Glyphosate Hazard and Risk Assessment: A Comparison of the Approaches of Two International Agencies
|
|
- Harry Lambert
- 6 years ago
- Views:
Transcription
1 Glyphosate Hazard and Risk Assessment: A Comparison of the Approaches of Two International Agencies David A. Eastmond Environmental Toxicology Graduate Program University of California, Riverside
2 Glyphosate Introduction! The most widely used pesticide in the world 826 million kg in 2014! It can be used as an acid or as various salts, in a range of formulation products. It is present in ~750 products in the United States and has been registered for use since 1974.! It targets a enzymatic pathway specific to plants and some bacteria and has historically been considered extremely safe.! It has been caught up in the controversy over genetically modified crops as a common genetic modification is to make the crops resistant to glyphosate. This allows glyphosate to be used to kill many types of weeds without affecting the crop.
3 Glyphosate Introduction (cont.)! In 2015, WHO s International Agency for Research on Cancer conducted a hazard assessment for glyphosate and concluded that it was a probable human carcinogen (Group 2A). Its conclusion was based on limited evidence of cancer in humans (NHL), sufficient evidence in animals, and evidence of genotoxicity and oxidative stress.
4 Photo credit: Global Justice Now
5 Glyphosate Introduction (cont.)! In May 2016, the WHO s Joint Meeting on Pesticide Residues performed a risk assessment on glyphosate and concluded that through the dietary route of exposure, the genotoxic and carcinogenic risks of glyphosate were minimal.! The goal of this presentation is to explain why these two groups could result in seemingly different conclusions.
6 Glyphosate structure Glycine
7 Definitions! Hazard Identification - A determination of the ability of a agent to cause an adverse effect.! Risk Assessment - A characterization of the likelihood or probability that a risk will occur under specific exposure conditions.
8 A Key Aspect of the JMPR Risk Assessment Determine whether glyphosate residues present in the diet pose a genotoxic and/or carcinogenic risk
9 Key Acceptability & Weighting Considerations for Genotoxicity Data! JMPR accepted both published and unpublished (primarily guideline) studies. [IARC only accepted publicly available and published studies.]! JMPR considerations for study weighting - More weight given to higher quality studies & those in validated or well established models - More weight given to in vivo studies than in vitro studies - More weight given to studies in phylogenetically close species (mammals) than in distant species (earthworms, Drosophila, frogs, fish, caiman, etc.)
10 Key Acceptability & Weighting Considerations! JMPR weighting considerations (continued) - More weight given to endpoints considered to be more serious (mutation, chromosome alterations) than to less serious and transient endpoints (DNA strand breaks, SCEs, etc.) - More weight given to studies conducted by more relevant, physiological routes of exposure (e.g. oral) than by non-physiological routes (e.g. intraperitoneal injection).
11 Summary of Genotoxicity Studies Evaluated JMPR IARC Primary Studies Evaluated Human biomonitoring 6 5 In vivo mammals In vitro mammalian cells Bacteria 40 6 Phylogenetically distant in vivo Phylogenetically distant in vitro 12 1 Metabolites in vivo (mammals) 5 1 Metabolites in vitro 16 3
12 Summary of Genotoxicity Studies Evaluated JMPR % Positive IARC Primary Studies Evaluated % Positive Human biomonitoring In vivo mammals In vitro mammalian cells Bacteria Phylogenetically distant in vivo Phylogenetically distant in vitro Metabolites in vivo (mammals) Metabolites in vitro
13 Bacterial Studies JMPR # Positive IARC # Positive Total Bacterial Studies Non standard, coexposures, etc Standard - Ames test or rec test Conclusion: Glyphosate is non-mutagenic and non-genotoxic in standard bacterial mutagenicity tests
14 In Vivo Studies in Mammals JMPR # Positive IARC # Positive Total Mammalian Studies Intraperitoneal administration Oral administration Conclusion: Glyphosate is inactive in vivo in standard mammalian genotoxicity tests when administered by the oral route
15 Human Biomonitoring Studies! Key Study by Bolognesi et al. (2009): Frequency of micronuclei in blood lymphocytes was measured in 3 communities in Columbia before, several days after, and 4 months after glyphosate spraying occurred.! Significant increases in MN were reported in the samples collected shortly after spraying as compared with the pre-spraying samples. - MN frequency issues reference/control frequencies were unusually low and frequencies among the exposed fell at the middle of the normal range. - Methodological concerns repeated measures? - Increases did not correlate with application rates
16 Human Biomonitoring Studies (cont.) - Those reporting exposure did not differ from those reporting no exposure - Authors stated that damage was small and transient, not possible to assign causality to the increases, of low biological relevance, and suggested exposure to other genotoxic agents. - JMPR considered these results to be equivocal whereas IARC considered them to be highly significant.
17 JMPR Genotoxicity Summary Studies Evaluated Human biomonitoring In vivo mammals In vitro mammalian cells Bacteria Phylogenetically distant in vivo Phylogenetically distant in vitro Result Equivocal Mixed, largely negative Mixed, many positive Negative Mixed, largely positive Mixed, largely positive
18 After Applying Weighting Criteria Studies Evaluated Result Quality Human biomonitoring Equivocal Medium In vivo mammals (oral route) Negative High to medium In vitro mammalian cells Mixed, many positive Medium to poor Bacteria Negative High to medium Phylogenetically distant in vivo Mixed, largely positive Medium to poor Phylogenetically distant in vitro Mixed, largely positive Medium to poor
19 Other Mechanistic Considerations! Negative for structural alerts for chromosomal damage, genotoxicity, mutagenicity and carcinogenicity using Derek computer program (Kier and Kirkland, 2013).! Only positive in 21 of 620 screening assays for biological activity in PubChem database. Positive responses were primarily related to its mechanism of action in plants and bacteria. At the concentrations tested, it had few off target cellular and molecular effects.! There is little evidence that glyphosate significantly affects the immune system, a key characteristic of agents that cause NHL in humans.
