THIRD WORLD NETWORK BIOSAFETY INFORMATION SERVICE
Dear Friends and Colleagues
Study Links Roundup and Non-Alcoholic Fatty Liver Disease in Rats
A new multiomic study has used cutting-edge profiling methods to describe the molecular composition of the livers of female rats fed with chronic ultra-low doses of the herbicide Roundup (glyphosate), thousands of times below what is permitted by regulators worldwide, over a 2-year period (Item 1). It found that the animals suffered from non-alcoholic fatty liver disease (NAFLD). This study is the first to show a causative link between an environmentally relevant level of Roundup consumption over the long-term and a serious disease (Item 2).
Protein composition profiling (“proteomics”) and small molecule metabolite biochemical profiling (“metabolomics”), which were used in this study, provided a definitive assessment of disease status. They confirmed that liver disease in rats resulted from chronic ultra-low dose Roundup exposure. This has potentially serious implications for human health.
This research is a follow-up to and supports the results of a previous study which found that rats given an extremely low, environmentally relevant dose of a commercial Roundup formulation via drinking water for 2 years had a higher incidence of liver and kidney damage compared to controls given plain drinking water.
The scientists call on regulators to reconsider the safety evaluation of glyphosate-based herbicides. Glyphosate is the most-widely used herbicide globally, and is also used in conjunction with herbicide-resistant GM crops.
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Item 1
MULTIOMICS REVEAL NON-ALCOHOLIC FATTY LIVER DISEASE IN RATS FOLLOWING CHRONIC EXPOSURE TO AN ULTRA-LOW DOSE OF ROUNDUP HERBICIDE
Robin Mesnage, , George Renney, , Gilles-Eric Séralini, , Malcolm Ward, and Michael N. Antoniou
Scientific Reports 7, Article number: 39328 (2017). doi:10.1038/srep39328
http://www.nature.com/articles/srep39328#content
Scientific Reports7, Article number: 39328 (2017). doi:10.1038/srep39328
http://www.nature.com/articles/srep39328#content
Abstract
The impairment of liver function by low environmentally relevant doses of glyphosate-based herbicides (GBH) is still a debatable and unresolved matter. Previously we have shown that rats administered for 2 years with 0.1 ppb (50ng/L glyphosate equivalent dilution; 4ng/kg body weight/day daily intake) of a Roundup GBH formulation showed signs of enhanced liver injury as indicated by anatomorphological, blood/urine biochemical changes and transcriptome profiling. Here we present a multiomic study combining metabolome and proteome liver analyses to obtain further insight into the Roundup-induced pathology. Proteins significantly disturbed (214 out of 1906 detected, q<0.05) were involved in organonitrogen metabolism and fatty acid β-oxidation. Proteome disturbances reflected peroxisomal proliferation, steatosis and necrosis. The metabolome analysis (55 metabolites altered out of 673 detected, p<0.05) confirmed lipotoxic conditions and oxidative stress by showing an activation of glutathione and ascorbate free radical scavenger systems. Additionally, we found metabolite alterations associated with hallmarks of hepatotoxicity such as γ-glutamyl dipeptides, acylcarnitines, and proline derivatives. Overall, metabolome and proteome disturbances showed a substantial overlap with biomarkers of non-alcoholic fatty liver disease and its progression to steatohepatosis and thus confirm liver functional dysfunction resulting from chronic ultra-low dose GBH exposure.
Item 2
ROUNDUP CAUSES NON-ALCOHOLIC FATTY LIVER DISEASE AT VERY LOW DOSES
http://www.gmwatch.org/news/archive/17402-roundup-causes-non-alcoholic-fatty-liver-disease-at-very-low-doses
The weedkiller Roundup causes non-alcoholic fatty liver disease at very low doses permitted by regulators worldwide, a new peer-reviewed study shows. The study is the first ever to show a causative link between consumption of Roundup at a real-world environmentally relevant dose and a serious disease.
The new peer-reviewed study, led by Dr Michael Antoniou at King’s College London, used cutting-edge profiling methods to describe the molecular composition of the livers of female rats fed an extremely low dose of Roundup weedkiller, which is based on the chemical glyphosate, over a 2-year period.
The dose of glyphosate from the Roundup administered was thousands of times below what is permitted by regulators worldwide.
The study revealed that these animals suffered from non-alcoholic fatty liver disease (NAFLD).
Dr Antoniou said: “The findings of our study are very worrying as they demonstrate for the first time a causative link between an environmentally relevant level of Roundup consumption over the long-term and a serious disease – namely non-alcoholic fatty liver disease.
