Study shows shortcomings of regulatory system

The glyphosate-based herbicide Roundup is an endocrine (hormone) disruptor in adult male rats, a new study shows.

The lowest dose tested of 10 mg/kg bw/d (bodyweight per day) was found to reduce levels of corticosterone, a steroid hormone produced in the adrenal glands. No other toxic effects were seen at that dose, so if endocrine disruption were not being specifically looked for, there would be no other signs that the dose was toxic.

The researchers didn’t test below that level, so we don’t know if when it comes to endocrine disruption, there are “safe” lower doses of Roundup. In technical parlance, this means that no NOAEL (no observed adverse effect level), was found.

How does this level relate to safety limits set by regulators?

One problem with trying to work out how the endocrine disruptive level of 10 mg/kg bw/d relates to “safe” levels set by regulators is that the experiment looked at Roundup, the complete herbicide formulation as sold and used, but regulators only look at the long-term safety of glyphosate alone, the supposed active ingredient of Roundup. Safe levels for Roundup chronic exposure have never been tested or assessed for regulatory processes. This is a serious omission because Roundup has been shown in many tests to be more disruptive to hormones than glyphosate alone.

Given this yawning data gap, let’s for a moment assume that the regulatory limits set for glyphosate alone can be used as a guide for the safe level of Roundup.

The endocrine disruptive level of Roundup found in the experiment, of 10 mg/kg bw/d, is is well above the acceptable daily intake (ADI) set for glyphosate in Europe (0.3 mg/kg bw/d) and the US (1.75 mg/kg bw/d). But this isn’t a reason to feel reassured, since with endocrine effects, low doses can be more disruptive than higher doses.

Another worrying factor is that 10 mg/kg bw/d is well below the NOAEL (no observed adverse effect level) for chronic toxicity of glyphosate: 500 mg/kg bw/d for chronic toxicity, according to the US EPA. In other words, the level of 500 mg/kg bw/d – a massive fifty times higher than the level of Roundup found to be endocrine disruptive in the experiment – is deemed by US regulators not to cause chronic toxicity. This experiment shows they are wrong by a long shot. They failed to see toxicity below that level because they failed to take endocrine disruptive effects from low doses into account and industry does not test for them.

Interestingly, the NOAEL for glyphosate in industry’s 3-generation reproductive studies in rats was much lower than that for chronic toxicity – 30 mg/kg bw/day for adults and 10 mg/kg bw/day for offspring. The latter figure is the same level of glyphosate as the level of Roundup found to be endocrine disruptive in the new study. These results show that the reproductive processes of the rats are sensitive to low doses that are apparently not overtly toxic. This in turn may suggest that the reproductive toxicity findings are due to endocrine disruptive effects.

Regulatory tests still do not include tests for endocrine disruption from low doses, in spite of the fact that scientists have known about the syndrome since the 1990s.

In the final section of the new study, the researchers discuss its implications. They note that the effects seen in the Roundup-treated rats were similar to adrenal insufficiency in humans and that “This condition manifests as fatigue, anorexia, sweating, anxiety, shaking, nausea, heart palpitations and weight loss. Chronic adrenal insufficiency could be fatal, if untreated. A progressive increase in its prevalence has been observed in humans…”

Since no safe dose has been established for Roundup with regard to endocrine disrupting effects, it should be banned.
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Analysis of endocrine disruption effect of Roundup® in adrenal gland of male rats

Aparamita Pandey, Medhamurthy Rudraiah,
Toxicology Reports 2 (2015) 1075–1085
http://www.sciencedirect.com/science/article/pii/S221475001530041X (open access)

Abstract

The effect of Roundup® on adrenal gland steroidogenesis and signaling pathway associated with steroid production was investigated. Doses of 10, 50, 100 and 250 mg/kg bw/d Roundup® were administered for two weeks to adult male rats. The 10 mg/kg bw/d dose which reduced circulatory corticosterone levels, but did not change food consumption and body weight, was selected for further study. The expression of cholesterol receptor (low density lipoprotein receptor), de novo cholesterol synthesis enzyme (3-hydroxy-3-methylglutaryl-coenzyme A synthase), hormone-sensitive lipase, steroidogenic acute regulatory protein (StAR) mRNA and phosphorylated form was decreased. Adrenocorticotropic hormone receptor (ACTH), melanocortin-2 receptor, expression was not changed but circulatory ACTH levels and adrenal cortex protein kinase A (PKA) activity were reduced. Surprisingly, exogenous ACTH treatment rescued steroidogenesis in Roundup®-treated animals. Apoptosis was evident at 250 mg/kg bw/d, but not at 10 mg/kg bw/d dose. These results suggest that Roundup® may be inhibitory to hypothalamic–pituitary axis leading to reduction in cyclic adenosine monophosphate (cAMP)/PKA pathway, StAR phosphorylation and corticosterone synthesis in the adrenal tissue.