20 JMPR Genotoxicity Conclusions JMPR: The overall weight of evidence indicates that administration of glyphosate and its formulation products at doses as high as 2000 mg/kg body weight by the oral route, the route most relevant to human dietary exposure, was not associated with genotoxic effects in an overwhelming majority of studies conducted in mammals, a model considered to be appropriate for assessing genotoxic risks to humans.
21 IARC Genotoxicity Conclusions IARC concluded that There is strong evidence that exposure to glyphosate or glyphosate-based formulations is genotoxic based on studies in humans in vitro and studies in experimental animals. One study in several communities in individuals exposed to glyphosate-based formulations also found chromosomal damage in blood cells; in this study, markers of chromosomal damage (micronucleus formation) were significantly greater after exposure than before exposure in the same individuals.
22 Cancer Epidemiology! JMPR: Overall, there is some evidence of a positive association between glyphosate exposure and risk of NHL from the case control studies and the overall meta-analysis. However, it is notable that the AHS, which is the only cohort study and is large and of high quality, found no evidence of association at any exposure level.! The conclusions by JMPR and IARC were similar.
23 Animal Cancer Bioassays The original studies for 20 chronic rodent bioassays were available to the JMPR. 3 were considered inadequate for further evaluation. Consequently,10 rat studies and 7 mouse studies were reviewed. IARC evaluated 5 rat studies and 2 mouse studies. For most, it did not have access to the original reports but based its conclusions on a re-evaluation of data presented in earlier JMPR and EPA reports. It concluded that glyphosate was carcinogenic largely based on an increase in rare kidney tumors in 1 mouse study and an increase in pancreatic tumors in 2 rat studies.
24 Statistical Considerations Multiple Comparisons! In a single sex and species combination of a standard rodent cancer bioassay, histopathology may be performed on 40 individual tissues.! Assuming that a control and 3 treatment doses were administered and the statistical analyses consisted of a trend test and pair-wise comparisons between the control and each dose for each tissue, a total of 160 separate statistical tests would be performed.! Using a p 0.05, one can estimate that 8 of these would be positive by random chance alone.
25 Sensitivity of the Trend Test Number of Number of Dose (ppm) animals tumors , , Trend test: p = (1-tailed)
26 Biological Significance Considerations! Dose response (trend test)! Significant increase of individual treatments (pairwise comparison)! Historical control frequencies! Magnitude of increase! Consistency/reproducibility! Other information relevance of doses and target site, preneoplastic lesions, decreased latency, etc.! Biological plausibility - Genotoxicity, SAR, structural alerts, PubChem results
27 Rat Chronic Bioassay Results! An increased incidence in tumors was observed in one or, in one case, two of the 10 studies in rats. Increases were seen in: - interstitial cell tumors of the testes (1 study) - pancreatic islet cell adenoma (1 study) - thyroid C-cell tumors (1 study) - skin keratoma (2 studies, males only)! The Group concluded that these findings were incidental, in part, because studies that used appreciably higher doses did not find any excess. For the skin keratomas, for one study there was no dose response relationship; and in the other study, only the test for trend was statistically significant, not the pairwise test at any dose.
28 Mouse Chronic Bioassay Results! Suggestive increases in tumor incidences were observed in some of the mouse studies. Two tumor types of particular note were: - Lymphomas (positive trend in 3 studies; negative trend in 1 (NS); and possible increase in another)! The increased trends were significant (p 0.05) by the trend test but not in pairwise comparisons. In one case, the trend test appeared to be driven by unusually low control incidence. The incidences in the high dose animals were typically well within the normal control range for lymphomas. Control frequencies for this type of tumor show considerable variability.
29 Mouse Chronic Bioassay Results! Suggestive increases in tumor incidences were observed in mouse kidney adenomas, an uncommon tumor in mice. - Kidney adenomas (positive trend in 4 studies)! Again, the increases were significant by the trend test but not in pairwise comparisons. For the adenomas, it was noted that the increases were marginal and the significance was driven by the highest dose, which for most studies was well above the currently recommended limit dose. Follow-up evaluations of two studies by two expert pathology groups previously had concluded that the increases were not glyphosate-related. Note: The tumor increases decreased in magnitude with the rescoring of the slides.
30 JMPR Chronic Bioassay Conclusions! The Meeting concluded that glyphosate is not carcinogenic in rats but could not exclude the possibility that it is carcinogenic in mice at very high doses. The doses administered to the mice were up to 50,000 ppm in the diet (approx mg/kg in males and 8700 mg/kg in females).
31 JMPR Cancer Conclusions In view of the absence of carcinogenic potential in rodents at human-relevant doses and the absence of genotoxicity by the oral route in mammals, and considering the epidemiological evidence from occupational exposures, the Meeting concluded that glyphosate is unlikely to pose a carcinogenic risk to humans from exposure through the diet.
