<html><body><div style="color:#000; background-color:#fff; font-family:HelveticaNeue-Light, Helvetica Neue Light, Helvetica Neue, Helvetica, Arial, Lucida Grande, sans-serif;font-size:14px"><div dir="ltr" id="yui_3_16_0_1_1427970508818_47336"></div><h1 id="yui_3_16_0_1_1427970508818_47494" style="" class="">Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate</h1><div id="yui_3_16_0_1_1427970508818_47492" style="" class=""><div id="yui_3_16_0_1_1427970508818_47493" style="" class=""> <a href="" style="" class="" id="openAuthor_au10">Kathryn Z Guyton</a></div>, <div id="yui_3_16_0_1_1427970508818_47624" style="" class=""> <a href="" style="" class="" id="openAuthor_au20">Dana Loomis</a></div>, <div id="yui_3_16_0_1_1427970508818_47634" style="" class=""> <a href="" style="" class="" id="openAuthor_au30">Yann Grosse</a></div>, <div id="yui_3_16_0_1_1427970508818_47629" style="" class=""> <a href="" style="" class="" id="openAuthor_au40">Fatiha El Ghissassi</a></div>, <div id="yui_3_16_0_1_1427970508818_47630" style="" class=""> <a href="" style="" class="" id="openAuthor_au50">Lamia Benbrahim-Tallaa</a></div>, <div id="yui_3_16_0_1_1427970508818_47631" style="" class=""> <a href="" style="" class="" id="openAuthor_au60">Neela Guha</a></div>, <div id="yui_3_16_0_1_1427970508818_47632" style="" class=""> <a href="" style="" class="" id="openAuthor_au70">Chiara Scoccianti</a></div>, <div id="yui_3_16_0_1_1427970508818_47633" style="" class=""> <a href="" style="" class="" id="openAuthor_au80">Heidi Mattock</a></div>, <div id="yui_3_16_0_1_1427970508818_47491" style="" class=""> <a href="" style="" class="" id="openAuthor_au90">Kurt Straif</a></div>, <div id="yui_3_16_0_1_1427970508818_47637" style="" class=""><a href="" id="yui_3_16_0_1_1427970508818_47636" style="" class=""><span id="yui_3_16_0_1_1427970508818_47635" style="" class="">on behalf of the International Agency for Research on Cancer Monograph Working Group, IARC, Lyon, France</span></a></div></div><div style="" class=""><span style="" class=""><span style="" class="">Published Online: </span>20 March 2015</span></div><div id="yui_3_16_0_1_1427970508818_47638" style="" class=""><span style="" data-uuid="2f95d6af-faf4-17ae-dbdb-6dd7fc7c28e3" class="" data-doi="10.1016/S1470-2045(15)70134-8" data-link-target="_blank"><a class="" target="_blank" href="http://www.altmetric.com/details.php?domain=www.thelancet.com&citation_id=3814653" style="display:inline-block;">
<img data-id="ea83398d-00c7-4ec8-483d-3b50310188d8" class="" alt="Article has an altmetric score of 948" src="https://d1uo4w7k31k5mn.cloudfront.net/v2/948.png" style="border:0; margin:0; max-width: none;" height="18px" width="88px">
</a>
</span></div><div id="yui_3_16_0_1_1427970508818_47720" style="" class="">DOI:
<a style="" class="" href="http://dx.doi.org/10.1016/S1470-2045%2815%2970134-8">http://dx.doi.org/10.1016/S1470-2045(15)70134-8</a></div><div style="" class="" id="container"><h2 style="" class=""><a style="" class="" href="http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2970134-8/fulltext#"><img data-id="9c1e19e9-7b34-5807-afcd-8d849babd6a4" style="" class="" id="imgShowHide" src="http://www.thelancet.com/templates/jsp/images/expand.gif" alt="show">Article Info</a></h2></div><div style="" class="" data-pb-dropzone="enhancedMetaDataDropZone">
<div style="" class="" id="0c6d4bed-f77c-4343-b653-11d5fc5890d9">
<div style="" class="">
<div style="" class=""><div style="" class=""> <span style="" class="" data-ajax-content="/pb/widgets/collections/findArticleCollections/S1470204515701348"></span> </div></div>
</div>
</div>
</div><ul id="yui_3_16_0_1_1427970508818_47640" style="" class=""><li id="yui_3_16_0_1_1427970508818_47639" style="" class=""><a style="" class="" href="http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2970134-8/abstract">Summary</a></li><li style="" class=""><a style="" class="" href="http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2970134-8/fulltext">Full Text</a></li><li style="" class=""><a style="" class="" href="http://www.thelancet.com/action/showFullTextImages?pii=S1470-2045%2815%2970134-8">Tables and Figures</a></li><li style="" class=""><a style="" href="http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2970134-8/references" class="">References</a></li></ul><div id="yui_3_16_0_1_1427970508818_47719" style="" class="">In
