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

Fabiana Manservisi; Corina Lesseur; Simona Panzacchi; Daniele Mandrioli; Laura Falcioni; Luciano Bua; Marco Manservigi; Marcella Spinaci; Giovanna Galeati; Alberto Mantovani; Stefano Lorenzetti; Rossella Miglio; Anderson Martino Andrade; David Møbjerg Kristensen; Melissa J Perry; Shanna H Swan; Jia Chen; Fiorella Belpoggi

doi:10.1186/s12940-019-0453-y

Lifestyle and Environment · Environmental Exposures

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

Manservisi F, Lesseur C, Panzacchi S, Mandrioli D, Falcioni L, Bua L, Manservigi M, Spinaci M, Galeati G, Mantovani A, Lorenzetti S, Miglio R, Andrade AM, Kristensen DM, Perry MJ, Swan SH, Chen J, Belpoggi F

Published March 12, 2019 Environmental health : a global access science source

DOI 10.1186/s12940-019-0453-y PMID 30857531 PMC PMC6413565

RRM Academy Synopsis

Roundup at the US daily intake limit altered some hormones in rats

Roundup Bioflow at the US acceptable daily intake altered some development and hormone measures in rats, a 2019 pilot study in Sprague Dawley rats found. Exposure began in the womb and continued into adulthood. Glyphosate alone changed fewer measures than Roundup Bioflow did. Each exposure was compared with a control group.

Key Findings

Anogenital distance on day 4 after birth was longer in Roundup Bioflow males and females and in glyphosate males than in controls (p < 0.01 for each comparison).
Roundup Bioflow females in the 6-week cohort reached first estrous at a mean of 42.63 days, against 39.88 in controls (p < 0.05). Glyphosate females in that cohort showed no significant delay.
In the 13-week cohort, Roundup Bioflow females had higher testosterone (p < 0.05), and Roundup Bioflow males and females both had a lower DHT to testosterone ratio (p < 0.01).
Thyroid-stimulating hormone was higher in glyphosate males in the 6-week cohort (p < 0.05) and in Roundup Bioflow males in the 13-week cohort (p < 0.01).
Vaginal opening age in females, estrous stage times in 13-week females and sperm parameters in males did not differ between groups. All dams that cohabited with males achieved and maintained pregnancy.

Interpretation

The Ramazzini Institute ran a pilot experiment in Sprague Dawley rats. Dams drank water containing glyphosate or Roundup Bioflow from gestation day 6 through lactation, and their offspring continued until sacrifice at 6 or 13 weeks after weaning. The control, glyphosate and Roundup Bioflow groups each had 8 dams. The 6-week cohort had 8 offspring of each sex per group, and the 13-week cohort had 10. The authors call the effects "subtle but potentially adverse" and note that the pilot used a limited number of animals and one dose level. They call for a life-course study to confirm the findings.

RRM Context

Restorative reproductive medicine asks what disturbs the hormones behind reproduction. The paper's background cites an Ontario farm study. It linked exposure before conception to pesticide products containing glyphosate with a higher risk of miscarriage. A small study linked glyphosate in the urine of pregnant women with shorter pregnancies. The authors call anogenital distance a valid marker of hormone effects in human development.

Our editorial summary of this paper, not the article's abstract.

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.

Topics

Lifestyle and Environment › Environmental Exposures › Pesticides and Agricultural Chemicals · Reproductive Endocrinology › Ovarian Hormones › Estrogen

Fabiana Manservisi, Corina Lesseur, Simona Panzacchi, Daniele Mandrioli, Laura Falcioni, Luciano Bua, Marco Manservigi, Marcella Spinaci, Giovanna Galeati, Alberto Mantovani, Stefano Lorenzetti, Rossella Miglio, Anderson Martino Andrade, David Møbjerg Kristensen, Melissa J Perry, Shanna H Swan, Jia Chen, Fiorella Belpoggi

F Manservisi, C Lesseur, S Panzacchi, D Mandrioli, L Falcioni, L Bua, M Manservigi, M Spinaci, G Galeati, A Mantovani, S Lorenzetti, R Miglio, A Andrade, Dave Kristensen, D Kristensen, M Perry, S Swan, J Chen, F Belpoggi

PMID 30857531 30857531 DOI 10.1186/s12940-019-0453-y 10.1186/s12940-019-0453-y Manservisi et al. 2019, Manservisi 2019

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

Roundup at the US daily intake limit altered some hormones in rats

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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