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Environ Health. 2019 Mar 12;18(1):15. doi: 10.1186/s12940-019-0453-y.

The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system.

Author information

1
Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010, Bentivoglio, Bologna, Italy.
2
Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
3
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, USA.
4
Department of Agricultural Sciences, University of Bologna, Bologna, Italy.
5
Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy.
6
Department of Statistical Sciences, University of Bologna, Bologna, Italy.
7
Department of Physiology, Division of Biological Sciences, Federal University of Paraná, Curitiba, Paraná, Brazil.
8
Danish Headache Center, Department of Neurology, Rigshospitalet, University of Copenhagen, 1165, Copenhagen, Denmark.
9
Department of Environmental and Occupational Health, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
10
Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010, Bentivoglio, Bologna, Italy. belpoggif@ramazzini.it.

Abstract

BACKGROUND:

Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including potential effects on the endocrine system The present pilot study examine whether exposure to GBHs at the dose of glyphosate considered to be "safe" (the US Acceptable Daily Intake - ADI - of 1.75 mg/kg bw/day), starting from in utero life, affect the development and endocrine system across different life stages in Sprague Dawley (SD) rats.

METHODS:

Glyphosate alone and Roundup Bioflow, a commercial brand of GBHs, were administered in drinking water at 1.75 mg/kg bw/day to F0 dams starting from the gestational day (GD) 6 (in utero) up to postnatal day (PND) 120. After weaning, offspring were randomly distributed in two cohorts: 8 M + 8F/group animals belonging to the 6-week cohort were sacrificed after puberty at PND 73 ± 2; 10 M + 10F/group animals belonging to the 13-week cohort were sacrificed at adulthood at PND 125 ± 2. Effects of glyphosate or Roundup exposure were assessed on developmental landmarks and sexual characteristics of pups.

RESULTS:

In pups, anogenital distance (AGD) at PND 4 was statistically significantly increased both in Roundup-treated males and females and in glyphosate-treated males. Age at first estrous (FE) was significantly delayed in the Roundup-exposed group and serum testosterone concentration significantly increased in Roundup-treated female offspring from the 13-week cohort compared to control animals. A statistically significant increase in plasma TSH concentration was observed in glyphosate-treated males compared with control animals as well as a statistically significant decrease in DHT and increase in BDNF in Roundup-treated males. Hormonal status imbalances were more pronounced in Roundup-treated rats after prolonged exposure.

CONCLUSIONS:

The present pilot study demonstrate that GBHs exposure, from prenatal period to adulthood, induced endocrine effects and altered reproductive developmental parameters in male and female SD rats. In particular, it was associated with androgen-like effects, including a statistically significant increase of AGDs in both males and females, delay of FE and increased testosterone in female.

PMID:
30857531
PMCID:
PMC6413565
DOI:
10.1186/s12940-019-0453-y
[Indexed for MEDLINE]
Free PMC Article

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