32 JMPR Overall Conclusions! The Meeting reaffirmed the group ADI for the sum of glyphosate, AMPA, N-acetyl-glyphosate and N- acetyl-ampa of 0 1 mg/kg bw on the basis of the NOAEL of 100 mg/kg bw per day for effects on the salivary gland in a long-term study of toxicity and carcinogenicity in rats and application of a safety factor of 100.
33 Overall Conclusions! In summary, the glyphosate toxicology and epidemiology data set is a complex one that required considerable expertise and scientific judgment to evaluate.! Decisions about whether glyphosate is genotoxic or carcinogenic were heavily dependent upon the information available, the evaluation criteria used, and the weights given to various types of evidence.
34 Overall Conclusions! The conclusions reached by IARC are reflective of the data to which it had access, and are generally consistent with its criteria for classifying carcinogens.! The JMPR had access to a larger data set. Its conclusions were also reflective of the data to which it had access, and were consistent with its specific emphasis on dietary exposure to pesticide residues. Its results indicate that the genotoxic and carcinogenic risks from glyphosate residues in the diet are very low.
35 Acknowledgments! JMPR Expert Group - Boobis, Busschers, Cerniglia, Cordier, Eastmond, Hartwig, Jacobs, Lenters, MacLachlan, Moretto, O Mullane, Piersma, Shah, Smith, Tice, Toledano, Yoshida and Zarn Foyer of WHO building in Geneva! JMPR Secretariat - Philippe Verger - Angelika Tritscher
EU assessment of the carcinogenic potential of glyphosate
EU assessment of the carcinogenic potential of glyphosate FIFRA Scientific Advisory Panel on Carcinogenic Potential of Glyphosate, 13-16 December 2016 Danièle Court Marques Pesticides Unit TABLE OF CONTENT
More informationThe Carcinogenicity of Glyphosate Kate Z. Guyton, PhD DABT
The Carcinogenicity of Glyphosate Kate Z. Guyton, PhD DABT Conflict of Interest Statement I declare no financial interests related to the subject matter of my presentation. IARC Evaluation of Glyphosate
More informationGlyphosate: Get the Facts NEPPSC
Glyphosate: Get the Facts NEPPSC January 8, 2019 Timothy Pastoor, PhD, DABT, ATS Pastoor Science Communications, LLC I am not affiliated with Monsanto, Bayer or any entity with interests in glyphosate
More informationGenotoxicity Testing Strategies: application of the EFSA SC opinion to different legal frameworks in the food and feed area
Genotoxicity Testing Strategies: application of the EFSA SC opinion to different legal frameworks in the food and feed area Juan Manuel Parra Morte. Pesticides Unit. EFSA. 19th Annual Conference of the
More informationHazard Assessment of Glyphosate Carcinogenicity and Reproductive Toxicity
Hazard Assessment of Glyphosate Carcinogenicity and Reproductive Toxicity Mark Martens, PhD, ERT on behalf of the Glyphosate Task Force (GTF) RAC Meeting, Helsinki December 7, 2016 Content Genotoxicity
More informationGlyphosate Cancer Risks and Failures of the Pesticide Regulatory Process
Glyphosate Cancer Risks and Failures of the Pesticide Regulatory Process Christopher J. Portier, Ph.D. 11 October, 2017 Brussels, Belgium Disclosures The opinions expressed here and the analyses done to
More information5.15 HEXYTHIAZOX (176)
Hexythiazox 225 5.15 HEXYTHIAZOX (176) TOXICOLOGY Hexythiazox is the ISO approved name for (trans-5-(4-chlorophenyl)-n-cyclohexyl-4-methyl-2-oxo- 3-thiazolidine-carboxamide (CAS No. 78587-05-0). Hexythiazox
More information5.36 THIOPHANATE-METHYL (077)
391 5.36 THIOPHANATE-METHYL (077) TOXICOLOGY is the International Organization for Standardization (ISO) approved common name for dimethyl 4,4 -(o-phenylene)bis(3-thioallophanate) (International Union
More informationCarcinogenicity of Glyphosate The IARC Monographs. Dana Loomis PhD Deputy Head Monographs Programme
Carcinogenicity of Glyphosate The IARC Monographs Dana Loomis PhD Deputy Head Monographs Programme Overview What are the IARC Monographs? How are IARC Monograph evaluations done? IARC evaluation of pesticides
More information5.17 PENTHIOPYRAD (253)
Penthiopyrad 189 5.17 PENTHIOPYRAD (253) TOXICOLOGY Penthiopyrad is the International Organization for Standardization (ISO) approved name for N-[2- (1,3-dimethylbutyl)-3-thienyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide
More informationDithianon DITHIANON (180)
Dithianon 201 5.11 DITHIANON (180) TOXICOLOGY Dithianon (C 14 H 4 N 2 O 2 S 2 ) is the International Organization for Standardization (ISO) approved name for 5,10-dihydro-5,10-dioxonaphtho[2,3-b]-1,4-dithiine-2,3-dicarbonitrile
More informationPart 2. Chemical and physical aspects
Part 2. Chemical and physical aspects 12. Chemical and physical aspects: introduction 12.1 Background information used The assessment of the toxicity of drinking-water contaminants has been made on the
More information5.3 AZINPHOS METHYL (002)
5.3 AZINPHOS METHYL (002) TOXICOLOGY Azinphos-methyl is the ISO approved common name for S-3,4-dihydro-4-oxo-1,2,3-benzotriazin-3- ylmethyl O,O-dimethyl phosphorodithioate (IUPAC) or O,O-dimethyl S-[(4-oxo-1,2,3-benzotriazin-
More informationCycloxydim CYCLOXYDIM (179)
Cycloxydim 125 5.9 CYCLOXYDIM (179) TOXICOLOGY Cycloxydim is the ISO approved name for (5RS)-2-[(EZ)-1-(ethoxyimino)butyl]-3-hydroxy-5-[(3RS)- thian-3-yl]cyclohex-2-en-1-one (IUPAC). The CAS chemical name
More information5. Summary of Data Reported and Evaluation
