The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation

Autor: Luciano Bua, Jianzhong Hu, Alberto Mantovani, Daniele Mandrioli, Giovanni Dinelli, Marcella Spinaci, Philip J. Landrigan, Rossella Miglio, Laura Falcioni, Fiorella Belpoggi, Stefano Lorenzetti, Jia Chen, Giovanna Galeati, Simona Panzacchi, Fabiana Manservisi, Melissa J. Perry
Přispěvatelé: Panzacchi S, Mandrioli D, Manservisi F, Bua L, Falcioni L, Spinaci M, Galeati G, Dinelli G, Miglio R, Mantovani A, Lorenzetti S, Hu J, Chen J, Perry MJ, Landrigan PJ, Belpoggi F.
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
GBH
Glyphosate
Acceptable daily intake
Health
Toxicology and Mutagenesis
Metabolite
Population
Glycine
Pilot Projects
Urine
13-week
010501 environmental sciences
01 natural sciences
Rats
Sprague-Dawley
Excretion
03 medical and health sciences
chemistry.chemical_compound
Sprague-Dawley rat
lcsh:RC963-969
Animal science
Glyphosate based herbicide
Animals
Humans
Medicine
Aminomethylphosphonic acid
education
0105 earth and related environmental sciences
education.field_of_study
Dose-Response Relationship
Drug
Herbicides
business.industry
Research
030111 toxicology
lcsh:Public aspects of medicine
Public Health
Environmental and Occupational Health
lcsh:RA1-1270
Rats
chemistry
Research Design
Toxicity
lcsh:Industrial medicine. Industrial hygiene
business
Glyphosate based herbicides
Roundup
Zdroj: Environmental Health, Vol 17, Iss 1, Pp 1-13 (2018)
Environmental Health
Popis: Background Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years. In this paper, we present the study design, the first evaluation of in vivo parameters and the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) in urine. Methods We exposed Sprague-Dawley (SD) rats orally via drinking water to a dose of glyphosate equivalent to the United States Acceptable Daily Intake (US ADI) of 1.75 mg/kg bw/day, defined as the chronic Reference Dose (cRfD) determined by the US EPA, starting from prenatal life, i.e. gestational day (GD) 6 of their mothers. One cohort was continuously dosed until sexual maturity (6-week cohort) and another cohort was continuously dosed until adulthood (13-week cohort). Here we present data on general toxicity and urinary concentrations of glyphosate and its major metabolite AMPA. Results Survival, body weight, food and water consumption of the animals were not affected by the treatment with either glyphosate or Roundup. The concentration of both glyphosate and AMPA detected in the urine of SD rats treated with glyphosate were comparable to that observed in animals treated with Roundup, with an increase in relation to the duration of treatment. The majority of glyphosate was excreted unchanged. Urinary levels of the parent compound, glyphosate, were around 100-fold higher than the level of its metabolite, AMPA. Conclusions Glyphosate concentrations in urine showed that most part of the administered dose was excreted as unchanged parent compound upon glyphosate and Roundup exposure, with an increasing pattern of glyphosate excreted in urine in relation to the duration of treatment. The adjuvants and the other substances present in Roundup did not seem to exert a major effect on the absorption and excretion of glyphosate. Our results demonstrate that urinary glyphosate is a more relevant marker of exposure than AMPA in the rodent model.
Databáze: OpenAIRE
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