Chemical Toxins, 2020 University of Jordan , Toxicology Majd Al-Qudah, MD

1. Toxic Gases
Classification, CO, CN, Smoke, Fumes, VSA
Prepared and presented by : Majd Al-Qudah, MD

2. Definitions
• Toxic gas is a chemical that has a median lethal concentration (LC50) in air
of more than 200 parts per million (ppm) but not more than 2,000 parts
per million by volume of gas or vapor, or more than 2 milligrams per liter
but not more than 20 milligrams per liter of mist, fume or dust, when
administered by continuous inhalation for 1 hour (or less if death occurs
within 1 hour) to albino rats weighing between 200 and 300 grams each.
• LC50 (lethal concentration fifty) the concentration of a substance in
air for which exposure is expected to cause the death of fifty percent of the
entire defined experimental animal population over a specified length of
time.

3. Classification
• These are based on LC50 rat 1 hr values, and include:
oHazard zone A—gases (mixtures) with an LC50 rat 1 hr that are less than or
equal to 200 ppm.
oHazard zone B—gases (mixtures) with an LC50 rat 1 hr that are greater than
200 ppm but less than or equal to 1000 ppm.
oHazard zone C—gases (mixtures) with an LC50 rat 1 hr that are greater than
1000 ppm but less than or equal to 3000 ppm.
oHazard zone D—gases (mixtures) with an LC50 rat 1 hr that are greater than
3000 ppm but less than or equal to 5000 ppm.

5. Carbon monoxide poisoning
Introduction
Epidemiology
Pathophysiology
Kinetics
Clinical presentation
Diagnosis
Management
Prevention

6. Carbon monoxide poisoning: introduction
• Carbon monoxide (CO) is an odorless, tasteless, colorless,
nonirritating gas formed by hydrocarbon combustion.
• The atmospheric concentration of CO is generally below 0.001
percent, but it may be higher in urban areas or enclosed
environments.
• CO binds to hemoglobin with much greater affinity than oxygen,
forming carboxyhemoglobin (COHb) and resulting in impaired
oxygen transport and utilization.
• CO can also precipitate an inflammatory cascade that results in CNS
lipid peroxidation and delayed neurologic sequelae.

7. Carbon monoxide poisoning: Epidemiology
• Fire-related smoke inhalation is responsible for most
cases of carbon monoxide (CO) poisoning.
• Non-fire related CO poisoning is responsible for up to 50,000
emergency department (ED) visits and 1200 deaths per year.
• Inadvertent, non-fire related CO poisoning likely causes around
400 deaths annually, while the number of intentional CO
poisonings resulting in death is twice as high.
• The mortality rate is higher for intentional poisoning than for
inadvertent exposure.
• Unlike intentional poisoning, unintended poisoning demonstrates
both seasonal and regional variation, and it is most common
during the winter months in cold climates.

8. Carbon monoxide poisoning: Epidemiology
• Potential sources of CO, other than fires, include poorly
functioning heating systems, improperly vented fuel-burning
devices (eg, kerosene heaters, charcoal grills, camping stoves ,
gasoline-powered electrical generators), and motor vehicles
operating in poorly ventilated areas (eg, warehouses, parking
garages).
• Methylene chloride (dichloromethane) is an industrial solvent and a
component of paint remover. Inhaled or ingested methylene chloride
is metabolized to CO by the liver, causing CO toxicity in the absence of
ambient CO

9. Carbon monoxide poisoning: Pathophysiology
• Carbon monoxide (CO) diffuses rapidly across the pulmonary capillary
membrane and binds to the iron moiety of heme (and other
porphyrins) with approximately 240 times the affinity of oxygen.
• The degree of carboxyhemoglobinemia (COHb) is a function of the
relative amounts of CO and oxygen in the environment, duration of
exposure, and minute ventilation.
• Nonsmokers may have up to 3 percent carboxyhemoglobin at
baseline; smokers may have levels of 10 to 15 percent .

11. Carbon monoxide poisoning: pathophysiology
• Once CO binds to the heme moiety
of hemoglobin, an allosteric change
occurs that greatly diminishes the
ability of the other three oxygen
binding sites to off-load oxygen to
peripheral tissues .
• This results in a deformation and
leftward shift of the oxyhemoglobin
dissociation curve, and compounds
the impairment in tissue oxygen
delivery.

