Persistent organic pollutants ( POP s) are organic compounds that are resistant to environmental degradation through chemical , biological , and photolytic processes. ^[1] Because of their persistence, POPs bioaccumulate with potential adverse impacts on human health https://en.wikipedia.org/wiki/Persistent_organic_pollutant

Additive and synergistic effects

Evaluation of the effects of POPs on health is very challenging in the laboratory setting. For example, for organisms exposed to a mixture of POPs, the effects are assumed to be additive . ^[17] Mixtures of POPs can in principle produce synergistic effects . With synergistic effects, the toxicity of each compound is enhanced (or depressed) by the presence of other compounds in the mixture. When put together, the effects can far exceed the approximated additive effects of the POP compound mixture. ^[3]

Health effects

POP exposure may cause developmental defects, chronic illnesses, and death. Some are carcinogens per IARC , possibly including breast cancer . ^[1] Many POPs are capable of endocrine disruption within the reproductive system , the central nervous system , or the immune system . People and animals are exposed to POPs mostly through their diet, occupationally, or while growing in the womb. ^[1] For humans not exposed to POPs through accidental or occupational means, over 90% of exposure comes from animal product foods due to bioaccumulation in fat tissues and bioaccumulate through the food chain. In general, POP serum levels increase with age and tend to be higher in females than males. ^[8]

Studies have investigated the correlation between low level exposure of POPs and various diseases. In order to assess disease risk due to POPs in a particular location, government agencies may produce a human health risk assessment which takes into account the pollutants' bioavailability and their dose-response relationships . ^[18]

Because the chemical must pass through a number of cell membranes before it can enter the blood, the ability of the chemical to cross these lipid-rich membranes determines whether it will be absorbed, and that ability depends on the chemical�s lipid solubility. Lipophilic hydrocarbons such as hexane, toluene, aromatics, cycloalkanes, and terpenes accumulate in the membrane lipid bilayer, affecting the structural and functional properties of these membranes. (36) As a result of accumulated hydrocarbon molecules, the membrane loses its integrity, and an increase in permeability to protons and ions has been observed in several instances. Consequently, dissipation of the pro ton motive force and impairment of intracellular pH homeostasis occur. In order for a poison to produce toxicity, a sufficient quantity of that chemical must be absorbed into the body.

Many studies have associated environmental exposure to chemicals with neurological impairments (NIs) including neuropathies, cognitive, motor and sensory impairments; neurodevelopmental disorders (NDDs) including autism and attention deficit hyperactivity disorder (ADHD); neurodegenerative diseases (NDGs) including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS). (29,37) The environmental chemicals shown to induce all these diseases include persistent organic pollutants (POPs), the plastic exudates bisphenol A and phthalates, low molecular weight hydrocarbons (LMWHCs) and polynuclear aromatic hydrocarbons (PAHs). It is reported here that though these chemicals differ widely in their chemical properties, reactivities and known points of attack in humans, a common link does exist between them. All are lipophilic species found in serum and they promote the sequential absorption of otherwise non-absorbed toxic hydrophilic species causing these diseases.

A neuroinflammatory response involving polarized microglial activity, enhanced astrocyte reactivity and elevated pro-inflammatory cytokine and chemokine load has long been implicated in AD and studies suggest this facilitates neurodegeneration. (29a) Neuroinflammation is also involved with oxidative stress. Reactive oxidative species (ROS) toxicity remains an undisputed cause and link between Alzheimer's disease (AD) and Type-2 Diabetes Mellitus (T2DM). Patients with both AD and T2DM have damaged, oxidized DNA, RNA, protein and lipid products that can be used as possible disease progression markers. Many studies have shown exposure to toxic substances such as toxic metals, pesticides, etc. cause neuroinflammation and likely collectively are factors in neurological conditions such as Alz . Disease. (29b)