March, 2015, 17 experts from 11 countries met at the International
Agency for Research on Cancer (IARC; Lyon, France) to assess the
carcinogenicity of the organophosphate pesticides tetrachlorvinphos,
parathion, malathion, diazinon, and glyphosate (<a style="" class="" href="http://www.thelancet.com/cms/attachment/2027792373/2046172392/si1.gif" target="_blank">table</a>). These assessments will be published as volume 112 of the IARC Monographs.<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib1" class="">1</a></sup></span></div><div id="yui_3_16_0_1_1427970508818_47642" style="" class=""><div style="" class="" id="tbl1"><div id="yui_3_16_0_1_1427970508818_47641" style="" class=""><h4 style="" class="">Table </h4><div style="" class="">IARC classification of some organophosphate pesticides</div></div><div style="" class=""><div style="" class=""><a href="" style="" class=""><img data-id="116d79e7-5dff-ae27-5f29-2059b6d8110d" style="" class="" src="http://www.thelancet.com/templates/jsp/_style2/images/dummy_table_thumb.gif" alt="Table thumbnail"></a></div></div><div style="" class=""><div style="" class="">EU=European Union.</div></div><div style="" class="" id="tbl1fn1"><a style="" class="" href="http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2970134-8/fulltext#back-tbl1fn1">*</a>See
the International Agency for Research on Cancer (IARC) preamble for
explanation of classification system (amended January, 2006).</div><div style="" class="" id="tbl1fn2"><a style="" class="" href="http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2970134-8/fulltext#back-tbl1fn2">†</a>The
2A classification of diazinon was based on limited evidence of
carcinogenicity in humans and experimental animals, and strong
mechanistic evidence; for malathion and glyphosate, the mechanistic
evidence provided independent support of the 2A classification based on
evidence of carcinogenicity in humans and experimental animals.</div></div></div><div id="yui_3_16_0_1_1427970508818_47490" style="" class="">The
insecticides tetrachlorvinphos and parathion were classified as
“possibly carcinogenic to humans” (Group 2B). The evidence from human
studies was scarce and considered inadequate. Tetrachlorvinphos induced
hepatocellular tumours (benign or malignant) in mice, renal tubule
tumours (benign or malignant) in male mice,<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib2" class="">2</a></sup></span>
and spleen haemangioma in male rats. Tetrachlorvinphos is a reactive
oxon with affinity for esterases. In experimental animals,
tetrachlorvinphos is systemically distributed, metabolised, and
eliminated in urine. Although bacterial mutagenesis tests were negative,
tetrachlorvinphos induced genotoxicity in some assays (chromosomal
damage in rats and in vitro) and increased cell proliferation
(hyperplasia in rodents). Tetrachlorvinphos is banned in the European
Union. In the USA, it continues to be used on animals, including in pet
flea collars.</div><div id="yui_3_16_0_1_1427970508818_47718" style="" class="">For parathion, associations with cancers in
several tissues were observed in occupational studies, but the evidence
in humans remains sparse. In mice, parathion increased
bronchioloalveolar adenoma and/or carcinoma in males, and lymphoma in
females. In rats, parathion induced adrenal cortical adenoma or
carcinoma (combined),<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib3" class="">3</a></sup></span>
malignant pancreatic tumours, and thyroid follicular cell adenoma in
males, and mammary gland adenocarcinoma (after subcutaneous injection in
females).<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib4" class="">4</a></sup></span>
Parathion is rapidly absorbed and distributed. Parathion metabolism to
the bioactive metabolite, paraoxon, is similar across species. Although
bacterial mutagenesis tests were negative, parathion induced DNA and
chromosomal damage in human cells in vitro. Parathion markedly increased
rat mammary gland terminal end bud density.<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib4" class="">4</a></sup></span> Parathion use has been severely restricted since the 1980s.</div><div id="yui_3_16_0_1_1427970508818_47643" style="" class="">The
