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Welcome to the Tox Spot!

Related imageCartoon from: Accessed 25 July 2019

WELCOME TO THE TOX SPOT!

In this blog, you will learn about four different toxic substances – Nightshade (plant), Ethylene glycol (solvent), Mercury (metal), and Neonicotinoids (pesticide).

This site is meant to help educate about these substances on a relatable level. Here, you will learn about how these substances can enter the body and how they affect the human body once inside. You will also learn about ways to combat toxicity and growing research surrounding these substances.

  • Nightshade – A plant most well known for its toxic family member (we all have one right?) Belladonna. As a mother of 2 (soon to be 3!) babies, this substance was of keen interest to me as it has been in the news several times in products marketed for infants. If that wasn’t reason enough to research this poisonous plant, it is also mentioned in a classic favorite movie Nightmare Before Christmas. Take a look into this famous flower and learn something new today!
  • Ethylene glycol – A solvent that’s like the sweet old lady at the supermarket who you always see but never knew her name. A sweet-tasting clear liquid, commonly known as Antifreeze. (You know, those big blue jugs you typically see outside at the gas station on a snowy winter morning.) This product is used in many common household items, which should be of special interest to those who have children or pets. As sweet as this solvent might be, it has a bitterly deadly side. Read on to find out more!
  • Mercury – A metal, a planet, a famous singer for Queen — what else can this product be?! How about deadly? For anyone over the age of 30, you are probably most familiar with this product as the red marker in old, glass thermometers. Ever wonder what happened to those things? Check out this blog to find out!
  • Neonicotinoid – A pesticide whose name is not as familiar as its consequences. A large environmental issue today is the death of our bee population, which can be linked back in large to this toxic substance. If you’re like me and not a fan of the rising price for honey, check out this pesticide, known as “Nicotine for Bees” and learn why the drug problem amongst bees needs to be addressed!

Nightshade – Berry Scary Toxicity

Image result for solanaceae Image from: Accessed 15 July 2019

Nightshade is a group of flowering plants otherwise known as “Solanaceae”, consisting of almost 3,000 different types, most of which are harmless and even part of every day consumption such as tomatoes, eggplant, and bell peppers. However, the one that usually comes to mind due to its poisonous qualities is “Belladonna” or Deadly Nightshade, a light purple flower with dark purple berries (seen below).

Image result for deadly nightshade Image from: Accessed 15 July 2019

Biotransformation

Nightshade plants contain steroidal alkaloids, which can be toxic when ingested however the biosynthesis is largely unknown. It is suggested that “specialized metabolites serve as a chemical barrier” and “affect the digestion and absorption of nutrients from food” according to an article published in 2015 by Cardenas, et al. Simulated tests for the ingestion of atropa belladonna suggest that the compound 3,4,5-trimethoxybenzaldehyde goes through toxic oxidation processes in the body, causing its deadly capabilities. For an in-depth scientific review of this hypothesis, read the article published in 2012 by Srivastava, et al. here.

Toxicokinetics and Mechanism of Action

Image result for nightmare before christmas deadly nightshadeImage from: Accessed 15 July 2019

Image result for nightmare before christmas deadly nightshade gif GIF from: Accessed 15 July 2019

When ingested, atropa belladonna is one of the most toxic plants in the world due to the high concentration of tropane alkaloids within the plant. Below is a list of information about tropane alkaloids.

  • Used in some pharmaceuticals for anticholinergic properties (for instance, Parkinson’s medication)
  • Can worsen certain conditions such as congestive heart failure and diabetes mellitus
  • Belladonna contains three major tropane alkaloids:
    • Atropine – works by blocking acetylcholine at muscarinic receptors, often used as an antidote in nerve agent and pesticide poisonings: side effects include tachycardia, hallucinations, dizziness (1)
    • Scopolamine – works as a competitive inhibitor for receptors in the parasympathetic nervous system, often used to aid in stopping nausea and vomiting: side effects include confusion, agitation, urinary retention (2)
    • Hyoscyamine – works as an antagonist of muscarinic receptors, often used for GI disorders such as Irritable Bowel Syndrome: side effects include irregular heart beat, dry mouth, headache (3)

Image result for muscarinic antagonist mechanism of actionImage from: Accessed 21 July 2019

 

Information derived from:

(1) RxList. 2019. “Atropen”. <https://www.rxlist.com/atropen-drug.htm#description> Accessed 15 July 2019.