12. Carbon monoxide poisoning: pathophysiology
• CO also interferes with peripheral oxygen utilization. Approximately
10 to 15 percent of CO is extravascular and bound to molecules such
as myoglobin, cytochromes, and NADPH reductase, resulting in
impairment of oxidative phosphorylation at the
mitochondrial level.
• The half-life of CO bound to these molecules is longer than that of
COHb. The importance of these non-hemoglobin-mediated effects
has been best documented in the heart, where mitochondrial
dysfunction due to CO can produce myocardial stunning despite
adequate oxygen delivery

13. Carbon monoxide poisoning: Kinetics
• Carbon monoxide (CO) is rapidly absorbed across the pulmonary
endothelium.
• Elimination is dependent upon the degree of oxygenation and, to a
lesser extent, minute ventilation.
• The half-life of CO while a patient is breathing room air is
approximately 250 to 320 minutes, while breathing high-flow oxygen
via a nonrebreathing face mask is about 90 minutes and with 100
percent hyperbaric oxygen is approximately 30 minutes.

14. Carbon monoxide poisoning: Clinical
presentation
• Symptoms and signs — The clinical findings of carbon monoxide (CO)
poisoning are highly variable and largely nonspecific.
• Moderately or mildly CO-intoxicated patients often present with
constitutional symptoms, including headache (the most common
presenting symptom), malaise, nausea, and dizziness.
• In the absence of concurrent trauma or burns, physical findings in CO
poisoning are usually confined to alterations in mental status. Patients may
manifest symptoms ranging from mild confusion to coma.
• Severe CO toxicity can produce neurologic symptoms such as seizures,
syncope, or coma, and also cardiovascular and metabolic manifestations
such as myocardial ischemia, ventricular arrhythmias, pulmonary edema,
and profound lactic acidosis.

17. Carbon monoxide poisoning: Diagnosis
• Acute carbon monoxide (CO) poisoning is usually suspected on the
basis of a suggestive history, while the diagnosis of chronic CO
intoxication is notoriously difficult. Standard pulse oximetry
(SpO2) CANNOT screen for CO exposure, as it does not differentiate
carboxyhemoglobin from oxyhemoglobin.
• The diagnosis of CO poisoning is based upon a compatible history and
physical examination in conjunction with an elevated
carboxyhemoglobin level measured by cooximetry of an arterial
blood gas sample. In hemodynamically stable patients, venous
samples are accurate and commonly used.

18. Carbon monoxide poisoning: Diagnosis
• Venous samples may be used to determine the carboxyhemoglobin
level, but they are less accurate in quantifying the associated acidosis.
However, venous samples are useful for screening large numbers of
potential CO victims in a disaster situation and for monitoring
changes in an individual’s carboxyhemoglobin level over time during
treatment.
• Blood PO2 measurements tend to be normal because PO2 reflects
O2 dissolved in blood, and this process is not affected by CO. In
contrast, hemoglobin-bound O2 (which normally comprises 98
percent of arterial O2 content) is profoundly reduced in the presence
of COHb.

19. Carbon monoxide poisoning: Management
• the most important interventions in the management of a CO-
poisoned patient are prompt removal from the source of CO
and institution of high-flow oxygen by face mask.
• Comatose patients, or those with severely impaired mental status,
should be intubated without delay and mechanically ventilated using
100 percent oxygen. For patients suffering from CO poisoning after
smoke inhalation, it is important to consider concomitant cyanide
toxicity, which can further impair tissue oxygen utilization and
exacerbate cellular hypoxia.

20. Carbon monoxide poisoning: Management
• Hyperbaric oxygen — Hyperbaric oxygen therapy (HBO) involves exposing
patients to 100 percent oxygen under supra-atmospheric conditions. This
results in a decrease in the half-life of carboxyhemoglobin (COHb), from
approximately 90 minutes on 100 percent normobaric oxygen to
approximately 30 minutes during HBO.
• treatment with hyperbaric oxygen (HBO) is considered in the following
circumstances:
●CO level >25 percent
●CO level >20 percent in pregnant patient
●Loss of consciousness
●Severe metabolic acidosis (pH <7.1)
●Evidence of end-organ ischemia (eg, ECG changes, chest pain, or altered mental
status)

22. Cyanide Poisoning
Introduction
Epidemiology
Pathophysiology
Clinical presentation
Diagnosis
Management

23. Cyanide Poisoning: Introduction
• Cyanide is a mitochondrial toxin that is among the most
rapidly lethal poisons known to man. Used in both ancient and
modern times as a method of execution, cyanide causes death
within minutes to hours of exposure. Though significant cyanide
poisoning is uncommon, it must be recognized rapidly to ensure
prompt administration of life-saving treatment.

