Controversy erupted over new findings that atrazine may be linked to global demise of frogs. Prof. Joe Cummins and Dr. Mae-Wan Ho review the evidence on the endocrine-disrupting and carcinogenic effects of atrazine, especially in the light of the non-linearity of biological activities, and call for a global ban of the herbicide.
Atrazine is an herbicide registered in the United States for the control of broadleaf weeds and some grassy weeds. It is currently used on corn, sorghum, sugarcane, wheat (to get rid of wheat stubble on fallow land following wheat harvests; wheat is not the target crop), guava, macadamia nuts, orchard grass and hay, range grasses, and southern turf grasses. Atrazine is most widely used on corn followed by sorghum and sugarcane. Atrazine is registered for use on range grasses for establishing permanent grass cover on rangelands and pastures under the Conservation Reserve Program (CRP) in four states: Oklahoma, Nebraska, Texas, and Oregon. The CRP is administered by the US Department of Agriculture (USDA).
There are prohibitions against grazing on these CRP lands, and cutting the grasses for hay, except in national emergencies, such as severe drought, and there are "right-of-way" uses with grazing restrictions. Atrazine is also registered for use on the following non-agricultural sites: lawns, golf courses, and sod farms [1]. Worlwide, atrazine is a leading agricultural chemical, and so extensively used that it has been identified as a significant pollutant in surface water, groundwater, in offshore areas and in the atmosphere.
Atrazine acts by inhibiting photosynthesis. Many atrazine-tolerant mutations have begun to appear in weeds, and this tolerance is predominantly based on detoxifying atrazine by binding it to glutathione [2], a mechanism in naturally atrazine-tolerant corn [3]. Efforts have been made to select or produce atrazine-tolerant mutants crops such as soybean that is otherwise difficult to rotate with atrazine-treated corn or potato.
Most of the crop-plant mutants had impaired productivity [4], but in potato, an atrazine-binding photosynthetic protein is mutated, and this makes it tolerant to the herbicide without impaired productivity [5]. Transgenic potato containing a complex of human cytochrome p450 genes was found to be tolerant to atrazine, and was proposed for phytoremediation of chemically polluted croplands [6]. Unfortunately, the cytochrome p450 enzymes are very important in metabolism of man-made chemicals, they both inactivate many carcinogens, and in some instances, activate pollutants to form carcinogens. Atrazine is used worldwide, but its continued application is hampered by appearance of atrazine-tolerant weeds.
Atrazine was in the news recently in connection with the global demise of frogs. Frogs were reported to be demasculinized or became hermaphrodite after being exposed at low ecologically relevant doses of the herbicide in the laboratory [7]. Levels as low as 0.1 parts per billion atrazine induced hermaphroditism. This was confirmed by fuller ecological evidence that atrazine is associated with hermaphroditism in frogs at levels an order of magnitude below the currently accepted standard [8,9].
Those findings were criticized on several grounds, but mainly on the basis that very low levels of atrazine produced a stronger impact than levels 250 times higher, and that the low levels of atrazine did not induce the cytochrome p450 enzyme aromatase [10]. Such criticism is significant, but should be considered in the light that endocrine disrupting chemicals often have more marked effect at lower doses [10], and the enzyme aromatase, though important in producing the feminizing hormone estrogen, shows complex cellular patterns of activation in animals exposed to feminizing pollutants [11].
The endocrine-disrupting effects of atrazine are not restricted to frogs. Atrazine reduced olfactory-mediated endocrine functions in salmon at levels commonly observed in polluted water [12]. And it was found to inhibit testosterone production in prepubertal rats [13].
The impact of atrazine on endocrine disruption is very serious. A study of aquatic ecosystems concluded that a single universal maximum on atrazine in catchments does not provide adequate environmental protection, and suggests flexible limits be set [14]. However, it may be far more reasonable to discuss eliminating further atrazine input into the aquatic environment altogether.
Another important factor that is almost never considered in environmental risk assessment is that biological activities are predominantly nonlinear: weak forces or extremely low concentrations of a chemical may have disproportionately large effects at times, and conversely, strong forces or high concentrations of the chemical may have no effects at all.
The debate over the biological effects of trace chemical pollutants, which Rachel Carson began some fifty years ago, is getting to resemble the debate over the biological effects of weak electromagnetic fields that erupted in the 1970s [15], and more recently the effects of microwaves emanating from mobile phones and antennas [16]. It is symptomatic of the basic inadequacy of the linear, mechanistic model of living systems that still dominates the scientific establishment, at a time when scientists across the disciplines are already working with non-linear dynamical models and even quantum coherent models of living systems [17].
It has not escaped our notice that in homeopathy, more dilute concentrations of substances are said to be 'potentised', and expected to produce stronger effects, or in any case, effects opposite to what the same substance would produce at high concentrations [18]. That, too, could fall within the spectrum of nonlinear behaviour of living systems, although it is much more difficult to explain [19, 20].
Andrew Marino and his coworkers [21] have recently devised nonlinear statistical methods for analyzing the biological effects of weak electromagnetic fields that may be relevant to a range of data including the endocrine-disrupting effects of atrazine and other environmental pollutants.
The International Agency for Research on Cancer determined that there is sufficient evidence for the carcinogenicity of atrazine in animals, but not in humans [22]. The United States Environmental Protection Agency (EPA) concluded that the cancer studies showing atrazine carcinogenic in animals were not applicable to human but EPA did make minor adjustments to the regulatory framework for atrazine based on the elevated pollution by that herbicide [23]. Recently, atrazine was found to potentiate arsenic toxicity in human cells [24], a result that causes concern in areas where drinking water is polluted with both toxins. Even though cancer has been a focus of regulatory action on the herbicide, impacts such as the intra-uterine growth retardation observed in communities with atrazine-polluted drinking water supplies [25] have been given scant consideration.
Atrazine can be present in parts per million in agricultural run-offs and can reach 40 parts per billion in precipitation [7]. The global impact of atrazine is staggering. Significant atrazine pollution has been found in the Lio-He and Yangtse rivers of China [26], and a review of the atmospheric dispersion of atrazine shows impacts of the herbicide even in isolated areas of the globe [27].
Prompt action to limit further pollution from atrazine may be delayed by the development of "super weeds" from current herbicide tolerant GM crops, and volunteer crops or weeds that develop multiple-herbicide tolerance by gene flow between commercial varieties. Some authorities and government regulators advise that herbicides such as atrazine should be used to control superweeds [28]. This is the height of lunacy and irresponsibility. There should be a global ban on atrazine.
Article first published 09/11/02
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