zinc toxicity

1. ZINC TOXICITY
By Sura Ali Ibrareim
Higher diploma in pharmacology & toxicology
Supervised by
Dr. Ammar A. Hussein
College of pharmacy
Baghdad Universty
2019

2. WHAT IS ZINC?
 Zinc(Zn) is a metallic chemical element and environmentally ubiquitous
and essential for life.
 Zinc is the 25th most abundant element, accounting for approximately
0.02% by weight of the earth’s crust
 Crystalline Zn is a bluish white metal, atomic weight, 65.38; atomic
number, 30; density, 7.13 g/cm3; melting point, 419.5°C; boiling
point,908°C;, Zn occurs only in the divalent state and does not occur as a
metal in nature
 It’s essential requirement for a body health, total body content of zinc is
about 2 gm, ,about 60% of zinc is present in muscles and 30% in bones
,it is also present in the brain,liver and skin
 zinc play a vital role in bringing a vitamin A from liver to the retina and
play important role in various signaling pathways ,cell prolifertion
,differentiation and apoptosis ..It’s essential for normal function of the
pancreas

3. SOURCES OF ZINC :
 Atmospheric; mostly in aerosols in the oxidized form.
 Water; present as simple hydrated metal ion, simple organic and
inorganic complexes , stable organic complexes, adsorbed on
organic and inorganic colloids.
 soils
 Foods:
1.Animal sources are Flesh Foods(meat), liver, milk(Cow milk) and
dairy products
2.Vegetables sources are legumes, pulses, nuts, beans, spinach and
cereal
 The colostrum is an especially rich source.

5. FUNCTION OF ZINC
 Zinc is a cofactor of enzymes (LDH , Alkaline phosphatase , Carbonic anhydrase ,
SOD , Carboxy peptidase )
 RNA polymerase requires Zn for protein biosynthesis ..
 Zn –functions as an antioxidant.
 synthesis of retinol binding protein require Zinc
 Zinc required for immunological functions.
 Zinc supplementation useful for treating acute diarrhea.
 Zinc supplementation improves birth weight of babies.
 Zn necessary to maintain normal levels of vitamin A. •
 Storage & secretion of insulin from β- cells of pancreas requires Zn
 Gustin –Saliva taste sensation
 Zinc as an anti -cancer agent
 Zn stabilizes membrane structure.
 Zn is essential for proper reproduction.

6. USES OF ZINC :
Zinc can be found in many things, including:
 Compounds used to make paint, rubber, dyes, wood
preservatives, and ointments
 Rust prevention coatings
 Vitamin and mineral supplements in treatment of acute
diarrhea in children, common cold and Wilson disease
 Heated or burned galvanized metal (releases zinc fumes)
 zinc compound is used as a common rodenticide such as
Zinc phosphide
 Organo-Zn compounds are used as fungicides, topical
antibiotics, and lubricants Metal alloy manufacturing,
petroleum refineries, nufacturing, cosmetics, woodworking,
embalming,dentistry, military smoke bomb manufacturing,
topical ointments in medicine

7. DEFICIENCY OF ZINC
 Zinc deficiency caused by: Dietary deficiency,malabsorption
(including inherited defect in zinc absorption), chronic alcoholism,
nephrotic syndrome, parental nutrition with inadequate zinc.
 Clinical symptoms: Hypogonadism (impaired spermatogenesis)
Growth failure ,Loss of taste sensation ,Impaired wound healing
,Skin lesions such as dermatitis.
 Acrodermatitis enteropathica: A rare inherited metabolic disease
of zinc deficiency.Caused by defective absorption of Zn in the
intestine.

