PART 2: ENDOCRINE DISRUPTION AND PESTICIDE HALL OF SHAME

SHORT ABSTRACT

• Ways of exposure to chemicals – agricultural use; use in cattle dips and in animal husbandry; use as household insecticides or in gardens; sanitary indoor use in schools, offices, hospitals, and other institutions; public health use; medical human use; veterinary products for pets.
• Biopesticides – represent a very small fraction of the global pesticides market, but they are the fastest-growing segment of the agrochemical industry.
• Ways of exposure to endocrine disruptors – humans are exposed to EDCs through ingestion, inhalation, and direct contact with skin. Wildlife is also exposed through food and water consumption.
• Pesticide Hall of Shame – BPA, dioxins, phthalates, heavy metals, organophosphate pesticides, pyrethroid insecticides, atrazine, 2,4-D, oxyfluorphen, epoxiconazole.

When I was growing up, my grandparents (on my mom’s side) had a small field. Nothing biggie, only 2 acres of land. They produced fruits and vegetables for the local market. I grew up eating “eco” food that smelled like…Food. Back in those days, maybe 20 years ago, the words “eco”, “bio” and “organic” weren’t in everybody’s dictionary. We grew our own food; we put animal manure as fertilizer; after the produce was ripe, we collected it, washed it with water, and ate it – either raw or cooked.

Fast forward 20 years and many things have changed. My grandparents aren’t alive anymore, the field is on sale and we buy our fruits and veggies from the local market. As time went on, industries became bigger, the need for food even bigger, and, of course – the need for speed, quantity, and visual quality was the biggest. So, people started using biocidal and plant protection products (pesticides). The smell of the product is not that seductive now, and you can buy fruits that last for 3 weeks (not kept in the fridge) and do not rot.

Today, the pesticide industry employs millions of people. Thousands of chemicals can be used as pesticides, and they are organized into different pesticide groups. Some domestic, cosmetic, agricultural, or veterinary products may contain more than one chemical from the same or different chemical group. Exposure to these chemicals can occur, for example, during:

• Agricultural use (spraying fields or seed treatment); as a side note: it has been estimated that as many as 25 million agricultural workers worldwide experience unintentional pesticide poisonings each year. (1)
• Use in cattle dips and in animal husbandry.
• Use as household insecticides (indoor), or in gardens.
• Sanitary indoor use in schools, offices, hospitals, and other institutions.
• Public health use (outdoor and indoor), for example: in parks and urban areas, for vector control (malaria, Chagas disease, dengue, and onchocerciasis)
• Medical human use: to treat head lice and scabies.
• Veterinary products for pets: to treat infestations with fleas and ticks. (2)

In short – you can run, but pesticides are probably on the soles of your sneakers. You take them and bring them with you everywhere you go.

Not all is dim, though, I assure you. There is light at the end of the tunnel. Even if you wear sneakers.

A worldwide demand for a reduction in the use of chemical pesticides, regarded by consumers as harmful, is leading to the development of innovative and less harmful plant protection strategies. Pesticides such as organochlorine insecticides and methyl bromide are discontinued due to their health hazards. Growing consumer awareness for food and agricultural products with less or no chemical residues, and growers’ and farmers’ demands for safer pesticides, have triggered a big demand for biopesticides. Biopesticides include microbial pesticides, entomopathogenic nematodes, baculoviruses, plant-derived pesticides, and insect pheromones. They are increasingly being tested as alternatives to chemical pesticides and key components of Integrated Pest Management (IPM). Biopesticides represent a very small fraction of the global pesticide market, but they are the fastest-growing segment of the agrochemical industry. (3)

We’ll talk more about the future better days a bit later. First – let me give you a small dose of fear with facts about endocrine disruption. I won’t scare you much, I promise. (I hope).

How I stumbled into the toxicology field is a short story, really. When I went to uni, I didn’t have the faintest idea of what I wanted to do with my life. I had only one goal: catch the morning bus. Oh yeah – and, pass all the exams. So, two goals. Time went by, I passed the exams and it was time to do the Master’s thesis. I decided to go into toxicology. I was offered a theme about pesticides as endocrine disruptors. It sounded pretty interesting, so I accepted it. I had heard the term endocrine disruption before, but I didn’t know any details. The more I read about it, the more I felt (in a way) responsible to inform people what it was. I got so deep in the research, that my mentor accused me of writing a Doctorate instead of a Master’s.

