WHO - Organización Mundial de la Salud.
· INFORME: Glyphosate and AMPA in Drinking-water (WHO/SDE/03.04/97)
o ….the major source of exposure to glyphosate is expected to be food. (pag. 3)
o ….as unlikely to present an acute hazard in normal use. (pag 4)
o 5.3 Long-term exposure and carcinogenicity (pag 5)
§ ….No effect on survival or appearance was noted. (pag 5)
§ ….There were no statistically significant increases in the frequency of neoplastic lesions. (pag 5)
o Glyphosate was consistently without mutagenic effect in a range of genotoxicity assays in vitro and in vivo (IPCS, 1994). (pag 7)
o No indication of genotoxic activity was seen in studies of gene mutation in bacteria, of DNA… No assays for gene mutation were performed in mammalian cells in vitro,… and the lack of genotoxicity of glyphosate, including in an assay for gene mutation in mammalian cells in vitro, indicate that such an assay with AMPA would be redundant. (pag 8).
o Because of their low toxicity… Under usual conditions, therefore, the presence of glyphosate and AMPA in drinking-water does not represent a hazard to human health. (pag 9)
FOOD AND AGRICULTURE ORGANIZATION. Codex Alimentarius.
Límite máximo de residuo de glifosato permitido en soja,
· Residuos de plaguicidas en los alimentos (Límites Máximos de Residuos. Límites Máximos de Residuos Extraños)
o Soja (seca) LMR (undef ) 20 (Imagen MHTML)
CODEX ALIMENTARIUS. Joint Meeting on Pesticides Residues
Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues
Rome, Italy, 20–29 September 2004
· TOXICOLOGY (pag 98)
o Long-term studies of toxicity and carcinogenicity were conducted in mice and rats. In the study of carcinogenicity in mice, no toxic effects were observed at up to the highest dose tested (1000 mg/kg bw per day), and there was no evidence of carcinogenicity…There was no evidence of a carcinogenic response to treatment in rats. (pag 99)
o The Meeting concluded that glyphosate is unlikely to be genotoxic….that glyphosate is unlikely to pose a carcinogenic risk to humans….Glyphosate had no effect on fertility in either two-generation study of reproductive toxicity in rats….AMPA had no genotoxic potential in vitro or in vivo…On the basis of the new toxicological data, the present Meeting concluded that AMPA is of no greater toxicological concern than its parent compound, thus confirming the conclusion of the 1997 JMPR. (pag 100)
o Toxicological evaluation
§ The Meeting concluded that it was not necessary to establish an ARfD for glyphosate in view of its low acute toxicity, the absence of relevant developmental toxicity in rats or rabbits as a consequence of acute exposure and the absence of any other toxicological effect that would be elicited by a single dose. (pag 101)
· DIETARY RISK ASSESSMENT. Long-term intake
o Estimated theoretical maximum daily intakes for the five GEMS/Food regional diets, based on recommended MRLs, were 1% of the ADI (Annex 3). The Meeting concluded that the long-term intake of residues of glyphosate resulting from uses that have been considered by the JMPR is unlikely to present a public health concern. (pag 103)
o
1997 JOINT MEETING OF THE FAO PANEL OF EXPERTS ON PESTICIDE RESIDUES IN FOOD AND THE ENVIRONMENT AND THE WHO CORE ASSESSEMENT GROUP
Lyon (IARC), 22 September-1 October 1997
· TOXICOLOGY
o No indication of genotoxic activity was seen in studies of gene mutation in bacteria, of DNA repair in bacteria and mammalian cells in vitro, or of micronucleus formation in vivo. No assays for gene mutation were performed in mammalian cells in vitro,… No teratogenic effects were observed…No increase in tumour incidence was seen in this study (as evaluated by the International Programme on Chemical Safety (IPCS)). (pag 127)
Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues Geneva, Switzerland, 20–29 September 2005
· Environmental fate
o The rate of degradation in field and in aquatic environments is such that glyphosate is not expected to persist in the environment. (pag 124)
