Economics

1. Environmental and Industrial Toxicants
Arsenic

2. Definition
•‘Metals’ originally included only gold, silver,
copper, iron, lead, and tin.
• Dense, malleable (able to be hammered or pressed
permanently out of shape without breaking or cracking),
lustrous
• Conduct heat and electricity, cations
•Many other elements since added to the list with
some of these characteristics
•‘Metalloids’ are elements with features intermediate
between metals and non-metals
•Example: Arsenic - near or in hazardous
waste sites and areas with high levels naturally occurring
in soil, rocks, and water

3. Heavy metal
•Heavy metal are chemicals elements with a specific
gravity that is at least 5 times the specific gravity of
water
•Arsenic 5.7; cadmium 8.65; lead 11.34; mercury
13.54
•A metal having an atomic weight greater than Na, a
density greater than 5 g/cm3
• Physical properties
• High reflectivity, electrical and thermal conductivity,
strength
•Some notion of toxicity
•Usually includes lead, cadmium and mercury

4. Metals in workplace
• Metals are extensively used in industrial operation thus
resulting in a high risk of exposure to workers and
environment
• Welding
• Grinding
• Soldering
• Painting
• Smelting
• Storage battery
• Recycling
• Industries with high potential of lead exposures include
construction work, most smelter operations, radiator repair
shops, and firing ranges.
• Cadmium is found in industrial workplaces, particularly where
any ore is being processed or smelted.
• Common sources of mercury exposure include
mining, production, and transportation of mercury, oil and gas industry as
well as mining and refining of gold and silver ores.

5. Recycling
industry
•Mercury is a naturally occurring trace element in fossil fuels
•It is predominantly present in the metallic form but may be
present in the form of inorganic salts and organic species.

6. •METALS/Chemicals for which medical
surveillance must be performed
1. Arsenic and any of its compound
2. Beryllium
3. Cadmium
4. Chromium
5. Lead
6. Manganese
7. Mercury

7. •Poisoning by
•Lead or compound of lead
•Arsenic
•Mercury
•Beryllium
•Cadmium
•Antimony
•Nickel
•Chromium

8. Understanding Metal Toxicity
1. Classification of Metal
2. Absorption, storage and excretion
of metal
3. Mode of action of metal toxicity
Fundamental concepts of : -

9. Classification of Metal
•Based upon physical properties
•High reflectivity and metallic cluster
•High electrical conductivity
•High Thermal conductivity
•Strength and Ductility - characterized by the
material's ability to be stretched
•Base upon biological perspective
•Solubility
•Oxidation state
•Heavy metal  Toxic metals

10. Absorption
•Respiratory Absorption
•Metal may be inhaled as vapor or aerosol (fume
or dust particulate)
• Fume or vapor of some metals & compound are readily
absorbed in from alveolar space (cadmium, mercury,
tetraethyl lead)
•Large particles trapped in upper respiratory tract,
cleared by mucociliary transport to pharynx and
swallowed (equivalent to oral exposure)
•Small particles may reach alveolar/gas exchange.
•Water soluble metal aerosols are rapidly absorbed
from alveoli into the blood

11. Absorption
•Gastrointestinal Absorption
• Metal may introduce into GI tract through food, water,
mucociliary clearance
• Metal are absorbed into the cells lining the intestinal tract by:
• Passive or facilitated diffusion
• Specific transport process
• Pinocytosis
• Depends on many factors
• Solubility of metal in fluids of the intestinal tract
• Chemical forms of metal (lipid soluble methyl mercury is completely
absorbed compare to inorganic mercury – poorly absorbed)
• Presence and composition of other materials in GI tract
• Composition for absorption sites between similar metals (zinc & cadmium or
calcium & lead)
• Physiological state of the person exposed

12. Excretion
•Kidney - Important route of excretion
• Metals in blood plasma are bound to plasma proteins
and AAs
• Metals bound to low molecular weight proteins and amino
acids are filtered in glomerulous into fluid of the renal
tubule
• Some metals (Cd & Zn) are effectively resorbed by
tubular epithelia before they reach the urinary bladder
where very little resorption occur