Endocrine disruption

The majority of POPs are known to disrupt normal functioning of the endocrine system. Low level exposure to POPs during critical developmental periods of fetus, newborn and child can have a lasting effect throughout its lifespan. A 2002 study ^[19] synthesizes data on endocrine disruption and health complications from exposure to POPs during critical developmental stages in an organism�s lifespan. The study aimed to answer the question whether or not chronic, low level exposure to POPs can have a health impact on the endocrine system and development of organisms from different species. The study found that exposure of POPs during a critical developmental time frame can produce a permanent changes in the organisms path of development. Exposure of POPs during non-critical developmental time frames may not lead to detectable diseases and health complications later in their life. In wildlife, the critical development time frames are in utero , in ovo , and during reproductive periods. In humans, the critical development timeframe is during fetal development . ^[20]

Reproductive system

The same study in 2002 ^[19] with evidence of a link from POPs to endocrine disruption also linked low dose exposure of POPs to reproductive health effects. The study stated that POP exposure can lead to negative health effects especially in the male reproductive system , such as decreased sperm quality and quantity, altered sex ratio and early puberty onset. For females exposed to POPs, altered reproductive tissues and pregnancy outcomes as well as endometriosis have been reported. ^[21]

Gestational weight gain and newborn head circumference

A Greek study from 2014 investigated the link between maternal weight gain during pregnancy, their PCB -exposure level and PCB level in their newborn infants, their birth weight , gestational age , and head circumference. The lower the birth weight and head circumference of the infants was, the higher POP levels during prenatal development had been, but only if mothers had either excessive or inadequate weight gain during pregnancy. No correlation between POP exposure and gestational age was found. ^[22] A 2013 case-control study conducted 2009 in Indian mothers and their offspring showed prenatal exposure of two types of organochlorine pesticides ( HCH , DDT and DDE ) impaired the growth of the fetus , reduced the birth weight, length, head circumference and chest circumference. ^[23] ^[24] ^��

Specific effects of POPs can include cancer, allergies and hypersensitivity, damage to the central and peripheral nervous systems, reproductive disorders, and disruption of the immune system. Some POPs are also considered to be endocrine disrupters, which, by altering the hormonal system, can damage the reproductive and immune systems of exposed individuals as well as their offspring; they can also have developmental and carcinogenic effects.

http://chm.pops.int/TheConvention/ThePOPs/tabid/673/Default.aspx

Persistent Organic Pollutants (POPs)� http://www.bluevoice.org/POPsFactSheet.php

General Health Effects of Persistent Organic Pollutants (POPs)

POPs can disrupt the endocrine, reproductive, and immune systems. The developing brain and nervous system may be most vulnerable.
POPs are capable of causing behavioral problems, cancer, diabetes and thyroid problems.
According to a landmark longitudinal study, babies whose mothers ate large amounts of highly contaminated fish (PCBs were measured) from Lake Michigan had lower birth weights, smaller head circumferences and shorter attention spans than babies whose mothers did not eat fish. Followed over 11 years, the exposed children have continued to do poorly in a range of skills and development tests, including deficits in general intellectual functioning, short- and long-term memory, and attention span.
The health of marine mammals has deteriorated significantly over the past two decades. Many of the newly emerging and resurgent diseases are associated with immune system dysfunction and suggest a broad environmental distress syndrome.
Marine mammals present a metabolic imbalance, so they are considered one of the most vulnerable organisms with respect to long-term toxicity of man-made chemicals such as organochlorines. Cetaceans (whales and dolphins) are known to have a poor ability to detoxify organic pollutants because they lack isozymes that are required to detoxify DDT and PCBs.

Among the POPs are synthetic estrogens know as xenoestrogens that saturate the environment and food supply. Vegetable crops are sprayed with pesticides and herbicides that accumulate in the environment and food products.� Meat and dairy products grown adding estrogen and hormones as well as antibiotics that accumulate in the environment and food products, and are commonly causing estrogenic effects and antibiotic resistance.�� In addition, meat and dairy products are grown with large amounts of corn and soy which are heavily sprayed and are mostly GMO as well, with the resulting major health problems related to glyphosate/Roundup \

Fruits and vegetables as well as the environment are also contaminated with polycycic aromatic hydrocarbons (PAHs) which are toxic and estrogenic.

