The document discusses the toxicology of phosphorus, highlighting its different types (yellow, red, and black), sources, and applications, particularly in industries and agriculture. It explains the symptoms and modes of poisoning, diagnostic procedures, and treatment protocols for acute and chronic exposures. Additionally, it reviews the regulatory framework surrounding industrial phosphorus use and the forensic implications of phosphorus poisoning.

1. ameena kadar
Grace college of pharmacy
palakkad

2. INTRODUCTION
 Phosphorus is an essential mineral element.
 It’s homeostasis in the body is controlled by hormonal and renal control systems.
 Toxic exposures have been reported to occur from its industrial use or from
suicidal ingestion of phosphorus containing materials.
 It is highly toxic to humans and animals.

3. CONTENTS
1. Phosphorus
 Types
 Sources
 Uses
 Importance
2. Sources of Poisoning
3. Toxicokinetics
4. Mode of action
5. Clinical Features
6. Diagnosis
7. Treatment
8. Autopsy Features
9. Forensic issues
10. Regulations.

4. PHOSPHORUS
 The name “phosphorus” is derived from Greek, meaning “light-bearing”.

5.  There are two main varieties :
 Yellow Phosphorus
 Red Phosphorus
1. Yellow (or White) Phosphorus :
 This is a yellowish, waxy, crystalline solid with a garlicky odour.
 On exposure to air, it oxidises into whitish fumes of phosphorus pentoxide.
 Hence, it is generally stored under water.
 It is highly combustible and ignites into flame at 340 C.
 It is luminescent and glows in the dark (phosphorescence).
 At room temperature, pure white phosphorus is a tetrahedral crystal with a
molecular formula of P4.
 It is extremely toxic when inhaled, ingested, or absorbed through burned areas.

7. 2. Red Phosphorus :
 This is a reddish or brownish, amorphous, odourless substance.
 It is insoluble and relatively harmless, since it is not absorbed from the GI tract.
 “Black phosphorus” is the inert, nontoxic allotropic form of elemental
phosphorus.
 Derivatives and related compounds of phosphorus include phosphoric acid,
phosphine, aluminium phosphide and zinc phosphide.

8.  Sources of Phosphorus
 Phosphorus is found in rocks, soil, plants and animal tissues.
 Commercial preparations of phosphorus are either white or yellow.
 Heating white phosphorus in the presence of an oxygen free and inert atmosphere
produces red phosphorus.

9. Uses :
1. Matches ;
 Yellow phosphorus was extensively used in the manufacture of friction matches
during the 19th century.
 However, because of its propensity to produce chronic poisoning in workers of the
match industry, most countries agreed at an international convention in Berne,
Switzerland in 1906 to prohibit the manufacture and import of yellow phosphorus
for the making of matches.
 Hence, these so-called “lucifer matches” gradually (and fortunately) faded out.
o Lucifer matches

10.  Today’s “safety match” contains only potassium chlorate and antimony sulfide .
 It has to be struck against a prepared surface to ignite it, which is provided by the sides of
the match box being coated with powdered glass and red phosphorus.
2. Fireworks ;
 Although the use of yellow phosphorus in fireworks is prohibited in Western
countries, it is still an important ingredient in several types of fireworks
manufactured in India.

11. 3. Military uses ;
 Yellow phosphorus is an ingredient of tracer bullets, incendiary bombs, smoke screens, and
air-sea rescue flares.
4. Insecticide and rodenticide ;
 There are several pastes and powders available in India which contain phosphorus (or zinc
phosphide) used for killing cockroaches and rats.
 Such pastes are usually mixed with molasses or butter and spread on bread as bait.
 Obviously, unintentional ingestion by children is quite possible leading to serious poisoning.
5. Fertilizers.

13.  Sources of Poisoning
 Phosphorus poisoning is of rare occurrence in farm animals because of lack of
exposure.
 Accidental ingestion of fertilizers, or immediately from clumps of fertilizers on
cultivated lands, fireworks, baits containing lumps of white phosphorus for pets,
rats kept on the pastures.
 Grazing of animals on the battlefield where certain explosives have been used.
 Finely divided phosphorus is mixed with fats and oils to promote their absorption
and over consumption of such fats and oils results in phosphorus poisoning.
 Usual Fatal Dose :
 About 60 mg (roughly 1 mg/kg body weight).

14. Toxicokinetics :
 White phosphorus is an inorganic chemical that is poorly soluble in water, soluble
in nonpolar organic solvents such as Benzene, soluble in more polar organic
solvents such as CS2, and is lipid soluble.
 It is the most reactive allotropic form of elemental phosphorus, oxidizing
spontaneously in the air at room temperature, and hydrating under certain
conditions.
 Phosphorus can be absorbed into the systemic circulation from the skin, lungs, and
intestinal tract.
 For all practical purposes, White or Yellow phosphorus are readily absorbed while
red phosphorus is not.
 The target organs of toxicity include the gastrointestinal tract, liver, kidney, bone
and the cardiovascular and central nervous systems.
 High Mortality rate seen following white phosphorus burns can be due to its
absorption from the burned surface, which may result in multi organ failure (mainly
liver and kidneys), hyperphosphatemia, hypocalcemia and electrocardiogram (ECG)
abnormalities.