13. Excretion
•Enterohepatic Circulation
•Absorbed metal may also excreted into
intestinal tract in bile, pancreatic
secretion or saliva
•Minor Pathways
• Hair (Hg, Zn, Cu and As)
• Nails
• Saliva
• Perspiration
• Exhaled air
• Lactation

14. Acute Toxicity of Metal
Organs and tissue affected are those involved
in the absorption and elimination
•Result of the accumulation of high, critical
concentrations of metal that at these sites with little
opportunity to detoxify, eliminated or adapted to metal
•Tx of acute metal intoxication is design to:
Enhance the elimination of the metal through
neutralization
Prevent irreversible damage to organs and tissue
Treat the symptoms of acute toxicity

15. Chronic Toxicity
•Duration of initial exposure to the onset of
signs and symptoms months to years
•Diagnosis of chronic metal intoxication
is more difficult than acute
intoxication
•Diagnosis – presence of excessive metals in
blood and urine
•Organ system not involve in absorption or
elimination of metal such as hematopoetic
or immune system may be affected

16. Mechanism of intoxication
•There is often little correlation between the
sensitivity of organ or tissue to the toxic
effects of metal and concentration in
that tissue
•95% percent of the body burden of lead in adults
are found in calcified tissue (bone and teeth);
however toxicity is manifest primarily in the
nervous systems, renal systems and
hematopoetic systems

17. Lead
• Types of lead
• Inorganic – PbO2
• Organic – Tetraethyl lead, tetrametyl lead, not water soluble lead
• Sources of exposure
• Mining/Smelting (melting, baking, cooking, burning, and producing)
• Cutting and welding lead-painted structure
• Manufacture/Recycling of lead storage batteries
• Production of lead based paints
• Routes of exposure
• Respiratory tract
• Dominant pathway – 50% absorbed
• Particle size of lead dust <5 micron
• Soluble
• Absorption
• Inorganic lead is poorly absorbed from GI tract

18. Cont`d
Transport and storage
• Pb is transported to all organs and tissue of body by blood
• 95% of Pb in blood is associated with the erythrocytes and remain
with plasma protein
• Lead accumulates in bone throughout life
• 90% of body burden of lead is found in bone and most
remaining 10% in kidneys and liver
• Biological half-life of lead bone is 10-20 years, while half life of lead
in soft tissues is several months
• Organ systems
• GI
• Hematopoetic
• Nervous & neuromuscular
• Renal and cardiovascular
• Reproductive system – low sperm count, abortions, stillbirths, low sperm
motility, premature baby

19. •Signs and symptoms include
• Muscle weakness, anemia, Insomnia, loss of memory,
headache, paralysis of extensor muscles of the wrist
Nutritional Supplementation
Antidote
•Calcium EDTA
•Use IM Dimercaprol as adjunctive
treatment in encephalopathy
•BLL > 70 g/dl or encephalopathy
• Hospital admission
• Administration of a parenteral chelator
•BLL > 45 g/dl- oral chelator

20. Cadmium
Sources
• By-product from smelting of lead & zinc ores
• Welding
• Food & smoking
Absorption, Storage, Elimination
• Poorly absorbed from GI
• Inhaled cadmium is absorbed more efficiently (10 – 50 %) depends on
size and solubility
• Inhaled cadmium is 60% more toxic than the ingested form.
• Absorb cadmium is bound to plasma proteins and transported to liver and
accumulated in kidney
• Biological half life –20 years
• Renal Tubular damage occurs when the Cd concentration reaches or
exceeds 200 ug/g wet weight in the kidney vortex

21. Cadmium
Toxic effects
•Mechanism
• Displacing or replacing zinc from the many (over
200) enzymes requiring zinc as a catalytic or
structural component
•Acute exposure to Cd fumes
• Cough, chest pain, irritation to upper Resp. tract,
respiratory damage
• Death
•Chronic
• Liver damage, anaemia, teratogenic effects, renal
tubular necrosis

22. Acute Exposure
No proven treatment
Supportive treatment includes
fluid replacement, oxygen, mechanical
ventilation.
With ingestion, gastric decontamination by
emesis or gastric lavage soon after exposure.
Activated charcoal not proven effective
Antidote
IM or slow IV infusion cadmium disodium
edetate 15-25mg/kg in dextrose 5%.