(2) RxList. 2019. “Scopolamine”. <https://www.rxlist.com/consumer_scopolamine/drugs-condition.htm> Accessed 15 July 2019.

(3) American Society of Health-system Pharmacists. 2019. “Hyoscyamine”. <https://medlineplus.gov/druginfo/meds/a684010.html> Accessed 15 July 2019

Target Organs and Signs/Symptoms of Toxicity

Image from: Accessed 15 July 2019

The above image is a set of mnemonic devices to remember Anticholinergic toxicity.

The main target of atropa belladonna is the central nervous system – mainly the postganglionic muscarinic receptors. Impact also includes smooth muscles due to their response in activation to acetylcholine.

TREATMENT

  • Activated charcoal
  • Gastric lavage
  • Hemodynamic monitoring
  • Ventilation for respiratory support
  • Benzodiazepines (for treatment of agitation)
  • Physostigmine (cholinesterase inhibitor that can cross the blood-brain barrier to help with central and peripheral nervous system activity)

Two interesting cases in which you can read about the above various treatments can be found in these articles:

Berdai, Labib, Chetouani, & Harandou. “Atropa belladonna intoxication: a case report”. The Pan Aferican Medical Journal. 2012: 11(72). <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361210/>

Demirhan, et al. “Anticholinergic toxic syndrome caused by atropa belladonna fruit (deadly nightshade): a case report”. Turkish Journal of Anaesthesiology and Reanimation. 2013: 41(6). <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894214/>

Unique News

In 2010 and again in 2017 the Food and Drug Administration reported a case where a homeopathic teething treatment for infants was found to contain dangerous amounts of Atropa belladonna, which could result in infant death. For information regarding the recalled product please see the below links:

Hyland’s Homeopathic Teething Tablets: Questions and Answers

Hyland’s Homeopathic Teething Tablets Recalled Nationwide

Hyland's Teething Tablets, Original Formula Natural Medicine 135 Image from: Accessed 15 July 2019

No conclusive biomarkers for nightshade toxicity exist.

Image result for deadly nightshade punsCartoon from: Accessed 15 July 2019

FREEZE…or actually the opposite…for Ethylene glycol

Left image: Chemical structure of ethylene glycol from: Accessed 20 June 2019.

Right image: Vial containing ethylene glycol from: Accessed 20 June 2019

Ethylene glycol is a liquid chemical that is colorless and odorless but does have a sweet taste. If ingested, this chemical is poisonous.

Sources

  • Most commonly known as “antifreeze” (think of the stuff you spray on your windshield to get the frost off on a chilly winter day)
  • Used as a coolant for car engines to keep from overheating in the summer
  • Used as raw material in upholstery and fiberglass
  • Found in household paints and detergents

This list is not exhaustive. Ethylene glycol has many uses and can be found in various products used every day. Please visit ChemicalSafetyFacts.org for more information regarding the above list and other possible uses.

*CONFUSION ALERT*

Image result for polyethylene glycolImage from: Accessed 20 June 2019

Miralax and other like stool softeners go by the generic name Polyethylene glycol. These are drastically different compounds. The main difference in the chemistry is that ethylene glycol has a fixed, stable value and molecular weight whereas polyethylene glycol is NOT fixed and the molecular weight can change. For more detailed information and a great visual breakdown of the differences, please visit Pediaa.com

Biotransformation

Ethylene glycol is extremely water soluble. If ingested, it is quickly absorbed by the gastrointestinal tract. It can be absorbed through the skin and lungs, however this is a much slower process. Half life of ingested ethylene glycol is between 2 and 8 hours (depending on child versus adult). After only 24 hours, it is difficult to detect in the urine or body tissues, suggesting a very quick biotransformation.