· DIETARY RISK ASSESSMENT. Short-term intake
o The Meeting therefore concluded that short-term dietary intake of glyphosate residues is unlikely to present a risk to consumers. (pag 144)
· Long-term intake
o The Meeting concluded that the long-term intake of residues of glyphosate and AMPA from uses that have been considered by the JMPR is unlikely to present a public health concern. (pag 144)
UNION EUROPEA
COMMISSION WORKING DOCUMENT - DOES NOT NECESSARILY REPRESENT THE VIEWS OF THE COMMISSION SERVICES
Review report for the active substance glyphosate
· 3. Overall conclusion in the context of Directive 91/414/EEC
o …the review has established that the residues arising from the proposed uses, consequent on application consistent with good plant protection practice, have no harmful effects on human or animal health. The Theoretical Maximum Daily Intake (TMDI; excluding water and products of animal origin) for a 60 kg adult is 15 % of the Acceptable Daily Intake (ADI), based on the FAO/WHO European Diet (August 1994). Additional intake from water and products of animal origin are not expected to give rise to intake problems.(pag 5)
· APPENDIX II
o No evidence of accumulation (< 1% after 7 days). No evidence of accumulation (for PMG anion < 3% after 5 days, for TMS cation much less). (pag 10)
o Not irritating Not irritating… Not genotoxic. Not genotoxic… (pag 11)
o No evidence of carcinogenicity. No evidence of carcinogenicity… No relevant effects. No relevant effects… (pag 12).
o Comprehensive database, mainly related to accidental or intencional oral intake of glyphosate products. No evidence of adverse health effects upon manufacturing; few reports of poisonings following oral ingestion confined to cases of clear misuse. (pag 13)
o No accumulation No accumulation… (pag 20)
ESTADOS UNIDOS DE NORTEAMERICA
Reregistration elegibility decisión document Glyphosate List A Case 0178 – Environmental Protection Agency
· Human Heealth Assessment
o Glyphosate does not cause mutations (pag 2)
o The Agency concluded that the chronic dietary risk posed by glyphosate food uses is minimal… However, due to glyphosate´s low acute toxicity and the absence of the other toxicological concerns (especially carcionogenicity), occupational and residencial exposure data are not required for reregistration. (pag 3)
· Human Risk Assessment
o EPA´s worst case risk assessment of glyphosate´s many registered fodd uses concluyes that human dietary exposure and risk are minimal…Exposure to worker and other applicators generally is not expected to pose undue risks, due to glyphosate´s low acute toxicity. (pag 4)
· Ecological Effects
o Glyphosate is no more than slightly toxic to birds and is practically non-toxic to fish, au}quatic invertebrates and honeybees. (pag 4)
· Ecological Effects Risk Assessment
o Based on current data, EPA has determined that the effects of glyphosate on birds, mammals, fish and invertebrates are minimal. (pag 5)
· Regulatory Conclusión
o The use of currently registered pesticide products containing the isopropilamine and sodium alts of glyphosate in accordance with the labeling specified in this RED wil not pose unreasonable risk or adverse effects to humans or the environment. Therefore, all uses of these products are eligible for reregistration. (pag 7)
· d. Carcinogenicity
o The Agency also concluded that this study was not conducted at high enough dose levels for an adequate negative carcinogenicity. (pag 13)
o …there was no progression to carcinomas; and there was no significant dose-related increase in severity or incidence of hyperplasia in either sex… Therefore, glyphosate was not considered to be carcinogenic in this study…. On June 26, 1991, the Agency classified glyphosate in Group E (evidence of non-carcinogenicity for humans), based on a lack of convincing evidence of carcinogenicity in adequate studies with two animal species, rat and mouse. (pag 14).
