(3) Upon being tested by agricultural GMO technology inspection institutions, it has been confirmed that they do not pose a danger to humans, animals, plants, microbes and the ecological environment.

Regarding imported GMOs, the State Council regulation also stipulated:

(1) The exporting country or region has already approved for corresponding use and entered the market;

(2) The exporting country or region has, through scientific tests, proved they are harmless to humans, animals, plants, microbes and the ecological environment.

1) Among the harm caused by GM food ingredients to the health of Chinese consumers, the glyphosate residue contained in the glyphosate-tolerent soybeans causes the greatest harm!

2) Accordingly, to examine the greatest harm caused by GM food to the Chinese consumers, shouldn't the truth about how Monsanto's Roundup herbicide obtained it's 'pesticide registration' in 1988 in China be clarified, and the truth about how Monsanto's RR soybean 40-3-2 and maize NK603 obtained their 'safety certificate' from the Chinese Ministry of Agriculture?

5.1 In the first aspect, Monsanto purposely did not inform the Chinese Ministry of Agriculture about the patent of glyphosate as a chelator, which causes systematic harm to the health of the soil, microbes, crops, animals and humans!

5.2 In the second aspect, Monsanto in 1988 did not inform the Chinese Ministry of Agriculture that the US EPA in 1985 had classified glyphosate as a possible carcinogen to humans!

5.3 In the third aspect, Monsanto purposely did not provide long-term, lifetime and three-generation study reports revealing the carcinogenicity of glyphosate.

5.4 In the fourth aspect, Monsanto purposely submitted a Roundup 'toxicology test report issued by Younger Laboratories on Dec. 23, 1985' in which it is seriously suspected, from the date, to signature to content, are all outright fraud.

Attachment 10:

“We Must Face the harm caused by imported GM soybeans to 1.3 billion Chinese people”by Mi Zhen-yu (Former Vice President, Academy of Military Science, Doctoral tutor, Lieutenant General) published by 'Science & Technology Abstracts Newspaper' on April 25, 2014 quoted:

During the past 20 years, the health level of the Chinese people has rapidly deteriated with various diseases rapidly increasing. The situation is shocking.

In 1996, the rate of newborn defects in China was 0.87%; in 2000, it increased to 1.09%; and in 2010, it increased to 1.53%. [5]

According to an American survey reported by Reference News on June 2, 2013, the rate of severe depression in people over 60 years old in China is as high as 40%; [6]

The Xinmin Evening News reported on Nov. 22, 2011, the rate of precocious puberty in Chinese girls has increased 10-foldin the past 10 years;

The first 'The Public health white paper' issued by the Beijing Municipal Government in 2010 revealed: Type II diabetes has increased 11.7 times;

The Zhengzhou Daily News reported on April 2, 2013: The number of children confirmed with autism has increased 100 times during the past 20 years;

The Chengdu Daily reported on Feb. 20, 2013: During recent years, the prevalence of childhood cancer is increasing, on average there is one cancer patient for each 10,000 children. Among juvenile cancer patients, leukemia, brain tumor, malignant lymphoma and neuroblastoma are the top 4 types.

The '2012 Chinese male sperm quality survey white paper' announced by the China Population Association in 2012 indicates: The total amount of infertility patients in China already exceed 50 million, accounting for 15.6% of the child-bearing age population. This number 10 years ago in 2002 was 8%, and 20 years ago in 1972 was 3%, 40 years ago during the 70s infertility patients were not more than 1%.

According to a report by the Xinhua website, the prevalance of Parkinson's patients in China has increased over 20 times during the last 20 years; [7]

At present, the prevalance ofcardiovascular disease has exceeded 13% [8]; and the percentage of people with chronic kindney disease has reached 10%. [9]

Source：Mi Zhen-yu, We Must Face the harm caused by imported GM soybeans to 1.3 billion Chinese people, Science & Technology Abstracts Newspaper, April 25, 2014. http://t.cn/8skNH8S

[5] Information Times, Within 100 newborns is 5.6 with defects, 2013-03-07
http://news.ifeng.com/gundong/detail_2013_03/07/22826084_0.shtml

[6] Reference Information, Overseas Media, Chinese old age seriously suffering from suppression, 2013-06-02
http://china.cankaoxiaoxi.com/2013/0602/218581.shtml

[7] Xinhua website, The prevalence of Parkinson's disease has increased over 20 times during the recent 20 years in China, 2007-04-12
http://news.xinhuanet.com/health/2007-04/12/content_5965118.htm

[8] Health Newspaper, 'China cardiovascular disease report 2012' announces that ever 10 seconds a person dies from cardiovascular disease in China, 2013-08-12
http://www.bj.xinhuanet.com/hbpd/health/yw/2013-08/12/c_116900727.htm

[9] Guangzhou Daily, The prevalence of chronic kidney disease in Guangdong province is higher than average in China, 2013-11-04
http://news.southcn.com/d/2013-11/04/content_83567059.htm

1) Since 2004, has the Ministry of Agriculture issued documents requesting to follow-up, investigate, and obtain feedback on the effects that have occurred after the GM soybean oil, GM soybean protein powder added food products have entered the market, especially to childrens' health? If the Ministry of Agriculture has issued such documents, request to disclose scanned copies of such documents.

2) If Ministry of Agriculture has not issued such documents, then how could the Ministry, as the responsible department for GM food products, follow and learn about the effects that have occurred after the GM soybean oil, GM soybean protein powder added food products have entered the market, especially to childrens' health, including beneficial effects or harmful effects?

• This either proves that the Ministry of Agriculture is negligent, they have not even 'issued documents requesting to follow-up, investigate, and obtain feedback on the effects that have occurred after the GM soybean oil, GM soybean protein powder added food products have entered the market, especially to childrens' health';

• Or it proves that the Ministry of Agriculture has obtained information showing that GM soybean oil, GM soybean protein powder added food has caused harm to consumer's health, especially to childrens' health, but refuses to disclose this.

