Common pesticides block male hormones

I recently read this abstract in Environmental Health Perspectives Magazine (A free resource from the US National Institutes of Health). It is a summary of testing conducted at the School of Pharmacy’s Center for Toxicology under the auspices of the University of London. Naturally the information was so compelling I had to read the entire report (The study report can be read in its entirety here).

Based on their testing, many common pesticides (frequently found in food as well as milk and drinking water) will disrupt testosterone production and uptake in humans and possibly other mammals. The researchers strongly recommended that all pesticides in use today be screened to check if they block testosterone, which is critical to male (and female) reproductive health & general development.

Thirty out of 37 pesticides tested by the University of London team altered or inhibited male hormone activity, including 16 that had no previously reported hormonal effects. Most are fungicides applied to fruit and vegetable crops, including strawberries, corn, wheat, & lettuce.

Traces of pesticides and herbicides are known to remain in fruits and vegetables; these same chemicals can migrate into the ground and contaminate groundwater while also contaminating surface water. Interestingly, certain pesticides and herbicides will travel with water vapor when it evaporates, so that the contamination can travel hundreds or even thousands of miles from where it was originally applied.

“Our results indicate that systematic testing for anti-androgenic activity of currently used pesticides is urgently required,” wrote the scientists from University of London’s Centre for Toxicology, led by Professor Andreas Kortenkamp. Funded by the European Commission, the University of London scientists selected the pesticides to test by identifying those found most often in European fruits and vegetables. They are approved for use in many countries, including the United States.

The researchers noted “a clear disparity” between today’s most widely used pesticides and the current knowledge of their risks, “with the majority of the published literature focused on pesticides that are no longer registered for use in developed countries.”

Of the tested compounds, the most potent in terms of blocking androgens was the insecticide fenitrothion, an organophosphate insecticide used on orchard fruits, grains, rice, vegetables and other crops.

Others with hormonal activity include fludioxonil, fenhexamid, dimethomorph and imazalil, which are all fungicides. Fungicides (Chemical compounds or biological organisms used to kill or inhibit fungi or fungal spores. Fungicides are used both in agriculture and to fight fungal infections in animals.) are often applied close to harvest, so they are frequently found as residue in food. Fungicides “are typically applied as mixtures in order to increase effectiveness and prevent development of resistant strains and therefore, human exposure to mixtures of these in vitro anti-androgens may be considerable,” wrote Kortenkamp and the other study authors, Frances Orton, Erika Rosivatz and Martin Scholze.

To learn more about persticides, herbicides, funcicides, rodenticides, and other nasties that might be in or on your food, visit the Pesticide Action Network’s excellent resource at whatsonmyfood.org.

For six of the pesticides that showed hormonal activity for the first time, the authors said that they strongly recommend the next round of testing, using live lab animals. “Due to estimated anti-androgenic potency, current use, estimated exposure, and lack of previous data, we strongly recommend that dimethomorph, fludioxonil, fenhexamid, imazalil, ortho-phenylphenol and pirimiphos-methyl be tested for anti-androgenic effects in vivo.”

For the first four pesticides, they called it “a matter of urgency.” They are used on strawberries, lettuce, grapes and other numerous fruits and vegetables in many countries around the world.

The University of London researchers evaluated the complex biochemical interactions using in-vitro assays.  In-vitro testing is a widely accepted lab technique. Scientists, however, are uncertain what actually happens in the human body at the concentrations of chemicals that people encounter in water, fruits, vegetables, eggs, meats, and milk. Fetuses and infants may be at a significantly elevated risk when exposed in the womb or through breast milk and formula. The presence of Growth Hormone and Growth Hormone Releasing Peptide in massive amounts in youngsters’ bodies can certainly compound the problem even further.

The research findings were released while the EPA continues to face strong opposition from the pesticide industry after expanding its Endocrine Disruptor Screening Program, which mandates testing of certain chemicals found in foods and water to determine if they interfere with androgens, estrogens, or thyroid hormones.

EPA announced the initial list of chemicals to be screened for their potential effects on the endocrine system on April 15, 2009 and the first test orders were issued on October 29, 2009. Testing will eventually be expanded to cover all pesticide chemicals. Now that screening is underway, EPA is reviewing test order responses and making available the status or test order responses (PDF) and/or any decisions regarding EPA testing requirements.