But, what is endocrine disruption??

Endocrine disruption is caused by chemicals called endocrine disruptors. Neat! A sentence that explains absolutely nothing to you. OK, so what are endocrine disruptors, then??

Endocrine disruptors (EDCs) are natural or synthetic compounds, that in certain doses (very important, those 2 words in bold and italics explain the light at the end of the tunnel!) interfere with the synthesis, binding, transport, action, secretion, or elimination of endogenous hormones. (4) Humans are exposed to EDCs through ingestion, inhalation, and direct contact with skin. Wildlife is also exposed through food and water consumption. (5)

EDCs can also be formed as breakdown products from other anthropogenic chemicals in the environment and in humans, wildlife, and plants. Humans and wildlife are exposed to multiple EDCs at the same time, and there is justifiable concern that different EDCs can act together (synergism) and result in an increased risk of adverse effects on human and wildlife health. (6) (7)

Other EDCs are high-production volume chemicals found in a myriad of household products. Bisphenol A (BPA), for example, is present in polycarbonate plastics, including beverage and food storage containers, epoxy resins that line the interior of metal cans, and in the ink used for thermal paper receipts. It’s the No.1 pesticide on our Pesticide Hall of Shame list. 

Many textiles contain contaminants, such as flame-retardants, including tetrabromobisphenol A and polybrominated diphenyl ethers. Some individuals have also been exposed to contaminants with adverse effects as a result of medical (diethylstilbestrol; DES), dental (diglycidyl methacrylate), or dietary (some phytoestrogens) interventions. Thus, exposure to EDCs is ubiquitous and unavoidable, and there is growing concern that living in an EDC-contaminated world may be contributing to adverse health trends, such as early puberty and infertility, because of growing evidence that a number of EDCs can produce varied effects. (8)

EDCs find their way into our environment through a surprising array of unchecked mechanisms. Ingested drugs, for example, are excreted in varying metabolized amounts (primarily in urine and feces) and end up in municipal sewage treatment plants where they then enter our waterways as treated wastewater effluent. EDCs leach from municipal landfills and can be found in the runoff from concentrated animal feeding operations and medicated pet excreta. EDCs also come from aquaculture, spray-drift from agriculture, and the direct discharge of raw sewage.

No endocrine system should be ruled out for being directly affected by environmental chemicals. Fat development and weight gain are good examples of complex physiological systems that are influenced by endocrine disruptors. There are a number of endocrine disruptors that have been shown to affect weight gain, insulin sensitivity, and glucose tolerance indicating a potentially important role for endocrine disruptors in the development of obesity, type 2 diabetes, and metabolic syndrome. The elements of the endocrine system that control weight gain and metabolism/energy expenditure include the adipose tissue, pancreas, GI tract, liver, skeletal muscle, bone, and brain, and endocrine disruptors that could specifically and directly affect each of these tissues by interfering with their various hormone systems. (9)

The point in life when exposure occurs may be critical for the effects of EDCs. Critical periods of urogenital tract and nervous system development in utero (meaning inside the womb) or in early postnatal life are especially sensitive to hormonal disruption. Damage during these ‘critical windows of development may be more likely to be permanent, yet, in mature individuals, ill effects of exposures can be alleviated when the causative agent is removed. (7) (8)

Children have a higher chemical exposure per kg body weight compared to adults and still underdeveloped protective mechanisms such as a competent immune system, detoxifying enzymes, liver metabolism, and the blood/brain barrier. Thus, efforts need to be made to reduce the exposure to EDCs of children and pregnant women. (7) 10

Furthermore, it is not simply the daily dose alone that is of concern, since many EDCs bioaccumulate in lipid compartments of tissues, giving rise to a mixed ‘‘body burden’’ of contaminants of different origins. (7)

So, which of those contaminants or pesticides should we avoid and run like hell from?

PESTICIDE HALL OF SHAME

1. Bisphenol A (BPA) – you can find it mostly in plastic bottles and food containers. We cannot isolate ourselves from plastic – it’s cheap and it’s everywhere. So what to do?

