Hypothetical adjustment of the acceptable daily intake and correction of the underrated risk: A case study of glyphosate-based herbicides

Following the introduction of genetically-engineered glyphosate-resistant (GEGR) crops, commercially known as Roundup Ready (RR), no pesticide’s active principle has been used as much as glyphosate; yet its safety measures have been sternly disputed.  After its classification by the International Agency for Research on Cancer (IARC) as probably carcinogenic to humans in 2015, scientists, activists, regulators and the general public revisited voluminous studies that outweighed the risk of this herbicide and raised ferocious concerns that warranted serious attention.  Recently published studies on glyphosate established at least four toxicological principles. First, glyphosate exhibited severe mammalian toxicity at concentrations orders of magnitude lower than its regulatory-promulgated ‘No Observed Adverse Effect Level’ (NOAEL) or even its ‘Chronic Reference Dose’ (cRfD) and ‘Acceptable Daily Intake’ (ADI).  Second, even though not transparently scrutinized or officially required for toxicological testing and risk assessment, glyphosate co-formulants and glyphosate-based herbicides (GBHs) are orders of magnitude more toxic than the principle active ingredient alone. Third, glyphosate and GBHs are cytotoxic and endocrine disruptors, and the latter explains why ultra low concentrations - yet environmentally relevant-cause severe chronic toxicity. Fourth, the endocrine disruption likely leads to epigenotoxicity that may be extended to offspring and unexposed descending generations.  Taken all together, it can be fairly said that confidence in the regulatory-certified ADI values is highly eroded. To resolve the paradoxical discrepancy between regulatory safety measures and elicited toxicities at concentrations far below these measures, ADI was refined using two safety or adjustment factors.  Together, these two factors scale down ADI by four orders of magnitude and bring it to an Adjusted ADI (AADI) value of 2.5 ng/kg bw/day. Contrary to regulatory ADI, the new AADI successfully explains many research findings which demonsted severe mammalian toxicity at concentrations in the neighborhood of nanograms a.i./kg bw/day. This distills confidence in the new AADI value, as well as the magnitude of the proposed safety factors.  Glyphosate uses as per human capita, in two countries representing the extremes of adopting RR crops (the USA) or not-adopting these crops (Egypt), were compared. The comparison confirms the association between growing RR crops and the escalated use of glyphosate, and shows that the American public is likely exposed to glyphosate residue at forty times higher levels than the Egyptian public.   Key words: Acceptable daily intake, adjuvant, chronic reference dose, co-formulants, food quality protection act, hazard, glyphosate, glyphosate-based herbicides, no observed adverse effect level, risk, roundup, roundup ready crops.