Information derived from the Agency for Toxic Substances & Disease Registry. “Environmental Health and Medicine Education”. Accessed 20 June 2019.

Toxicokinetics and Mechanism of Action

Toxicity from dermal exposure or inhalation is unlikely.

Ingestion: When ethylene glycol is ingested, the liver metabolizes it. This can cause a feeling of intoxication, but the actual compound has a low toxicity. However, the liver uses several oxidation processes that break ethylene glycol down into different compounds that are more toxic than ethylene glycol:

  • Ethylene glycol: Prior to oxidation – 2-8 hours after ingestion: Central nervous system affected characterized by dizziness, upset stomach, drowsiness, and/or seizures (1)
  • Glycolaldehyde: First oxidation stage – 12-36 hours after ingestion: Metabolic process affected characterized by buildup of acid in body (metabolic acidosis), increased heart rate, jaundice, damage to mitochondria (1)
  • Glycolic acid: Second oxidation stage – 24-72 hours after ingestion: Kidneys affected characterized by back pain and changes in urine output (2)
  • Glyoxylic acid: Third oxidation stage – 36-72 hours after ingestion: Kidneys and tissues affected charaterized by renal trouble, dehydration, spasms (3)
  • Oxalic acid: Fourth oxidation stage – within 72 hours after ingestion: Brain, heart, kidneys, and lungs affected characterized by organ failure and possibly death (4)

Figure 2.(4)

Information derived from sources in order as they appear:

(1) Agency for Toxic Substances and Disease Registry. (2012) “Ethylene glycol and proylene glycol toxicity what is the biological fate of ethylene glycol?” Environmental Health and Medicine Education.

(2) PubChem. (2019). “Glycolic acid”. U.S. national Library of Medicine.

(3) Toxnet. (2013). “Glyoxylic acid”. Environmental Health & Toxicology.

(4) Eder, et al. (1998). “Ethylene glycol poisoning: toxicokinetic and analytical factors affecting laboratory diagnosis”. Clinical Chemistry. 44:1.

Target Organs and Signs/Symptoms of Toxicity

Related imageImage from: Accessed 20 June 2019

This visual is a good depiction of the information described above. Different products of the ethylene glycol oxidation process target different organs.

  • CNS – mirrors alcohol intoxication: nausea, convulsions, coma
  • Kidneys – kidney failure, metabolic acidosis
  • Liver – yellowing of skin and sclera (whites of eyes)
  • Overall organ system failure – severe bodily shock, death

Only about 4 ounces of ethylene glycol is needed to cause death in an average-sized male

Treatment

Tests:

  • Arterial blood gas analysis
  • Liver function panel
  • Complete blood count / Ethylene glycol blood test
  • Urinalysis
  • Test for bodily functions such as CT scan, EKG, chest x-ray

Medical treatments:

  • Activated charcoal
  • Intravenous sodium bicarbonate (for acidosis)
  • Fomepizole (antidote)

Information for signs/symptoms/treatment derived from: MedlinePlus. “Ethylene glycol poisoning”. Accessed 20 June 2019.

Biomarkers

  • Blood gasses
  • Urinalysis
  • Serum calcium concentration (newer biomarker)

This abstract from an article published in 2017 by Hodgman, Marraffa, Wojcik, & Grant shows why newer biomarkers are necessary for ethylene glycol poisoning.

“Abstract

The diagnosis of ethylene glycol intoxication can be challenging. Definitive testing for ethylene glycol is not readily available and clinical decisions are often based on clinical suspicion and the results of more readily available tests. One of these findings is hypocalcemia, presumable through complexation with the ethylene glycol metabolite oxalate.”