Conclusion: These facts thoroughly prove:

1) The Ministry of Agriculture's 'Agricultural GMOs Safety Evaluation Administration Method' and implementation by the Ministry has not assured us that GMOs developed abroad or within China are safe.  On the contrary, the 'Safety Certificate' offered by the Ministry that states GMOs 'do not present a danger to mankind, animals, plants, microbes and the ecological environment,' in fact  has allowed Monsanto's glyphosate-tolerant GM soy, maize and canola products, which do cause systematic harm “to mankind, animals, plants, microbes and the ecological environment,' to flood the Chinese market in large scale!

2) The Ministry of Agriculture and the China Disease Control & Prevention Center have both colluded with Monsanto, who has provided them with  'fake samples, carried out false tests, and falsified safety conclusions.' The Ministry of Agriculture and the China Disease Control & Prevention Center, in partnership with Monsanto, have cheated the Chinese government and Chinese people, have seriously violated the State Council's 'Agricultural GMOs Safety Administration Regulation,'and are hereby alleged to have committed the 'crime of endangering public security with dangerous methods'!

3) As a State Party to the United Nation's Convention on Biodiversity and its Cartagena Biosafety Protocol, China should strictly implement these legally binding international documents. On the issue of GMO food safety, the Cartagena Biosafety Protocol stipulates, 'Lack of scientific certainty due to insufficient relevant scientific information and knowledge regarding the extent of the potential adverse effects of a living modified organism on the conservation and sustainable use of biological diversity in the Party of import, taking also into account risks to human health, shall not prevent that Party from taking a decision, as appropriate, with regard to the import of the living modified organism in question as referred to in paragraph 3 above, in order to avoid or minimize such potential adverse effects.' The above described facts prove that the Ministry of Agriculture has blatantly violated these stipulations of the Protocol. 

4) We must therefore perform a cancer-like surgery:  first, investigate the extent of the collusion between officials in the Ministry of Agricultureand Monsanto in cheating the Chinese government and the Chinese People; second,  carry out a shakeup and reorganization of the leadership of the ministry; and third, establish new leadership with a clear understanding that ecological agriculture is the only correct sustainable development direction for China's agriculture. Only after establishing such a new leadership, and not before, can we make the necessary revision to the ministry's 'Agricultural GMOs Safety Evaluation Administration Method' in accordance with the principle of giving top priority to the continuous safety, health, survival and reproduction of the Chinese nation!

5) Furthermore, we cannot exclude the possibility that GMOs could very likely be used by overseas evil forces as a means of bio-warfare, causing massive safety danger, therefore the agricultural GMO issue also is a major issue concerning bio-defense. Therefore, the agricultural GMO issue is no longer an issue that can be regulated, supervised and administrated by one government department, such as the Ministry of Agriculture, but must be regulated, supervised and administrated by a special agency of the National Security Council. This special agency should be formed by members of the National Security Council, military medical research institutions undertaking bio-defense tasks, biochemical warfare tasks, and specialists carrying out research in agricultural GMOs, inspection and quarantine, public health, environment protection etc.

6) After investigating the responsibility of the Ministry of Agriculture officials colluding internally and externally with Monsanto and cheating the Chinese government and Chinese people, we suggest that the 'Agricultural GMO Biosafety Evaluation Administration Method' at least should be supplemented with the following clauses:

Therefore, we request: Much more severe punishment should be included by the revised 'Agricultural GMO Biosafety Administration Method,' and those who purposely release GMOs into the environment and the market, without giving concern to the consequences, should be considered equivalent to thugs and charged with the crime of 'using dangerous means to harm public safety.' Not only should criminal responsibility be investigated, but also apply massive severe economic punishment, therefore evil persons will not dare to act in such way!

Finally, regarding the revision process of the 'Agricultural GMO Biosafety Evaluation Administration Method,' we request:

Summary of Main Points

1) Wu Hui-qiong (1999): Glyphosate and test rat “Liver microsomal protein content decreased significantly … protein content reduction might be associated with protein synthesis ability reduction caused by impaired liver cell damage.”

2) Geng De-gui et al. (2000): Causes obvious genetic damage to yellow eel”

3) Nan Xuyang (2001): Different concentration of glyphosate “causes certain degree of effect on RBC micronucleus rate and the rate of nuclear anomalies of toads”

4) Nan Xuyang (2002): 'causes rather large effect on Crucian carp hemoglobin, red blood cells and white blood cells, with rather obvious time duration effect.”

5) Nan Xuyang et al. (2003): “causes certain degree of biological toxicity to loaches”.

6) Kang Jufang et al. (2008): “causes reproduction toxicity to mice with a certain mutagenic effect”.

7) Wang Fei (2008): “Can lead to liver cell survival rate decrease, cell membrane permeability increase, inhibit cell ion transport, induce DNA damage, mitochondrial membrane potential decreased, leakage of Cyt C, AIF apoptosis factors, causes cell apoptosis and necrosis, obvious damage to liver cells”.

8) Huang Ting (2010): Could cause mice sperm number reduce, sperm deformity rate increase, epididymis and testis weight and coefficient decline, suggesting Roundup causes obvious reproductive toxicity in male mice”.

9) Li Qiao et al. (2010): “Glyphosate causes certain acute toxicity to sea urchin embryos during different phases of development”.

10) Zhao Wei et al. (2011): “Glyphosate can reduce total antioxidant capacity, damage protein and lipid, cause oxidative damage of the body, cause development of various diseases”.

11) Yu Hui et al. (2012): “Glyphosate causes reproductive toxicity to mice and has certain mutagenic effect”.

12) Zeng Ming et al. (2014): 'The study indicates, 60-180 mg·L-1 concentration glyphosate causes obvious damage to GC-1 cells, its mechanism might be oxidative stress induced by gyphosate, leading to cell permeability increase and DNA damage.' 