5. Summary of Data Reported and Evaluation 5.1 Exposure data Static electric and magnetic fields arise from both natural and man-made sources, whereas electric and magnetic fields in the extremely low-frequency
More informationExplanatory note. On an opinion proposing harmonised classification and labelling at EU level of. glyphosate (ISO); N-(phosphonomethyl)glycine
Explanatory note On an opinion proposing harmonised classification and labelling at EU level of glyphosate (ISO); N-(phosphonomethyl)glycine EC Number: 213-997-4 CAS Number: 1071-83-6 This note has been
More informationGenotoxicity of formaldehyde in vitro and in vivo. Günter Speit
Genotoxicity of formaldehyde in vitro and in vivo Günter Speit Universität Ulm Institut für Humangenetik D-89069 Ulm (Germany) guenter.speit@uni-ulm.de CEFIC-2012 Günter Speit 1 Genotoxicity of formaldehyde
More informationVICH GL23: Studies to evaluate the safety of residues of veterinary drugs in human food: genotoxicity testing
6 November 2014 EMA/CVMP/VICH/526/2000 Committee for Medicinal Products for Veterinary Use (CVMP) VICH GL23: Studies to evaluate the safety of residues of veterinary drugs in human food: genotoxicity testing
More informationGlyphosate and Cancer Risk. Jeffrey Jenkins, Ph.D. Department of Environmental and Molecular Toxicology Oregon State University
Glyphosate and Cancer Risk Jeffrey Jenkins, Ph.D. Department of Environmental and Molecular Toxicology Oregon State University Cancer and Human Health Cancer is considered the most severe health condition
More informationGlyphosate and Cancer Buying Science
Glyphosate and Cancer Buying Science Glyphosate and Cancer Buying Science Quality? Glyphosate and Cancer Buying Science Quality? Influence? Glyphosate and Cancer Buying Science Quality? Influence? BfR
More informationCase 3:16-md VC Document Filed 10/27/17 Page 1 of 176 EXHIBIT 38
Case 3:16-md-02741-VC Document 649-8 Filed 10/27/17 Page 1 of 176 EXHIBIT 38 Case 3:16-md-02741-VC Document 649-8 Filed 10/27/17 Page 2 of 176 UNITED STATES DISTRICT COURT NORTHERN DISTRICT OF CALIFORNIA
More informationDISCUSSION GROUP 3. Mechanism of carcinogenicity. EFSA Scientific Colloquium on Acrylamide carcinogenicity, 22/23 May
DISCUSSION GROUP 3 Mechanism of carcinogenicity EFSA Scientific Colloquium on Acrylamide carcinogenicity, 22/23 May 2008 1 1. Review the recent evidence for the mutagenicity and genotoxicity of acrylamide
More informationDose and Response for Chemicals
Dose and Response for Chemicals 5 5 DOSE AND RESPONSE FOR CHEMICALS All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy. Paracelsus, 16th
More informationMethodologies for development of human health criteria and values for the lake Erie drainage basin.
3745-1-42 Methodologies for development of human health criteria and values for the lake Erie drainage basin. [Comment: For dates of non-regulatory government publications, publications of recognized organizations
More informationThe carcinogenicity of benzene. The IARC Monograph Vol 120. Kurt Straif, MD MPH PhD. PSA, Stavanger, 25 October 2018
The carcinogenicity of benzene. The IARC Monograph Vol 120 Kurt Straif, MD MPH PhD PSA, Stavanger, 25 October 2018 The encyclopaedia of The IARC Monographs evaluate Chemicals Complex mixtures Occupational
More informationPesticides used for vector control in drinking-water sourcesand containers.
12.126 Pesticides used for vector control in drinking-water sourcesand containers. In setting local guidelines or standards in the context of local storage practices and realistic insecticide application
More informationECHA Committee for Risk Assessment: Evaluation of the Classification and Labelling of Glyphosate
ECHA Committee for Risk Assessment: Evaluation of the Classification and Labelling of Glyphosate Tim Bowmer, Committee Chairman Ari Karjalainen, Dossier Manager for Glyphosate 10 May 2017 1 Established
More informationAddendum to the 12th Report on Carcinogens
Addendum to the 12th Report on Carcinogens Published by the U.S. Department of Health and Human Services, National Toxicology Program The twelfth edition of the National Toxicology Program (NTP) Report
More informationACRYLAMIDE - EU Summary of Activities
6.1 In vivo DNA damaging effects of acrylamide in rats. France / French Food Safety Agency (AFSSA) C ( C December 2003 DNA damage of acrylamide in the main organs of rats will be studied using the in vivo
More informationINITIAL STATEMENT OF REASONS TITLE 27, CALIFORNIA CODE OF REGULATIONS
INITIAL STATEMENT OF REASONS TITLE 27, CALIFORNIA CODE OF REGULATIONS PROPOSED AMENDMENT TO: SECTION 25705(b) SPECIFIC REGULATORY LEVELS POSING NO SIGNIFICANT RISK GLYPHOSATE SAFE DRINKING WATER AND TOXIC
More informationGLYPHOSATE (addendum)
GLYPHSATE (addendum) First draft prepared by Rudolf Pfeil 1 and Vicki Dellarco 2 1 Toxicology of Pesticides and Biocides, Federal Institute for Risk Assessment, Berlin, Germany 2 ffice of Pesticide Programs,
More informationIncorporating Computational Approaches into Safety Assessment
Incorporating Computational Approaches into Safety Assessment Kristi Muldoon Jacobs, Ph.D. Supervisory Toxicologist, DFCN, Office of Food Additive Safety Director (Acting), RIS, Office of Dietary Supplement
More informationCOMMITTEE FOR VETERINARY MEDICINAL PRODUCTS
The European Agency for the Evaluation of Medicinal Products Veterinary Medicines Evaluation Unit EMEA/MRL/452/98-FINAL June 1998 COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS NITROXINIL SUMMARY REPORT 1.
