The Environmental Protection Agency has released new Roundup safety limits setting new residue standards for the active ingredient in Monsanto Co.’s widely used pesticide, limiting its use on various fruits, vegetables and other agricultural products.
The federal regulator adopted a range of limits for the chemical glyphosate, from as little as 0.2 parts per million for bulb vegetables, berries and other small fruit to 100 ppm for animal forage and hay.
The new limits were developed 12 months after the government-funded pesticide research body known as Inter-Regional Research Project No. 4 filed a petition seeking the changes. The EPA followed most of IR-4’s recommendations, but held back on allowing significant increases for some root vegetables and oil seed crops.
The agency said it looked at margins of exposure to the general population under the proposed limits and concluded that there was neither short-term nor intermediate-term health risks. Glyphosate is also not expected to pose a cancer risk to humans, according to the EPA.
“Based on these risk assessments, the EPA concludes that there is a reasonable certainty that no harm will result to the general population or to infants and children from aggregate exposure to glyphosate residues,” the agency said.
Numerous studies to date have documented the toxicity of commercial Roundup. Severe malformations have occurred in embryos of the South African clawed frog Xenopus laevis and chickens. In frogs, dilutions of 1/5000 of the formulation (equivalent to 430 μM of glyphosate) were sufficient to induce malformations, including shortening of the anterior−posterior axis, microcephaly, microphthalmia, cyclopia, and craniofacial malformations at tadpole stages. Embryos injected with pure glyphosate showed similar phenotypes, suggesting that glyphosate itself, was responsible for these developmental abnormalities. Roundup produced similar effects in chicken embryos, which showed a loss of rhombomere domains, reduction of the optic vesicles, and microcephaly.
The study researchers confirmed that the mechanism by which glyphosate and Roundup caused the observed teratogenic effects in Xenopus embryos was via disruption of the retinoic acid signalling pathway. This resulted in dysregulation of the shh, slug and otx2 regulatory genes, which are crucial to the development of the central nervous system . The study, while not a classical toxicological study, is relevant to human risk assessment because the retinoic acid signalling pathway is a central signalling pathway in embryonic development that operates in virtually all vertebrates, whether amphibians, birds, or mammals.
Jayawardena et al. (2010) found nearly 60% malformations in tadpoles of the tree frog Polypedates cruciger treated with an environmentally relevant concentration of 1 ppm Roundup. Effects included kyphosis, scoliosis, and edema . Relyea (2012) found that environmentally relevant concentrations of Roundup induced relatively deeper tails similar to the adaptive changes caused by the presence of a predator in the tadpoles of the wood frog (Rana sylvatica or Lithobates sylvaticus) and leopard frog (R. pipiens or L. pipiens) . A study on tadpoles of Scinax nasicus (Lajmanovich et al., 2005) found that exposure to glyphosate herbicide caused craniofacial and mouth deformities, eye abnormalities and bent, curved tails, as well as mortality. Malformations and mortality increased with dose and time of exposure. A 2-day exposure to 3.07 mg/l glyphosate herbicide caused only 10% mortality but caused malformations in 55% of the test animals .
Malformations have also been found in mammals treated with glyphosate herbicides. A toxicological study by Dallegrave et al. (2003) found that the offspring of pregnant rats dosed with 500, 750 and 1000mg/kg Roundup on days 6–15 after fertilisation had increased skeletal abnormalities, including at doses that were not maternally toxic. Malformations consisted of the absence of bones or parts of bones, shortened and bent bones, asymmetry, fusions, and clefts. The percentage of altered foetuses increased with dose. The authors concluded that the formulated product was more toxic than the technical glyphosate evaluated by the World Health Organisation .
Scientific and political debate has continued for many years over the public health, environmental, and socioeconomic consequences of GM soy cultivation in producer countries . More recently, concerns expanded to include potential risks to animal and human health posed by glyphosate residues in the animal feed and human food chain [8,9]. Residues of up to 17 mg/kg of glyphosate have been found in harvested soybean crops .
Two mammalian toxicological studies suggest that the LOAEL for glyphosate should be even lower than the ADI of 0.1 mg/kg bw/d that we derive from the industry-sponsored studies.
Romano et al. (2010) found that Roundup is a potent endocrine disruptor and disturbed the reproductive development of rats with exposure during puberty. Adverse effects, including delayed puberty and reduced testosterone production, were found at all dose levels, including the LOAEL of 5 mg/kg. There was a clear dose-response relationship.
Benedetti et al. (2004) found that Glyphosate-Biocarb caused “irreversible” damage to rat liver cells, including at the LOAEL of 4.87 mg/kg, with a clear dose-response relationship.
Several studies specify that glyphosate herbicides are genotoxic and thus have the potential to increase the risk of birth defects and cancer. Cytogenetic monitoring of crop sprayers in Cordoba, Argentina revealed that the number of chromosomal aberrations in peripheral blood cells was significantly higher in the exposed group in comparison to the unexposed group. The pesticides most commonly used by the exposed group were glyphosate, cipermetrine, and atrazine.
An epidemiological study on Ecuadorian populations showed that people exposed to aerial glyphosate spraying showed a higher degree of DNA damage than a control population living 80 km away. Mañas et al. found that glyphosate was genotoxic in the comet assay in Hep-2 cells and in the micronucleus test at 400 mg/kg in mice.
Glyphosate herbicides and glyphosate’s main metabolite, AMPA, altered cell cycle checkpoints in sea urchin embryos by interfering with the DNA repair machinery. The failure of cell cycle checkpoints is known to lead to genomic instability and cancer in humans. Glyphosate and AMPA have also been found to cause irreversible damage to DNA that may increase the risk of cancer. AMPA damaged DNA in human cells at doses of 2.5-7.5mM and caused chromosomal breaks at 1.8mM.
The surfactants and other adjuvants in glyphosate formulations enhance the toxic effects of glyphosate, as they enable it to penetrate more easily through the cell membrane. The adjuvants alone are also toxic.
Any evaluation and recommendations of the effects of pesticide exposures must take into consideration the effects of repeated and continuous exposures. Bolognesi (2003) found that chromosomal damage caused by pesticides was temporary in short or time-limited exposures but cumulative in continuous exposures to agrochemicals.
The safety of glyphosate herbicides has been successfully challenged in several court cases. In New York in 1996, a court ruled that Monsanto was no longer allowed to market Roundup as safe, non-toxic, biodegradable or environmentally friendly. In France in 2007, Monsanto was forced to withdraw advertising claims that Roundup was biodegradable and leaves the soil clean after use. In March 2010, in a case brought by residents, a court in Santa Fe province, Argentina instituted a regional ban on the spraying of glyphosate and other agrochemicals in populated areas on grounds of “severe damage to the environment and to the health and quality of life of the residents”.
In June 2012 criminal charges were brought by affected residents against two soy producers and a crop-spraying airplane pilot, in a case heard by a court in Cordoba, Argentina. Plaintiffs charged the defendants with malicious contamination over the spraying of glyphosate and other agrochemicals in Ituzaingó, an area on the outskirts of Cordoba reportedly characterized by a high incidence of cancer and birth defects.
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