23. Arsenic
•Sources
•Arsenic containing mineral ores
•Arsine is the most toxic form of arsenic.
•Industrial processes
• Semiconductor manufacturing (gallium
arsenide)
• Fossil fuels
• Wood treated with arsenic preservatives
• Metallurgy
• Smelting (copper, zinc, lead) and refining of
metals and ores
• Glass manufacturing
•Commercial products
• Wood preservatives
• Pesticides
• Herbicides
• Fungicides

24. Arsenic
• Toxicokinetics
• T1/2 of inorganic arsenic in the blood is 10 hrs and of
organic arsenic is around 30 hours
• 2-4 weeks after the exposure cases, most of the remaining
arsenic in the body is found in keratin-rich tissues (nails,
hair, skin)
• Inorganic arsenic is converted to organic arsenic
(biomethylation to monomethyl arsonic- MMA or DMA) in the liver
• This may represent a process of detoxification
• Renally excreted (30-50% of inorganic arsenic is excreted in
about 3 days)
• Both forms are excreted depend on the acuteness of the
exposure and dose
Palmer
Keratosis

25. Bodily system affected Symptoms or signs Time of onset
Systemic Thirst
Hypovolemia, Hypotension
Minutes
Minutes to hours
Gastrointestinal Garlic or metallic taste
Burning mucosa
Nausea and vomiting
Diarrhea
Abdominal pain
Hematemesis
Immediate
Immediate
Minutes
Minutes to hours
Minutes to hours
Minutes to hours
Hours
Hours
Hematopoietic system
(formation of blood or blood cells
in the body)
Hemolysis
Hematuria
Lymphopenia
Pancytopenia
Minutes to hours
Minutes to hours
Several weeks
Several weeks
Pulmonary
(primarily in inhalational
exposures)
Cough
Dyspnea
Chest Pain
Pulmonary edema
Immediate
Minutes to hours
Minutes to hours
Minutes to hours
Liver Jaundice
Fatty degeneration
Central necrosis
Days
Days
Days
Kidneys Proteinuria
Hematuria
Acute renal failure
Hours to days
Hours to days
Hours to days
Manifestations of acute arsenic poisoning

26. • Gastric lavage
• Activated charcoal does not bind well inorganic arsenic
• Whole bowel irrigation with polyethylene glycol
• Skin decontamination in dermal exposure
• Supportive care
• Antidote
• Chelation therapy should be instituted quickly (minutes to hours)
• IM Dimercaprol 3mg/kg for 2 days: Succimer (DMSA)- PO;
DMPS – PO, IV
• Oral pencillamine 100mg/kg/day (max. 1g/day
Note: BAL and other chelators are not useful for arsenic
poisoning

27. MERCURY
•Was used as “cure” for almost
every ailment in the past
•Incident of methyl mercury
• Minimata Bay 1953 – 1960
• Methylmercury - The highly toxic compound bioaccumulated in fish and
shellfish when eaten by the people, gave rise to Minamata disease
• On grain in Iraq 1971 – 1972
•Metabolism – Three form
• Elemental – Hgo
• Inorganic : Hg+ and Hg 2+
• Organic

28. MERCURY
•Absorption
• Hgo via respiratory tract (80% retained)
• Hg+ and Hg 2+ about 7% retained
• Organic Hg about 70% retained
•Distribution and Metabolism
• Oxidation finally to Hg2+
• Affinity for kidney
•Excretion (half life 70 days for organic, 35-90 days for
elemental)
• Mainly via urine
• Organic Hg mainly faecal
•Cross placenta

29. Symptoms of chronic and acute toxicity of
inorganic mercury
Acute Chronic
Nausea
Headache
Diarrhea
Abnormal pain
Metallic taste
Ataxia – lack of muscle
coordination
Dysarthria – motor
speech disorder
Dysphagia – difficulty in
swalloing
Impaired vision
Loss if coordination
Hearing
Taste & smell
Inorganic mercury intoxication

30. Biological Effects
• Central Nervous System
• Neuropsychiatric by Hgo
• Tremor, insomnia, emotional instability (erethism), depression
• Sensorimotor for organic Hg
• Tremor, loss of senses, incoordination, paralysis
• Mechanism
• Disrupts metabolism and causes degeneration of neurons
• Kidney
• Mainly inorganic – tubular damage
• Others
• Stomatitis
• Gingivitis
• Excessive salivation