More informationMaria João Silva H. Louro 1, T. Borges 2, J. Lavinha 1, J.M. Albuquerque 1
Maria João Silva H. Louro 1, T. Borges 2, J. Lavinha 1, J.M. Albuquerque 1 1 National Institute of Health Dr. Ricardo Jorge 2 General-Directorate of Health, Lisbon, Portugal Venice.,10-03-2015 The number
More informationMANGANESE & HEALTH: A BALANCE OF STORIES
MANGANESE & HEALTH: A BALANCE OF STORIES November 2014 1 Overview 2. Analysis of Literature on Carcinogenicity & Mutagenicity 1. Uses of inorganic Mn substances 3. Research to better understand Carcinogenicity
More informationA review of human carcinogens -Part F: Chemical agents and related occupations
A review of human carcinogens -Part F: Chemical agents and related occupations In October 2009, 23 scientists from 6 countries met at the International Agency for Research on Cancer (IARC) to re-assess
More informationN-Methylneodecanamide (MNDA)
United States Prevention, Pesticides EPA-730-F-99-008 Environmental Protection And Toxic Substances July 1999 Agency (7505C) New Pesticide Fact Sheet Description of the Chemical N-Methylneodecanamide (MNDA)
More informationA Weight of Evidence Approach to Cancer Assessment. Alan R Boobis Imperial College London
A Weight of Evidence Approach to Cancer Assessment Alan R Boobis Imperial College London a.boobis@imperial.ac.uk Disclosure Statement Member of Board of Trustees of ILSI, Board of Directors of ILSI Europe
More informationRenewal Assessment Report
Renewal Assessment Report 31 August 2015 Glyphosate Addendum 1 to RAR Assessment of IARC Monographs Volume 112 (2015): Glyphosate RMS: Germany - i - Glyphosate Version history 31 August 2015 Version history
More informationDIBROMOACETONITRILE. 1. Exposure Data
DIBROMOACETONITRILE Data were last evaluated in IARC (1991). 1. Exposure Data 1.1 Chemical and physical data 1.1.1 Nomenclature Chem. Abstr. Serv. Reg. No.: 3252-43-5 Chem. Abstr. Name: Dibromoacetonitrile
More informationCaptan (Pesticides) Summary. Risk assessment report. Food Safety Commission of Japan. Conclusion in Brief
2017 Food Safety Commission, Cabinet Office, Government of Japan doi: 10.14252/foodsafetyfscj.2017003s Food Safety 2017; Vol. 5, No. 2, 61 66 Risk assessment report Captan (Pesticides) Summary Food Safety
More informationDichlorvos DICHLORVOS (025)
Dichlorvos 63 5.7 DICHLORVOS (025) TOXICOLOGY Dichlorvos is the International Organization for Standardization (ISO) approved common name for 2,2-dichlorovinyl dimethyl phosphate (International Union of
More informationPesticide Product Labels What the label says.and Why. Dr. Jeff Birk BASF Corporation Regulatory Manager
Pesticide Product Labels What the label says.and Why Dr. Jeff Birk BASF Corporation Regulatory Manager Regulation of Pesticides The pesticide industry is regulated by the USEPA. The pesticide industry
More informationCOMMITTEE FOR VETERINARY MEDICINAL PRODUCTS
The European Agency for the Evaluation of Medicinal Products Veterinary Medicines Evaluation Unit EMEA/MRL/114/96-FINAL June 1996 COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS EPRINOMECTIN SUMMARY REPORT
More informationRadiofrequency Radiation
Radiofrequency Radiation A Possible Human Carcinogen? Ron Melnick Retired Toxicologist NTP/NIEHS Expert Forum: Wireless Radiation and Human Health Hebrew University Medical School January 23-26, 2017 IARC
More informationRecent Results from the IARC Monographs: Carcinogenicity of Consuming Red & Processed Meat, Coffee and Very Hot Beverages
Recent Results from the IARC Monographs: Carcinogenicity of Consuming Red & Processed Meat, Coffee and Very Hot Beverages Dana Loomis, PhD & Kurt Straif MD, PhD Conflict of Interest Statement I declare
More informationCOMMITTEE FOR VETERINARY MEDICINAL PRODUCTS
The European Agency for the Evaluation of Medicinal Products Veterinary Medicines Evaluation Unit EMEA/MRL/527/98-FINAL January 1999 COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS AZAMETHIPHOS SUMMARY REPORT
More information5.24 TRIAZOLE FUNGICIDE METABOLITES
Triazole metabolites 355 5.24 TRIAZOLE FUNGICIDE METABOLITES TOXICOLOGY 1,2,4-Triazole, triazole alanine, triazole acetic acid, triazole pyruvic acid and triazole lactic acid are the common metabolites
More informationBAuA Federal Institute for Occupational Safety and Health Federal Office for Chemicals Friedrich-Henkel-Weg Dortmund, Germany
BAuA Federal Institute for Occupational Safety and Health Federal Office for Chemicals Friedrich-Henkel-Weg 1-25 44149 Dortmund, Germany RE: CLH Report for Glyphosate, EC Number 213-997-4 Dear Sirs, Below
