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Pricipales of Dental Toxicology

      Iyad Abou Rabii DDS, OMFS, MRes, PhD




                 QASSIM UNIVERSITY
Pricipales of Dental Toxicology
                    Iyad Abou Rabii DDS, OMFS, MRes, PhD

Dental Toxicology
Study of poisons and their effects, particularly on living systems.

And Searching for treatments


Forensic toxicology (the use of toxicology and other disciplines such as analytical
chemistry, pharmacology and clinical chemistry to aid medical or legal
investigation of death)

Mercury
Facts
  Mercury is the most toxic substance that people are exposed to.
  • Potential health risks associated with mercury amalgams include:
  • Mercury inhibits sulfhydryl (-SH) group containing enzymes
  • Mercury's links to neurological diseases like Alzheimer's disease and autism
  • Harm to unborn babies
  • Vulnerability to toxicity, particularly among vulnerable pregnant women
    and young children
  • Greater exposure to the effects of mercury due to chewing and drinking
    beverages
  • Interaction with other metals and dental materials that increases risks

Mercury Types
  There is three types of Mercury
  • Inorganic
  • Organic: Especially in fishes leaving Lakes and rivers are also contaminated
    when there is a direct discharge of mercury industrial
                                                                                      [ ‫ا ر‬
  • Mercury vapor.

Pharmacodynamics
  Mercury can pass the skin barrier, blood-brain and the placental barrier and
                                                                                      ‫ | ]ا‬Pricipales of Dental Toxicology




    thus cause devastating effects on the functioning and growth of the brain
    and the growing foetus.
  • The most likely routes of exposure are inhalation of inorganic mercury
    vapour after a spill or during a manufacturing process, or ingestion of
    methyl mercury from contaminated fish, absorption through skin.
  • Ditribution
  • According to Mercury type
  • Vapor : The most dangerous form absorbed in the lungs and stored in the
    CNS



                                                                                      1
• Oraganic Mercury : Lipophile absorbed in the intestin, most of it excerted
                                            with feces
                                          • Inorganic : Accumulate in the blood, plasma, and kidney (scereted in the
                                            urine)
                                          • Mercury plasmatic half-life is about 60-70 days

                                       Mecury in dentistry
                                         Mercury is a component of the amalgam used for "silver" fillings. The other
                                           major ingredients are silver, tin, copper, and zinc. When mixed, these
                                           elements bond to form a strong, stable substance.
                                         • Mercury vapour from amalgam is the most dangerous form of mercury,
                                           most rapidly crossing the blood-brain barrier and mother’s placenta, and
                                           ensuring adverse developmental effects at lower levels than other forms.
                                         • The mercury-free dentists cite the potential for excess exposure to mercury
                                           when removing amalgam fillings as a serious concern for dental
                                           practitioners, some of whom have devised various strategies for reducing
                                           the amount of mercury exposure for both patients and dental staff during
                                           the removal of mercury fillings.

                                       Arsenic
                                       Arsenic is a poisonous chemical often used in herbicides and pesticides and is classified as a Class
                                       1 carcinogen, meaning it is highly toxic to humans.
                                       “arsenic has been linked to cancer of the bladder, lungs, skin, kidney, nasal passages, liver, and
                                       prostate”. Other side effects of consuming arsenic can include nausea, vomiting, diarrhea, partial
                                       paralysis and blindness.

                                       Medical Use of arsenic
                                          • Arsphenamine as well as Neosalvarsan was indicated for syphilis but has been superseded
                                            by modern antibiotics.
                                          • Arsenic trioxide has been used in a variety of ways over the past 500 years, but most
                                            commonly in the treatment of cancer.
                                          • The US Food and Drug Administration in 2000 approved this compound for the treatment
                                            of patients with acute leukemia
                                          • It was also used as Fowler's solution in psoriasis.[
                                          • Recently new research has been done in locating tumours using arsenic-74 (a positron
                                            emitter).
                                          • Arsenic is used in dentistry as gel in order to produce the necrosis of the pulp before
                                            endodontic therapy, in that case intensive car soul be taken to prevent its leakage
[ ‫ا ر‬