31. Antidote
• IM dimercaprol
• Oral Penicillamine

32. CHROMIUM
•Uses
•Alloy with iron (stainless steel), cobalt, nickle
•Tanning leather
•Wood preservative
•Anticorrosive in cooling system, boiler, oil
drilling mud
•Cement

33. Health Effects CHROMIUM
•Acute
• Acute renal tubular necrosis
•Chronic
• Skin allergic
• perforation of nasal septum
• Skin ulceration
• Cancer of respiratory tract (genotoxic mechanism)

34. Antidote
•None.
Management
•Perform gastric lavage and administer
activated charcoal
•Provide symptomatic and supportive
therapy

35. Anticoagulant Rodenticides
•Coumarins/Dicumarol/Warfarin
Toxicity
•This compounds inhibit hepatic synthesis of vitamin
K
• The toxic is highly variable.
Manifestations
•Epistaxis, intraocular bleeding, haemoptysis, bleeding
gums occassional paralysis due to cerebral
haemorrhage

36. Management of toxicity
•Administer activated charcoal and cathartic.
•Supportive and symptomatic therapy.
Antidote
•Phytomenadione 0.1mg/kg

37. Boric acid and Borates
•Used in baby talcum powder, anti-cockroach, laundry
soaps.
Toxicty
•Acts as cellular poison. They concentrate in tissues
such as kidneys and cause problems.
•Chronic exposure leads to high mortality in infants
•Fatal oral dose: 0.1g to 0.5g/kg
•Vomiting, diarrhoea, hyperpyrexia, jaundice,

38. Management
•Maintain airway and ventilaton
•Treat coma, convulsion, hypotension
•Induce emesis, perform gastric lavage
•Administer activated charcoal
•Hemodialysis

39. Carbontetrachloride
•Found in degreasers, fire extinguishers, spot removes
and dry cleaning solvent.
•Induces hepatotoxicity and carcinogenicity.
Toxicity
•CNS depressant and hepatotoxicity.
•Fatal oral dose: 3 to 5ml.
•Toxicity may arise from inhalation or absorption
through skin.

40. Manifestattions
• Nausea, vomiting, abdominal pain, headache, visual
disturbances, dizziness, and confusion.
Management
• Inhalation: remove from exposure and give oxygen.
• Skin: Remove contaminated clothing and washing
• Eye: irrigate exposed eye with normal saline or water.
• Antidote: No specific antidote available.
40

41. Chlorates
•The usual chlorates: sodium chlorate, potassium
chlorate and barium chlorate.
•Weed killers, gargles
Toxicity
•Chlorates are oxidising agents cause haemolysis with
methaemoglobin: they are also nephrotoxic
•Fatal oral dose: 7.5-35g

42. Manifestations
•Abdominal pain, vomiting, diarrhoea, haemolysis…
Management
•Maintain airway and assist ventilation
•Induce emesis, perform gastric lavage
Antidote
•Methylene blue injection 1-2mg/kg

43. Anionic/Nonionic Detergents
•Are only mildly irritating.
•Cationic detergents may be caustic
•Fatal dose: no information available
•Mortality and morbidity are rare.
Manifestations
•N/V/D, intestinal distension.
•Rarely dehydration.

44. Management
•Give oral fluids, induce emesis
•Administer IV fluids to correct dehydration
•Activated charcoal is ineffective
•If corrosive injury is suspected, consult…..
Antidote
•No specific antidote.

45. Hydrogen Peroxide
•H2O2 is an oxidizing agent used in mouth washes,
bleaching, antiseptic, and hair bleach.
Toxicity
•It is an oxidizing agent which breaks down to oxygen
and water.
•Fatal Dose: 1.5g/kg (30% soln)
•Toxic Dose: up to 5% strength
Manifestation
•N/V, mild irritation
•Severe burn /irritation to the mucosa

46. Management
•Dilution, irrigate eyes and skin with
water
•Activated charcoal and catharitics are
not effective.
•Avoid emesis
•Maintain A,B,C,D
Antidote: None

