Atrazine Poisoning Worse Than Suspected, binds glutathione, potentiates arsenic toxicity; has endocrine olfactory effects

[Guest guest]

[For instance, consider atrazine's effects within a fedtus, infant, or toddler

whose glutathione is low due to recent or chronic infection.]

Atrazine Poisoning Worse Than Suspected

http://www.i-sis.org.uk/full/atrazineFull.php

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

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].

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.

1.US Environmental Protection Agency " OVERVIEW OF ATRAZINE RISK ASSESSMENT "

May 2, 2002 Reregistration Branch 3, Health Effects division, Office of

Pesticides Programs A.

2.De Prado R, -ez N, and -Gutierrez J. Identification of

two mechanisms of atrazine resistance in Setaria faberi and Setaria viridius

biotypes. 2000 Pesticide Biochemistry and Physiology 2000, 67,114-24.

3.Cherifi M, Ravelton M, Picciocchi A, Ravanel P and Tissut M. Atrazine

metabolism in corn seedlings, Plant Physiol Biochem 2001, 39,665-72.

4.Frey J. Genetic flexibility of plant chloroplasts, Nature 1998, 398, 115-6.

5.Smeda R, Hasegawa P, Goldborough P, Singh N and Weller S. A serine to

threonine substitution in the triazine herbicide-binding protein in potato cells

results ih atrazine rtesistance without impairing productivity, Plant Physiol

1993, 103,911-7.

6.Inui H, Kodama T, Ohkawa Y and Ohkawa H. Herbicide metabolism and cross

tolerance in transgenic potato plants co-expressing human CYP1A1,CYP2B6, and

CYP2C19, Pesticide Biochemistry and physiology 2000, 66,116-29.

7. T, A, Lee M, Mendoza M, Noriega N, Stuart A and Vonk A.

Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at

low ecologically relevant doses, PNAS 2002, 99,5476-80.

8. T, Haston K, Tsui M, Hoang A, Haeffele C. and Vonk A.

Atrazine-induced hermaphroditism at 0.1ppb in American leopard frogs (Rana

pipiens: Laboratory and field evidence " ) Environmental Health Perspectives 2002,

doi:10.1289/eph.5932 (available at http://dx.doi.org/) online 23 October 2002

9. T, Haston K, Tsui M, Hoang A, Haeffele C. and Vonk A. Feminization of

male frogs in the wild, Nature 2002, 419,895-6.

10.Renner R. Conflict brewing over herbicide’s link to frog deformities,

Science 2002, 298,938-9.

11.Mosconi G, Carnevali M, Franzoni M, Cottone E, Lutz I, Kloas W, Yamamoto K,

Kikuama S and Polzonetti-Magni A. Environmental estrogens and reproductive

biology in amphibians Minireview, 2002 General and Comparative Endocrinology

2002, 126,125-9.

12. A and Lower N. The impact of two pesticides on olfactory-mediated

endocrine function in mature male Atlantic salmon. Comparative Biochemistry and

Physiology Part B 2001, 129,269-76.

13.Friedman A. Atrazine inhibition of testosterone production in rat males

following prepubertal exposure, Reproductive Toxicology 2002, 16, 275-9.

14.Graymore M, Stagnitti F and G. Impacts of atrazine on equatic

ecosystems Environment International 2001, 26,483-95.

15.Marino A and Ray J. The Electric Wilderness, San Francisco Press, 1986,

ISBN 0-911302-55-7.

16. " Cancer study revives cellphone safety fears " by Duncan Graham-Rowe, New

Scientist 24 October 2002.

17.See Musumeci F. (ed.) Energy and Information Transfer in Biological

Systems, Proceedings of Conference, September 18-22, Acireale, Sicily, World

Scientific, in press, 2002.

18.Ullman D. Homeopathy is nanopharmacology. ISIS Report November 5, 2002

19.Ho MW. The strangeness of water and homeopathic ‘memory’, Science in

Society 2002, 15, 22-25.

20. " Molecules clump on dilution " by Mae-Wan Ho, Science in Society 2002, 15,

21.

21.Marino AA, Wolcott RM, Chervenak R, Jourd’heuil F, Nilsen E and Frilot II

C. Nonlinear dynamical law governs magnetic field induced changes in lymphoid

phenotype. Bioelectromagnetics 2001, 22, 529-46.

22.International Agency for Research on Cancer " Overall Evaluations of

Carcinogenicity to Humans

6-Chloro-N-ethyl-N¢-(1-methylethyl)-1,3,5-triazine-2,4-diamine " VOL.: 73 (1999)

(p. 59)

23.UNITED STATES ENVIRONMENTAL PROTECTION AGENCY REVISED HUMAN HEALTH RISK

ASSESSMENT Atrazine April 16, 2002 Reregistration Branch 3 Health Effects

Division Office of Pesticide Programs

24.Tchounwou P, B, Ishaque A and Schneider J. Atrazine potentiation of

arsenic trioxide-induced cytotoicity and gene expression in human liver

carcinoma cells (HepG2) " Molecular and cellular Biochemistry 2001, 222, 49-59.

25.Munger R, Isacson P; Hu S; Burns T; Hanson J; Lynch CF; Cherryholmes K; Van

Dorpe P; Hausler WJ Jr " Intrauterine growth retardation in Iowa communities with

herbicide-contaminated drinking water supplies " Environ Health Perspect 1997,

105,308-14.

26.Gfrerer M, Martens D, Gawik B, Wenzi T, Zhang A, Quan X, Cheng S, Chen J,

Platzer B, Lankmayr E and Kettrup A. Triazines in the aquatic systems of the

eastern Chinese Rivers Liao-He and Yangtse. Chemosphere 2002, 47, 455-66.

27.Dijk H and Guicherit R. Atmospheric dispersion of current use pesticides: A

review of the evidence from monitoring studies. Water, Air and Soil Pollution

1999, 115,21-70.

28. " WHAT MAKES A WEED? " AGBIOTECH INFOSOURCE Issue 58 October, 2000 Published

by Ag-West Biotech Inc. http://www.agwest.sk.ca/e_infosrc.shtml