13) Zhao Wenhong et al. (2013): 'Conclusion: Glyphosate causes certain toxicity to mice sertoli cells, can induce cell apoptosis and inhibit cell proliferation, and the harm increases with glyphosate dosage increase; At the same time can inhibit the expression of ABP and wave shape protein mRNA.'

Summary of Main Points

1) Kale, P.G. et al, (1995): Roundup and others total nine herbicides and pesticides were tested for their mutagenicity using the Drosophila sex-linked recessive lethal mutation assay. These are Ambush, Treflan, Blazer, Roundup, 2,4-D Amine, Crossbow, Galecron, Pramitol, and Pondmaster. All chemicals induced significant numbers of mutations in at least one of the cell types tested.

2) Yousef MI et al. (1995): Two sublethal doses of Carbofuran (carbamate insecticide) and Glyphosate (organophosphorus herbicide) treatment resulted in a decline in body weight, libido, ejaculate volume, sperm concentration, semen initial fructose and semen osmolality. This was accompanied with increases in the abnormal and dead sperm and semen methylene blue reduction time. The hazardous effect of these pesticides on semen quality continued during the recovery period, and was dose-dependent. These effects on sperm quality may be due to the direct cytotoxic effects of these pesticides on spermatogenesis and/or indirectly via hypothalami-pituitary-testis axis which control the reproductive efficiency.

3) Savitz, D.A. et al (1997): A variety of chemicals (atrazine, glyphosate, organophosphates, 4-[2,4-dichlorophenoxy] butyric acid, and insecticides)... Based on these data, despite limitations in exposure assessment, the authors encourage continued evaluation of male exposures, particularly in relation to miscarriage and preterm delivery.

4）Claudia Bolognesi et al. (1997): In this study, the formulated commercial product, Roundup, and its active agent, glyphosate, were tested in the same battery of assays for the induction of DNA damage and chromosomal effects in vivo and in vitro. ... A DNA-damaging activity as DNA single-strand breaks and 8-OHdG and a significant increase in chromosomal alterations were observed with both substances in vivo and in vitro. A weak increment of the genotoxic activity was evident using the technical formulation.

5) Lioi, M.B. et al. (1998): The pesticides gliphosate, vinclozolin, and atrazine have been studied ... In our experimental conditions, each chemical compound tested produced a dose-related increase in the percent of aberrant cells and an increase of SCE/cell.

6) Peluso M. (1968): Roundup is able to induce a dose-dependent formation of DNA adducts in the kidneys and liver of mice. The levels of Roundup-related DNA adducts observed in mouse kidneys and liver at the highest dose of herbicide tested (600 mg/kg) were 3.0 +/- 0.1 (SE) and 1.7 +/- 0.1 (SE) adducts/10(8) nucleotides, respectively. The Roundup DNA adducts were not related to the active ingredient, the isopropylammonium salt of glyphosate, but to another, unknown component of the herbicide mixture. Additional experiments are needed to identify the chemical specie(s) of Roundup mixture involved in DNA adduct formation.

7) Peggy J. Perkins at el. (2000): Comparative toxicity of Roundupt and its surfactant polyoxyethyleneamine (POEA) to Xenopus laevis, and comparing Roundup formulation and the Rodeo formulation (with no surfactant POEA), using Frog Embryo Teratogenesis Assay—Xenopus (FETAX). A comparison of LC50 concentrations indicated that the Roundup formulation of glyphosate was 700 times as toxic as the Rodeo formulation. Even though a limited number of tests were performed to evaluate the effects of the surfactant POEA on X. laevis, each test showed a lower LC50 value for POEA alone than for either Roundup or Rodeo. More studies are needed, but it seems likely that the surfactant itself is responsible for the greater toxicity displayed by the Roundup formulation of glyphosate. It seems less likely that the greater toxicity is due to enhanced uptake of glyphosate by the embryos.

8) Walsh, L.P. et al. (2000): In conclusion, Roundup disrupted steroidogenesis in Leydig cells through a post-transcriptional reduction in StAR protein expression. The use of StAR as an end point in studies concerning endocrine disruption merits further consideration. Although Roundup decreased steroidogenesis, the active ingredient of this herbicide, glyphosate, did not alter steroid production, indicating that at least one other component of the formulation is required to disrupt steroidogenesis. Because the formulation of Roundup is proprietary, further studies are needed to identify the components in Roundup and their ability to disrupt steroidogenesis.

9) Daruich, J. et al. (2001): We determined the effects of these compounds on the levels and activities of the P450scc enzyme (which converts cholesterol to pregnenolone) and the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzyme (which converts pregnenolone to progesterone). Of the pesticides screened, only the pesticide Roundup inhibited dibutyryl [(Bu)(2)]cAMP-stimulated progesterone production in MA-10 cells without causing cellular toxicity. Roundup inhibited steroidogenesis by disrupting StAR protein expression, further demonstrating the susceptibility of StAR to environmental pollutants.

10) T E Arbuckle et al. (2001): For late abortions, preconception exposure to glyphosate (OR = 1.7; 95% CI, 1.0-2.9), ... was associated with elevated risks. Postconception exposures were generally associated with late spontaneous abortions.

11) Marc J et al. (2002): Roundup delayed the activation of CDK1/cyclin B in vivo. Roundup inhibited also the global protein synthetic rate without preventing the accumulation of cyclin B. In summary, Roundup affects cell cycle regulation by delaying activation of the CDK1/cyclin B complex, by synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/cyclin B regulator, our results question the safety of glyphosate and Roundup on human health.

12）Dallegrave, E. et al. (2003): The aim of this study was to assess the teratogenicity of the herbicide glyphosate-Roundup (as commercialized in Brazil) to Wistar rats. Dams were treated orally with water or 500, 750 or 1000 mg/kg glyphosate from day 6 to 15 of pregnancy. Results showed a 50%, mortality rate for dams treated with 1000 mg/kg glyphosate. Skeletal alterations were observed in 15.4, 33.1, 42.0 and 57.3% of fetuses from the control, 500, 750 and 1000 mg/kg glyphosate groups, respectively. We may conclude that glyphosate-Roundup is toxic to the dams and induces developmental retardation of the fetal skeleton.

