Vincent van Gogh certainly had his issues (to put it mildly), but now some researchers think they may have found a reason why the painter was apparently in the habit of licking his used brushes, which were coated in lead paint. Lead poisoning, as we now know, results in a range of symptoms ranging from;
- stomach pains
- uric burps
- and a range of neurological afflictions, including the depression and delusions with which the great Impressionist is now so closely associated.
There were health risks in the painterly profession was well known as far back as the 1700s, though the cause—chronic exposure to lead via their beloved paints—remained unknown until recent times. In 1897, about half of all American municipalities used lead pipes to distribute water. Employing data from Massachusetts, this paper compares infant death rates in cities that used lead water pipes to rates in cities that used nonlead pipes. In the average town in 1900, the use of lead pipes increased infant mortality by 25 to 50 percent.(1)
Spain 1746 – 1828 France (d. 82)
MARYLAND: Spanish quixotic artist Francisco Goya was the most central and known Spanish artist of late 18th and early 19th centuries. In 1793, an acute and undiagnosed syndrome left him wholly deaf at the age of 46. For years, scholars had a hunch that he might had had lead poisoning due to paints or gone through bacterial meningitis or syphilis. However, at last following 200 years, savants finally managed to expose the exact disease that troubled the Spanish painter, which is an autoimmune illness known as Susac’s syndrome that affected his hearing. Following a stroke which left him paralyzed on his right side, Goya died and was buried on 16 April 1828 at the age of 82.(1)
What exactly is Susac’s syndrome?
It is an exceptional condition that triggers folks’ immune structure to influence small blood vessels in the brain, retina and inner ear. Adverb headaches, trouble in thoughts, psychiatric concerns and loss of vision, balance and hearing are the most widespread symptoms of this chaos. As per the panel of investigators from the University of Maryland in the US, Goya went through the symptoms such as headaches, giddiness, hallucinations, vision troubles and ringing in his ears.
Harboring on the matter, author of study from the said varsity, Ronna Hertzano holds that Susac’s syndrome has the potential to cause permanent hearing loss. Following a stroke which left him paralyzed on his right side, Goya died and was buried on 16 April 1828 at the age of 82.(1)
Fluoride dosages of 1 part per million, found in Artificially Fluoridated Water (public water supply):
- Worsen arthritis
- Can inhibit enzyme systems
- Damage the immune system
- Contribute to calcification of soft tissues
- Cause dental fluorosis in children. These are unsightly white, yellow or brown spots that are found in teeth exposed to fluoride during childhood. In 1993, the Subcommittee on Health Effects of Ingested Fluoride of the National Research Council admitted that 8% to 51% and sometimes up to 80% of the children living in fluoridated areas have dental fluorosis. Malnourished people, particularly children, usually targeted for fluoridation, are at greater risks to experience fluoride’s harmful effects. 97% of western Europe has chosen fluoride free water.
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People typically associate chemotherapy with cancer treatment. However, doctors often use chemotherapy drugs (e.x., methotrexate) to treat individuals with autoimmune conditions such as rheumatoid arthritis (RA). Doctors typically prescribe these drugs at much lower dosages for people with RA than they would for those with cancer. This is because the goal of treatment is not to kill cancer cells but to change the behavior of the overactive immune cells. The lower dosage also helps to reduce the severity of potential side effects of ?. Early treatment with chemotherapy drugs can help slow the progression of RA and reduce or prevent joint damage and other serious complications. (3)
Many patients with rheumatoid arthritis have stayed on this drug for 20 years or more. It used to be recommended that every patient who reached a certain lifetime dose of methotrexate receive a liver biopsy, but that is no longer recommended by rheumatology organizations as long as blood tests related to liver function remain normal. Some dermatology organizations remain concerned about liver damage in this setting, particularly in patients with psoriasis. (3)
Carcinogenicity of biopharmaceuticals
While new pharmaceuticals are constantly being developed to alleviate disease in humans, it is recognized that these pharmaceuticals can also be associated with adverse effects due to their chemical structure and/or inherent pharmacologic activity. Therefore, non-clinical and clinical evaluation of human pharmaceuticals is required to demonstrate both effi cacy and safety in the intended clinical therapeutic situation. Carcinogenicity is one of the major safety concerns that is largely de- risked in the non-clinical studies. In this chapter, we focus on the carcinogenic risk of proteins produced by recombinant biotechnology, generally called biopharmaceuticals, as specifi c aspects make them different from conventional small molecules.