24. Cyanide Poisoning: Epidemiology
• There were 3165 human exposures to cyanide from 1993 to 2002.
Of these, 2.5 percent were fatal.
• Cyanide poisoning may result from a broad range of exposures
• Fire – In industrialized countries, the most common cause of cyanide
poisoning is domestic fires. Cyanide can be liberated during the combustion
of products containing both carbon and nitrogen. These products include
wool, silk, polyurethane (insulation/upholstery), polyacrylonitriles (plastics),
melamine resins (household goods), and synthetic rubber.

25. Cyanide Poisoning: Introduction
• Industrial – Metal extraction in mining, electroplating in jewelry production,
photography, plastics and rubber manufacturing, hair removal from hides,
and rodent pesticide and fumigants have all been implicated in cyanide
poisonings. Skin contact with cyanide salts can result in burns, which allow for
enhanced absorption of cyanide through the skin. The combination of cyanide
salts and acid, as utilized in electroplating, results in the release of cyanide
gas, which can lead to lethal inhalational exposures. Splashes of cyanide
solutions can result in dermal as well as mucosal absorption.

26. Cyanide Poisoning: Pathophysiology
Cyanide consists of a carbon
molecule triple bonded to
nitrogen. This compound is
highly reactive to metals
such as ferric ions .

27. Cyanide Poisoning: Pathophysiology
• Upon absorption, the compound enters the cellular
mitochondria and disrupts cytochrome oxidase a3 by
binding to the ferric ion.
• By halting the electron transport chain, adenosine triphosphate
production is inhibited leading to anaerobic glycolysis.
• The absorbed cyanide is primarily metabolized through the liver with
an enzyme called rhodanese that catalyzes the conversion of
cyanide to thiocyanate. This molecule can be excreted via the
kidneys.
• With large doses of cyanide, this mechanism is overwhelmed largely
due to insufficient sulfur donors.

28. A high concentration of
cyanide exposure
causes sudden
inhibition of cellular
respiration.

29. Cyanide Poisoning: Clinical presentation
• Signs And Symptoms
• mild poisoning headache, nausea, metallic taste, drowsiness,
dizziness, anxiety, mucous membrane irritation and hyperpnoea.
• Later frank dyspnea, bradycardia, hypotension, arrythmias and
periods of cyanosis and unconsciousness develop.
• In severe cases, progressive coma, convulsions and cardiovascular
collapse with shock and pulmonary edema can occur, with a fatal
outcome.

31. Cyanide Poisoning: Diagnosis
• Diagnosis is often difficult.
• It may be suspected in a person following a house fire who has a
decreased level of consciousness, low blood pressure, or high blood
lactate. Blood levels of cyanide can be measured but take time.
• Levels of 0.5–1 mg/L are mild, 1–2 mg/L are moderate, 2–3 mg/L are
severe, and greater than 3 mg/L generally result in death.

32. Cyanide Poisoning: Management
• Hydroxocobalamin: Cyanide has a greater affinity to bind with
hydroxocobalamin rather than cytochrome oxidase a3 forming
cyanocobalamin.
• Amyl nitrite: has a rapid onset of action and short half-life. Amyl nitrate
primarily works by converting hemoglobin to methemoglobin, which binds
to cyanide and allows cytochrome oxidase a3 to reactivate the electron
transport chain
• Sodium thiosulfate: acts as a sulfur donor in the conversion of cyanide to
thiocyanate through rhodanese. It has poor penetration into the
mitochondria, which is the site of action, causing slow onset. With a short
half-life and delay onset, sodium thiosulfate must be given in combination
with other therapies.

34. Smoke
Introduction
Chemical composition
Dangers
Smoke inhalation

35. Smoke: Introduction
• Smoke is a collection of airborne particulates and gases emitted
when a material undergoes combustion or pyrolysis, together with
the quantity of air that is entrained or otherwise mixed into the
mass.
• It is commonly an unwanted by-product of fires
(including stoves, candles, internal combustion engines, oil lamps,
and fireplaces), but may also be used for pest control (fumigation),
communication (smoke signals), defensive and offensive capabilities
in the military (smoke screen), cooking,
or smoking (tobacco, cannabis, etc.).

