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. 2018 May 29;17(1):52.
doi: 10.1186/s12940-018-0393-y.

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

Simona Panzacchi  1 , Daniele Mandrioli  1   2 , Fabiana Manservisi  1   3 , Luciano Bua  1 , Laura Falcioni  1 , Marcella Spinaci  3 , Giovanna Galeati  3 , Giovanni Dinelli  2 , Rossella Miglio  4 , Alberto Mantovani  5 , Stefano Lorenzetti  5 , Jianzhong Hu  6 , Jia Chen  7 , Melissa J Perry  8 , Philip J Landrigan  9 , Fiorella Belpoggi  10
Affiliations

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

Simona Panzacchi et al. Environ Health. .

Abstract

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.

Keywords: 13-week; GBH; Glyphosate; Glyphosate based herbicides; Roundup; Sprague-Dawley rat.

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Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Average body weight: dams during gestation (a), treatment starting at gestation day 6 (↓); dams (b), male (c) and female (d) offspring during lactation; male (e) and female (f) offspring after weaning. At week 6 after weaning 8 male and 8 female pups per group were sacrificed
Fig. 2
Fig. 2
Average water consumption: dams during gestation (a), treatment starting at gestation day 6 (↓); dams and litter (b) during lactation; male (c) and female (d) offspring after weaning. At week 6 after weaning 8 male and 8 female pups per group were sacrificed
Fig. 3
Fig. 3
Average feed consumption: dams during gestation (a), treatment starting at gestation day 6 (↓); dams and litter (b) during lactation; male (c) and female (d) offspring after weaning. At week 6 after weaning 8 male and 8 female pups per group were sacrificed
Fig. 4
Fig. 4
Average urinary concentrations of glyphosate and AMPA, expressed in mg/kg, collected at terminal sacrifices. Dams glyphosate (a) and AMPA (b) excretion; 6-week cohort male and female offspring; glyphosate (c) and AMPA (d) excretion; 13-week cohort male and female pups Glyphosate (e) and AMPA (f) excretion
See this image and copyright information in PMC

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