• Use BPA – free products.
• Reduce the use of canned food.
• Avoid putting plastic containers in the microwave and dishwasher, because the plastic may break down over time and allow BPA to leach into foods. (This was advised by the National Institutes of Health)
• Use something else – glass, porcelain, stainless steel…

2.  Dioxins – Dioxins are a group of chemically-related compounds that are persistent environmental pollutants (POPs). They accumulate in the food chain, mainly in the fatty tissue of animals. More than 90% of human exposure is through food, mainly meat and dairy products, fish, and shellfish. Many national authorities have programs in place to monitor the food supply. They are highly toxic and can cause reproductive and developmental problems, damage the immune system, interfere with hormones, and also cause cancer. Due to the omnipresence of dioxins, all people have background exposure, which is not expected to affect human health. However, due to the highly toxic potential, efforts need to be undertaken to reduce current background exposure. Prevention or reduction of human exposure is best done via source-directed measures, i.e. strict control of industrial processes to reduce the formation of dioxins. (11)

3. Phthalates –  No point in trying to run away from these ones – they are everywhere. You’ll find phthalates in perfume, most cosmetics and hair products, insect repellent, carpeting, vinyl flooring, the coating on wires and cables, shower curtains, raincoats, plastic toys, and your car. And on the soles of your sneakers. You’ll find them in the food, air, and water. (12) So, what? Stop breathing and drinking water? Or move to Mars? Neither for now. A good idea would be to invest in water filters and try to ditch plastic as much as you can. I’d say ditch your perfume too (just in case), but I never advise something that I wouldn’t do, because damn it, Marc Jacobs’ OH, LOLA! smells really nice (not saying that one, in particular, has phthalates (I have no data to offer). It’s what I use these days. Sigh! 

4. Heavy metals – Cadmium, mercury, lead, chromium, and arsenic. Again, a good water filter is a good idea. It won’t make you young again but buy it anyway. Dust more often and clean the floors regularly. Watch which paint you’re buying. Watch the soles of your sneakers. Avoid eating sharks (even if they like eating you), swordfish, King mackerel, tilefish, and tuna (especially if you’re pregnant – avoid those fish, and – sea shells, as they absorb everything bad). 

5. Organophosphate pesticides – Organophosphates poison insects and other animals, including birds, amphibians, and mammals, primarily by phosphorylation of the acetylcholinesterase enzyme (AChE) at nerve endings. Respiratory paralysis. If by any chance a person is poisoned by these pesticides (it happens by accident when working with them). Persons attending the victim should avoid direct contact with heavily contaminated clothing and vomitus. All caregivers should have appropriate protective gear when in contact with a patient poisoned by organophosphates and wear rubber gloves while washing pesticides from skin and hair. More research is being done on what exactly they cause in humans due to chronic exposure. (13)

6. Pyrethroid insecticides – Some of these ones are suspected endocrine disruptors (not proven yet) and highly toxic to fish (this one is proven).

7. Atrazine – It is linked to endocrine disruption (demasculinizing the frogs), reproductive effects and cancer. It is a herbicide used in corn production. Germany and Italy banned it in 1991. (14)

8. 2,4–D (or 2,4-Dichlorophenoxyacetic acid) – A herbicide. In humans, 2,4-D exposure can occur through inhalation, skin absorption, ingestion, and skin/eye contact. Once absorbed in the body, there is little evidence that 2,4-D is accumulated and only a small percentage is transformed in 2,4-D conjugates with sugars or amino acids. A single dose of 2,4-D is excreted within a few days, mainly through the urine, but also in the bile and feces. It is reported that 2,4–D has a negative effect on the endocrine system (especially the thyroid and gonads) and on the immune system. Exposure most likely would result from inhalation or dermal contact during 2,4-D’s manufacture, formulation, or application, but it has been found in low levels in groundwater supplies. (15)

9. Oxyfluorphen – is a selective herbicide. Tests on animals (rats) have proven that dietary exposure to high concentrations is associated with adverse effects on the adrenal, thyroid, and thymus glands. (16)

10. Epoxiconazole –  this is a fungicide that was proven to have an effect on the reproductive development of the offspring in tests with rats. The high dose of epoxiconazole had marked fetotoxic effects, while the lower dose caused increased birth weights. The high dose of epoxiconazole led to an increase in the progesterone level (sevenfold increase) as well as a twofold increase in the testosterone level. Thus, it seems important to survey and minimize the exposure of the human population to azole fungicides (among which is also epoxiconazole). (17)

If you’ve come thus far in reading this, I can now talk about the light at the end of the tunnel. As I said in my previous post – the most important question is how much of what? Most of these chemicals are safe at the very low levels that occur in some foods. This assessment is based on a review of hundreds of studies. Eat well and as eco as possible. Drink filtrated water and exercise. Sleep well. There – you read a 2600-word post just to be told something you’ve heard a million times. But, I doubt your grandma knew so many details. (I can see you wanna smack me now, so I’ll just shut up until my next post).