13) Lajmanovich RC et al. (2003): Larval maldevelopment (craniofacial and mouth deformities, eye abnormalities and bent curved tails) occurred in all tests and increased with time and GLY-F concentration.

14) Cox, C. (2004): Glyphosate has been shown to have carcinogenic effects.  Three recent studies found a link between glyphosate exposure and non-Hodgkin's lymphoma (a type of cancer).

15) Marc, J. et al. (2004): Several glyphosate-based pesticides from different manufacturers were assayed in comparison with Roundup 3plus for their ability to interfere with the cell cycle regulation. All the tested products, Amega, Cargly, Cosmic, and Roundup Biovert induced cell cycle dysfunction.

16) Marc, J et al. (2004): We conclude that formulated glyphosate's effect on the cell cycle is exerted at the level of the DNA-response checkpoint of S phase. The resulting inhibition of CDK1/cyclin B Tyr 15 dephosphorylation leads to prevention of the G2/M transition and cell cycle progression.

17) Benedettia, A.L. et al. (2004): The object of this study was to analyze the hepatic effects of the herbicide Glyphosate-Biocarb (as commercialized in Brazil) in Wistar rats. ... We may conclude that Glyphosate-Biocarb may induce hepatic histological changes as well as AST and ALT leaking from liver to serum in experimental models.

18）John F Acquavella et al. (2004): This study by Monsanto reported: Sixty percent of farmers had detectable levels of glyphosate in their urine on the day of application.The geometric mean (GM) concentration was 3 ppb, the maximum value was 233 ppb, and the highest estimated systemic dose was 0.004 mg/kg.For spouses, 4% had detectable levels in their urine on the day of application. Their maximum value was 3 ppb. For children, 12% had detectable glyphosate in their urine on the day of application, with a maximum concentration of 29 ppb.

19）Marc, J. et al.（2005）：The surfactant polyoxyethylene amine (POEA), the major component of commercial Roundup, was found to be highly toxic to the embryos when tested alone and therefore could contribute to the inhibition of hatching.

20) Lajmanovich, R.C. et al. (2005): Larval maldevelopment (craniofacial and mouth deformities, eye abnormalities and bent curved tails) occurred in all tests and increased with time and GLY-F conentration. ... Malformation were minimal at 3.07 mg/L exposed for one day, whereas greater that 90% were malformed at a GLY-F level of 7.5 mg/L. The current test confirmed the malformation effects of GLY-F on tadpoles.

21) Beuret CJ et al. (2005): The present study has investigated the effects that 1% glyphosate oral exposure has on lipoperoxidation and antioxidant enzyme systems in the maternal serum and liver of pregnant rats and their term fetuses at 21 days of gestation. The results suggest that excessive lipid peroxidation induced with glyphosate ingestion leads to an overload of maternal and fetal antioxidant defense systems.

22) Richard S et al. (2005): We show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation.

23) Sparling DW et al. (2006): Hatching success at the highest concentration was significantly lower (73%) than in other treatments (80-100%). ... Genetic damage, as measured by flow cytometry, increased with treatment concentration except for the highest dose. ... There also is a risk that the health of turtle embryos may be affected in ways not measured in the present study.

24) Oliveira AG et al. (2007): The exposure to the herbicide resulted in alterations in the structure of the testis and epididymal region as well as in the serum levels of testosterone and estradiol, with changes in the expression of androgen receptors restricted to the testis. The harmful effects were more conspicuous in the proximal efferent ductules and epididymal ducts, suggesting higher sensitivity of these segments among the male genital organs. The effects were mostly dose dependent, indicating that this herbicide may cause disorder in the morphophysiology of the male genital system of animals.

25) César Paz-y-Miño et al. (2007): We analyzed the consequences of aerial spraying with glyphosate added to a surfactant solution in the northern part of Ecuador. ... The results showed a higher degree of DNA damage in the exposed group (comet length = 35.5 μm) compared to the control group (comet length = 25.94 μm). These results suggest that in the formulation used during aerial spraying glyphosate had a genotoxic effect on the exposed individuals.

26) Bellé R et al. (2007): New insights in cancer biology lead to two fundamental concepts about the very first origin of cancerogenesis. Cancers result from dysfunction of DNA-damaged checkpoints and cancers appear as a result of normal stem cell (NCS) transformation into a cancer stem cell (CSC). The second aspect suggests a new definition of 'cancer', since CSC can be detected well before any clinical evidence. Since early development starts from the zygote, which is a primary stem cell, sea urchin early development allows analysis of the early steps of the cancerization process. In the field of toxicology and incidence on human health, the sea urchin experimental model allows assessment of cancer risk from single or combined molecules long before any epidemiologic evidence is available. Sea urchin embryos were used to test the worldwide used pesticide Roundup that contains glyphosate as the active herbicide agent; it was shown to activate the DNA-damage checkpoint of the first cell cycle of development.

27) Dallegrave E et al. (2007): The results showed that glyphosate-Roundup did not induce maternal toxicity but induced adverse reproductive effects on male offspring rats: a decrease in sperm number per epididymis tail and in daily sperm production during adulthood, an increase in the percentage of abnormal sperms and a dose-related decrease in the serum testosterone level at puberty, and signs of individual spermatid degeneration during both periods. There was only a vaginal canal-opening delay in the exposed female offspring. These findings suggest that in utero and lactational exposure to glyphosate-Roundup may induce significant adverse effects on the reproductive system of male Wistar rats at puberty and during adulthood.

28) McComb et al. (2007): In in vitro tests found that glyphosate acts in the mitochondria of the rat liver cells as an oxidative phosphorylation decoupling agent.

29) Soso AB et al. (2007):The results indicate that the presence of glyphosate in water was deleterious toRhamdia quelenreproduction, altering steroid profiles and egg viability.