More informationRevised Glyphosate Issue Paper: Evaluation of Carcinogenic Potential EPA s Office of Pesticide Programs December 12, 2017
Revised Glyphosate Issue Paper: Evaluation of Carcinogenic Potential EPA s Office of Pesticide Programs December 12, 2017 DP Barcode: D444689 TXR#: 0057688 Table of Contents List of Acronyms... 7 List
More informationLecture -2- Environmental Biotechnology
Lecture -2-1-General Bioassay in pollution Monitoring 1 1 Genotoxicity test At the early testing stages, the genotoxicity assays for predicting potential heritable germ cell damage are the same as used
More informationOverview of this case:
Overview of this case: Overview of this case: Overview of this case: Overview of this case: Not the first lawsuit: How the trial works: 1. Opening statements 2. Plaintiff s case 3. Monsanto s case 4. Rebuttal
More informationAspartame: the experimental evidence of cancer risks
Ramazzini Institute Cesare Maltoni Cancer Research Center Aspartame: the experimental evidence of cancer risks Dr. Morando Soffritti, MD International Scientific Conference on Early exposures and childhood
More informationCOMMITTEE FOR VETERINARY MEDICINAL PRODUCTS
The European Agency for the Evaluation of Medicinal Products Veterinary Medicines and Inspections EMEA/MRL/769/00-FINAL January 2001 COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS COUMAFOS SUMMARY REPORT
More informationOctober 31, Brief summaries of each expert s significant conclusions regarding the epidemiological and toxicological data are provided below.
VIA EMAIL Dear Members of the European Commission, Parliament and Member States, This letter contains a link to six expert scientist 1 reports explaining the connection between glyphosate-based formulations
More informationHYDROGEN PEROXIDE HUMAN HEALTH EFFECTS. CAS No.: EINECS No.: REPORT VERSION: Draft of 24 April 2001
EUROPEAN COMMISSION DIRECTORATE-GENERAL HEALTH AND CONSUMER PROTECTION Directorate C - Scientific Opinions Unit C2 - Management of Scientific Committees; scientific co-operation and networks Scientific
More informationRisk Assessment of Chemicals in Foods- WHO Principles and Methods
Risk Assessment of Chemicals in Foods- WHO Principles and Methods Presented by Dr Debabrata Kanungo DK 31-07-2018 Seminar on Food Additives: A Global Perspect on Safety Evaluation and Use July 19-20, 2018
More informationRegulation of Genotoxic and Carcinogenic Impurities in
Regulation of Genotoxic and Carcinogenic Impurities in Pharmaceuticals Impurities in Drugs: Monitoring, Safety and Regulation The Israel Chapter of PDA July, 15 16, 2008 David Jacobson-Kram, Ph.D. DABT
More informationRisk Assessment Report on. Bis(hydroxylammonium)sulfate. CAS No.: EINECS no.:
Scientific Committee on Health and Environmental Risks SCHER Risk Assessment Report on Bis(hydroxylammonium)sulfate CAS No.: 10039-54-0 EINECS no.: 233-118-8 The SCHER adopted this opinion at its 21 st
More informationThe Chronic Cancer Bioassay Is Frequently Conducted for Pesticides When It Is Not Always Needed to Protect Human Health
The Chronic Cancer Bioassay Is Frequently Conducted for Pesticides When It Is Not Always Needed to Protect Human Health Douglas C. Wolf, DVM, PhD, FIATP, ATS Senior Fellow Product Safety Syngenta Crop
More informationRisk Assessment Report on Vinyl acetate. Human Health Part. CAS No.: EINECS No.:
Scientific Committee on Health and Environmental Risks SCHER Risk Assessment Report on Vinyl acetate Human Health Part CAS No.: 108-05-4 EINECS No.: 203-545-4 The SCHER adopted this opinion at its 26 th
More informationSTUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: GENERAL APPROACH TO ESTABLISH AN ACUTE REFERENCE DOSE
VICH GL54 (SAFETY) ARfD November 2016 For Implementation at Step 7 STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: GENERAL APPROACH TO ESTABLISH AN ACUTE REFERENCE DOSE (ARfD)
More informationDiquat in drinking-water
Diquat in drinking-water Draft background document for development of WHO Guidelines for Drinking-water Quality Diquat is the International Organization for Standardization (ISO) approved common name for
More informationEuropean Food Safety Authority (EFSA)
STATEMENT ADOPTED: 5 July 2018 doi: 10.2903/j.efsa.2018.5383 Statement on the impact of the harmonised classification on the conclusion on the peer review of the pesticide risk assessment of the active
More informationIMPURITIES: GUIDELINE FOR RESIDUAL SOLVENTS PDE FOR CUMENE
INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE DRAFT CONSENSUS GUIDELINE IMPURITIES: GUIDELINE FOR RESIDUAL SOLVENTS Released for
More informationNew Pesticide Fact Sheet
United States Prevention, Pesticides Environmental Protection And Toxic Substances May 2005 Agency (7505C) New Pesticide Fact Sheet Picaridin Description of the Chemical Use Patterns and Formulations Generic
More informationToxStrategies, Inc. and Summit Toxicology
Deborah Proctor Chad Thompson, Mark Harris, Mina Suh, Laurie Haws, Chris Kirman and Sean Hays ToxStrategies, Inc. and Summit Toxicology November 2012 Research Project funded by the Cr 6 Panel of the American
More informationComments DRAFT Preamble to the IARC Monograph. Health and Safety Department International Union, UAW 8000 East Jefferson Avenue Detroit, MI 48214
Comments DRAFT Preamble to the IARC Monograph Health and Safety Department International Union, UAW 8000 East Jefferson Avenue Detroit, MI 48214 The International Union, UAW affirms the importance of the
More informationInternational Safety Assessment of Sweeteners
ILSI SEA Region Seminar on Uses and Safety of Sweeteners (May 2013) http://www.ilsi.org/sea_region/pages/vieweventdetails.aspx?webid=4d540914-eeb6-40e4-89eb- 0B73BA3D76C1&ListId=478BE3CB-581B-4BA2-A280-8E00CCB26F9C&ItemID=73
More informationDICHLOROACETONITRILE. 1. Exposure Data
DICHLOROACETONITRILE Data were last evaluated in IARC (1991). 1. Exposure Data 1.1 Chemical and physical data 1.1.1 Nomenclature Chem. Abstr. Serv. Reg. No.: 3018-12-0 Chem. Abstr. Name: Dichloroacetonitrile
More informationMemo n 24: Peter CLAUSING. Toxicologist, Germany. The Hague, October 15 th -16 th, 2016
Memo n 24: Peter CLAUSING Toxicologist, Germany The Hague, October 15 th -16 th, 2016 CONTACTS : emilie@monsanto-tribunal.org witnesses@monsanto-tribunal.org 1 Dr. Peter Clausing, born in 1950, graduated
More information3-MCPD and glycidol and their esters
Toxicological Risk Assessment of 3-monochloropropane-1,2-diol (3-MCPD) Esters and Glycidol Esters: Is there a Need for Concern? Ivonne M.C.M. Rietjens Division of Toxicology Wageningen University ivonne.rietjens@wur.nl
More informationFolpet (Pesticides) Summary. Risk assessment report. Food Safety Commission of Japan. Conclusion in Brief
2017 Food Safety Commission, Cabinet Office, Government of Japan doi: 10.14252/foodsafetyfscj.2017002s Food Safety 2017; Vol. 5, No. 2, 67 71 Risk assessment report Folpet (Pesticides) Summary Food Safety
More informationApproaches to Integrating Evidence From Animal and Human Studies in Chemical Assessments
Approaches to Integrating Evidence From Animal and Human Studies in Chemical Assessments Kris Thayer, National Center for Environmental Assessment (NCEA) Integrated Risk Information System (IRIS) Division
More informationPQRI PODP Extractables & Leachables Workshop Leachable Evaluation of a Container Closure System - What to do When Above the Threshold
PQRI PODP Extractables & Leachables Workshop Leachable Evaluation of a Container Closure System - What to do When Above the Threshold William P. Beierschmitt, PhD, DABT, FATS Drug Safety Research and Development
More informationPQRI PODP Extractables & Leachables Workshop Derivation of the Parenteral Safety Concern Threshold (SCT)
PQRI PODP Extractables & Leachables Workshop Derivation of the Parenteral Safety Concern Threshold (SCT) Presented by: Douglas J Ball, MS, DABT Toxicology Consultant April 2018 Agenda TTC Cramer Classification
More informationA case study in risk assessment: aspartame
A case study in risk assessment: aspartame Herman B.W.M.Koëter Managing Director,, Brussels, Belgium Thanks to Dr Iona Pratt of the Irish Food Safety Authority for use of a number of the slides in this
More informationInterpretation of Epidemiologic Studies
Interpretation of Epidemiologic Studies Paolo Boffetta Mount Sinai School of Medicine, New York, USA International Prevention Research Institute, Lyon, France Outline Introduction to epidemiology Issues
More informationDistinguishing between Mode and Mechanism of Action
Distinguishing between Mode and Mechanism of Action Michael Dourson Toxicology Excellence for Risk Assessment Center University of Cincinnati College of Medicine Conflict of Interest Statement The research
More informationInternational Agency for Research on Cancer (IARC) - Summaries & Evaluations
International Agency for Research on Cancer (IARC) - Summaries & Evaluations AFLATOXINS Naturally Occurring Aflatoxins (Group1) Aflatoxin M1 (Group 2B) For definition of Groups, see Preamble Evaluation.
