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Source¹

Brown recluse spiders primarily reside in the central and southern regions of the United States and are the most commonly found amongst the Loxosceles genus. These spiders are nocturnal meaning they prefer dark, warm and sheltered environments during the day and are non-aggressive. They are brown and give the appearance of a dark violin, however, identification is often confirmed from observing their eyes. Interestingly enough, brown recluse spiders only have six eyes unlike others containing eight eyes. Despite their color, shape, leg position and eyes—they are well recognized for their “red, white and blue” ringed bite.

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Biotransformation²/ Mechanism of Action

The venom of brown recluse spiders contains a variety of enzymes such as sphingomyelinase D, hyaluronidase, alkaline phosphatase and 5-ribonucleotide phosphohydrolase. Together these components cause blood coagulation. More specifically, platelet aggregation is stimulated when sphingomyelinase D reacts with sphingomyelin which releases N-acylsphingosine and choline when calcium or amyloid protein is present. The lack of blood flow around the bite site causes tissue necrosis. Polymorphonuclear leukocyte infiltration also partakes in the ischemia with the releasing of inflammatory mediators and associating with the local reaction.

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Toxicokinetics³

Brown recluse spiders only bite as a defense mechanism. The site of the bite will initially begin with two small puncture wounds and surrounded by erythema. Next the center of the reaction site will become pale while the outer edge remains red. Vasospasm of the reaction site will increase pain to severe levels. Throughout the next few days a blister forms and the center of the bite site will transform into a blue, hard, stellate ulcer. Eventually the wound will heal by secondary intention with the potential of skin sloughing. Total time of healing can last several weeks.

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Carcinogenicity

No carcinogenic effects reported

Target Organs

 The skin receives the most amount of harm, however, additional systematic effects are possible depending on bite and venom amount

Signs and Symptoms

The individual may or may not feel the sting from the bite or even see the brown recluse spider. Generally, the symptoms from the venom do not arise for several hours but may include:

Redness

Blister

Fever

Nausea

Itching at site

Chills

Sweating

Discomfort

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Treatment³

Unfortunately, with spider bites, the only form of treatment is managing symptoms as antivenin success has not been well supported with evidence. Initially the individual should apply first aid and elevate the extremity containing the bite above the heart. Applying an ice pack to the wound could help stop the necrosis process and cleaning the wound with soapy water will help prevent infection. Pain management is dependent on the individual and their reaction, however, can range from simple NSAIDs to potential need of opioids. If an infection develops, a hospital visit may be necessary for antibiotics and in rare circumstances, surgical excision.

References

1. https://www.livescience.com/39996-brown-recluse-spiders.html
2. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/brown-recluse-spider
3. https://www.ncbi.nlm.nih.gov/books/NBK537045/#:~:text=Systemic%20symptoms%20of%20brown%20recluse,coagulation%2C%20seizures%2C%20and%20death.
4. https://www.healthline.com/health/brown-recluse-spider#symptoms

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Source¹:

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Methylene chloride is a compound that is developed from natural elements such as methane gas or wood alcohol. In a liquid form, the solvent is colorless, easily evaporated, not easily burned and tends to have mildly sweet odor. Used as an industrial solvent and as a paint stripper, this compound may also be found in aerosol, pesticide and photographic film products. The methylene chloride found in the environment is a result of product release.

Biotransformation²:

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Occurs in two locations-

Cell:

Occurs in the cytosolic fraction of the liver cell and results in carbon dioxide end product in addition to formaldehyde and formic as metabolic intermediates through the use of glutathione dependent enzymes. This pathway is generally indicating of carcinogenic activity.

Liver:

Through the P-450 mixed function oxidase pathway, carbon monoxide, carbon dioxide and chloride become an end product when methylene chloride is metabolized by microsomal oxidative dechlorination. The percentage of carbon monoxide produced is directly correlated with methylene chloride concentration. This pathway is primarily focused on detoxification.

Toxicokinetics³:

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The primary route of methylene chloride exposure is through inhalation which absorbs at a rapid rate. As the concentration increases, the level of blood oxygen decreases which causes the cardiac output to increase in attempt to obtain more oxygen. Increased ventilation then leads to an increase of respiratory exposure and saturation may occur. Obesity plays a role in absorption and body fat has been proven to store methylene chloride, however, the compound tends to be eliminated fairly quickly once steady state is reached. Methylene chloride is distributed throughout the blood and is eliminate through urine after being metabolized in the liver.

Carcinogenicity¹:

According to the DHHS, human carcinogen is anticipated in reference to significant evidence found in animal studies. . In addition, OSHA has concluded there is evidence of increased cancer risk for individuals working with methylene chloride and has declared the compound as a human carcinogen.