Bye now.

REFERENCES:

1. Alavanja, Michael C.R.: “Pesticides Use and Exposure Extensive Worldwide.”Reviews on environmental health 24.4 (2009): 303–309. Print. Online source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946087/  (06.10.2016)
2. Online source: http://www.who.int/ceh/capacity/Pesticides.pdf (06.10.2016)
3. Online source: http://www.slideshare.net/ResearchImpactcom/biopesticides-market-research-report (06.10.2016)

4. McQueen C: Comprehensive Toxicology 2nd ed, Elsevier, 2010: 5341. 

5. McQueen C: Comprehensive Toxicology 2nd ed, Elsevier, 2010: 5507

6. Bergman A, Heindel JJ, Jobling S, Kidd KA, Zoeller RT: State of the Science of Endocrine Disrupting Chemicals, WHO, World Health Organization; UNEP, United Nation Environment Programe, 2010: xvi. Online source: apps.who.int/iris/bitstream/10665/78101/1/9789241505031_eng.pdf (06.10.2016)

7. Bojana Najdovska: In Silico Prediction of Potential Endocrine Disruption of Substances Found in Plant Protection Products and Biocidal Products Registered in Republic of Slovenia. Master’s Degree. September, 2016

8. Frye CA, Bo E, Calamandrei G, Calza L, Dessı-Fulgheri F, Fernandez M, Fusani L, Kah O, Kajta M, Le Page Y, Patisaul HB, Venerosi A, Wojtowicz AK, Panzica AK: Endocrine Disrupters: A Review of Some Sources, Effects, and Mechanisms of Actions on Behaviour and Neuroendocrine Systems. Journal of Neuroendocrinology: From Molecular to Translational Neurobiology 2012; 24 (1): 144–159. Online source: https://www.ncbi.nlm.nih.gov/pubmed/21951193 (06.10.2016)

9. Bergman A, Heindel JJ, Jobling S, Kidd KA, Zoeller RT: State of the Science of Endocrine Disrupting Chemicals, WHO, World Health Organization; UNEP, United Nation Environment Programe, 2010: 11-12. Online source: apps.who.int/iris/bitstream/10665/78101/1/9789241505031_eng.pdf (06.10.2016)

10. Bergera E, Potouridisb T, Haegerc A, Püttmannb W, Wagnera M: Effect-Directed Identification of Endocrine Disruptors in Plastic Baby Teethers. Journal of Applied Toxicology 2015; 35 (11): 1254-61. Online source: https://www.ncbi.nlm.nih.gov/pubmed/25988240 (06.10.2016)

11. Online source: http://www.who.int/mediacentre/factsheets/fs225/en/ (06.10.2016)
12. Online source: https://toxtown.nlm.nih.gov/text_version/chemicals.php?id=24 (06.10.2016)
13. Online source: https://www.epa.gov/sites/production/files/documents/rmpp_6thed_ch5_organophosphates.pdf (06.10.2016)
14. Online source: http://www.panna.org/resources/atrazine (06.10.2016)
15. Online source: http://npic.orst.edu/factsheets/24Dgen.html (06.10.2016)
16. Online source: http://www.fs.fed.us/foresthealth/pesticide/pdfs/122205_Oxyfluorfen.pdf (06.10.2016)
17. Taxvig C., Hass U., Axelstad M., Dalgaard M, Boberg J., Raun Andeasen H. and Vinggaard AM: Endocrine-Disrupting Activities In Vivo of the Fungicides Tebuconazole and Epoxiconazole. Toxicol. Sci. (2007) 100 (2): 464-473. Online source: http://toxsci.oxfordjournals.org/content/100/2/464.long (06.10.2016)