Chapter 8 Carcinogenicity of Biopharmaceuticals
Maggie Dempster, et al.,
The anti-TNF hidden problem
2008 FDA black box warning: a possible increased risk of lymphoma and other malignancies in children treated with anti-TNF agents. – 9 cases in registries (mainly lymphomas) – FDA Post-marketing 48 pediatric malignancies (20 in JIA, 28 in IBD), after a median of 2.5 years (range 1 month-7 years), 50% lymphomas, most while using other drugs (steroids, azathioprine, MTX, mercaptopurine) (1)
20th April 1902: Marie and Pierre Curie prove the existence of radium by isolating radium chloride. HistoryPod. https://www.youtube.com/watch?v=UgHmGxXO4Wg
Uranium Reserves: https://en.wikipedia.org/wiki/File:Uranium_Reserves.png.
Global, regional and national burden of rheumatoid arthritis 1990–2017: a systematic analysis of the Global Burden of Disease study 2017
Global, regional and national burden of rheumatoid arthritis 1990–2017: a systematic analysis of the Global Burden of Disease study 2017. https://ard.bmj.com/content/78/11/1463
Conclusions RA is a major global public health challenge. The age-standardised prevalence and incidence rates are increasing, especially in countries such as Canada, Paraguay and Guatemala. Early identification and treatment of RA is vital especially among females, in order to reduce the ongoing burden of this condition. The quality of health data needs to be improved for better monitoring of disease burden.Rheumatoid arthritis is a major global public health challenge. Its age-standardised prevalence rate ranges from 91 to 471 cases per 100 000 population.
Sat0576 The Prevalence Of Rheumatoid Arthritis: A Systematic Review Of Population-Based Studies.
Conclusion: The average point- and period-prevalence of RA were 51/10,000 and 56/10,000 respectively. The RA prevalence was higher in urban areas than rural areas, suggesting an impact of environmental differences. Population database studies were more consistent than sampling studies, and linked databases appeared to provide the best estimate of RA period-prevalence when rheumatologists clinically verified RA. (1)
Rheumatoid arthritis world map - DALY - WHO2004.
Global, regional and national burden of rheumatoid arthritis 1990–2017: a systematic analysis of the Global Burden of Disease study 2017. Saeid Safiri, et al,
Dr. Zach Bush, a triple-board certified endocrinologist gave a lecture connecting soil health, and the widespread use of pesticides in the US, to the rising rates of chronic disease. https://www.youtube.com/watch?v=HL6OPzQe9Is
Other testing techniques can find yet more information. Pesticides, antibiotics, personal care products, pharmaceuticals, alcohol and tobacco have all also been measured in wastewater. As most state authorities will tell you, testing for SARS-CoV-2 in wastewater can be a helpful indicator of presence of COVID-19 in the area, but it’s not a guarantee that there’s an infectious person in the community as viral shedding can happen for several months after infection in some people. Similarly, the virus denatures and dissolves fast in wastewater, so a clean sewage reading doesn’t mean there’s no COVID-19 around.(1)
1. Explainer: Wastewater - How does wastewater testing work? Ellen Phiddian. Cosmos, Chemistry. March 12, 2021 https://cosmosmagazine.com/science/chemistry/explainer-wastewater/
Sergi Díez. February 2009. Reviews of Environmental Contamination and Toxicology. 198:111-32. Source (1)
Hg - Mercury toxicity - Mercury ingestion - Thimerosal - Mercury poisoning - Acute mercury poisoning - Chronic mercury poisoning - norganic mercury exposure - Organic mercury exposure - Elemental mercury exposure - Inorganic mercury salt exposure - Mercury salts - Methyl mercury - Methylmercury - Acrodynia - Pink disease - Acrodynic erythema - Dermatopolyneuritis - Erythredema - Swift('s) disease - Hydrargyria - Hydrargyrism - Mercurialism
Mercury (Hg) toxicity - Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects.(1) Mercury body burden has also been associated with or implicated in a number of immune or autoimmune conditions including arthritis, rheumatoid arthritis, schizophrenia, allergic disease, amyotrophic lateral sclerosis, autoimmune thyroiditis, autism/attention deficit hyperactivity disorder, eczema, epilepsy, psoriasis, multiple sclerosis, scleroderma, and systemic lupus erythematosus. (8)