· g. Mutagenicity
o No increases in reverse mutations were observed at any concentration…. No mutagenic response was observed either with or without metabolic activation up to the limit of cytotoxicity (10 mg/Ml)…. No significant clastogenic effects were observed…. No increases in mutations were observed in either study. (pag 17)
· i. Neurotoxicity
o … there was no evidence of neurotoxicity seen in any of the existing studies at very high doses and this chemical lacks a leaving group… (pag 18)
· 3. Risk Assessment. a. Dietary
o EPA concludes that the chronic dietary risk posed by this pesticide on these food uses is minimal. (pag 24)
· b. Ecological Effects Risk Assessment
o Based on the current data, it has been determined that effects to birds, mammals, fish and invertebrates are minimal. (pag 53).
o Based on this, minimal risk is expected. (pag 54)
· 1. Eligibility Decisión
o will not pose unreasonable risks or adverse effects to humans or the environment. (pag 57)
· 2. Eligible and Ineligible Uses
o The Agency has determined that all uses of glyphosate are eligible for reregistration. (pag 58)
o Soybeans 20 Current Tolerance 1 (ppm) (pag 65)
United States Department of Health and Human Services, Public Health Service, National Institutes of Health, NTP Technical Report on Toxicity Studies of Glyphosate (CAS No. 1071-83-6)
· ABSTRACT
o There was no evidence of adverse effects on the reproductive system of rats or mice. (pag 5)
o Glyphosate was not mutagenic in Salmonella,… (pag 6)
· … tests showed no evidence that glyphosate is genotoxic…. There was no evidence of genetic or reproductive toxicity of glyphosate…. there was no histopathologic evidence of liver injury. (pag 36).
·
Federal Register / Vol. 69, No. 217 / Wednesday, November 10, 2004 / Rules and Regulations, ENVIRONMENTAL PROTECTION AGENCY, 40 CFR Part 180, [OPP–2004–0323; FRL–7683–9]
Glyphosate; Pesticide Tolerance
· TABLE 1.—AGGREGATE RISK ASSESSMENT FOR CHRONIC (NON-CANCER) EXPOSURE TO GLYPHOSATE… TABLE 2.—AGGREGATE RISK ASSESSMENT FOR SHORT-TERM EXPOSURE TO GLYPHOSATE. (pag 65085)
· TABLE 3.—AGGREGATE RISK ASSESSMENT FOR INTERMEDIATE-TERM EXPOSURE TO GLYPHOSATE… 5. Aggregate cancer risk for U.S. population. Glyphosate has no carcinogenic potential. 6. Determination of safety. Based on these risk assessments, EPA concluyes that there is a reasonable certainty that no harm will result to the general population, and to infants and children from aggregate exposure to glyphosate residues. (pag 65086)
Federal Register / Vol. 71, No. 244 / Wednesday, December 20, 2006 / Rules and Regulations, ENVIRONMENTAL PROTECTION AGENCY, 40 CFR Part 180, [EPA–HQ–OPP–2006–0177; FRL–8105–9]
Glyphosate; Pesticide Tolerance
· B. Toxicological Endpoints
o For hazards that have a threshold below which there is no apreciable risk,… iii. Cancer. Glyphosate is classified as a not likely human carcinogen, so a cancer dietary exposure analysis is not necessary. (pag 76182)
· …glyphosate does not appear to produce a toxic metabolite produced by other substances…( pag 76183)
· 2. Prenatal and postnatal sensitivity.
o Based on the available data, there was no evidence of quantitative or qualitative increased susceptibility following in utero glyphosate exposure to rats and rabbits, or following prenatal/postnatal exposure in the 2- generation reproduction study in rats. A developmental neurotoxicity study was not required. (pag 76183)
· E. Aggregate Risks and Determination of Safety
o …There were no toxic effects attributable to a single dose…. chronic residencial exposure to residues of glyphosate is not expected…. Glyphosate has been classified by the Cancer Peer Review Committee as ‘‘a Group E’’ chemicalnegative as a human carcinogen – based on the absence of carcinogenicity in mice and rats. Therefore, a cancer risk assessment was not conducted. (pag 76183)
Public Health Goal for GLYPHOSATE in Drinking Water
Prepared by
Pesticide and Environmental Toxicology Section
· SUMMARY
o Glyphosate is not mutagenic or teratogenic and there is no evidence for reproductive toxicity in multigeneration studies in rats. We consider the results from a rabbit teratology study with a no-observed-adverse-effect level (pag 1)
· Carcinogenic Effects
o Therefore , no dose-response assessment was conducted for glyphosate carcinogenicity in developing a PHG. (pag 9)
· Noncarcinogenic Effects (pag 9)