15. Mode of Action :
■ Yellow phosphorus, a protoplasmic poison is a potent hepatotoxin.
■ In large doses, it can cause shock and cardiovascular collapse since it is also toxic to
the heart.
■ Locally, it produces severe irritation of skin and mucosa.
■ Rate of absorption is greatly enhanced if phosphorus is administered in an oily
vehicle.

17. Clinical Features :
 Fulminant Poisoning:
 This results from ingestion of a massive dose, i.e. more than 1 to 2
grams.
 The dominant clinical picture is one of peripheral vascular collapse.
 Death usually occurs in 12 to 24 hours, and signs of hepatic or renal
damage are not seen.
 Acute Poisoning:
 Today, most cases of phosphorus poisoning fall in this category.
 The clinical manifestations characteristically occur in three stages.
 a. First Stage (upto 3 days)—
 i. Local effects include severe burning pain, vomiting, diarrhoea, and
abdominal pain.
 ii. Breath smells of garlic.
 iii. Vomitus and stools may be luminous in the dark.

18.  There may be haematemesis. Faint fumes may emanate from the stools (Smoky
stool syndrome).
 b. Second Stage (upto several days after the first stage subsides)—
 This is an essentially symptom-free (treacherous) period, and the patient may
feel well enough to be discharged from the hospital.
 c. Third Stage—
 i. This is due to the systemic effects of phosphorus after it has been absorbed.
 ii. There is a return of the digestive symptoms with increased severity.
 iii. In addition, manifestations of liver damage are prominent—tender
hepatomegaly, jaundice which may progress to an olive green hue, pruritis,
bleeding from multiple sites, and finally hepatic encephalopathy characterised
by drowsiness, confusion, ataxia, flapping tremor of hands (asterixis), stupor,
and coma.
 At this stage there is a mousy odour to the breath (foetor hepaticus).

19.  iv. Renal damage results in oliguria, haematuria, albuminuria, and acute renal
failure.
 v. ECG changes include tachycardia, ST and T waves changes, QTC
prolongation, low voltage QRS, and various arrhythmias.
 vi. There may be terminal convulsions before death supervenes.
 vii. Early hypoglycaemia has a grave prognosis.
 Survival for three or more days is a good prognostic sign.
 Recent reports on phosphorus poisoning have indicated that the classical three
phases of toxicity are not always encountered in these patients.
 The incidence of phosphorescent vomitus or faeces, oral mucosal burns, and
presence of a garlicky odour on the breath or in gastric contents are also quite
rare.
 Therefore, the absence of these findings does not preclude serious toxicity.

20. Diagnosis :
 History
 Clinical symptoms particularly acute gastroenteritis.
 Garlic odour of the vomitus and intestinal contents.
 Postmortem lesions
 Estimation of phosphorus in the blood, vomitus, intestinal contents and faeces.
 Differential Diagnosis :
 Inorganic pisoning (As, Pb, Hg) causing gastroenteritis and diarrhoea.
 Organophosphate compounds.

21. Diagnosis of Acute Poisoning :
 Garlicky odour of breath and vomitus.
 Fuming or luminous vomitus and stools.
 Evidence of hepatic and renal failure.
 Hypokalaemia, hyperchloraemia, hypocalcaemia and both hyperphosphataemia
and hypophosphataemia have been reported.
 Hypoprothrombinaemia and thrombocytopenia may occur following ingestion,
and lead to a delayed onset of haematemesis, haematochezia, haematuria, and
haemorrhages into the skin and mucous membranes.
 Dermal contact with phosphorus results in acutely painful corrosion with yellow,
necrotic, severely painful second or third degree chemical burns emitting garlic-
like odour.
 Absorption from damaged skin may result in acute systemic phosphorus
poisoning.

22.  Chronic Poisoning:
a. This usually results from long-term occupational exposure to the fumes of
phosphorus pentoxide and results in the condition called Phossy Jaw (Glass Jaw,
Lucifer’s Jaw) which was first described by Bristowe in 1862.
Fistula draining
foul-smelling pus

23. Phossy jaw

24. i. Main features include toothache (usually originating in a carious tooth), which
because of its recurrence would be eventually extracted leading to exposure of
bone followed by necrosis, sequestration, and osteomyelitis of jaw (invariably the
lower jaw).
b. Chronic exposure to red phosphorus or phosphorus sesquisulfide may cause
dermatitis.

