Glyphosate does not have the same biological properties as organophosphate insecticides, and an extensive battery of neurotoxicology and general toxicity studies in laboratory animals has found no evidence that glyphosate inhibits cholinesterase activity, or causes neuropathy or other disorders in the nervous system. The largest and most comprehensive study of pesticide applicators (Kamel et al, 2007) has found no association between the use of glyphosate and Parkinson’s disease.
1.5 Human exposure to glyphosate
During the assessment process for pesticides that may leave residues in food, chemicals are assigned an Acceptable Daily Intake (ADI), which is the level of intake of a chemical that can be ingested daily over a lifetime without any appreciable risk to health.
The current ADI for glyphosate, set by the Australian DoHA in 1985, is 0.30 mg/kg bw/d, based on a NOEL of 30 mg/kg bw/d (the highest administered dose) in a three-generation reproduction study in rats. There is a 100-fold safety factor between the pivotal NOEL and the ADI, comprised of a ten-fold component to account for extrapolation from animals to humans and a further ten-fold component to account for variation in sensitivity within the human population. The toxicological studies cited by EOS do not demonstrate any need to revise the ADI.
By comparison with the ADI, the actual level of exposure for Australians is probably much lower. Based on the consumption of food commodities for which the APVMA has set Maximum Residue Limits (MRLs), the National Estimated Daily Intake (NEDI) of glyphosate is 0.02 mg/kg bw/d, or only six percent of the ADI. Even this value may be conservative. Following a dietary survey of pregnant Australian women and analysis of composite food samples they provided, McQueen et al (2012) have estimated that maternal dietary exposure to glyphosate is 0.001 mg/kg bw/d. This dose is 0.33% of the ADI, and is also only 5% of the NEDI of 0.02 mg/kg bw/d. Internationally, the JMPR (2004a) estimated theoretical maximum daily intake for glyphosate is 1% of the WHO ADI of 0–1.0 mg/kg bw/d.
Evidence suggests that exposure of glyphosate product users is also relatively low. This may be due to the relatively low dermal absorption rate, which the EU (2002) assessment estimated to be less than 3% for glyphosate and no more than 1% for glyphosate trimesium. In a biomonitoring study of American farming families, Acquavella et al (2004) detected glyphosate in the urine of 60% of farmers, 4% of their spouses and 12% of their children on the day of application. According to the JMPR (2004b) assessment, the maximum systemic (absorbed) doses from a single mixing / loading / application event were 0.004, 0.00004 and 0.0008 mg/kg bw in the farmers, spouses and children, respectively. These values represent 1.3%, 0.013% and 0.27% of the Australian ADI for glyphosate.
1.6 Overseas assessment activity
The US EPA and the Canadian PMRA initiated routine scheduled re-registration reviews of glyphosate in 2009 and 2010, respectively. Both these regulators will use the reviews to consider new research on glyphosate, relating to potential effects on environmental and human health. The EPA will assess studies on the immunotoxicity and acute and subchronic neurotoxicity of glyphosate, the ecotoxicity of products containing the surfactant POEA, and the ecological risk posed by aminomethyl phosphonic acid (AMPA, a degradation product of glyphosate). The review is scheduled for completion in 2015 (US EPA, 2009). In addition to the re-registration review, the EPA is also evaluating glyphosate under the Endocrine Disruptor Screening Program. The Canadian review, targeted for completion in 2014, will include health and environmental risk assessments of the POEA/glyphosate combination (see http://www.hc-sc.gc.ca/alt_formats/pdf/pubs/pest/decisions/rev/rev2010-02-eng.pdf).
The APVMA currently has no data before it suggesting that glyphosate products registered in Australia and used according to label instructions present any unacceptable risks to human health, the environment and trade.
The weight and strength of evidence shows that glyphosate is not genotoxic, carcinogenic, or neurotoxic.
Glyphosate causes malformations in toad and chicken embryos treated by incubation and/or injection, but these findings are not predictive of a developmental hazard to humans because of the routes of administration used. Studies in birds and/or rats have reported that some glyphosate-based herbicide formulations (GBHFs) cause foetal skeletal abnormalities, toxicity to the male reproductive system and interference with the maturation of the male reproductive organs during puberty. However, the relevant studies were affected by flawed design, methodology and / or reporting, and the claimed effects on puberty have been inconsistent in different studies.
Glyphosate is not a teratogen in rats and rabbits treated via oral administration and has not shown reproductive toxicity in multi-generation dietary studies in rats. Epidemiological studies have found no consistent or convincing evidence of reproductive dysfunction in human populations reportedly exposed to glyphosate. Glyphosate is therefore extremely unlikely to cause reproductive or developmental toxicity in humans under normal conditions of exposure.
The potential for glyphosate to cause endocrine disruption will be clarified by the current review under the US EPA’s Endocrine Disruptor Screening Program. In studies published so far, glyphosate has shown a lack of activity in the Hershberger and uterotrophic assays in rats or in tests for interaction with oestrogen and androgen receptors, inhibition of steroidogenesis, or interference with metamorphosis in amphibians. At present, there is no scientific justification for classifying glyphosate as an endocrine disruptor.
Surfactants present in the test GBHFs may have confounded the results of in vitro studies of their effects on hormonal regulation and cellular toxicity. Furthermore, the relevance of some test systems to human hazard and risk assessment is unproven.
Most studies with GBHFs have not identified which of their chemical constituents caused the reported effects on cells and laboratory animals, or characterised their mode of action.
The toxicological studies cited by EOS do not demonstrate a need to revise the current Australian ADI of 0.3 mg/kg bw/d for glyphosate. The available evidence indicates that there are very wide margins between the ADI and the actual intake of glyphosate via food and from exposure while preparing and applying glyphosate products.
The APVMA will monitor the US and Canadian reviews of glyphosate and consider any new information that emerges.