47. Phenol
•Such as creosol, creosote, hydroquinone, eugenol,
local anaesthetics.
•Phenol is obtained from coal tar
Toxicity
•Phenol denatures protein and penetrates tissues well.
•It is potent irritant and corrosive.
•Fatal Oral Dose: Adults-2g…..infants-50 to 500mg.
Manifestations
•Reddness, ocular burns, N/V/D, abdominal cramps,
cyanosis, hypotension, pulmonary oedema

48. Management
•Emesis and lavage are contraindicated.
•Do not dilute with liquids.
•Treat coma, seizures, hypotension and
arrhythmias
Antidote: None

49. Pesticides
•What are categorized as pesticides?
•“A pesticide is any substance or mixture
of substances intended for preventing,
destroying, repelling, or mitigating any
pest or functions as a plant regulator.

50. What are the common groups of pests?
•INSECTS
•WEEDS
•BACTERIA
•VIRUSES
•FUNGI
•RODENTS

51. INSECTICIDES
• Organophosphates - Baytex EC 50,
• Organochlorine - Aldrin
• Pyrethroids - Baygon mosquito
coil

52. WEEDICIDES
•Paraquat - Gramoxone
•Propanil - 3 4 DPA
•Glyphosate - Roundup
•Chlorophenoxy - MCPA

53. RODENTICIDES & FUNGICIDES
• Zinc phosphide - Run rat
• Coumarins - Racumin
• Brodifacoum - Klerat Pellets
•
Sulphur - Morisal WP,
• Dithiocarbamate - Metaxil

54. ORGANOPHOSPHATES AND CARBAMATES
• Group of chemicals share a common mechanism of
cholinesterase inhibition and hence can cause similar
symptoms.
•Phosphorylation of the acetylcholinesterase
(AChE) at nerve endings.
•Loss of available AChE results accumulation
of acetylcholine at receptor sites and effector
organ to become over stimulated by the
excess acetylcholine.

55. ORGANOPHOSPHATES AND CARBAMATES
Contd.
•Clinical Features are based on excessive
cholinergic stimulation.
•Unlike organophosphate poisoning, carbamate
poisoning tend to be of shorter duration
because the inhibition of nerve tissue AChE is
reversible.

56. CLINICAL FEATURES
• Eye contact: Irritation or pain, lacrymation, swelling,
blurring of vision.
• Inhalation: Cough, difficulty in breathing,
bronchitis, pneumonia.
• Ingestion: Nausea, vomiting, diarrhoea, sweating,
salivation, small or pin point pupils, muscle twitching,
fasciculation.

57. Management of Organophosphate and Carbamate poiosning
Contd…
•Atropine:
The following features of cholinergic syndrome is an
indication for atropine therapy.
•Poor air entry in to the lungs due to bronchorrhoea
and bronchospasm.
•Excessive sweating
•Bradycardia
•Hypotension
•Miosis

58. Management of Organophosphate and Carbamate poiosning
Contd…
•Initial dose: 1.8 – 3 mg, 3-5 of 0.6 mg
vials rapidly IV into a fast flowing IV drip
depending on the condition.
•After 5 min. check the five parameters
and if there is no improvement double
the dose.

59. Management of Organophosphate and Carbamate poiosning
Contd…
•Once atropinised clinical features:
•Clear lungs
•Adequate heart rate ( > than 80 beats/m.)
•Blood pressure (> 80 mmHg systolic)
•Dry skin
•Pupils no longer pinpoint
•Set up an infusion with 10-20% of total amount
of atropine.

60. Management of Organophosphate and Carbamate poiosning
Contd…
•Target end points for atropine therapy.
•Clear chest
•Heart rate between 80-100 beats/min.
•Pupils no longer pinpoint.
•Systolic blood pressure > 80 mmHg.
•Dry axillae.

61. Management of Organophosphate and Carbamate poiosning
Contd…
•Excess atropine causes confusion, urinary retention,
hyperthermia, bowel ileus and tachycardia.
•In this condition atropine should be ceased and the patient
reviewed after 30 min. to see whether the features of
toxicity have settled.
•.