25.  Burning issues of White Phosphorus

27. Treatment :
1. Acute Poisoning:
 Gastric lavage with potassium permanganate (1:5000), which oxidises
phosphorus into relatively less toxic phosphoric acid and phosphates. Some
authorities recommend administration of copper sulfate solution (250 gm in a
glass of water), which converts phosphorus to non-toxic copper phosphide.
Alternatively, a 0.2% solution of copper sulfate may be used for stomach wash.
It must however be noted that copper sulfate being a highly toxic substance by
itself is not a desirable antidote, and in fact is placed in the international list of
obsolete antidotes.
 Do not administer milk or any oily/fatty foods, since this will enhance the
absorption of phosphorus.
 Vitamin K by IV drip (65 mg) slowly, to combat hypoprothrombinaemia.
 Intravenous fluids—
 Isotonic saline and sodium lactate to treat shock, dehydration, and acidosis.
 Glucose to combat hypoglycaemia.
 Calcium gluconate for hypocalcaemia.

28.  Whole blood/fresh frozen plasma to correct coagulation defects.
 Steroids and inotropic support for shock.
 Anticonvulsants for seizures.
 Some investigators suggest the use of N-acetylcysteine (NAC) in patients with
stage I phosphorus toxicity.
• A dose regimen of 150 mg/kg in 200 cc D5W for 15 minutes, followed by 50
mg/kg in 500 cc D5W for 4 hours, and then 100 mg/kg in 1000 cc D5W for 16
hours is recommended.
• It is presumed that NAC may be effective in preventing progression of liver
damage when given in stage I of the illness.
 Treatment of dermal burns:
• After initial flushing with large volumes of water to remove any residual chemical
material, clean wounds with a mild disinfectant soap and water.
• Loose, nonviable tissue should be removed by gentle cleansing with surgical soap
or formal skin debridement. Intravenous analgesia may be required.

29. • Removal and debridement of closed blisters is controversial.
• Current consensus is that intact blisters prevent pain and dehydration, promote
healing, and allow motion; therefore, blisters should be left intact until they rupture
spontaneously or healing is well underway, unless they are extremely large or
inhibit motion.
• Prophylactic topical antibiotic therapy with silver sulfadiazine is recommended for
all burns except superficial partial thickness (first-degree) burns.
• For first-degree burns bacitracin may be used, but effectiveness is not documented.
• I.V. Depending on the site and area, the burn may be treated open (face, ears, or
perineum) or covered with sterile nonstick porous gauze.
• Alternatively, a petrolatum fine-mesh gauze dressing may be used alone on partial-
thickness burns.
• Daily dressing changes are indicated if a burn cream is used; changes every 3 to 4
days are adequate with a dry dressing.
• Analgesics such as paracetamol with codeine may be used for pain relief if
needed.

30. • Phosphorus particles in dermal burns can be visualised by employing the use of
Wood’s lamp.
• Phosphorus will fluoresce under ultraviolet light.
• With the exposed areas immersed in water, loose or embedded phosphorus particles
that are visualised under UV light can be mechanically but delicately removed
safely under water.
• This technique may be a safer alternative than either the use of copper sulfate or
silver nitrate, and may be the method of choice .
2. Chronic Poisoning:
a. Removal of patient from source of exposure.
b. Dental treatment and follow-up.

31. Autopsy Features :
1. Garlicky odour in the vicinity of the mouth and in the gastric contents.
2. Jaundice.
3. Bleeding points in the skin (subcutaneous haemorrhages).
4. Luminous gastric contents.* The contents will fluoresce under UV light.
5. Congestion and inflammation of affected skin and mucosa.
6. Enlarged fatty liver. Later there is evidence of aute yellow atrophy.
Histopathological examination may reveal features of acute fulminant hepatitis:
collapsed reticulin framework, with fibrosis between the hepatocytes showing
bubbly, vacuolated cytoplasm.
7. There may also be fatty degeneration of heart and kidneys.
8. Viscera for chemical analysis must be preserved in saturated saline and not
rectified spirit, otherwise luminosity especially of the stomach contents will be
lost.

32. Forensic Issues :
■ Accidental poisoning:
 This used to be common in the past because of unrestricted use of
phosphorus in matches and fireworks.
 Today, most cases of accidental poisoning result from inadvertent
ingestion of cockroach or rat poison by children, or because of
contamination of food by these substances.
■ Suicidal poisoning:
 This was also previously quite common, especially in Western countries.
 A popular method appears to have been to soak several “lucifer” match
heads in water or brandy, mix with sugar, and consume the resultant
potion.
 Today, rat pastes containing phosphorus are occasionally implicated in
suicidal ingestions.

33. ■ Homicidal poisoning:
 Formerly, phosphorus was quite frequently employed for committing
murder.
 Several accounts are mentioned in the literature where poisoning was
accomplished by mixing phosphorus in soup, jam, or rum, and
administered to unsuspecting victims.

34. Regulations :
 EPA requires industry to report spills of white phosphorus of more than 1 pound.
 White phosphorus levels in workplace air regulated by
 Occupational Safety and Health Administration (OSHA).
 National Institute for Occupational Safety and Health (NIOSH).
 American Conference of Governmental Industrial Hygienists (ACGIH).
 All three organizations set the inhalation exposure limit for white phosphorus in
the workplace during an 8 hours workday at 0.1 milligram per cubic meter of air.

35. REFERENCES :
 Modern Medical Toxicology by V V Pillay, 4th edition , page no: 67-70.