Pe rsistent Organic Pollutants Effects on Infant Thyroid

POPs from in-utero exposure were found to disrupt thyroid function in newborns. The POPs were found to be at levels which generally occur in the population. Adequate thyroid hormone level in-utero is crucial for normal neurological development. Inadequate thyroid during pregnancy can result in problems such as lower IQ, heart problems, and short stature. All of these POPs are more toxic when iodine is deficient.

[PAN, https://www.panna.org & U.S. EPA, https://www.epa.gov/sites/production/files/2014-03/documents/pahs_factsheet_cdc_2013.pdf ;

& U.S. ATSDR, Tox Profile, PAHs, https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=122&tid=25 ; & Environmental Working Group, https://www.ewg.org ; ]

Persistent Organic Pollutants ( POPs ), Polyaromatic Hydrocarbons ( PAHs ), and PM25 air pollution have been documented to have significant adverse neurological and developmental/ behavioral (31) and respiratory effects (35abc, etc.) . Paint thinners or removers had a significant positive OR for ALS (28,34). PBDE (flame retardants) exposure in childhood have been shown to have adverse effects on mental development, psychomotor control, and IQ. (34) Toxic chemicals known as PFAS are found in everyday products like waterproof jackets and nonstick pans. They�re linked to cancer and endocrine conditions, and they�ve contaminated drinking water sources across the country.

(28) Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study , Int. J. Environ. Res. Public Health 2020 , 17 (8), 2882; & (b) A n update of human exposure and toxicity. Arch Toxicol. 2017 Feb;91(2):549-599. Mostafalou S, Abdollahi M. Pesticides ;

https://pubmed.ncbi.nlm.nih.gov/27722929/ ; & (c) Fayaz F, Pottoo FH, Shafi S, Wani MA, Wakode S, Sharma A. Denouement of Chemicals on Amyotrophic Lateral Sclerosis: Is Green Chemistry the Answer. Med Chem. 2020;16(8):1058-1068 , https://pubmed.ncbi.nlm.nih.gov/32282307/ ; & (d) ; Prospective study of chemical exposures and amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2009 May;80(5):558-61. Weisskopf MG, Morozova N, et al (formaldehyde) https://pubmed.ncbi.nlm.nih.gov/19372290/ ;

(29) The contribution of neuroinflammation to amyloid toxicity in Alzheimer's disease , J Neurochem , 2016 Feb;136(3):457-74.; & (b) Oxidative toxicity in diabetes and Alzheimer's disease: mechanisms behind ROS/ RNS generation , J Biomed Sci . 2017 Sep 19;24(1):76.

(31) Toxic Metals, Pesticides, Herbicides, and Other Endocrine-Disrupting Chemicals, www.myflcv.com/endoTM.html ;

(34) a) Pesticides, chemical and industrial exposures in relation to systemic lupus erythematosus, Lupus. 2014 May; 23(6): 527�536.

& (b) Developmental neurotoxicity of persistent organic pollutants: an update on childhood outcome. [Berghuis SA, Bos AF, Sauer PJ, Roze E. 2015. Arch Toxicol . 89(5):687-709];

(35) Environmental pollutants and child health-A review of recent concerns
[ Vrijheid M, Casas M, Gascon M, Valvi D, Nieuwenhuijsen M. 2016. Int J Hyg Environ Health. 219(4-5):331-42]; & (b) Prenatal exposure to environmental contaminants and behavioural problems at age 7-8 years. [ Sioen I, Den Hond E, Nelen V, et al. 2013. Environ Int. 59:225-31.]

& (c) NO2 and PM2.5 Exposures and Lung Function in Swiss Adults: Estimated Effects of Short-Term Exposures and Long-Term Exposures with and without Adjustment for Short-Term Deviations, Environmental Health Perspectives, Vol. 129, No. 1 , Jan 2021

(36) Mechanisms of membrane toxicity of hydrocarbons. Microbiol Rev. 1995 Jun; 59(2): 201�222.

(37) Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases , Interdisip Toxicol . 2013 Sep;6(3):103-10.