Unique Exposure

There are no readily available cases of unique exposure to ethylene glycol, however there are many incidents of its use in suicide attempts and accidental ingestion by children and pets. The CDC has provided a list of trade names for ethylene glycol. While ethylene glycol is naturally a clear substance, neon colors are typically added to it to identify it as antifreeze.

Image result for antifreezeImage result for antifreezeRelated image

Images from: pink, blue, green Accessed 20 June 2019

Mercury — A Hug without u is just toxic

Mercury…it’s just chemistry. Don’t overreact.

Related imageImage from

Mercury is a transition metal on the periodic table and is a shiny liquid at room temperature. The reason for the periodic symbol Hg is because of the Greek name “hydrargyrum”, translating to liquid silver. While there are many uses for mercury, it is an extremely toxic element and must be handled with the upmost care.

The past:

In the 20th century, mercury was used in many forms such as pills, ointments, and steam baths as the primary treatment for syphilis. Side effects of this included tooth loss and neurological damage.

The Romans put their prisoners in mercury mines. The punishment ended up being a shortened life span.

The Chinese thought that mercury could aid in potency for older men.

The present:

Mercury is used in certain dental fillings but is limited to ages 6 years and above.

Mercury vapor is used in streetlights and fluorescent lamps.

Mercury thermometers were ban in several states in 2001 and the ones still existing today are not able to be calibrated for use.

Information above derived from Blaszczak-Boxe, Agata. (2014). “Facts about mercury (Hg)”. Live Science.

Image result for mercury punsImage from

Methylmercury is the most toxic form of mercury and can be transferred to humans from consuming certain seafoods. Pregnant women are warned against eating fish high in mercury such as shark, swordfish, and sushi due to the damaging effects on the nervous system to developing embryos. An article by Bose-O’Reilly, McCarty, Steckling, and Lettmeier published in 2011 titled “Mercury exposure and children’s health” provides an interesting in-depth look at the harmful effects of exposure. Read the abstract to the article below:

“Acute or chronic mercury exposure can cause adverse effects during any period of development. Mercury is a highly toxic element; there is no known safe level of exposure. Ideally, neither children nor adults should have any mercury in their bodies because it provides no physiological benefit. Prenatal and postnatal mercury exposures occur frequently in many different ways. Pediatricians, nurses, and other health care providers should understand the scope of mercury exposures and health problems among children and be prepared to handle mercury exposures in medical practice. Prevention is the key to reducing mercury poisoning. Mercury exists in different chemical forms: elemental (or metallic), inorganic, and organic (methylmercury and ethyl mercury). Mercury exposure can cause acute and chronic intoxication at low levels of exposure. Mercury is neuro-, nephro-, and immunotoxic. The development of the child in utero and early in life is at particular risk. Mercury is ubiquitous and persistent. Mercury is a global pollutant, bio-accumulating, mainly through the aquatic food chain, resulting in a serious health hazard for children. This article provides an extensive review of mercury exposure and children’s health.”

BIOTRANSFORMATION

Studies have shown that the half life of methylmercury (MeHg) is about 50 days. Since it takes so long for the body to process MeHg, it is easy for it to build up into a toxic amount, especially in high-fish diets. Methylmercury builds up in the brain in an inorganic form and essentially gets locked in. “Intestinal flora can demethylate MeHg to inorganic Hg, which is poorly absorbed by the GI tract” (National Research Council Committee on the Toxicological Effects of Methylmercury, 2000).

This short (less than one minute) video, gives a broad explanation of biotransformation of ethyl and methyl mercury.

TOXICOKINETICS and MECHANISM of ACTION

  • Ingestion – most common form of methylmercury uptake by humans, about 95% absorbed through the GI tract
  • Inhalation – 75-85% absorbed through the lungs through air pollutants
  • Dermal – 3% absorbed through the skin with exposure to Hg in the environmentFIGURE 2-2. Methylmercury kinetics.Graphic and information from

When mercury enters the body, it distributes to the soft tissues and then to the brain. MeHg binds to hemoglobin and passes easily through the blood-brain barrier. It also easily crosses the placental barrier in pregnant women and can pass through the breast milk. The graphic below depicts what happens to the neurons of a developing fetus when the mother consumes methylmercury.