30) Hokanson R et al. (2007): Among the chemicals most commonly used, both commercially and in the home, is the herbicide glyphosate. Although glyphosate is commonly considered to be relatively non-toxic, we utilizedin vitroDNA microarray analysis of this chemical to evaluate its capacity to alter the expression of a variety of genes in human cells. We selected a group of genes, determined by DNA microarray analysis to be dysregulated, and used quantitative real-time PCR to corroborate their altered states of expression. We discussed the reported function of those genes, with emphasis on altered physiological states that are capable of initiating adverse health effects that might be anticipated if gene expression were significantly altered in either adults or embryos exposedin utero.

31) Mañas F et al. (2009): AMPA is the major environmental breakdown product of glyphosate. The purpose of this study is to evaluate the in vitro genotoxicity of AMPA using the Comet assay in Hep-2 cells after 4h of incubation and the chromosome aberration (CA) test in human lymphocytes after 48h of exposition. Potential in vivo genotoxicity was evaluated through the micronucleus test in mice. In the Comet assay, the level of DNA damage in exposed cells at 2.5-7.5mM showed a significant increase compared with the control group. In human lymphocytes we found statistically significant clastogenic effect AMPA at 1.8mM compared with the control group. In vivo, the micronucleus test rendered significant statistical increases at 200-400mg/kg. AMPA was genotoxic in the three performed tests.

32) Nora BenachourandGilles-Eric Séralini (2009): We have evaluated the toxicity of four glyphosate (G)-based herbicides in Roundup (R) formulations, from 10⁵ times dilutions, on three different human cell types. This dilution level is far below agricultural recommendations and corresponds to low levels of residues in food or feed. The formulations have been compared to G alone and with its main metabolite AMPA or with one known adjuvant of R formulations, POEA. HUVEC primary neonate umbilical cord vein cells have been tested with 293 embryonic kidney and JEG3 placental cell lines. All R formulations cause total cell death within 24 h, through an inhibition of the mitochondrial succinate dehydrogenase activity, and necrosis, by release of cytosolic adenylate kinase measuring membrane damage. They also induce apoptosis via activation of enzymatic caspases 3/7 activity. This is confirmed by characteristic DNA fragmentation, nuclear shrinkage (pyknosis), and nuclear fragmentation (karyorrhexis), which is demonstrated by DAPI in apoptotic round cells. G provokes only apoptosis, and HUVEC are 100 times more sensitive overall at this level. The deleterious effects are not proportional to G concentrations but rather depend on the nature of the adjuvants. AMPA and POEA separately and synergistically damage cell membranes like R but at different concentrations. Their mixtures are generally even more harmful with G. In conclusion, the R adjuvants like POEA change human cell permeability and amplify toxicity induced already by G, through apoptosis and necrosis. The real threshold of G toxicity must take into account the presence of adjuvants but also G metabolism and time-amplified effects or bioaccumulation. This should be discussed when analyzing the in vivo toxic actions of R. This work clearly confirms that the adjuvants in Roundup formulations are not inert. Moreover, the proprietary mixtures available on the market could cause cell damage and even death around residual levels to be expected, especially in food and feed derived from R formulation-treated crops.

33) Mariana, A. et al. (2009): We studied the effect of chronic pesticide exposure in rats injected i.p. for 5weeks with doses between 1/50 and 1/250 LD50 of dimethoate, glyphosate and zineb, either alone or in combination. All tested agrochemicals increased the oxidative stress status in the plasma, liver, and testes, and also modified hormonal parameters involved in reproductive function. The increase in oxidative stress and damage biomarker levels, as well as the alteration of the antioxidant defence system decreased testosterone, FSH and LH levels in the plasma of pesticide-treated rats.

34) Mañas F et al. (2009): In the present study glyphosate was genotoxic in the comet assay in Hep-2 cells and in the MNT test at 400 mg/kg in mice. ... The results showed an increase in these enzyme activities. According to the obtained results we cannot discard the oxidative stress as a potential genotoxicity mechanism. Due to the fact that the results were not conclusive we believe it is necessary to carry on researching the possible connection between oxidative stress an genetic damage.

35) Prasad S et al. (2009）：Glyphosate treatment significantly increases CAs (chromosomal aberrations) and MN (micronuclei) induction at both treatments and time compared with the vehicle control (P < .05). The cytotoxic effects of glyphosate were also evident, as observed by significant decrease in mitotic index (MI). The present results indicate that glyphosate is clastogenic and cytotoxic to mouse bone marrow.

36) Robin Mesnage et al. (2009): In January 2009, a farming couple contacted us because two of their three children were born with congenital malformations. One had a somatotropic deficiency, an imperforate anus and a small atrial septal defect at birth. Another was suffering from hypospadias, had a micropenis, a total deficiency of growth hormone and presented also an imperforate anus. All these disorders are rarely encountered in the same person or family. Yet, in some cases these symptoms with others have been grouped under the Stratton-Parker syndrome, whose etiology remains unknown. They noticeably overlap our cases. Only males are affected up to date and all cases occurred sporadically, some authors have therefore proposed an X-linked recessive inheritance. Due to the absence of known familial antecedents, and lack of genetic origins evidenced to date, the hypothesis of an environmental origin can be explored. In particular, many pesticides were used by this family around pregnancies. The father sprayed, without protection, more than 1.3 tons of pesticides per year including 300 liters of glyphosate based herbicides. Among them are well-known endocrine disruptors such as carbendazim, 2,4-Dichlorophenoxyacetic acid, glyphosate, ioxynil, linuron, trifluralin and vinclozolin. The whole family had close contact with the father, consumes products of their garden and can be exposed through the consumption of pigs and poultry fed with the farm harvest.