Kids are more prone to the toxic effects of heavy metals. Infants and young children are far more sensitive as the rapidly developing body systems in the fetus, infants and young. Childhood exposure to some metals can result in learning difficulties, memory impairment, damage to the nervous system, and behavioral problems such as aggressiveness and hyperactivity. At higher doses, heavy metals can cause irreversible brain damage. Children may receive higher doses of metals from food than adults, since they consume more food for their body weight than adults.(2)
- The half life of mercury in the brain is 18 to 30 years
- Half-life' of mercury in human body is about 70 days
- Produces inflammatory reactions in the kidney
- In humans, mercury poisoning results in inhibition of endocrine function, atherosclerosis, cardiac effects such as hypertension
- Hg0 and MeHg accumulate in the central nervous system (CNS) and are neurotoxic, whereas the inorganic Hg salts are nephrotoxic
- In severe cases such as in Minamata and Niigata (Japan), and the Wabigoon-English River system (Ontario, Canada), mercury poisoning can result in fetal death, neurological disorders resembling cerebral palsy, deafness, and visual impairment.
- Kawasaki disease - Exposure to inorganic Hg can also induce Kawasaki disease in children which results from a weakening of the immune system
- Minamata Disease - Caused by the release of methylmercury from the Chisso Corporation's chemical factory from 1932 to 1968. Mercury sulphate in the wastewater was metabolized to methylmercury by bacteria in the sediment
Three Forms of mercury:
1. Elemental Mercury - Hg0 metallic mercury/mercury vapor and or quicksilver. Health effects (3)
- mercury vapor (Hg0) from dental amalgam restorations 
- Historically, dental amalgam is one of the most commonly used tooth fillings. (1, 2) It is made of two nearly equal parts:
1. Liquid mercury
2. A powder containing silver, tin, copper, zinc and other metals
- Mercury released from dental amalgams ranges from 9 to 17 mg/day
- Autopsy studies show that dental amalgams are a source of mercury in human tissue - typically 2 to 12 times more mercury compared to individuals without dental amalgams
- primary target organs of elemental mercury are the brain and kidney
- mercuric oxide (HgO) diffuses readily and is lipid soluble and easily crosses the blood-brain barrier and lipid bilayers of cells and cell organelles such as mitochondria
- from ingestion is poorly absorbed with a bioavailability of less than 0.01%
2. Organic Mercury such as methylmercury [CH₃Hg]⁺ and ethyl mercury [C2H5Hg]⁺
- exposure in the general population are methylmercury (MeHg) from seafood. Methyl/etheyl mercuries can be absorbed by the human gut and skin
- In addition to methylmercury, there are a numberof other organomercurials to which humans might be exposed:
- 1. Dimethylmercury, is notoriously toxic, but found use as an antifungal agent and insecticide
- 2. Merbromin and phenylmercuric borate are used as topical antiseptics
- 3. Nitromersol is used as a preservative for vaccines and antitoxins.
- 4. Thiomersal is a compound containing ethyl mercury used to prevent bacterial and fungal growth in some inactivated vaccines in multi-dose vials.
- Human body lacks a mechanism to excrete organometallic mercury
- Methylmercury is a neuro toxin causing damage to the cental nervous system (CNS). It accumulates in the liver, brain, kidney.
3. Inorganic Mercury (Hg+ and Hg2+)
- exposure in the general population include vegetables, grains (7) and soils from areas surrounding coal-fired power plants. (6)
- found in foods with high levels of high fructose corn syrup (4),
- are water soluble with a bioavailability of 7% to 15% after ingestion; they are also irritants and cause gastrointestinal symptoms.(4)
- it reacts quickly with intracellular molecules such as enzymes, glutathione etc, thus inhibiting the actions of these molecules and affecting normal cellular functions. Even at very low concentrations, it decreases levels of glutathione (GSH) in cells. GSH is a powerful antioxidant in cells and thereby increases oxidative stress
- kidney, is the main site of accumulation which produces inflammatory reactions in the kidney
- is excreted via urine and feces, sweat, tears and breast milk.
