PMID- 29843719 OWN - NLM STAT- MEDLINE DCOM- 20181217 LR - 20240318 IS - 1476-069X (Electronic) IS - 1476-069X (Linking) VI - 17 IP - 1 DP - 2018 May 29 TI - 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. PG - 52 LID - 10.1186/s12940-018-0393-y [doi] LID - 52 AB - 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. FAU - Panzacchi, Simona AU - Panzacchi S AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. FAU - Mandrioli, Daniele AU - Mandrioli D AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. AD - Department of Agricultural Sciences, University of Bologna, Viale Fanin 44, 40127, Bologna, Italy. FAU - Manservisi, Fabiana AU - Manservisi F AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. AD - Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano dell'Emilia, Bologna, Italy. FAU - Bua, Luciano AU - Bua L AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. FAU - Falcioni, Laura AU - Falcioni L AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. FAU - Spinaci, Marcella AU - Spinaci M AD - Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano dell'Emilia, Bologna, Italy. FAU - Galeati, Giovanna AU - Galeati G AD - Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano dell'Emilia, Bologna, Italy. FAU - Dinelli, Giovanni AU - Dinelli G AD - Department of Agricultural Sciences, University of Bologna, Viale Fanin 44, 40127, Bologna, Italy. FAU - Miglio, Rossella AU - Miglio R AD - Department of Statistical Sciences, University of Bologna, Via Belle Arti 41, 40126, Bologna, Italy. FAU - Mantovani, Alberto AU - Mantovani A AD - Department of Food safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161, Rome, Italy. FAU - Lorenzetti, Stefano AU - Lorenzetti S AD - Department of Food safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161, Rome, Italy. FAU - Hu, Jianzhong AU - Hu J AD - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY, 10029, USA. FAU - Chen, Jia AU - Chen J AD - Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, USA. FAU - Perry, Melissa J AU - Perry MJ AD - Department of Environmental and Occupational Health, Milken Institute School of Public Health, The George Washington University, 950 New Hampshire Ave, Washington, DC, 20052, USA. FAU - Landrigan, Philip J AU - Landrigan PJ AD - Arnhold Institute for Global Health, Icahn School of Medicine at Mount Sinai, 1216 Fifth Avenue, New York, NY, 10029, USA. FAU - Belpoggi, Fiorella AU - Belpoggi F AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. belpoggif@ramazzini.it. LA - eng GR - P30 ES023515/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180529 PL - England TA - Environ Health JT - Environmental health : a global access science source JID - 101147645 RN - 0 (Herbicides) RN - TE7660XO1C (Glycine) SB - IM MH - Animals MH - Dose-Response Relationship, Drug MH - Glycine/*analogs & derivatives/toxicity/urine MH - Herbicides/*toxicity/*urine MH - Humans MH - Pilot Projects MH - Rats MH - Rats, Sprague-Dawley MH - Research Design MH - Glyphosate PMC - PMC5972408 OTO - NOTNLM OT - 13-week OT - GBH OT - Glyphosate OT - Glyphosate based herbicides OT - Roundup OT - Sprague-Dawley rat COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: N/A COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/05/31 06:00 MHDA- 2018/12/18 06:00 PMCR- 2018/05/29 CRDT- 2018/05/31 06:00 PHST- 2018/02/02 00:00 [received] PHST- 2018/05/10 00:00 [accepted] PHST- 2018/05/31 06:00 [entrez] PHST- 2018/05/31 06:00 [pubmed] PHST- 2018/12/18 06:00 [medline] PHST- 2018/05/29 00:00 [pmc-release] AID - 10.1186/s12940-018-0393-y [pii] AID - 393 [pii] AID - 10.1186/s12940-018-0393-y [doi] PST - epublish SO - Environ Health. 2018 May 29;17(1):52. doi: 10.1186/s12940-018-0393-y.