insecticides malathion and diazinon were classified as “probably
carcinogenic to humans” (Group 2A). Malathion is used in agriculture,
public health, and residential insect control. It continues to be
produced in substantial volumes throughout the world. There is limited
evidence in humans for the carcinogenicity of malathion. Case-control
analyses of occupational exposures reported positive associations with
non-Hodgkin lymphoma in the USA,<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib5" class="">5</a></sup></span> Canada,<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib6" class="">6</a></sup></span> and Sweden,<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib7" class="">7</a></sup></span>
although no increased risk of non-Hodgkin lymphoma was observed in the
large Agricultural Health Study cohort (AHS). Occupational use was
associated with an increased risk of prostate cancer in a Canadian
case-control study<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib8" class="">8</a></sup></span> and in the AHS, which reported a significant trend for aggressive cancers after adjustment for other pesticides.<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib9" class="">9</a></sup></span> In mice, malathion increased hepatocellular adenoma or carcinoma (combined).<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib10" class="">10</a></sup></span>
In rats, it increased thyroid carcinoma in males, hepatocellular
adenoma or carcinoma (combined) in females, and mammary gland
adenocarcinoma after subcutaneous injection in females.<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib4" class="">4</a></sup></span>
Malathion is rapidly absorbed and distributed. Metabolism to the
bioactive metabolite, malaoxon, is similar across species. Malaoxon
strongly inhibits esterases; atropine reduced carcinogenesis-related
effects in one study.<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib4" class="">4</a></sup></span>
Malathion induced DNA and chromosomal damage in humans, corroborated by
studies in animals and in vitro. Bacterial mutagenesis tests were
negative. Compelling evidence supported disruption of hormone pathways.
Hormonal effects probably mediate rodent thyroid and mammary gland
proliferation.</div><div id="yui_3_16_0_1_1427970508818_47488" style="" class="">Diazinon has been applied in agriculture
and for control of home and garden insects. There was limited evidence
for diazinon carcinogenicity in humans. Positive associations for
non-Hodgkin lymphoma, with indications of exposure–response trends, were
reported by two large multicentre case-control studies of occupational
exposures.<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib5" class="">5</a></sup></span><sup style="" class="">,</sup> <span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib6" class="">6</a></sup></span>
The AHS reported positive associations with specific subtypes, which
persisted after adjustment for other pesticides, but no overall
increased risk of non-Hodgkin lymphoma.<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib11" class="">11</a></sup></span>
Support for an increased risk of leukaemia in the AHS was strengthened
by a monotonic increase in risk with cumulative diazinon exposure after
adjustment for other pesticides. Multiple updates from the AHS
consistently showed an increased risk of lung cancer with an
exposure–response association that was not explained by confounding by
other pesticides, smoking, or other established lung cancer risk
factors.<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib12" class="">12</a></sup></span>
Nonetheless, this finding was not replicated in other populations. In
rodents, diazinon increased hepatocellular carcinoma in mice and
leukaemia or lymphoma (combined) in rats, but only in males receiving
the low dose in each study. Diazinon induced DNA or chromosomal damage
in rodents and in human and mammalian cells in vitro. Some additional
support for human relevance was provided by a positive study of a small
number of volunteers exposed to a diazinon formulation.<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib13" class="">13</a></sup></span></div><div id="yui_3_16_0_1_1427970508818_47489" style="" class="">Glyphosate