37) Gasnier C et al. (2009): Glyphosate-based herbicides are the most widely used across the world; they are commercialized in different formulations. Their residues are frequent pollutants in the environment. In addition, these herbicides are spread on most eaten transgenic plants, modified to tolerate high levels of these compounds in their cells. Up to 400 ppm of their residues are accepted in some feed. We exposed human liver HepG2 cells, a well-known model to study xenobiotic toxicity, to four different formulations and to glyphosate, which is usually tested alone in chronic in vivo regulatory studies. We measured cytotoxicity with three assays (Alamar Blue, MTT, ToxiLight), plus genotoxicity (comet assay), anti-estrogenic (on ERalpha, ERbeta) and anti-androgenic effects (on AR) using gene reporter tests. We also checked androgen to estrogen conversion by aromatase activity and mRNA. All parameters were disrupted at sub-agricultural doses with all formulations within 24h. These effects were more dependent on the formulation than on the glyphosate concentration. First, we observed a human cell endocrine disruption from 0.5 ppm on the androgen receptor in MDA-MB453-kb2 cells for the most active formulation (R400), then from 2 ppm the transcriptional activities on both estrogen receptors were also inhibited on HepG2. Aromatase transcription and activity were disrupted from 10 ppm. Cytotoxic effects started at 10 ppm with Alamar Blue assay (the most sensitive), and DNA damages at 5 ppm. A real cell impact of glyphosate-based herbicides residues in food, feed or in the environment has thus to be considered, and their classifications as carcinogens/ mutagens/reprotoxics is discussed.

38) Romano RM et al. (2010): These results suggest that commercial formulation of glyphosate is a potent endocrine disruptor in vivo, causing disturbances in the reproductive development of rats when the exposure was performed during the puberty period.

39) Jayawardene, U.A et al. (2010): Glyphosate recorded the highest percentage of malformation (69%) compared to other pesticides in 1.00 ppm concentration. Malformations observed were mainly in the spine, such as hunched back (kyphosis) and curvature (scoliosis), while edema and skin ulcers were also observed

40) Paganelli, A.et al. (2010): Xenopus laevis embryos were incubated with 1/5000 dilutions of a commercial GBH. The treated embryos were highly abnormal with marked alterations in cephalic and neural crest development and shortening of the anterior−posterior (A-P) axis. Alterations on neural crest markers were later correlated with deformities in the cranial cartilages at tadpole stages. Embryos injected with pure glyphosate showed very similar phenotypes. Moreover, GBH produced similar effects in chicken embryos, showing a gradual loss of rhombomere domains, reduction of the optic vesicles, and microcephaly. This suggests that glyphosate itself was responsible for the phenotypes observed, rather than a surfactant or other component of the commercial formulation. A reporter gene assay revealed that GBH treatment increased endogenous retinoic acid (RA) activity in Xenopus embryos and cotreatment with a RA antagonist rescued the teratogenic effects of the GBH. Therefore, we conclude that the phenotypes produced by GBH are mainly a consequence of the increase of endogenous retinoid activity.

41) Rick A. Relyea (2012): Even more striking was the discovery that Roundup induced morphological changes in the tadpoles. In wood frog and leopard frog tadpoles, Roundup induced relatively deeper tails in the same direction and of the same magnitude as the adaptive changes induced by dragonfly cues. To my knowledge, this is the first study to show that a pesticide can induce morphological changes in a vertebrate. Moreover, the data suggest that the herbicide might be activating the tadpoles' developmental pathways used for antipredator responses. Collectively, these discoveries suggest that the world's most widely applied herbicide may have much further-reaching effects on nontarget species than previous considered.

42) Fabio Leonardo Meza-Joya et al. (2012): Glyphosate formulation at application rates above 5.4 µg a.e./cm²(in vivo) and concentrations above 95 µg a.e./mL (in vitro) showed clear evidence of cytotoxicity. In vivo and in vitro exposure ofE. johnstoneie rythrocytes to the glyphosate formulation induced DNA breaks in a dose-dependent manner with statistically significant values (P < 0.05) at all doses tested. DNA damage initially increased with the duration of exposure and then decreased, suggesting that DNA repair events were occurring during in vivo and in vitro exposures.

43) Koller VJ et al. (2012): Glyphosate(G) is the largest selling herbicide worldwide; the most common formulations (Roundup, R) contain polyoxyethyleneamine as main surfactant.Recent findings indicate that G exposure may cause DNA damage and cancer in humans. R induced acute cytotoxic effects at concentrations >40 mg/l after 20 min, which were due to membrane damage and impairment of mitochondrial functions.Both G and R induced DNA migration in single-cell gel electrophoresis assays at doses >20 mg/l.Furthermore, an increase of nuclear aberrations that reflect DNA damage was observed.The frequencies of micronuclei and nuclear buds were elevated after 20-min exposure to 10–20 mg/l, while nucleoplasmatic bridges were only enhanced by R at the highest dose (20 mg/l).R was under all conditions more active than its active principle (G).Comparisons with results of earlier studies with lymphocytes and cells from internal organs indicate that epithelial cells are more susceptible to the cytotoxic and DNA-damaging properties of the herbicide and its formulation.Since we found genotoxic effects after short exposure to concentrations that correspond to a 450-fold dilution of spraying used in agriculture, our findings indicate that inhalation may cause DNA damage in exposed individuals.

44) Vandenberg LN et al. (2012): For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity.... We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.

45) Benedetti D et al. (2013): Soybean cultivation is widespread in the State of Rio Grande do Sul (RS, Brazil), especially in the city of Espumoso. Soybean workers in this region are increasingly exposed to a wide combination of chemical agents present in formulations of fungicides, herbicides, and insecticides. ... Comet assay and BMCyt (micronuclei and nuclear buds) data revealed DNA damage in soybean workers. Cell death was also observed (condensed chromatin, karyorhectic, and karyolitic cells). Inhibition of non-specific choline esterase (BchE) was not observed in the workers. The trace element contents of buccal samples were analyzed by Particle-Induced X-ray Emission (PIXE). Higher concentrations of Mg, Al, Si, P, S, and Cl were observed in cells from workers. No associations with use of personal protective equipment, gender, or mode of application of pesticides were observed.Our findings indicate the advisability of monitoring genetic toxicity in soybean farm workers exposed to pesticides.