8. RECOMMENDED DIETARY ALLOWANCES (RDAS)
FOR ZINC
Age Male Female Pregnancy Lactation
0–6 months 2 mg* 2 mg*
7–12 months 3 mg 3 mg
1–3 years 3 mg 3 mg
4–8 years 5 mg 5 mg
9–13 years 8 mg 8 mg
14–18 years 11 mg 9 mg 12 mg 13 mg
19+ years 11 mg 8 mg 11 mg 12 mg

9. TOXIC SALTS OF ZINC
 Zinc is normally present in our body. Poisonous salts are compounds of
chloride, phosphide, sulfate (white vitriol), oxide and stearate.
 Zinc stearate is used as a cosmetic (baby powder).Inhalation it may
cause pneumonitis.
 Zinc chloride is used to clean metals before soldering. it is strong
corrosive action ,destroy mucous membrane of mouth , esophagus
and stomach .
 Zinc phosphide is used as rodenticide. it steel grey crystlline powder
,garlic odor,react with gastric acid librete phosphin gas,cause dyspnea,
pulmonary odema ,bradycardia, circulatory collapse, neurological
symptoms, coma and death.
 Zinc gluconate using as intranasal gel or spray but it used should be
avoided due to it cause loss of the sense of smell (irreversible
anosmia).
 Zinc sulfate is used to treat and prevent zinc deficiency and in te
treatment of acute diarrhea in children

10. DRUGS OF ZINC SALTS

11. Tooth paste and rat paste tubes

12. ROUTE OF EXPOSURE
 Inhalation :
inhalation of Zn oxide fume generated by welding and certain other
industrial processes causes metal fume fever, a self-limited flu like illness
is an acute, manifested by fever, chills, myalgia, nausea, fatigue, and
infrequently shortness of breath that occurs after inhalation of Zn oxide
inhalation of Zn chloride, from smoke bombs, causes severe pulmonary
injury severe chemical pneumonia. and may be fatal.
 Ingestion
Food or drink contaminated by exposure to galvanized surfaces can cause
nausea, vomiting, cramps, and diarrhea that is seldom fatal.
 Dermal
mucous membrane exposure comes from aerosolized zinc compounds or
topical ointments containing zinc. Dermal symptoms toxicity generally
produces local irritation, dermatitis,erythema, and ulcerations
 supplements rich in Zn

14. ZINC TOXICITY
 Zinc toxicity is rare and can be either acute, leading to short term
side effects, or chronic, resulting in long term issues.
 Salts of zinc are locally irritating, and after absorption cause
metabolic acidosis, hypocalcemia, damage to the liver and kidneys,
and affects the CNS.
 The symptoms of acute toxicity will appear soon after taking a high
dose of zinc and can include: On ingestion, there is a metallic taste
,nausea, vomiting associated with irritation and corrosion GI tract,
The vomitus and the stool may contain blood,acute renal failure
,tubular necrosis , stomachache ,diarrhea ,headaches.
 If taken high levels of zinc over a long period, they can experience
chronic zinc toxicity, which may lead to the following: low levels of
HDL , decreased immune function ,copper deficiency, Nausea,
gastric ulcer, pancreatitis, diarrhea,,excessive salivation, vomiting,
stomach cramps and anemia .
 People who work in metallurgy, such as welders, can develop a
condition known as metal fume fever from Inhalation of zinc oxide .

15. FATAL DOSE
 Zinc chloride: 40–70 mg/kg
 Zinc phosphide: 20–40 mg/kg.
 Zinc sulfate: 15 g (10–30 g).
 Zinc oxide fumes: 500 mg/m³
 Fatal period: 3–5 h to few days

16. MECHANISM OF TOXICITY:
 Its mechanism is still unknown ,micromolar amounts of the free zinc ion
kills some organisms. The free zinc ion is a powerful Lewis acid up to
the point of being corrosive. When ingested, metallic zinc readily
dissolves in the hydrochloric acid of the stomach, and displaces the
chloride to give the corrosive zinc chloride.) can cause damage to the
stomach lining due to the high solubility of the zinc ion in the acidic
stomach.
 Zinc toxicity has also been linked to alterations of blood lipoprotein
levels, with increased levels of LDL and decreased levels of HDL seen.
 Zinc toxicity may take months to resolve.
 Zinc toxicosis, however, can cause severe disease, and commonly
results in anaemia.. One hypothesis is that erythrocyte antioxidant
pathways are inhibited leading to erythrocyte membrane oxidative
damage These include direct damage of red blood cells

