Bismuth toxicity

1. BISMUTH
toxicity
By maysam N. al-khattab
Higher diploma in pharmacology &toxicology
Supervised by
Dr. Ammar A. Hussain
College of pharmacy
Baghdad university
October 2019

2. Bismuth crystal
Jewelry bismuth

3. “All things are poison and nothing without poison;
only the dose determines that a thing is not
poison.”

4. BISMUTH Bi
Atomic number 83
Atomic weight 208.980
Melting point 271 °C
Discovered by GERMANY
BI
O
OO OH

5. Physical properties
• Solid
• Colour Crystalline, with pink tint .
• No Odour
• No thermal conductivity
• high electrical resistance
• Diamagnetic

6. Found
• Free in nature
• Earth crust
• Seawater
• In soil with lead

7. Uses
• Found in fire detection
device
• fire sprinklers.
• Ceramic glaze
• Hunting shot
• Pharmacy products
• cosmetics
• Paints
• A catalyst in rubber production

8. Epidemiology and history
• it was distinct from lead in 1753 .
• Elemental bismuth is nontoxic.
• bismuth salt have therapeutic uses and
responsible the toxicities.
• In the early 20th century acute kidney was
reported in children administered IM bismuth
salt for the treatment of gingivostomatitis
Historically bismuth tartrate were used to treat
syphilis, while bismuth sodium triglycollamate
has been used to treat warts, stomatitis and
upper respiratory tract infections.
Bismuth got its
name from the
German word
*wissmuth
*meaning white
mass

9. Today
• Xenobiotic
• Inorganic bismuth compound ’’ subnitrate ’ subcarbonat” used for
gastrointestinal disorder (diarrhea ,flatulence ,constipation ,cramp
,dyspepsia )
• Lipid soluble organic Colloidal bismuth subcitrate ’subgallate
‘subsalicylate (pepto bismol) ranitidin bismuth citrate ‘ used to treat
peptic ulcer and H.pylori associated with gastritis
• Potential application include the use of bismuth subnitrate to prevent
cisplatin nephrotoxicity but not have been applied in practice
• The use of a particle emitting bismuth compounds as
radiotherapeutics agent and as anti-tumor agent .

10. • ‘Bismuth iodoform paraffin paste’ surgical packing past for
treatment of flatus and odor associated with ileostomies &
colostomies and treatment of ulcer.
• transdermal application of a bismuth-containing skin cream.

12. • Antimicrobial Anti-inflammatory antisecretory action
• The first, a distribution half-life, is approximately 1 to 4 hours.
• The second, the apparent plasma half life , lasts 5 to 11 days.
• The third is the apparent half-life of urinary excretion lasting between 21
and 72 days
• urinary bismuth detected as late as 5 months after the last oral dose

14. compartion
Normal
concentration plasma half life 5-11 d
blood 0.003 -0.5 mg/l
brain 0.6mg/kg
Toxicandlethal
concentration
blood 1–100mg/l
brain 3–25mg/kg

15. Clinical manifestation
Acute:
• Abdominal pain
• Nausea
• Vomating
• Oliguric,anuria , renal insufficiency secondary to acute tubular
necrosis 111

16. Chronic:
•signs of Encephalopathy
i. Sever confusion may developed over weeks but develop over 24-48 hr.
lead to coma
ii. Myoclouns
iii. poor coordination ,loss of memory ,problem with language
iv. Less common visual hallucination .*
• renal failure
• Generalized pigmentation of the skin Deposition of bismuth sulfied into
the mucosa cause a Blue-black discoloration of the gumline (bismuth
line )a blackening of the stool.

17. Mechanism of toxicity
• Patient on chronic bismuth therapy with a lipid soluble group
xenobiotic.
• The main target organs for bismuth toxicity are kidney, brain, and
bone
• Bismuth enter the body by ingestion of bismuth –containing
medication .
• 99% eliminated and 1 % absorbed
• peak absorption ranges between 15 and 60 minutes
• Once in the circulation, bismuth binds to α2-macroglobulin, IgM, β-
lipoprotein, and haptoglobin. Bismuth rapidly enters liver, kidney,
lungs, and bone.
• Bismuth can cross the placenta and blood brain barrier

18. Purple Bismuth
Necklace

19. TOXICOKINETICS
Absorption
• The gastrointestinal absorption of bismuth salts depends on their
water solubility.
• peak bismuth concentration within 1 hour of ingestion , with no
detectable bismuth in the blood
• Repeated dose daily increase its concentration in plasma level.

20. . Distribution
• in the kidney ,lung, spleen, liver, brain and muscle .
• In the kidney, bismuth is bound to a protein which is distinct
from metallothionein.
• The brain concentration of bismuth higher when ingestion of
lipid soluble compounds
• The tissue distribution of the metal also is affected by its
physical form.
• In rats, co-administration of selenium with bismuth produced a
50 percent reduction in the kidney bismuth concentration
possibly because synthesis of the bismuth-binding protein was
inhibited by selenium

21. Excretion
• 90% of absorbed bismuth is eliminated through the urine and feces
• A six week course of colloidal bismuth subcitrate 480 mg daily,
significantly increased urine bismuth excretion continued for at least
(three month)after cessation of therapy .
• The elimination half-life is reported to be about 21 days, depending on
bismuth compounds.

23. Diagnosis
For encephalopathy :
I. History of exposure
II. Blood or urine test( Icp-ms)
III. Abdominal X-ray may detect radiopaque material .*
IV. Black stool and negative test for blood
V. Salcylate level should be obtained in case of bismuth subsalicylate
exposure .

24. For acute kidney injury :
I. Hematuria and proteinuria
II. On renal biopsy or postmortem examination of the kidney
identified nuclear inclusion bodies

25. Treatment
1. withdrawal of the bismuth containing compound
2. Gastric lavage
3. Replace fluids and electrolytes*
4. Benzodiazepin may be used for myoclonic activity
5. BAL and ( DMPS) have been used with some success as chelating
agents *.
6. (BAL) in doses of 3 mg/kg may be tried within 8 to 12 hours of a
bismuth poisoning. Later administration may be ineffective due to
rapid absorption.
7. The use of EDTA contraindicated .
8. Hemodialysis in patient with renal failure .

26. Case study
• A 76 year-old man died nine days after taking 80 "De-Nol" tablets (9.6
g CBS) The admission blood bismuth concentration was 1600 µg/L.
Within hours this patient developed MELENA and became oliguric
with rapidly deteriorating renal function requiring dialysis. He
developed an acute abdomen on day five but was deemed unfit for
surgery and died. A perforated duodenal ulcer was found at autopsy
and the kidneys contained bismuth in concentrations of 11 mg/g and
16 mg/g respectively. Bismuth nephropathy had contributed to renal
failure precipitated by acute gastrointestinal hemorrhage

27. References
• Handbook of Forensic Toxicology for Medical by d.kimberley molina Exa
miners/Metals and Metalloids
• gold frank toxicology emergency
• casarett and doulls toxicology the basic scince of poison
• ASPET