36. Smoke: Introduction
• Smoke inhalation is the primary cause of death in victims of
indoor fires. The smoke kills by a combination of thermal
damage, poisoning and pulmonary irritation caused by carbon
monoxide, hydrogen cyanide and other combustion products.
• Smoke is an aerosol (or mist) of solid particles and liquid droplets.

37. Smoke: Chemical composition
The composition
of smoke
depends on the
nature of the
burning fuel and
the conditions
of combustion.
Complete
combustion
Incomplete
combustion
invisible
part
nuclei mode
accumulation
mode
Coarse mode
Visible
part

38. Smoke: Chemical composition
• Invisible component : complete combustion :
• Fires with high availability of oxygen burn at a high temperature
and with a small amount of smoke produced
• the particles are mostly composed of ash, or with large
temperature differences, of condensed aerosol of water.
• High temperature also leads to production of nitrogen oxides.
Sulfur content yields sulfur dioxide, Carbon and hydrogen are
almost completely oxidized to carbon dioxide and water.

39. Smoke: Chemical composition
• Invisible component : Incomplete combustion :
• Fires burning with lack of oxygen produce a significantly wider palette
of compounds, many of them toxic.
• Partial oxidation of carbon produces carbon monoxide,
• nitrogen-containing materials can yield hydrogen
cyanide, ammonia, and nitrogen oxides.
• Hydrogen gas can be produced instead of water.
• Contents of halogens such as chlorine (e.g. in polyvinyl chloride )
may lead to the production of hydrogen
chloride, phosgene, dioxin,
and chloromethane, bromomethane and other halocarbons.
• Hydrogen fluoride can be formed from fluorocarbons

40. Smoke: Chemical composition
• Invisible component : Pyrolysis
• is the thermal decomposition of materials at elevated temperatures in
an inert atmosphere. It involves a change of chemical composition and
is irreversible.
• Pyrolysis of polychlorinated biphenyls (PCB), e.g. from burning
older transformer oil, and to lower degree also of other chlorine-containing
materials, can produce 2,3,7,8-tetrachlorodibenzodioxin, a
potent carcinogen, Pyrolysis of fluoropolymers, e.g. teflon, in presence of
oxygen yields carbonyl fluoride; which hydrolyzes readily to HF and CO2 .

41. Smoke: Chemical composition
• The visible particulate
matter in such smokes is most
commonly composed
of carbon (soot). Other
particulates may be composed of
drops of condensed tar, or solid
particles of ash.
• Soot is a mass of
impure carbon particles resulting
from the
incomplete combustion of hydroca
rbons.

42. Smoke: Chemical composition
• Smoke particulates, like other aerosols, are categorized into three
modes based on particle size:
• nuclei mode, with geometric mean radius between 2.5–20 nm, likely
forming by condensation of carbon moieties.
• accumulation mode, ranging between 75–250 nm and formed by
coagulation of nuclei mode particles
• coarse mode, with particles in micrometer range
• Most of the smoke material is primarily in coarse particles. Those
undergo rapid dry precipitation, and the smoke damage in more
distant areas outside of the room where the fire occurs is therefore
primarily mediated by the smaller particles.

44. Smoke: Dangers
• Smoke from oxygen-deprived fires contains a significant
concentration of compounds that are flammable. A cloud of smoke,
in contact with atmospheric oxygen, therefore has the potential of
being ignited – either by another open flame in the area, or by its
own temperature. This leads to effects like backdraft and flashover.
• Smoke inhalation is also a danger of smoke that can cause serious
injury and death.

45. Smoke Inhalation
• When smoke is inhaled, toxic products of combustion injure airway
tissues and/or cause metabolic effects.
• Hot smoke usually burns only the pharynx because the incoming gas
cools quickly. An exception is steam, which carries much more heat
energy than smoke and thus can also burn the lower airways (below
the glottis).
• Many toxic chemicals produced in routine house fires (eg, hydrogen
chloride, sulfur dioxide, toxic aldehydes, ammonia) cause chemical
burns. Some toxic products of combustion, such as carbon
monoxide or cyanide, impair cellular respiration systemically.