62. Management of Organophosphate and Carbamate poiosning
•Pralidoxime:
Give 30 mg/kg loading dose of pralidoxime over 10-20
min. followed by a continuous infusion of 8-10 mg/kg per
hour until clinical recovery (for example 12-24 hours after
atropine is no longer required or the patient is extubated)
or 7 days which is later.
Less severely poisoned patients can be given intermittent
doses (1 gram 6 hourly by slow IV bolus over 10 – 20
mins).
•Oximes are not required for carbamate poisoning.

64. ORGANOCHLORINES
•Very few organochlorines are used now as
pesticides.
•Organochlorines are very toxic if ingested or
inhaled.
•Some are readily absorbed through the intact
skin.
•Skin contact: Dermatitis
•Inhalation: Inhalation can give rise to
irritation of eyes, nose, throat and cough.
•Ingestion: Nausea, vomiting, diarrhoea,
abdominal pain, headache, dizziness,
convulsions and coma.

65. Management of Organochlorine poisoning
•For convulsions give diazepam 5-10 mg IV
slowly (Paediatric dose 0.2 mg/kg).
• Repeat if necessary. Up to 40 mg/day can be
given orally as maintenance dose.
•Continue diazepam for 3-4 days after
convulsions have been controlled.
•10 ml of 10% calcium gluconate IV can also be
used to control convulsions.

66. PYRETHRINS & PYRETHROIDS
•Pyrethrum is an insecticide extracted from
chrysanthemum flower.
•Active ingredients of pyrethrum are known as
pyrethrins.
•Synthetic compounds structurally related to
pyrethrins are known as pyrethroids.
•Inhalation: Allergic manifestations such
as wheezing.

67. PYRETHRINS & PYRETHROIDS Contd…
•Ingestion: After ingestion pyrethrums have
low toxicity, vomiting, epigastric pain and
diarrhoea are the common features.
•Eye contact: Lacrymation, oedema of the
eyelids.
•Skin contact: Allergic dermatitis.

68. PARAQUAT
•Paraquat is a widely used herbicide .
• It is a safe herbicide because it is inactivated
by contact with soil.
•Paraquat has life threatening effects on the
gastrointestinal tract, kidney, liver and
other organs.
•The lung is the primary target organ of
paraquat poisoning.

69. PARAQUAT Contd…
•Skin contact: prolonged contact will produce
blistering, abrasion and ulceration.
• Although absorption across intact skin is
slow, abraded or eroded skin allows efficient
absorption.

70. Management of Paraquat poisoning
•An absorbent ( Activated charcoal) should be given
orally or via a nasogastric tube as early as possible.
•Fuller earth

71. PROPANIL & CHLOROPHENOXY COMPOUNDS
•Propanil is a selective herbicide of low toxicity.
However, in self poisoning with large doses
methaemogloninaemia is cause, which can
be fatal.
•Chlorophenoxy compounds are well absorbed
from the gastrointestinal tract.
•They are less well absorbed from the lung.
Cutaneous absorption appears to be minimal.

72. Management of Propanil poisoning
•If symptoms of methaemoglobinaemia are present
(tachycardia, tachopnoea or confusion) or if the levels are
over 30%,
• give 1% methylene blue 0.1 ml/kg IV over 5 minutes.
•The same dose may be repeated within 1 hour if there is
no improvement.
•If IV preparation is not available give methylene blue 300
mg daily orally.
• If methylene blue is not available give ascorbic acid 1 g IV
twice daily.

73. RODENTICIDES
•Coumarins, indandiones and brodifacoum are used
as rodenticides.
•Brodifacoum is a highly lethal 4- hydroxycoumarin
vitamin K antagonist anticoagulant poison
•They are fairly safe for human beings due to the low
concentration of the active ingredient.
• Their toxicity is due to depression of the synthesis
of factors essential for coagulation of blood.

74. Management of Rodenticide poisoning
• If there has been no bleeding, but the PT is prolonged, give vitamin
K1 10-50 mg orally two to four times a day (paediatric dose 0.4
mg/kg/dose).
• For prolonged PT with less severe bleeding, give vitamin K1 10 to 15
mg SC or IM (for a child 1 to 5 mg).
• In severe haemorrhage with prolonged prothrombin time (PT) give
vitamin K1 (phytomenadione) 20 mg by slow IV injection (0.6
mg/kg for children under 12 years).
• In severe bleeding, it may be necessary to give fresh frozen plasma
or fresh blood.

75. Thank you !!!