Mechanism of Action^1,2:

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Metabolized primarily in the liver where methylene chloride is transformed to carbon monoxide. As a result, carboxyhemoglobin levels increase while the ability to carry oxygen throughout the blood decreases. These levels have potential to diverge even more even hours after exposure.

Target Organs:

• Cardiovascular system
• Respiratory system
• Central nervous system
• Skin

Signs & Symptoms²:

Duration of exposure contributes to level of toxicity. Shorter durations appear to be less likely to cause permanent disabilities. Meanwhile, long term exposures have proven to produce liver toxicity in animal studies with indications of similar effects on humans.

Skin Contamination:

• Irritation
• Burns

Inhalation:

• Nausea
• Vomiting
• Light headedness
• Extremity numbness
• Fluctuating blood enzyme levels
• Difficulty breathing
• Bronchitis/pulmonary edema
• Unconsciousness
• Death

Genetic susceptibility^1,3:

No structural abnormalities were observed. Behavioral alterations and mentally retarded development was found in animal studies. Methylene chloride has been proven to cross the placental barrier in both rats and humans, including breast milk. Depending on the concentration, this ingestion exposure could result in fatal poisoning.

Treatments:

Immediate removal from exposing environment

Oxygen treatment to decrease carboxyhemoglobin and increase oxygen levels

Liver function tests to identify potential hepatic toxicity

Biomarkers³:

Methylene chloride exposure may be confirmed through blood, breath or urine. Correlations have been observed between methylene chloride levels in urine and the respiratory tract. Carbon monoxide concentrations within the alveolar air is another indication of exposure, however, must be confirmed through another indication. Carboxylhemoglobin levels significantly increase during methylene chloride exposure and are dependent on duration.

Summary Found Here

References:

1. https://www.atsdr.cdc.gov/MMG/MMG.asp?id=230&tid=42#:~:text=Metabolic,hours%20after%20exposure%20has%20ceased.
2. https://www.osha.gov/laws-regs/regulations/standardnumber/1910/1910.1052AppB
3. https://www.euro.who.int/__data/assets/pdf_file/0013/123061/AQG2ndEd_5_7Dichloromethane.pdf

Iron Toxicity

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Introduction:

Iron is a metal that plays a vital role in the human body. This element cannot be produced and must be absorbed through foods or supplements.

High iron foods include^2,3:

• Fortified cereals
• Beef
• Shellfish
• Dried fruit
• Large white beans
• Spinach
• Unsweetened chocolate
• Quinoa
• White button mushrooms
• Squash/pumpkin seeds

Biotransformation^4,5:

Hemoglobin is an iron protein complex that is responsible for carrying oxygen and is eventually eliminated as waste. When broken down, hemoglobin transforms into several metabolites including bilirubin. The liver is primarily responsible for eliminating bilirubin and in the event that the liver is unable to such as disease or infection, the levels may increase and become toxic. High concentrations can lead to irreversible brain injury as well as alter eye/skin color.

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Toxicokinetics⁶:

While the toxicokinetics of iron poisoning is still under investigation, several factors have helped with potential discoveries. Iron is not a xenobiotic and is in fact highly reactive to other elements. As a result, many mechanisms have developed in order to prevent iron induced damage. With no exact mechanism for iron excretion, toxic doses lead to an over saturation of iron in the blood. The liver and gastrointestinal system are responsible for metabolizing and eliminating iron as well as the metabolites while also receiving potential damage.

Carcinogenicity⁷:

Iron is found to be carcinogenic in animal models and human experiments after discovery of target genes in iron-induced carcinogenesis

Target Organs^8,9:

Liver, heart and sometimes the pancreas as well as other endocrine systems

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Signs and Symptoms⁹:

Includes nausea, abdominal pain, diarrhea, dehydration and bloody/dark stool. Sometimes dizziness, change in pulse, low blood pressure, headache, fever, shortness of breath, change in skin pigment also occur.

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Genetic Susceptibility and Heritable Traits:

• Hemochromatosis- gene mutation that alters the amount of iron in your body following absorption from food ingested and ultimately leads to iron overload
• Anemia- some studies indicate that iron deficiency may have a genetic contribution
• Sickle cell anemia- inherited abnormal hemoglobin that deprives the body of oxygen

Treatment:

• Complete bowel irrigation- manually washing the body of excess iron
• Chelation therapy- IV administration of chemical that binds to iron and helps elimination through urine

Biomarkers:

Below are common biomarkers and concentrations in relation to iron

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Essentiality and Deficiency:

Iron is responsible for oxygenating the blood, helps transform blood sugar to energy, supports the immune system as well as healthy skin, hair and nails. Too much or too little iron is easily noticeable and can have serious effects on the human body. Iron deficiency can lead to serious danger if not treated.