47. Smoke Inhalation
• Burns and smoke inhalation often occur together but may
occur separately.
• Symptoms of smoke inhalation include:
• Local irritation: Cough, wheezing
• Hypoxic manifestations: Confusion, lethargy, coma
• Carbon monoxide poisoning: Headache, nausea, weakness,
confusion, coma

48. Smoke Inhalation
• Diagnosis
• Carboxyhemoglobin levels
• Bronchoscopy
• Chest x-ray
• Treatment
• Oxygen
• Sometimes endotracheal intubation

50. Fumes
• any smoke like or vaporous
exhalation from matter or
substances, especially of an
odorous or harmful nature
• Suspended solids less than 1 μ m
in diameter usually released from
metallurgical or chemical processes
(e.g., zinc and lead oxides).

51. Metal fume fever
• Also known as brass founders' ague, brass shakes, zinc shakes, galvie
flu, metal dust fever, welding shivers, or monday morning fever,is an
illness primarily caused by exposure to chemicals such as zinc oxide ,
aluminum oxide, or magnesium oxide which are produced as byproducts
in the fumes that result when certain metals are heated. Other common
sources are fuming silver, gold, platinum, chromium
(from stainlesssteel), nickel, arsenic, manganese, beryllium, cadmium,
cobalt, lead, selenium, and zinc.
• Welders are commonly exposed to the substances that cause metal fume
fever from the base metal, plating, or filler. Brazing and soldering can also
cause metal poisoning due to exposure to lead, zinc, copper, or cadmium.
In extreme cases, cadmium (present in some older silver solder alloys) can
cause loss of consciousness.

52. Metal fume fever- Cause
• Metal fume fever is due to the inhalation of certain metals,
either as fine dust or most commonly as fumes. Simple metal
compounds such as oxides are equally capable of causing it.
The effects of particularly toxic compounds, such as nickel
carbonyl, are not considered merely metal fume fever.
• Exposure usually arises through hot metalworking processes. It may also be
caused by electroplated surfaces or metal-rich anti-corrosion paint, such as
cadmium passivated steel or zinc chromate primer
on aluminum aircraft parts.
• The most plausible metabolic source of the symptoms is a dose-
dependent release of certain cytokines, an event which occurs by
inhaling metal oxide fumes that injure the lung cells. This is not an
allergic reaction, though allergic reactions to metal fumes can occur.

53. Metal fume fever- Signs and symptoms
• The signs and symptoms are generally flu-like.
including fever, chills, nausea, headache, fatigue, muscle aches, joint pains,
lack of appetite, shortness of breath, pneumonia, chest pain, change in
blood pressure, and coughing. A sweet or metallic taste in the mouth may
also be reported, along with a dry or irritated throat which may lead to
hoarseness.
• Symptoms of a more severe metal toxicity may also include a burning
sensation in the body, shock, no urine output, collapse, convulsions,
shortness of breath, yellow eyes or yellow skin, rash, vomiting, watery or
bloody diarrhea or low or high blood pressure, which require prompt
medical attention.
• Flu-like symptoms normally disappear within 24 to 48 hours. Full recovery
often requires one to three weeks.

54. Metal fume fever- Diagnosis
• Depends upon a good occupational history. Diagnosis of metal fume fever can be
easily missed because the complaints are non-specific, resemble a number of
other common illnesses, and presentation occurs typically 2–4 hours after the
exposure
• Physical symptoms vary among persons exposed, depending largely upon the
stage in the course of the syndrome during which examination occurs. Patients
may present with wheezing or crackles in the lungs. They typically have an
increased white blood cell count, and urine, blood plasma and skin zinc levels
may (unsurprisingly) be elevated. Chest x-ray abnormalities may also be present
• An interesting feature of metal fume fever involves rapid adaptation to the
development of the syndrome following repeated metal oxide exposure. Workers
with a history of recurrent metal fume fever often develop a tolerance to the
fumes. This tolerance, however, is transient, and only persists through the work
week. After a weekend hiatus, the tolerance has usually disappeared. This
phenomenon of tolerance is what led to the name "Monday Fever"

55. Metal fume fever- Treatment
• Treatment of mild metal fume fever consists of bedrest, keeping the
patient well hydrated, and symptomatic therapy (e.g. aspirin for
headaches) as indicated.
• The consumption of large quantities of cow's milk, either before or
immediately after exposure is a traditional remedy. However, the
United Kingdom Health and Safety Executive challenges this advice,
warning, "Don’t believe the stories about drinking milk
before welding. It does not prevent you getting metal fume
fever’’

56. Metal fume fever- Prevention
• Avoidance of direct contact with potentially toxic fumes,
• Improved engineering controls (exhaust ventilation systems),
• Personal protective equipment (respirators)
• Education of workers regarding the features of the syndrome
itself and
• Proactive measures to prevent its development.

