-standing research in pharmacology and the relevant research evidence that has continued to emerge in recent years, I must honestly tell the Council of Agriculture that it is currently inappropriate to open up the use of glufosinate as a defoliant on adzuki beans.
The reason I oppose it is that when glufosinate is used as a defoliant, it poses a high reproductive toxicity risk to farmers applying it and to consumers (especially pregnant women and embryos), and it also has negative effects on the liver and kidneys. Because agricultural practices in Taiwan, China lack professional plant doctor system guidance, and pesticide applicators also lack appropriate education and training, the risks are difficult to control. Below is my detailed explanation. Because the text is long, it is divided into 3 articles for reference by all sectors.
Glufosinate reproductive toxicity research has been recognized by the EU, yet Bayer sponsored a report attempting to overturn it
The risks of greatest concern in the use of glufosinate should be reproductive toxicity and neurotoxicity. In 2018, the EU already declined to approve its registration due to reproductive toxicity issues. In fact, as early as 1996, research reports began to present scientific evidence regarding the reproductive toxicity of glufosinate, and the 2005 assessment report prepared by the European Food Safety Authority (EFSA) for the glufosinate registration case also clearly concluded that glufosinate could indeed cause serious embryonic developmental problems in the absence of obvious maternal toxicity, and in that report its reproductive toxicity was classified as Category 1B.
To overturn this EU ruling, which was equivalent to requiring glufosinate to be removed from the market, Bayer, as the owner at the time, of course quickly did everything it could to present evidence and arguments in rebuttal. With funding from Bayer, a 76-page analytical review report led by Schulte-Hermann and jointly authored by experts and scholars from 15 scientific research institutions/communities was published in 2006. This report is precisely the main reference material used this time by our country's Institute of Toxicology to assess the toxicity of glufosinate.
The report mainly used the research materials that could be collected at the time (including materials provided by Bayer) as well as an understanding of the content of relevant EU regulations to conduct an in-depth discussion of the appropriateness of EFSA's classification of glufosinate reproductive toxicity as 1B. The report was published by the journal Regulatory Toxicology and Pharmacology as a Supplementary issue (2006, 44:S1-S76).
This highly weighty/persuasive report was submitted in the name of the Science Partners Evaluation Groups. Science Partners LLC is a private company headquartered in Cambridge, Massachusetts, United States. The corresponding author, Professor Gerald N. Wogan, holds the title of member of the United States National Academy of Sciences and retired from the Massachusetts Institute of Technology (MIT) in 2001.
The pesticide company's subsequently submitted data did not gain EFSA's acceptance, and in 2018 the final ruling was that glufosinate "shall not be approved"
Although EFSA pointed out that glufosinate carries reproductive toxicity risks, through Bayer's efforts glufosinate was still approved by the European Commission in 2007, but on the condition that "a risk assessment report for mammals and non-target organisms must be submitted within two years." However, according to EFSA's 2012 review report, the supporting data subsequently submitted by the company evidently still did not gain the acceptance of EFSA's review experts. After the company Bayer voluntarily withdrew the application in 2017, EFSA in 2018 made the final ruling not to approve the registration application on the basis of reproductive toxicity issues.
Looking at the above comprehensively, glufosinate went through more than a decade of controversial offensive and defensive battles over registration. The company's struggle to defend its own rights and interests indeed exhausted every possible effort, yet ultimately failed. If it had not been untenable on principle, this truly could not have been explained away in a few words such as trade barriers or the market not meeting expectations (the Bureau of Animal and Plant Health Inspection and Quarantine originally claimed that glufosinate was not banned by the EU, but rather voluntarily withdrawn from the market due to poor sales).
Toxicological review should comprehensively examine existing scientific research reports to avoid "overgeneralizing from a partial view"
Since there are many reports in the EU pointing out the reproductive toxicity risks of glufosinate and leading to a decision of "non-approval," why does our country's competent business unit responsible for toxicological safety assessment and review insist on the safety of glufosinate while also presenting a report at the expert meeting emphasizing that "under normal use there is no concern of causing reproductive toxicity"?
A careful examination of the content of the report presented by the business unit makes it not difficult to find that its argumentative basis mainly follows the above-mentioned analytical report funded by Bayer and published by Schulte-Hermann et al. in 2006. The entire report interprets the mechanism of reproductive toxicity mainly around the inhibition of glutamine synthetase (GS) activity, and holds that high doses may be required to lead to reduced ammonia detoxification activity and insufficient fetal glutamine supply resulting in nutritional deficiency, and only then indirectly affect fetal development, on which basis its reproductive toxicity can be classified as a negligible mild level.
When I listened to these related statements during the meeting, I believed that the competent authority's argumentation in toxicology and safety assessment was overly based on overgeneralizing from a partial view, and that its professional capacity was evidently insufficient in the comprehensive collection and integration of relevant scientific research report materials.
Based on the relevant scientific and technological reports in recent years that I have personally reviewed, research on the reproductive toxicity of glufosinate has without exception focused on metabolic and neurotoxic issues related to glutamate receptor function, and discussions of its mechanism of action have also mostly emphasized apoptosis/gene expression deficiency caused by obstruction of key processes in embryonic development and differentiation. The above interpretation of the mechanism of reproductive toxicity by the competent business unit has simply missed the point. The safety assessment review report completed in this way truly makes it hard for people to let go of concerns about reproductive toxicity. Therefore, during the meeting I repeatedly emphasized that before opening up the use of glufosinate as a defoliant on adzuki beans, the necessary operations for relevant risk control must first be properly carried out as a precondition.
California in the United States legislated as early as 1984 to regulate "reproductive toxicity" caused by pesticides
Scientific and technological development advances with the times. As pointed out in earlier discussion, after an important pesticide is launched, related scientific and technological research and development, including pharmacology and safety assessment, usually continues and continually moves forward. When research finds that there may be potential negative effects in use, the management of the pesticide's use must be appropriately adjusted, and in severe cases it may even have to be removed from the market.
Reproductive toxicity is a rather serious issue in pesticide application management, because what is affected is not only the fate of a newborn for a lifetime; the whole family must also endure the pain and suffering alongside. In the United States, globally recognized as a leader in agricultural science and technology, California is its largest agricultural state, and California was also the first state in the entire United States to legislate to regulate pesticide reproductive toxicity. As early as 1984 it specially passed the "Birth Defects Prevention Act (SB950)," mainly to prevent problems such as reproductive toxicity and teratogenicity caused by pesticides.
Understanding the mechanism of reproductive toxicity has been an extremely important topic in the development of life science research since entering the new century. In female animals, reproductive toxicity mainly affects the embryonic development process, while in male animals it mainly affects testicular function and sperm development. In recent years, the elucidation of the physiological/biochemical and gene expression molecular bases related to reproductive toxicity caused by specific drugs has made people even more reluctant to take lightly the management of such side effects in drug use. (Article to be continued)