Below compares essentiality and deficiency

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Conclusion:

Here is a great video discussing the physiology of iron in the human body including diseases

https://www.youtube.com/watch?v=ahCy97FVUpM

References:

1. https://www.vivaeve.com/taking-iron-supplements-use-them-safely-heres-how/
2. https://www.myfooddata.com/articles/food-sources-of-iron.php
3. https://www.spatone.com/en-au/about-iron/role-of-iron-in-the-body
4. https://toxtutor.nlm.nih.gov/12-001.html
5. https://nursekey.com/5-hematology/
6. https://pubmed.ncbi.nlm.nih.gov/10022330/
7. https://pubmed.ncbi.nlm.nih.gov/19018762/#:~:text=Indeed%2C%20iron%20is%20carcinogenic%20in,is%20not%20random%20in%20vivo.
8. https://slideplayer.com/slide/5706139/
9. https://www.grepmed.com/images/5406/toxicology-diagnosis-overdose-toxicity-stages-iron
10. https://www.researchgate.net/figure/Clinical-classification-of-biomarkers-of-iron-status-1_tbl1_26245487
11. https://www.verywellhealth.com/iron-supplements-benefits-4178814

Introduction⁽¹⁾:

Glufosinate is synthetic herbicide derived from glutamate with the help of phosphinic acid and used to control weeds primarily in agricultural crops. Glofasinate is considered a contact herbicide meaning only the area in contact with the compound is effected rather than the entirety of the plant.

Chemical Structure                                                            Purchase Here

Mode of Action⁽¹⁾:

Glufosinate is proven effective on the basis of successful inhibition of glutamine synthetase activity. Glutamine synthetase is essential for multiple metabolic systems and a lack of quickly becomes lethal. As a result of decrease of amino acids in photorespiration, glyoxylate significantly increases the cessation of photosynthesis and thus the plant is unable to survive.

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Toxicity⁽¹⁾:

Oral toxicity is low in animals and humans, however, has a greater hazardous effect than glyphosate. Symptoms of toxicity in animals include hypothermia, CNS excitation and possible cardiovascular effects. Certain animals such as cattle, sheep and dogs are more effected than others like mice or rats. As a contact herbicide, animals displayed reactions including nausea, vomiting and mobility weakness when in contact with treated environment.

Neurotoxic Effects of Glufosinate

Carcinogenicity⁽¹⁾:

No supportive evidence proving carcinogenic to humans, however, some evidence suggests the potential of breast cancer cell growth in humans.

Teratogenic⁽¹⁾:

Observations in case studies include neuroepithelium apoptosis in developing mice embryos

Reproductive⁽¹⁾:

Very high doses result in reproductive development disturbances by having a strong effect on the endocrine system as a disruptor

Treatment⁽²⁾:

Basic- establishing a proper airway, monitor for breathing irregularities and shock, flush any contact contamination with water immediately, administer 200 mls of water orally in the of ingestion and not emetics

Advanced- intubation, positive pressure ventilation, IV drip of D5W/SRP, lactated ringers may be required with hypovolemia patients, observe for potential fluid overload, anticipate seizure activity and be prepared to administer drug therapy

Resourceful Administration Video

References:

1. “Glufosinate.” Glufosinate – an Overview | ScienceDirect Topics, https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/glufosinate
2. National Center for Biotechnology Information. PubChem Database. Glufosinate, CID=4794, https://pubchem.ncbi.nlm.nih.gov/compound/Glufosinate (accessed on May 26, 2020)

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Howdy! Welcome to my toxicology blog post. I have worked in pharmacy for roughly five years and unfortunately, have seen a fair share of pediatric toxicity cases. I find the wide variety of treatments most interesting depending on the poison, venom or element. I chose glufosinate because I raised livestock growing up and this particular pesticide is known for having an extreme effect on livestock animals. Next, I decided to present iron toxicity for my element because while iron is an important ingredient in our body– a certain level must be maintained in order to prevent serious complications. For my third blog, I decided to step out of my comfort zone and cover a solvent I was not familiar with. Methylene chloride is found in several common household products such as aerosol and paint thinners so I felt as though readers should be aware of potential exposures. Lastly, my animal of choice was the brown recluse spider. As a West Texas resident, we have these buddies everywhere! While children and the elderly are primarily the individuals in great danger, anyone who receives a bite is in for a rough couple of weeks. Overall, I thoroughly enjoyed composing each blog and I am hopeful individuals will become more familiar with potential toxicological exposures around us every day!

Best wishes,

Caitlyn