58. What Are Volatile Substance Of
Abuse?
Volatile substance abuse (VSA) (glue sniffing, inhalant
abuse, solvent abuse), the deliberate inhalation of volatile
substances in order to achieve intoxication.
 Chemicals present in many house hold and industrial products
 Vapors/gases inhaled for its mind altering properties.

60. Commonly Abused Inhalants
Volatile solvents :
oGlues (n-hexane, toluene, xylene)
oCorrection fluids & Marker pens(1,1,1 trichloroethane, toluene)
o Paint thinners & removers (dichloromethane, toluene, xylene)
o Dry cleaning fluids (trichloroethylene, 1,1,1 trichloroethane)
oNail polish remover (acetone esters)
oPetrol (benzene, n-hexane, toluene, xylene)

61. Toluene also known as toluol , is
an aromatic hydrocarbon. It is a
colorless, water-insoluble liquid with the
smell associated with paint thinners.

62. Commonly Abused Inhalants
Aerosols :
oDeodorants, hair spray, refrigerants (freons, flurocarbon propellant)
 Gases
oLighter fluids (butane, propane)
oPropellants in whipped creams (nitrous oxide)
oAnesthetic gases (NO, ether etc.)
Nitrites
oRoom odorizers and liquid incense (amyl, butyl, isobutyl nitrites)

65. Modes Of Abuse
Solvents can be breathed in through the nose or the mouth
by “sniffing” or “snorting” vapors from containers, spraying
aerosols directly into the nose or mouth, “bagging” by
inhaling vapors from a plastic or paper bag, or “huffing” from
a solvent-soaked rag stuffed into the mouth

66. Why Volatile Substance Are Abused?
A rapid high - much faster than drugs or alcohol.
Relatively cheap, easy to buy.
Not illegal, easily available.
Escape from reality and conflicts.
Novelty seeking and peer influence.
As a replacement for other substances.

67. Neurobiological Considerations
 An abuser intakes 20-30 times exposure of substances than an
accidental exposure (>6000 ppm).
 Solvents are highly lipophilic thus cross biological membranes easily.
 Affect cell membranes in a similar way to anesthetics.
 Not known to have any unique receptors or mimic an endogenous
ligands.

68. Small doses can rapidly lead to euphoria
and other disturbances of behavior similar
to those caused by ethanol (alcohol), and
may also induce delusions and
hallucinations.
Higher doses may produce life-
threatening effects such as convulsions
and coma.
Death may ensue indirectly after, for
example, inhalation of vomit, or from
direct cardiac or central nervous system
toxicity.

69. Acute Effects
 Inhibition of NMDA subunits
 GABA agonistic activity
Disruption of :
 Activity of numerous voltage gated ion channels
 Calcium signaling
 ATPases
 G proteins

72. Sudden Sniffing Death Syndromes
 Severe dysrhythmias (nitrites, toluene, benzene)
 Sudden cold injury to airways (freons)
 Severe burn injury to airway tracts (butane, propane)
 Suffocation (bagging)
 Aspiration & choking
 Severe brain hypoxemia
Accidents & falls

73. Chronic exposure
• Most damage to white matter structures and the lipid
component of the myelin sheath.
• neuropsychological deficits(impairments in processing speed,
sustained attention, memory retrieval, executive function and
language) are consistent with white matter pathology.
• Significant improvements in previously identified
impairments(impaired associate learning and attention
deficits)following 2 years abstinence from petrol sniffing.

