Shock additional finding of malformations in second generation offspring from glyphosate-exposed rats

Exposure to environmentally relevant doses of a glyphosate-based herbicide during pregnancy has been found not only to impair female fertility in rats, but to induce foetal growth retardation and malformations, including abnormally developed limbs, in their second-generation offspring.

Argentinian researchers tested the glyphosate-based herbicide – one commonly used in Argentina – in pregnant female rats at two doses, which were added to their food. The rats were mated and dosed from the 9th day after conception until their pups were weaned. This first generation of offspring and their offspring in turn (second generation) were followed and monitored for reproductive effects.

The lower dose of glyphosate tested, 2 mg/kg bw/day (2 mg per kg of bodyweight per day), was in the order of magnitude of the reference dose (RfD) of 1 mg/kg bw/day recently set for glyphosate by the US Environmental Protection Agency, based on industry's developmental toxicity studies. The "reference dose" is the dose that is supposed to be safe to ingest on a daily basis over a lifetime.

The authors added that this dose is representative of the glyphosate residues found in soybean grains and is in the order of magnitude of the environmental levels detected in Argentina.

The higher dose of glyphosate, 200 mg of glyphosate/kg bw/day, was selected based on the industry-declared no-observed adverse effect level (NOAEL) of 1000 mg/kg bw/day for maternal toxicity established in rats. In other words, according to industry's own tests, this dose should not have been toxic to the mothers and thus should not have harmed the foetuses. But harmful effects did occur.

In agreement with the results of the industry tests, glyphosate-based herbicide treatment did not produce signs of toxicity to the embryo or abnormal maternal or nursing behaviour. Also, it did not alter the body weight gain of the first generation female offspring, nor vaginal opening onset (an indicator of puberty).

However, although all glyphosate herbicide-exposed first generation female rats became pregnant, they had a lower number of implantation sites of fertilized eggs, compared with controls. The second generation offspring from both glyphosate herbicide-exposed groups showed delayed growth, evidenced by lower foetal weight and length, and a higher incidence of abnormally small foetuses.

Also, to the authors' surprise, malformations (conjoined foetuses and abnormally developed limbs) were detected in the second generation of offspring from the higher dose of glyphosate herbicide group. Foetal abnormalities were found in 3 out of 117 foetuses, each one from different mothers within the first generation of offspring (i.e. 3 out of 13 litters were affected). A statistically significant correlation was found between glyphosate herbicide exposure and foetal malformations.

In conclusion, the study showed that exposure during pregnancy to low doses of glyphosate herbicide impaired female reproductive performance and induced foetal growth retardation and malformations in second-generation offspring. It also showed that the industry-declared no-observed adverse effect level (NOAEL) of 1000 mg/kg bw/day for maternal toxicity is not a reliable indicator of reproductive safety.

Findings reflected in other studies

Other research supports the new study findings that exposure to glyphosate herbicides can negatively affect birth outcomes.

The findings of malformations reflect epidemiological findings that people living in an Argentine town in the heart of the GM soy and maize growing area, where glyphosate-based herbicides are sprayed in large amounts, suffer birth defects at twice the national average rate.

In addition, a recent birth cohort study found a significant correlation between high glyphosate urine levels and shortened gestational lengths.

Other controlled laboratory in vivo studies cited by the authors of the new study reveal male and female reproductive development impairment from glyphosate-based herbicide exposure.
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Perinatal exposure to a glyphosate-based herbicide impairs female reproductive outcomes and induces second-generation adverse effects in Wistar rats
María M. Milesi, Virginia Lorenz, Guillermina Pacini, María R. Repetti, Luisina D. Demonte, Jorgelina Varayoud, Enrique H. Luque
Archives of Toxicology, 9 June 2018
https://link.springer.com/article/10.1007/s00204-018-2236-6

Abstract

Glyphosate-based herbicides (GBHs) are the most globally used herbicides raising the risk of environmental exposition. Here, we investigated whether perinatal exposure to low doses of a GBH alters the female reproductive performance, and/or induced second-generation effects related to congenital anomalies or growth alterations. Pregnant rats (F0) received a GBH through food, in a dose of 2 mg (GBH-LD: GBH-low dose group) or 200 mg (GBH-HD: GBH-high dose group) of glyphosate/kg bw/day from gestational day (GD) 9 until weaning. Body weight gain and vaginal canal-opening of F1 females were recorded. Sexually mature F1 females were mated to evaluate their reproductive performance by assessing the pregnancy rate, and on GD19, the number of corpora lutea, the implantation sites (IS) and resorption sites. To analyze second-generation effects on F2 offspring, we analyzed the fetal morphology on GD19, and assessed the fetal length and weight, and the placental weight. GBH exposure neither altered the body weight gain of F1 females, nor vaginal opening onset. Although all GBH-exposed F1 rats became pregnant, a lower number of IS was detected. F2 offspring from both GBH groups showed delayed growth, evidenced by lower fetal weight and length, associated with a higher incidence of small for gestational age fetuses. In addition, higher placental weight and placental index were found in F2 offspring from GBH-HD dams. Surprisingly, structural congenital anomalies (conjoined fetuses and abnormally developed limbs) were detected in the F2 offspring from GBH-HD group. In conclusion, perinatal exposure to low doses of a GBH impaired female reproductive performance and induced fetal growth retardation and structural congenital anomalies in F2 offspring.