EPA has developed a second list of chemicals for screening and draft policies and procedures that the Agency will use to require testing of chemicals on the second list. On November 17, 2010, EPA published three related Federal Register Notices:

• November 17, 2010 – Second List of Chemicals for Tier 1 Screening. This list includes 134 chemicals and substances that have been listed as priorities within EPA’s drinking water and pesticides programs. More information about the second list of chemicals.
• November 17, 2010 – Draft Policies and Procedures for Screening Safe Drinking Water Act Chemicals. More information about the draft policies and procedures for the second list.
• November 17, 2010 – Draft Amendment to the Existing Information Collection Request (ICR). Describes the information collection activities associated with Tier 1 screening of the second list of chemicals under the EDSP and provides EPA’s estimates for the related paperwork burden and costs.

None of the 16 pesticides with the newly discovered hormonal activity are included in the EPA’s program, which means they are not currently screened and there are no immediate plans to do so.

The EPA’s program has been incredibly slow to fully implement, mostly due to a longstanding dispute over analytical testing methods and selection of compounds to be tested. Environmental groups criticize the EPA for taking so long to require manufacturers to test such a small group of compounds, and chemical industry representatives contend that the tests could cost up to one million US dollars per chemical and that the techniques have not really been fully validated for repeatability and accuracy. Chemical industry representatives also stress that positive results don’t necessarily mean that the pesticides are actually harming human reproduction or development (This reminds me of the “Big Tobacco” arguments a few years ago).

This issue is concerning to me; we are forced to balance long-term human health and genetic survival with cheap, plentiful supplies of “food”. These are difficult decisions to make, since it can mean the difference between starvation and satiety to many communities, especially in developing nations.

Some research has linked pesticide consumption to abnormally formed genitalia in baby boys, such as cryptorchidism and hypospadias, and even decreased sperm counts in men. Male fertility is reported to be declining in many countries, and testicular cancer is increasing. Some scientists have dubbed this compilation of male disorders “testicular dysgenesis syndrome”, and suggest that man-made endocrine disrupting chemical compounds play a significant and long-lasting role.

The water quality improvement industry can play a significant role in helping consumers protect themselves from immediate and future pesticide consumption by providing Point of Entry (POE) and Point of Use (POU) water treatment systems. Many proven technologies like Granular Activated Carbon absorption/adsorption, Nanofiltration, Distillation, and Reverse Osmosis (hyperfiltration) purification are able to address numerous chemical compounds that can be found in water.

Activated carbon is extremely effective at addressing pesticides, herbicides and volatile organic compounds in water, as seen below:

 A number of ProFlow systems are designed to address these issues as part of an overall home water quality protection program to help protect from pesticides and herbicides.

When considering an investment in water treatment technology, always consult with your local WQA certified water specialist or licensed plumber with appropriate specialized water quality management training.

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Abstract

Background: Evidence suggests that there is widespread decline in male reproductive health and anti-androgenic pollutants may play a significant role. There is also a clear disparity between pesticide exposure and endocrine disrupting data, with the majority of the published literature focused on pesticides that are no longer registered for use in developed countries.

Objective: The aim of this study was to utilise estimated human exposure data to select pesticides to test for anti-androgenic activity, focusing on highest use pesticides.

Methods: We used European databases to select 134 candidate pesticides based on highest exposure, followed by a filtering step according to known or predicted receptor mediated anti-androgenic potency, based on a previously published quantitative structure-activity relationship (QSAR) model. In total, 37 pesticides were tested for in vitro androgen receptor (AR) antagonism. Of these, 14 were previously reported to be AR antagonists (“active”), 4 were predicted AR antagonists using the QSAR, 6 were predicted to not be AR antagonists (“inactive”), and 13 with unknown activity, which were “out of domain” and therefore could not be classified with the QSAR (“unknown”).

Results: All 14 pesticides with previous evidence of AR antagonism were confirmed as anti-androgenic in our assay and 9 previously untested pesticides were identified as anti-androgenic (dimethomorph, fenhexamid, quinoxyfen, cyprodinil, λ-cyhalothrin, pyrimethanil, fludioxonil, azinphos-methyl, pirimiphos-methyl). In addition, 7 compounds were classified as androgenic.

Conclusions: Due to estimated anti-androgenic potency, current use, estimated exposure, and lack of previous data, we strongly recommend that dimethomorph, fludioxonil, fenhexamid, imazalil, ortho-phenylphenol and pirimiphos-methyl be tested for anti-androgenic effects in vivo. The lack of human biomonitoring data for environmentally relevant pesticides presents a barrier to current risk assessment of pesticides on humans.

Citation: Orton F, Rosivatz E, Scholze M, Kortenkamp A 2011. Widely Used Pesticides with Previously Unknown Endocrine Activity Revealed as in Vitro Anti-Androgens. Environ Health Perspect :-. doi:10.1289/ehp.1002895

Received: 25 August 2010; Accepted: 10 February 2011; Online: 10 February 2011