Mercury poisoning of unborn baby graphicGraphic from

TARGET ORGANS and SIGNS/SYMPTOMS of TOXICITY

  • Central Nervous System – Muscular hypotonia (low muscle tone), tremors, ataxia (slurred speech, drooling)
  • Kidneys – kidney failure
  • Lungs – shortness of breath
  • Skin – pustules, cyanotic (bluish coloring), scaling

An external file that holds a picture, illustration, etc. Object name is nihms-294964-f0006.jpgImage depicts skin issues after exposure to a broken mercury thermometer. Image and above information from Bose-O’Reilly, McCarty, Steckling, and Lettmeier. (2011) “Mercury exposure and children’s health”. Current Problems Pediatric Adolescent Health Care.

For more information please visit Children’s Health Defense which houses over 240 studies and 89 peer-reviewed published articles about the dangers of mercury toxicity. These articles cover mental retardation and autism linked to mercury poisoning in children.

TREATMENT

  • Remove contamination  – remove person from the source (example, area with broken lightbulb) and remove contaminated clothing
  • Acute inhalation may require bronchodilators or intubation
  • Activated charcoal for poisoning via ingestion
  • Gastric lavage
  • Oral laxative
  • Chelation – agent usually used is dimercaprol (except for exposure to methylmercury as it can increase toxicity to CNS)
  • Blood dialysis

Information derived from eMedicineHealth. “Mercury Poisoning”. Accessed 29 May 2019.

BIOMARKERS

The main biomarkers are scalp and hair samples. However, increasing health concerns present the need for more or newer biomarkers. See the abstract from the article by Branco, et al. from 2017 called “Biomarkers of mercury toxicity: Past, present, and future trends” originally published in the Journal of Toxicology and Environmental Health for information regarding the need for newer biomarkers.

“Mercury (Hg) toxicity continues to represent a global health concern. Given that human populations are mostly exposed to low chronic levels of mercurial compounds (methylmercury through fish, mercury vapor from dental amalgams, and ethylmercury from vaccines), the need for more sensitive and refined tools to assess the effects and/or susceptibility to adverse metal-mediated health risks remains. Traditional biomarkers, such as hair or blood Hg levels, are practical and provide a reliable measure of exposure, but given intra-population variability, it is difficult to establish accurate cause–effect relationships. It is therefore important to identify and validate biomarkers that are predictive of early adverse effects prior to adverse health outcomes becoming irreversible. This review describes the predominant biomarkers used by toxicologists and epidemiologists to evaluate exposure, effect and susceptibility to Hg compounds, weighing on their advantages and disadvantages. Most importantly, and in light of recent findings on the molecular mechanisms underlying Hg-mediated toxicity, potential novel biomarkers that might be predictive of toxic effect are presented, and the applicability of these parameters in risk assessment is examined.”

ESSENTIALITY

There is no known function for mercury in the human body. The uses for mercury such as lightbulbs and thermometers are being phased out for safety purposes.

Related imageImage from

And remember…If a mercury rectal thermometer broke in uranus the element of surprise might overcome you but be sure you planet to get to the doctor soon and get periodically checked afterwords.

The Buzz About Neonicotinoids!

So what’s the buzz about?

Graphic derived from: Brunning, Andy. “Neonicotinoid pesticides – the facts”. Compound Interest. 2018. <https://www.compoundchem.com/2015/04/14/neonicotinoids/>

Neonicotinoids were introduced relatively recently (1980s) have a variety of chemical structures, as they make up a broad group of pesticides. However, they have been linked to the fall of the bee population and other large environmental concerns. The article by Blacquiere, Smagghe, Gestel, and Mommaerts explains why this class of pesticides poses globally concerning issues, including factor such as “residue levels in plants” and “reported side-effects with special attention for sublethal effects”.