The Largest Public Health Burden is Not Toxicity but the Loss of Immune Tolerance
“Autoimmunity, which can include autoantibody formation, represents a breakdown of tolerance against self-antigens. Self-reactive lymphocytes may occur in healthy individuals, and in the absence of related pathology, autoimmunity represents pre- or sub-clinical immune dysregulation. Thus, the term autoimmunity should be distinguished from autoimmune disease, as it does not denote clinical or symptomatic disease…autoantibodies may precede autoimmune diagnoses by several years, and nearly all autoimmune diseases are characterized by circulating autoantibodies. Antinuclear antibodies (ANAs) are highly sensitive for a variety of autoimmune conditions, including systemic lupus erythematosus (SLE), scleroderma, and Sjögren’s syndrome.”
Exposure to inorganic mercury can also induce Kawasaki disease in children which results from a weakening of the immune system. Exposure to some metals, such as mercury and lead, may also cause development of autoimmunity, in which a person's immune system attacks its own cells. This can lead to joint diseases such as rheumatoid arthritis, and diseases of the kidneys, circulatory system, and nervous system.(2)
Image and video source: Kawasaki Disease: A Parents Guide
The Selenium-Mercury link
Selenium is an essential trace element and it is necessary to achieve the activity of the 25-30 selenoenzymes that are required to protect the central nervous system and the brain from oxidative damage. High MeHg levels bind selenium by irreversibly inhibiting selenoenzyme activity, with detrimental affects. However, a diet rich in selenium (present in many foods, including fish), may replenish MeHg-bound selenium, thereby protecting the activity of brain cells.
Heavy Metal Testing
Claude Monet, Bordighera (1884), oil on canvas, 65 x 80.8 cm, The Art Institute of Chicago. Yellows used here are based on cadmium pigments. There were periods during Monet's long career that became dominated by motifs of trees. In Bordighera, he captures the forms of trees poised above the town, with their richly-coloured bark and intense coloured foliage. Monet passed away of lung cancer on 5 December 1926 at the age of 86.
Health Effects of Cadmium (Cd) Exposure
- Renal toxicity -> decreased GFR
- Increased risk of Osteoporosis in menopausal women -> Ammonium increases bone reabsorption
- Estrogen-like effect (acts as estrogen)
According to the Agency for Toxic Substances and Disease Registry, foods account for more than 90 percent of human exposure to cadmium. On average, people consume about 30 micrograms of cadmium daily through a normal diet, absorbing 1 to 3 micrograms. There is currently no evidence that these trace levels pose a hazard to healthy, non-smoking adults, however, studies have shown that smokers can absorb twice that amount per day.
Source: The Facts on Cadmium, http://www.dartmouth.edu/~toxmetal/toxic-metals/more-metals/cadmium-faq.html
Cadmium Pigments In Artists' Paints
Cadmium sulfide (CdS) was suggested as a pigment in 1819 by Stromeyer. It became commercially available 1840s due to scarcity of metal required for its production. Cadmium sulfide selenides(CdSe) (cadmium sulfoselenides),was originally commercialized in 1910.
The following are commonly used cadmium pigments in artists' paints:
Light shades of cadmium yellow is cadmium zinc sulfide, typically a greenish yellow, solid solution of CdS and ZnS. Colour Index Pigment Yellow 35 (PY35).
Deep shades of cadmium yellow is cadmium sulfide (CdS).Colour Index Pigment Yellow 37 (PY37).
Cadmium orange is cadmium sulfoselenide, a solid solution of CdS and CdSe. Depending on the sulfur to selenide ratio, Colour Index Pigment Orange 20 (PO20) or Colour Index Pigment Red 108 (PR108) is obtained.
Cadmium red is cadmium sulfoselenide. Colour Index Pigment Red 108 (PR108).
Cadmium green is sometimes a mixture of cadmium yellow and viridian(blue-green pigment ) to give a bright, pale green mixture.