“Our results also suggest that regulators should reconsider the safety evaluation of glyphosate-based herbicides.”
Potentially serious implications for human health
The new results demonstrate that long-term consumption of an ultra-low dose of Roundup at a glyphosate daily intake level of only 4 nanograms per kilogram of bodyweight per day, which is 75,000 times below EU and 437,500 below US permitted levels, results in NAFLD.
Regulators worldwide accept toxicity studies in rats as indicators of human health risks. So the results of this latest study have serious implications for human health.
NAFLD currently affects 25% of the US population and similar numbers of Europeans. Risk factors include being overweight or obese, having diabetes, or having high cholesterol or high triglycerides (a constituent of body fat) in the blood. However, some people develop NAFLD even if they do not have any of these known risk factors. The new study raises the question of whether exposure to Roundup is a hitherto unrecognized risk factor.
Symptoms of NAFLD include fatigue, weakness, weight loss, loss of appetite, nausea, abdominal pain, spider-like blood vessels, yellowing of the skin and eyes (jaundice), itching, fluid build-up and swelling of the legs and abdomen, and mental confusion.
NAFLD can progress to the more serious condition, non-alcoholic steatohepatitis (NASH). NASH causes the liver to swell and become damaged.
Most people with NASH are between the ages of 40 and 60 years. It is more common in women than in men. NASH is one of the leading causes of cirrhosis in adults in the United States. Up to 25% of adults with NASH may have cirrhosis.
Background to the study
The rat body tissues used in this analysis were obtained from a previous study led by Prof Gilles-Eric Séralini of the University of Caen, France. In this original investigation, rats were given an extremely low, environmentally relevant dose of a commercial Roundup formulation at 0.1ppb (parts per billion)/50ppt (parts per trillion) glyphosate via drinking water for 2 years. Daily intake of glyphosate from the Roundup was 4 nanograms per kilogram of body weight per day, which is thousands of times below what is permitted by regulators.
Analysis of the organs and blood/urine biochemical levels in the original study by Prof Séralini suggested a higher incidence of liver and kidney damage in the animals given Roundup compared to controls given plain drinking water.
Dr Antoniou’s group has conducted distinct followup investigations on the rat body tissues from this ultra-low-dose Roundup treatment group, using in-depth molecular analytical procedures and statistical analytical methods that are appropriate for this type of research.
In the first followup investigation, a transcriptomics (gene function profile) analysis was performed on the livers and kidneys from the female animals. The results strongly supported the observations made at an anatomical (organ) and blood/urine biochemical level in the Séralini study – namely that the organs of the animals given Roundup suffered more structural and functional damage than the controls.
The transcriptomics results indicated an increased incidence of fibrosis (scarring), necrosis (areas of dead tissue), phospholipidosis (disturbed fat metabolism) and damage to mitochondria (the centres of respiration in cells) in the Roundup-fed animals.
However, although transcriptomics analysis is able to predict health or disease status of an organ, it does not provide definitive proof of harm. This is mainly because it does not give a direct measure of the actual biochemistry of the organ under study. Also, alterations in gene function resulting from a test do not always result in the types of changes in physical composition that could lead to disease.
Definitive confirmation of liver disease from low dose of Roundup
In the new study the researchers undertook a followup protein composition profile (“proteomics”) and small molecule metabolite biochemical profile (“metabolomics”) investigation of the same liver samples to confirm the prediction of disease suggested by the transcriptomics gene expression profile analysis. As the proteomics and metabolomics directly measure the actual composition of the organ, these analytical methods provide a definitive assessment of its health or disease status.
Overall, metabolomics and proteomics disturbances showed a substantial overlap with biochemical hallmarks of NAFLD and its progression to steatohepatosis (serious fatty liver disease). Therefore they definitively confirm that serious liver disease has resulted from chronic ultra-low dose Roundup exposure.
The findings in detail
Proteins significantly disturbed (214 out of 1906 detected), as shown by the proteomics profiling, reflected a type of cell damage from reactive oxygen (peroxisomal proliferation), steatosis (serious fatty liver disease) and necrosis (areas of dead tissue).
The metabolomics analysis (55 metabolites altered out of 673 detected) confirmed lipotoxic (excess fatty tissue) conditions and oxidative stress. Metabolite alterations were also associated with hallmarks of serious liver toxicity.
The new study
Mesnage R, Renney G, Séralini GE, Ward M, Antoniou MN. Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide. Scientific Reports, 2016; 6subsection_299328.