Journal Article Review Dr. Diana Marangu

Transcription

1 Journal Article Review Dr. Diana Marangu

2 Glyphosate in Roundup Glyphosate Tolerant Crop e.g. NK603

3

4

5 Background Mandatory chronic animal feeding studies for edible GMOs and formulated pesticides are not requested by authorities. Longstanding debate on the length of mammalian toxicity studies and frequency of metabolic analyses. Formulated Roundup has adjuvants & more representative of environmental pollution than glyphosate alone. Séralini GE et al. Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food Chem Toxicol Nov;50(11):

6 Objectives To determine the direct or indirect long term consequences of the genetic modification itself in Roundup tolerant maize (NK603), or due to the formulated Roundup mixture used on GMOs both NK603 maize and formulated Roundup mixture. Mortality, Anatomopathological observations and Biochemical analyses Protocol authorized by the French Ministries of Agriculture and Research

7 Methods - Plants 2 MAIZE VARIETIES: NK603 & nearest isogenic nontransgenic control (qpcr) 3 FIELDS Maize grown as Livestock Feed in Canada CONTROL NK603 NK603 + R ( 3 L/ha) Similar normal conditions, same location, spaced sufficiently to avoid cross-contamination Imported to France from Canada : Canadian Food Inspection Authority

8 Methods - Rats and Diets Ethical guidelines of animal experimentation (CEE 86/609) : France 11% 11% 11% 67% Sprague Dawley Rats 2 same sex rats per cage Similar conditions Followed up by vets Balanced Diet 33% of the diet Maize 11 or 22 or 33 % NK603 or 33% control Fed ad libitum R added in drinking water in rats fed with control maize

9 Sample Size: 200 Rats Good Practice Laboratory environment; according to OECD guidelines 100 MALES randomly assigned into 10 groups rats r] 1. 11% of the diet - NK % of the diet - NK % of the diet - NK % of the diet - NK603 + R 5. 22% of the diet - NK603 + R 6. 33% of the diet - NK603 + R 7. Normal + 0.1ppbR in tap water 8. Normal + 0.9%R [1/2MRL] 9. Normal + 0.5%R [1/2MAWD] 10.Normal maize [controls] 100 FEMALES randomly assigned into 10 groups 1. 11% of the diet - NK % of the diet - NK % of the diet - NK % of the diet - NK603 + R 5. 22% of the diet - NK603 + R 6. 33% of the diet - NK603 + R 7. Normal ppbR in tap water 8. Normal + 0.9%R [1/2MRL] 9. Normal + 0.5%R [1/2MAWD] 10.Normal maize [controls] MRL maximum residue level MAWD minimum agricultural working dilution

10 Biochemical Analyses & Anatomopathological Observations Sample Test Frequency Blood from the tail vein under short isoflurane anaesthesia [31 parameters] Hormones testosterone, estradiol Hematological WBCs, platelets, Hb, MCV Renal function tests: Na, K, Ca, Cl, PO 4, U, Cr Liver function tests: ALT, AST, Albumin, Globulin, Total Protein, Glucose, GGT, Cholesterol, Fibrinogen, PT, APTT Inflammatory marker: CRP [12 and 24 months] Before treatment and after 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 MONTHS Urine [16 parameters] Clinical Monitoring Organ retrieval Na, K, Ca, Cl, PO 4, ph, Clearance Careful observation and palpation of animals, recording of clinical signs, measurement of any tumors that may arise, food and water consumption, and individual BW 25% BW loss, tumor >25% BW, h gic bleeding/prostration [Brain, colon, heart, kidneys, liver, lungs, ovaries, spleen, testes, adrenals at least these 10 organs + Tumors] Weight, Hisology (H&E), Electron microscopy [kidney, liver & tumor] Same as above Twice weekly Sacrificed at the END OF 2 YEARS or according to ethical guidelines

11 1 Richard et al Differential effects of glyphosate and roundup on human placental cells and aromatase. Environ. Health Perspect. 113, Gasnier, et al Defined plant extracts can protect human cells against combined xenobiotic effects. J. Occup. Med. Toxicol. 6, 3. FORMULATED ROUNDUP Discussion Threshold effect pathological effects occur from low to high doses of R, not proportional to the dose of R. Mammary tumors - most deaths were in females; striking in R alone. R is a sex endocrine disruptor in vivo! 1. Disrupts aromatase which synthesizes estrogen 1 2. Interferes with estrogen & androgen receptors. 2

12 3 Baskaran et al Chemopreventive potential of ferulic acid in 7,12-dimethylbenz[a] anthracenei induced mammary carcinogenesis in Sprague-Dawley rats. Eur. J. Pharmacol. 4 Chang et al Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells. Eur. J. Clin. Invest. 36, Discussion PATHOLOGICAL EFFECTS SEEN EVEN IN NK603 MAIZE WITHOUT R. Modified EPSPS drive the amino acid biosynthesis in the shikimate pathway as well as 2 metabolites phenolic acids e.g. Caffeic & Ferrulic acid which were low! 1. Lower protective effects against carcinogenesis Modulate estrogen receptors and the estrogenic pathway. 4

13 Discussion 90 DAY TRIAL INADEQUATE the first large tumors occurred at around 4months (in humans this would translate to around 13-22yrs) of exposure in males and 7 months in females. EPIDEMIOLOGICAL STUDIES? No traceability or labeling of GMOs in USA.??Kenya NK603 and R cannot be regarded as safe as long as safety is not proven by further investigations.

14