75. Neurological Sequelae
Diplopia, ataxia, depressed reflexes, nystagmus, tremor.
optic neuropathy (toluene)
EEG slowing, peripheral neuropathy (n-hexane)
Trigeminal neuralgia (trichloroethylene)
Parkinsonism
Sensorimotor polyneuropathy (methyl butyl ketone)

76. Neuropsychiatric Sequelae
 Subcortical dementia
 Low IQ
 Memory retrieval delay
 Poor attention & concentration
 Insomnia, apathy,
 Aggression with trivial provocation
 Depression
 Psychosis ( florid hallucinations)

77. Effects On Other Organs
Renal :
 RTA(toluene), Good pasture's syndrome (toluene; n-hexane), Electrolyte
imbalance
CVS :
 Arrhythmias, sinus bradycardia, decreased myocardial contractility, hypoxia
induced heart block, myocarditis
 RS :
 Dyspnea, wheezing, chemical pleuritis, emphysema (toluene).

78. Effects On Other Organs
GIT :
 Nausea, vomiting , hepatotoxicity, induce CYT P-450 (toluene), Anorexia(lead).
DERMA :
 staining, perioral eczema ,contact dermatitis, burns.
HEMATO :
 bone marrow suppression, leukemia, aplastic anemia (benzene).

79. Embryopathy
“FETAL SOLVENT SYNDROME”
Children born to mothers using toluene
in pregnancy show growth retardation,
craniofacial dysmorphism, hearing loss,
cleft palate, developmental delay,
cerebellar dysfunction.

81. Danger Of Early Use
 Increased risk of dependence
 Subsequent shifting to other class of drugs (gateway
hypothesis)
Mood disorders
Poor achiever
Suicides
Early medical complications

82. Management
• General Principles:
• Acute medical management (in case of intoxication)
• Detailed history (including products used, other substances, psychiatric
symptoms).
• Physical examination including detailed Neurological (especially in chronic
abusers).
• Lab investigations for Liver & Kidney function, ECG.
• Pharmacological management for withdrawal symptoms and associated
medical / psychiatric conditions.
• Psychosocial interventions

83. Management-Pharmacotherapy:
• Some recommend BZDs to be used for treatment of withdrawal
symptoms as inhalant act as CNS depressants.
• Baclofen (around 50mg/d) has been found useful in reducing craving
and withdrawal symptoms in a case series.
• Buspirone (40mg/d) was found useful in reducing frequency of
petrol inhalational abuse in a case report.
• Lamotrigine (100mg/d) was also found to reduce craving and
maintain abstinence in a case of inhalant dependence.

85. Prevention
• Tackling supply:
Product elimination/modification Warning labels Educating
manufacturers/suppliers Sales controls
• Tackling demand:
Legal control Information and education with skills-building

86. References
• https://en.wikipedia.org/wiki/List_of_highly_toxic_gases#Definition
• Carbon monoxide poisoning
• Authors: Peter F Clardy, MD, Scott Manaker, MD, PhD, Holly Perry, MD
• Cyanide poisoning
• Authors: Shoma Desai, MD, Mark Su, MD, MPH
• Acute Cyanide Poisoning: Hydroxocobalamin and Sodium Thiosulfate Treatments with Two
Outcomes following One Exposure Event Andrew Meillier and Cara Heller
• https://en.wikipedia.org/wiki/Cyanide_poisoning#Mechanism
• Cyanide poisoning: pathophysiology and treatment recommendations
• D. M. G. Beasley* and W. I. Glass**
• https://www.msdmanuals.com/professional/injuries-poisoning/burns/smoke-
inhalation?query=smoke%20inhalation
• Smoke Production and Properties Archived 21 August 2008 at the Wayback Machine - SFPE
Handbook of Fire Protection Engineering

87. References
• (Lubeman etal, Br J Pharmacol 2008, May 154 (2): 316-326)
• (Geibprasert etal, Am J Neuroradiol 2010, May,31:803-08)
• (Mathew etal, Addict Sci clin Pract 2011, Jul; 6(1):18-31)
• (Guidelines on Inhalants, National Inhalant Prevention Coalition Website updated 2012)
• Kumar etal, Indian J Psychiatry 2008, Apr-Jun; 50(2): 117-120
• https://rarediseases.org/rare-diseases/formaldehyde-poisoning/
• https://en.wikipedia.org/wiki/Metal_fume_fever
• Chloroform Toxicological overview Prepared by K Foxall CHAPD HQ, HPA 2007 Version 1

88. Thank You
Prepared and presented by : Majd Al-Qudah, MD
Supervisor: Prof. Abdelkader Battah
Course title: Chemical Toxins . 2020