Did you know that Neonicotinoids literally translates to “new nicotine-like insecticides”?

Shutterstock image from Mother Jones’s webpage here

Neonicotinoids affect the central nervous system of insects. Some major groups within this class are:

Imidacloprid – used to control sucking reflex in insects

Acetamiprid – causes hyperactivity and muscle spasms

Clothianidin – systemic neurotoxin

Thiacloprid – used to control sucking and biting reflexes in insects

Thiamethoxam – paralytic effects

Read more at Gardening Know How: What Are Neonicotinoids Pesticides And How Do Neonicotinoids Work https://www.gardeningknowhow.com/plant-problems/pests/pesticides/what-are-neonicotinoids.htm

BIOTRANSFORMATION

In 2009, one of the first studies in biotranformation of neonicotinioids was published by Pandey, Dorrian, Russell, and Oakeshott, showing how this group of pesticides selects the species on which it reacts. Find the abstract below and check out the full article linked here

Abstract

We report the isolation of a Pseudomonas sp. which is able to transform imidacloprid and thiamethoxam under microaerophilic conditions in the presence of an alternate carbon source. This bacterium, Pseudomonas sp. 1G, was isolated from soil with a history of repeated exposure to imidacloprid. Both insecticides were transformed to nitrosoguanidine (NNO), desnitro (NH), and urea (O) metabolites and a transformation pathway is proposed. This is the first conclusive report of bacterial transformation of the ‘magic nitro’ group which is responsible for the insect selectivity of neonicotinoid insecticides.

TOXICOKINETICS

The good news: This class of insecticides is widely favored due to the low risk in humans and larger mammalian creatures. A search in PubMED revealed that there are 98 peer-reviewed articles focusing on toxicokinetics of neonicotinoids and only one article relating to humans on this subject.

What did the article reveal?

Inhalation of imidacloprid resulted in gastrointestinal and respiratory distress with the patient making a full recovery.

What do other articles say?

Overall, neonicotinoids “generally have low acute toxicity to mammals, birds, and fish” (Tomizawa & Casida, 2005) and “studies reported low rates of adverse health effects from acute neonic exposure” (Cimino, Boyles, Thayer, and Perry, 2017). For a more visual representation on neonictinoids toxicity in insects:

Image found here
 
MECHANISM OF ACTION and TARGETED ORGANS
 
The graphic below shows the mechanism of action for neonicotinoids, which work very similarly to nicotine but have much stronger effects on insects than on mammals.
Graphic from here
 
The nAChRs are found in the post-synaptic dendrites of all neurons in the brain and spinal cord. This is why this group of insecticides affect the central nervous system.
 
SIGNS & SYMPTOMS OF TOXICITY
 
There have been only a few reported cases of Neonicotinoid toxicity in humans:
 
– Attempted suicide cases by oral ingestion of imidacloprid
  • Drowsiness
  • Dizziness
  • Vomiting
  • Fever

-Accidental inhalation of imidacloprid

  • Sweating
  • Aggitation
  • Disorientation

Human health issues studied for acetamiprid as depicted by the below graphic from:

TREATMENTS

There are no antidotes for neonicotinoid poisoning. Current treatments include

  • supportive care
  • symptomatic treatments (ie medications given for nausea)
  • washing exposed area (if dermal contact)

BIOMARKERS

There is a significant lack of biomarkers in assessing neonicotinoid toxicity in humans. This group of insecticides has a short half-life, suggesting that the best way to measure intake would be with urine samples.

For more information on this subject, see table 3 of the article “Biological Monitoring of Human Exposure to Neonicotinoids Using Urine Samples, and Neonicotinoid Excretion Kinetics” (Harada, et al 2016).

BEE AWARE

While neonicotinoids may not pose a large direct threat to humans, they are one of the leading causes of the honeybee deaths. Check out this link to find out why bees are important! https://www.travelfordifference.com/bee-awareness-month-save-the-bees/

Image from