is a broad-spectrum herbicide, currently with the highest production
volumes of all herbicides. It is used in more than 750 different
products for agriculture, forestry, urban, and home applications. Its
use has increased sharply with the development of genetically modified
glyphosate-resistant crop varieties. Glyphosate has been detected in air
during spraying, in water, and in food. There was limited evidence in
humans for the carcinogenicity of glyphosate. Case-control studies of
occupational exposure in the USA,<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib14" class="">14</a></sup></span> Canada,<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib6" class="">6</a></sup></span> and Sweden<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib7" class="">7</a></sup></span>
reported increased risks for non-Hodgkin lymphoma that persisted after
adjustment for other pesticides. The AHS cohort did not show a
significantly increased risk of non-Hodgkin lymphoma. In male CD-1 mice,
glyphosate induced a positive trend in the incidence of a rare tumour,
renal tubule carcinoma. A second study reported a positive trend for
haemangiosarcoma in male mice.<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib15" class="">15</a></sup></span>
Glyphosate increased pancreatic islet-cell adenoma in male rats in two
studies. A glyphosate formulation promoted skin tumours in an
initiation-promotion study in mice.</div><div id="yui_3_16_0_1_1427970508818_47647" style="" class="">Glyphosate has been
detected in the blood and urine of agricultural workers, indicating
absorption. Soil microbes degrade glyphosate to aminomethylphosphoric
acid (AMPA). Blood AMPA detection after poisonings suggests intestinal
microbial metabolism in humans. Glyphosate and glyphosate formulations
induced DNA and chromosomal damage in mammals, and in human and animal
cells in vitro. One study reported increases in blood markers of
chromosomal damage (micronuclei) in residents of several communities
after spraying of glyphosate formulations.<span style="" class=""><sup style="" class=""><a href="" style="" id="back-bib16" class="">16</a></sup></span>
Bacterial mutagenesis tests were negative. Glyphosate, glyphosate
formulations, and AMPA induced oxidative stress in rodents and in vitro.
The Working Group classified glyphosate as “probably carcinogenic to
humans” (Group 2A).</div><div id="yui_3_16_0_1_1427970508818_47711" style="" class=""><br></div><div id="yui_3_16_0_1_1427970508818_47713" dir="ltr" style="" class=""><a id="yui_3_16_0_1_1427970508818_47712" href="http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2970134-8/fulltext">http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2970134-8/fulltext</a><br></div><div id="yui_3_16_0_1_1427970508818_47646"> </div><div id="yui_3_16_0_1_1427970508818_47645" class="signature"><div id="yui_3_16_0_1_1427970508818_47644" style="color:rgb(255, 127, 0);"><font style="color:rgb(255, 127, 0);font-weight:bold;font-family:arial, helvetica, sans-serif;" size="2"><span style="font-family:bookman old style, new york, times, serif;"><span style="font-family:arial, helvetica, sans-serif;">===============================</span><br>Chuck Palazzo<br>Agent Orange Action Group</span><br>http://aoag.org/<br><span style="font-family:bookman old style, new york, times, serif;">Chapter 160, </span></font><font style="color:rgb(255, 127, 0);font-weight:bold;font-family:arial, helvetica, sans-serif;" size="2"><span style="font-family:bookman old style, new york, times, serif;"><font style="color:rgb(255, 127, 0);font-weight:bold;font-family:arial, helvetica, sans-serif;" size="2"><span style="font-family:bookman old style, new york, times, serif;">Hoa Binh, </span></font>Veterans For Peace</span><br>http://vfp-vn.ning.com/</font><font size="1"><font class="yui_3_2_0_2_133065404731860" style="font-weight:bold;font-family:arial, helvetica, sans-serif;" size="2"><br></font></font><span class="yiv118013358"></span><br><font size="1"><font style="font-weight:bold;font-family:arial, helvetica, sans-serif;" size="2">chuck_pal@yahoo.com<br>================================</font></font></div><div><span><br></span></div></div></div></body></html>