46) Thongprakaisang S et al. (2013): Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study.

Summary of Main Points

'Advances of Endocrine Disrupting Chemicals Research' by Chinese scholar Ren Jin, Jiang Ke, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences.

Summary: EDC is becoming a front-edge topic of ecological environment studies, and receiving close attention by governments of each nation. This paper summarizes advances in the studies of the harms caused by EDCs, their mechanism, kinds of compounds, and especially emphasizes on the new concept of potential harm caused by low concentrations but long-term exposure to such chemical compounds, discussed in detail the challenge traditional environment toxicology and environment analysis chemistry has faced, the important strategic position of biological analysis, chemical instrument analysis and biosensors technology in the screening process of EDCs.

'Endocrine Disruptor Screening Program (EDSP)' issued on April15， 2009 by EPA points out:

In the 1990's, some scientists proposed that certain chemicals might be disrupting the endocrine systems of humans and wildlife. A variety of chemicals have been found to disrupt the endocrine systems of animals in laboratory studies, and compelling evidence shows that endocrine systems of certain fish and wildlife have been affected by chemical contaminants, resulting in developmental and reproductive problems.

Based on this and other evidence, Congress passed the Food Quality Protection Act and the Safe Drinking Water Act (SDWA) Amendments in 1996 requiring that EPA screen pesticide chemicals for their potential to produce effects similar to those produced by the female hormones (estrogen) in humans and giving EPA the authority to screen certain other chemicals and to include other endocrine effects. Based on recommendations from an Advisory Committee, EPA has expanded the EDSP to include male hormones (androgens) and the thyroid system, and to include effects on fish and wildlife.

'Environmental causes of cancer: endocrine disruptors as carcinogens' published in 2010 by Nature Reviews Endocrinology emphasizes:

Environmental endocrine disrupting chemicals (EDCs), including pesticides and industrial chemicals, have been and are released into the environment producing deleterious effects on wildlife and humans. The effects observed in animal models after exposure during organogenesis correlate positively with an increased incidence of malformations of the male genital tract and of neoplasms and with the decreased sperm quality observed in European and US populations. Exposure to EDCs generates additional effects, such as alterations in male and female reproduction and changes in neuroendocrinology, behavior, metabolism and obesity, prostate cancer and thyroid and cardiovascular endocrinology. This Review highlights the carcinogenic properties of EDCs, with a special focus on bisphenol A. However, humans and wildlife are exposed to a mixture of EDCs that act contextually. To explain this mindboggling complexity will require the design of novel experimental approaches that integrate the effects of different doses of structurally different chemicals that act at different ages on different target tissues.

Vandenberg LN et al.（2012）reveals: For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. ... We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.

The EPA on April 14, 2009 announced the preliminary list for the Endocrine Disruptor Screening Program, which included glyphosate.

Oversea 17 studies find evidence that glyphosate is an EDC!

1）Yousef MI et al. (1995): Pesticide treatment resulted in a decline in body weight, libido, ejaculate volume, sperm concentration, semen initial fructose and semen osmolality. This was accompanied with increases in the abnormal and dead sperm and semen methylene blue reduction time. The hazardous effect of these pesticides on semen quality continued during the recovery period, and was dose-dependent. These effects on sperm quality may be due to the direct cytotoxic effects of these pesticides on spermatogenesis and/or indirectly via hypothalami-pituitary-testis axis which control the reproductive efficiency.

2) Walsh, L.P. et al.(2000): The pesticide Roundup inhibited dibutyryl [(Bu)(2)]cAMP-stimulated progesterone production in MA-10 cells without causing cellular toxicity. Roundup inhibited steroidogenesis by disrupting StAR protein expression, further demonstrating the susceptibility of StAR to environmental pollutants.

3) Marc J et al. (2002): In summary, Roundup affects cell cycle regulation by delaying activation of the CDK1/cyclin B complex, by synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/cyclin B regulator, our results question the safety of glyphosate and Roundup on human health.

4) Marc, J et al. (2004): At a concentration that efficiently impeded the cell cycle, formulated glyphosate inhibited the synthesis of DNA occurring in S phase of the cell cycle. The extent of the inhibition of DNA synthesis by formulated glyphosate was correlated with the effect on the cell cycle. We conclude that formulated glyphosate's effect on the cell cycle is exerted at the level of the DNA-response checkpoint of S phase. The resulting inhibition of CDK1/cyclin B Tyr 15 dephosphorylation leads to prevention of the G2/M transition and cell cycle progression.

5) Marc, J et al. (2004): Roundup Biovert induced cell cycle dysfunction. The threshold concentration for induction of cell cycle dysfunction was evaluated for each product and suggests high risk by inhalation for people in the vicinity of the pesticide handling sprayed at 500 to 4000 times higher dose than the cell-cycle adverse concentration.

6) Beuret CJ et al (2005): The present study has investigated the effects that 1% glyphosate oral exposure has on lipoperoxidation and antioxidant enzyme systems in the maternal serum and liver of pregnant rats and their term fetuses at 21 days of gestation. The results suggest that excessive lipid peroxidation induced with glyphosate ingestion leads to an overload of maternal and fetal antioxidant defense systems.

7) Richard S et al. (2005): We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation.

8) Oliveira AG et al. (2007): The exposure to the herbicide resulted in alterations in the structure of the testis and epididymal region as well as in the serum levels of testosterone and estradiol, with changes in the expression of androgen receptors restricted to the testis. The harmful effects were more conspicuous in the proximal efferent ductules and epididymal ducts, suggesting higher sensitivity of these segments among the male genital organs. The effects were mostly dose dependent, indicating that this herbicide may cause disorder in the morphophysiology of the male genital system of animals.