17. MECHANISM OF TOXICITY:
 Copper deficiency secondary to excessive zinc intake has been well
described in patients taking large doses of supplemental zinc for
treatment of sickle cell anemia, aphthous ulcers, and prostate cancer, as
well as in zinc coin ingestion.These patients uniformly presented with
signs and symptoms of neutropenia and anemia either the microcytic or
sideroblastic .
 zinc and copper have a competitive absorption relationship within
enterocytes mediated by metallothionein, a zinc- and copper-binding
protein that binds copper with greater affinity than zinc .
 Metallothionein expression is regulated by dietary zinc content alone.
When large amounts of dietary zinc are ingested, metallothionein
expression increases, more zinc is bound to metallothionein and more
zinc-metallothionein complexes are excreted. Because of the difference
in binding affinities between zinc and copper (copper binds
metallothionein with greater affinity), a potential for pronounced copper
excretion exists. Therefore, a substantial increase in zinc ingestion
potentially would cause a dramatic decrease in copper absorption.

18. ZINC TOXICITY(EXCESS) AND ZINC DEFICIENCY

19. TREATMENT AND MANAGEMENT
 1. Metal fume fever is self-limiting.
 2. Pulmonary symptoms may be treated
with oxygen and beta 2-adrenergic agonist therapy.
 3. Aggressive fluid resuscitation may be
needed following oral exposure, as GI losses may be significant.
 removal of the zinc source and supportive therapies, including blood
transfusion, intravenous fluid therapy, gastroprotectants , anti-nausea
medications, antioxidants, antibiotics, and sometimes chelation
 When a metallic zinc object is ingested, increasing gastric pH with antacids
and gastroprotectants helps to reduce the rate of zinc dissolution until the
object can be removed. Chelation with d-penicillamine or calcium disodium
EDTA may be considered if zinc concentrations do not improve after
removal of the zinc source.
 Calcium disodium ethylenediaminetetraacetate (CaNa2EDTA) is the chelator
of choice based on case reports that demonstrate normalization of zinc
concentrations, but there are few clinical data to confirm the efficacy of this
agent.


20. METAL FUME FEVER
 is A flu-like, febrile syndrome including fever, chills,
 headaches, cough, dyspnea, fatigue, and
myalgias that typically resolve within 36
hrs. Symptoms usually occur within 6 hrs
of exposure. that may occur after inhaling fumes from heated
metals.
 This typically occurs during welding. Zinc oxide
 There is no antidote. After removal from the source, the
symptoms are selflimiting.
 Treatment is supportive and aimed at symptomatic relief

21. CASE STUDY
A 35 yr old woman had received treatment involving daily
oral doses of 440-660 mg zinc sulfate over a period of 10
months, plus a daily vitamin preparation amounting to an
additional 80 mg of zinc sulfate per day. The patient
subsequently developed a severe copper deficiency, involving
hypochromic-microcytic anemia, leukopenia and neutropenia.
This status could not be corrected by a 2-month oral dosing
period, but symptoms declined after a 5-day iv administration
at a total dose of 10 mg copper. It was concluded that the
elimination of excess zinc is slow and will block the intestinal
absorption of copper .

22. RFERENCES :
 Review ofForensic Medicine and Toxicology 3rd Edition
 Modern medical Toxicology 4th edition
 Handbook on the Toxicology of metals 3rd edition
 Toxicology Recall 1ST edition
 www.medicalnewstoday. Com /articles
 www.mayoclinicproceedings.org/article/S0025-6196(11)62239-8/fulltext