1. Cadmium Colors—It Began with Medicine, Natural Pigments Inc, https://www.naturalpigments.com/artist-materials/cadmium-colors/
2. The Episodic Table of Elements, A CHEMISTRY PODCAST ABOUT THE FASCINATING TRUE STORIES BEHIND EACH ELEMENT ON THE PERIODIC TABLE.
Distributed in the organism in muscles, liver and kidneys -> binds to proteins
Slowly excreted via the kidneys
Kidneys: 10-30 years
Blood: 3-4 months
Kidney damage measured:
Reduced GFR (shown on blood work)
Earliest signs of kidney damage = measure proteins, NAG and B2 and A1 microglobulin
Early still = beta 2 and alpha 1 microglobulin and retinol-binding protein as well as N-acetyl glucoamindase (NAG)
The damage is believed to be irreversible
Bioavailability: Heavy metal -> excreted exclusively in the urine = cannot be metabolised by the liver
Measured in the urine (heavy metal)
If seen in the blood = recently exposed
Women have higher levels than men
CFR - Code of Federal Regulations Title 21 - FDA: Regulations prescribing conditions under which food additive substances may ..V- Sec. 172.325 Bakers yeast protein. Less than 0.3 parts per million (ppm), Arsenic 0.1 ppm, Cadmium 0.4 ppm, Lead, 0.05 ppm Mercury, and 0.3 ppm Selenium
Sec. 172.898 Bakers yeast glycan. (b) The additive meets the following specifications on a dry weight basis: Less than 0.4 part per million (ppm) arsenic, 0.13 ppm cadmium, 0.2 ppm lead, 0.05 ppm mercury, 0.09 ppm selenium, and 10 ppm zinc.
1. The provisional tolerable weekly intake (PTWI) of Cd set by the Joint FAO/WHO Expert Committee on Food Additives,
or EFSA Panel on Contaminants in the Food Chain (CONTAM)
A person weighs 60 kg (132 lbs) and eats approx. 100 g dark chocolate per week.
Calculate what proportion of PTWI such an intake constitutes if the cadmium content corresponds to the limit value.
100 g of chocolate contains 0.08 mg = 80 .g of cadmium
A person weighing 60 kg may consume 150 µg cadmium / week
100 g of chocolate will thus correspond to 80 x 100/150 = 53% of PTWI
Exposure levels: Cd can have health effects at much lower exposure levels. Uptake, distribution and excretion: Recorded orally or pulmonarily (depending on particle size)
Itai-itai (IID), Cadmium and Rheumatoid Disease
There was an endemic disease of unknown etiology in the Jinzu River basin of Toyama, Japan. It was a painful condition called 'itai-itai' (itai, meaning ouch). Patients complained of bone pain, especially in the pelvic girdle and legs while walking. It was in 1946, just after the Second World War, when itai-itai disease began to be medically evaluated. The local agricultural association requested Kanazawa University to conduct an investigation, Nagasawa et al., () conducted this investigation and published their results the following year. In that paper, the authors referred to this endemic disorder as a rheumatoid disease.
The 35-year history of 'itai-itai' has been divided into three periods: (1) 1955−1961, an early phase of epidemiology, symptom characterization and attempts at treatment; (2) a middle period during which diagnostic criteria were formalized and research focused on the influence of heavy metal contamination, particularly Cd; and (3) around 1970−1990, a third period in which the role of Cd accumulation in disease etiology was firmly established.
Itai-itai disease (IID) is the most severe form of chronic cadmium (Cd) intoxication of human. The patients of IID suffer from renal anemia, tubular nephropathy and osteopenic osteomalacia, and 90% of the patients are post-menopausal women. Experiments suggest concurrent administration of estradiol helps the vitamin D therapy for IID patients and the removal of Fe at the mineralization front of bone (3) is important for the recovery to normal bone remodeling.
1. Keiko Aoshima, Itai-itai disease: Renal tubular osteomalacia induced by environmental exposure to cadmium—historical review and perspectives.
Soil Science and Plant Nutrition, 2016, Pages 319-326. https://www.tandfonline.com/doi/full/10.1080/00380768.2016.1159116
2. Takashi Umemura and Yumi Wako. Pathogenesis of osteomalacia in itai-itai disease. Journal of Toxicologic Pathology, 2006: 19: 69-74. https://www.jstage.jst.go.jp/article/tox/19/2/19_2_69/_pdf.