9) Dallegrave E et al. (2007):  The results showed that glyphosate-Roundup did not induce maternal toxicity but induced adverse reproductive effects on male offspring rats: a decrease in sperm number per epididymis tail and in daily sperm production during adulthood, an increase in the percentage of abnormal sperms and a dose-related decrease in the serum testosterone level at puberty, and signs of individual spermatid degeneration during both periods. There was only a vaginal canal-opening delay in the exposed female offspring. These findings suggest that in utero and lactational exposure to glyphosate-Roundup may induce significant adverse effects on the reproductive system of male Wistar rats at puberty and during adulthood.

10) Nora Benachour et al. (2009): We have evaluated the toxicity of four glyphosate (G)-based herbicides in Roundup (R) formulations, from 105 times dilutions, on three different human cell types. This dilution level is far below agricultural recommendations and corresponds to low levels of residues in food or feed. The formulations have been compared to G alone and with its main metabolite AMPA or with one known adjuvant of R formulations, POEA. HUVEC primary neonate umbilical cord vein cells have been tested with 293 embryonic kidney and JEG3 placental cell lines. All R formulations cause total cell death within 24 h, through an inhibition of the mitochondrial succinate dehydrogenase activity, and necrosis, by release of cytosolic adenylate kinase measuring membrane damage. They also induce apoptosis via activation of enzymatic caspases 3/7 activity. This is confirmed by characteristic DNA fragmentation, nuclear shrinkage (pyknosis), and nuclear fragmentation (karyorrhexis), which is demonstrated by DAPI in apoptotic round cells. G provokes only apoptosis, and HUVEC are 100 times more sensitive overall at this level. The deleterious effects are not proportional to G concentrations but rather depend on the nature of the adjuvants. AMPA and POEA separately and synergistically damage cell membranes like R but at different concentrations. Their mixtures are generally even more harmful with G. In conclusion, the R adjuvants like POEA change human cell permeability and amplify toxicity induced already by G, through apoptosis and necrosis. The real threshold of G toxicity must take into account the presence of adjuvants but also G metabolism and time-amplified effects or bioaccumulation. This should be discussed when analyzing the in vivo toxic actions of R. This work clearly confirms that the adjuvants in Roundup formulations are not inert. Moreover, the proprietary mixtures available on the market could cause cell damage and even death around residual levels to be expected, especially in food and feed derived from R formulation-treated crops.

11) Gasnier C et al. (2009): Glyphosate-based herbicides are the most widely used across the world; they are commercialized in different formulations. Their residues are frequent pollutants in the environment. In addition, these herbicides are spread on most eaten transgenic plants, modified to tolerate high levels of these compounds in their cells. Up to 400 ppm of their residues are accepted in some feed. We exposed human liver HepG2 cells, a well-known model to study xenobiotic toxicity, to four different formulations and to glyphosate, which is usually tested alone in chronic in vivo regulatory studies. We measured cytotoxicity with three assays (Alamar Blue, MTT, ToxiLight), plus genotoxicity (comet assay), anti-estrogenic (on ERalpha, ERbeta) and anti-androgenic effects (on AR) using gene reporter tests. We also checked androgen to estrogen conversion by aromatase activity and mRNA. All parameters were disrupted at sub-agricultural doses with all formulations within 24h. These effects were more dependent on the formulation than on the glyphosate concentration. First, we observed a human cell endocrine disruption from 0.5 ppm on the androgen receptor in MDA-MB453-kb2 cells for the most active formulation (R400), then from 2 ppm the transcriptional activities on both estrogen receptors were also inhibited on HepG2. Aromatase transcription and activity were disrupted from 10 ppm. Cytotoxic effects started at 10 ppm with Alamar Blue assay (the most sensitive), and DNA damages at 5 ppm. A real cell impact of glyphosate-based herbicides residues in food, feed or in the environment has thus to be considered, and their classifications as carcinogens/mutagens/reprotoxics is discussed.

12) Romano RM et al. (2010): These results suggest that commercial formulation of glyphosate is a potent endocrine disruptor in vivo, causing disturbances in the reproductive development of rats when the exposure was performed during the puberty period.

13) Jayawardene, U.A et al.(2010): Glyphosate recorded the highest percentage of malformation (69%) compared to other pesticides in 1.00 ppm concentration. Malformations observed were mainly in the spine, such as hunched back (kyphosis) and curvature (scoliosis), while edema and skin ulcers were also observed

14) Paganelli, A.et al. (2010): Xenopus laevis embryos were incubated with 1/5000 dilutions of a commercial GBH. The treated embryos were highly abnormal with marked alterations in cephalic and neural crest development and shortening of the anterior−posterior (A-P) axis. Alterations on neural crest markers were later correlated with deformities in the cranial cartilages at tadpole stages. Embryos injected with pure glyphosate showed very similar phenotypes. Moreover, GBH produced similar effects in chicken embryos, showing a gradual loss of rhombomere domains, reduction of the optic vesicles, and microcephaly. This suggests that glyphosate itself was responsible for the phenotypes observed, rather than a surfactant or other component of the commercial formulation. A reporter gene assay revealed that GBH treatment increased endogenous retinoic acid (RA) activity in Xenopus embryos and cotreatment with a RA antagonist rescued the teratogenic effects of the GBH. Therefore, we conclude that the phenotypes produced by GBH are mainly a consequence of the increase of endogenous retinoid activity.

15) Koller VJ (2012): Comparisons with results of earlier studies with lymphocytes and cells from internal organs indicate that epithelial cells are more susceptible to the cytotoxic and DNA-damaging properties of the herbicide and its formulation. Since we found genotoxic effects after short exposure to concentrations that correspond to a 450-fold dilution of spraying used in agriculture, our findings indicate that inhalation may cause DNA damage in exposed individuals.

16) R. Mesnagea (2013): Among them, POE-15 clearly appears to be the most toxic principle against human cells, even if others are not excluded. It begins to be active with negative dose-dependent effects on cellular respiration and membrane integrity between 1 and 3ppm, at environmental/occupational doses. We demonstrate in addition that POE-15 induces necrosis when its first micellization process occurs, by contrast to glyphosate which is known to promote endocrine disrupting effects after entering cells.

17) Thongprakaisang S (2013): Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study.

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