More informationCOMMITTEE FOR VETERINARY MEDICINAL PRODUCTS
The European Agency for the Evaluation of Medicinal Products Veterinary Medicines and Inspections EMEA/MRL/451/98-FINAL June 1998 COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS BACITRACIN SUMMARY REPORT (1)
More informationImpact of genotoxicity in risk assessment of pesticides, their metabolites and degradates
Impact of genotoxicity in risk assessment of pesticides, their metabolites and degradates Claudia Bolognesi Environmental Carcinogenesis Unit, National Institute for Cancer research, Genova New Pesticide
More informationDEVELOPMENT OF THE CHROMIUM PUBLIC HEALTH GOAL
DEVELOPMENT OF THE CHROMIUM PUBLIC HEALTH GOAL Robert A. Howd, Ph.D. Chief, Water Toxicology Unit Office of Environmental Health Hazard Assessment, California Environmental Protection Agency Oakland and
More informationMATERIAL SAFETY DATA SHEET
Page 1 of 6 1. IDENTIFICATION OF THE SUBSTANCE/PREPARATION AND THE COMPANY/UNDERTAKING Pfizer Inc Pfizer Pharmaceuticals Group 235 East 42nd Street New York, New York 10017 1-212-573-2222 Emergency telephone
More informationSpecial Review Decision: Imazapyr
Re-evaluation Note REV2016-02 Special Review Decision: Imazapyr (publié aussi en français) 7 January 2016 This document is published by the Health Canada Pest Management Regulatory Agency. For further
More informationCOMMITTEE FOR VETERINARY MEDICINAL PRODUCTS
The European Agency for the Evaluation of Medicinal Products Veterinary Medicines Evaluation Unit EMEA/MRL/0128/96-FINAL July 1996 COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS CEFAPIRIN SUMMARY REPORT (1)
More informationEFSA Statement regarding the EU assessment of glyphosate and the socalled
EFSA Statement regarding the EU assessment of glyphosate and the socalled Monsanto papers Background On 29 May 2017, EFSA received a request from the European Commission to produce a statement concerning
More informationThe effect of REACH implementation on genotoxicity and carcinogenicity testing Jan van Benthem
The effect of REACH implementation on genotoxicity and carcinogenicity testing Jan van Benthem National Institute for Public Health and the Environment Laboratory for Health Protection Research Bilthoven
More informationCOMMITTEE FOR VETERINARY MEDICINAL PRODUCTS
The European Agency for the Evaluation of Medicinal Products Veterinary Medicines and Inspections EMEA/MRL/175/96-FINAL December 1999 COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS ALTRENOGEST SUMMARY REPORT
More informationOverview of US EPA Assessment Activities for Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonate (PFOS)
Overview of US EPA Assessment Activities for Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonate (PFOS) Jennifer Seed, PhD Risk Assessment Division Office of Pollution Prevention and Toxics US
More information5.30 PROPYLENE OXIDE (250)
347 5.30 PROPYLENE OXIDE (250) TOXICOLOGY (PPO) is the International Organization for Standardization (ISO) approved name for methyloxirane (International Union of Pure and Applied Chemistry [IUPAC]) with
More informationalternative short-chain fluorinated product technology
The extensive toxicology data behind alternative short-chain fluorinated product technology SOT RASS-MISS Webinar 9 December 2015 Robert C. Buck, PhD Technical Fellow The Chemours Company Wilmington, Delaware,
More informationEuropean Public MRL assessment report (EPMAR)
8 September 2015 EMA/CVMP/632934/2014 Committee for Medicinal Products for Veterinary Use European Public MRL assessment report (EPMAR) Propyl 4-hydroxybenzoate and its sodium salt (all food producing
More informationTo: Recipients of JACC 42. HV/mls/JACC 42 corrigendum Brussels, 15 December 2004
EUROPEAN CENTRE FOR ECOTOXICOLOGY AND TOXICOLOGY OF CHEMICALS AISBL To: Recipients of JACC 42 HV/mls/JACC 42 corrigendum Brussels, 15 December 2004 Dear Sir or Madam, Corrigenda to JACC No. 42 - Tetrafluoroethylene
More informationCase 3:16-md VC Document Filed 10/28/17 Page 1 of 38 EXHIBIT 96
Case 3:16-md-02741-VC Document 655-6 Filed 10/28/17 Page 1 of 38 EXHIBIT 96 Case 3:16-md-02741-VC Document 655-6 Filed 10/28/17 Page 2 of 38 UNITED STATES DISTRICT COURT NORTHERN DISTRICT OF CALIFORNIA
More informationChapter 6 Physical and chemical quality of drinking water
Chapter 6 Physical and chemical quality of drinking water Chapter 6 Physical and Chemical Quality of Drinking Water Chapter 6 Chapter 6 Physical and chemical quality of drinking water 6.1 Introduction
More informationESTIMATION OF TOXICITY TO HUMANS
240 TABLE 21-5. (continued) Mammalian bone marrow chromosome aberration test Mammalian erythrocyte micronucleus test Rodent dominant lethal assay Rodent heritable translocation assays Bacterial DNA damage
More informationOpinion of the Scientific Committee on Food on an additional list of monomers and additives for food contact materials (adopted the 18 September 1998)
Opinion of the Scientific Committee on Food on an additional list of monomers and additives for food contact materials (adopted the 18 September 1998) The Committee (re)evaluated a number of monomers and
More informationConsiderations on the statistical methods used to assess carcinogenicity studies of pesticides with emphasis on glyphosate
Considerations on the statistical methods used to assess carcinogenicity studies of pesticides with emphasis on glyphosate by Peter Clausing, PAN Germany Hamburg - April 2016 Introduction Much of the controversy
More informationCOMMITTEE FOR MEDICINAL PRODUCTS FOR VETERINARY USE
European Medicines Agency Veterinary Medicines and Inspections EMEA/MRL/904/04-FINAL June 2004 COMMITTEE FOR MEDICINAL PRODUCTS FOR VETERINARY USE ALTRENOGEST SUMMARY REPORT (3) 1. Altrenogest (or allyltrenbolone)
More information