                                       Lead
                                         Lead is a toxic element existed in the dental clinic (amalgam fillings, Xray
‫ | ]ا‬Pricipales of Dental Toxicology




                                           shields, Xray films), once in the body lead can
                                         • Inhibit heme biosynthesis Heme is the essential structural component of
                                           hemoglobin, myoglobin and cytochromes.
                                       • Binds to sulfhydryl groups (-SH groups) of proteins (including a lot of
                                       important metabolic enzymes)

                                       Pharmacodynamique
                                       Absorbtion
                                         • Skin: alkyl lead compounds, because of lipid solubility (methyl and
                                           tetraethyl lead)

  2
• Inhalation: up to 90% depending upon particle size
  • GI: adults 5 to 10%, children 40%
Distribution
  Initially carried in red cells and distributed to soft tissues (kidney and liver);
     redistributed to bone, teeth and hair mostly as a phosphate salt. Rates of
     absorption and distribution are greatly influenced by dietary intake and
     body stores of phosphate, calcium and iron relative to lead
  • high PO4, Pb storage in bone
  • high Vitamin D, Pb storage in soft tissue
  • low PO4, Pb sequestered in soft tissue
  • high Ca++, Pb sequestered in soft tissue
• Half life in blood 30-60 days, bone 20-30 years

Source of exposure
# GI - paint, pottery,amalgam
# Inhalation - metal fumes, amalgam dust
# Skin -tetraethyl lead in gasoline

Fluoride as Toxic material
Fuorosis
  Fluorosis occurs when teeth are developing.
  • The most critical ages are from 0 to 6 years. After 8 years, risk of fluorosis is
    essentially past.
  • During the critical ages F intake in excess of 0.1mg/kg body weight/day can
    lead to fluorosis.
  • This is roughly 1mg/day for a 1 to 2 year old or 1.5 to 2 mg for a 5 year old.
  •
  • Remember that all forms of F intake comprise the daily consumption.
  • This includes
  • water intake (up to 1.5mg/day)
  • Foods (0.3 to 1.0mg) and especially significant in young children
  • Swallowed toothpaste. Children under 2 years swallow 50% of toothpaste
    during tooth brushing and at 5years, 25%, both of which may amount to
    1mg F/day.                                                                          [ ‫ا ر‬

Probable toxic dose (PTD)
PTD is 5 mg F/kg body weight.
                                                                                        ‫ | ]ا‬Pricipales of Dental Toxicology




       For a 20 kg 5 to 6 year old this would be 100 mg
       for a 10 kg 2 year old, 50 mg.
 F content of dental products or treatments may exceed these values for young
children. For example,
       a gel tray containing 5 ml of APF contains 61.5mg F (F is absorbed more
quickly when in acidic form.),
       100ml of 0.2 or 0.4% F mouth rinse contains 91 or 97mg F and a
       tube of fluoridated toothpaste contains as much as 230mg F.


Best Practice of luoride administration

                                                                                        3
Current clinical recommendations for preventive F measures are
                                        1) to determine total F intake per day from all sources in order to assess over or
                                       under F exposure
                                       2) determine caries risk
                                       3) institute a regimen commensurate with individual caries risk status which
                                       emphasizes bioavailability of post-eruptive topical F (e.g. regular use of F
                                       dentifrice and other home products if indicated)
                                       4) administer professional topical F treatments, the timing of which should also
                                       be gauged to caries risk (This may not be needed in low risk individuals) and
                                       5) administer systemic topical F if indicated. (The latter is currently under review.
                                       Present Academy of Pediatric Dentistry recommendations are presented below.


                                       Toxicological management in dentistry
                                       Prevention
                                         1. Consider all sources of exposure
                                         2. Best practice
                                         3. Management of Dental wastes

                                       Dignosis
                                         1. History of exposure
                                         2. Biological fluids analysis (blood mercury, whole blood lead level, arsenic
                                            blood and urinary levels)

                                       Treatment
                                          Remove from exposure
                                          • Chelating agents
                                          • 1.Lead: Calcium disodium EDTA (IV). 2, 3-dimercaptosuccinic acid (Succimer)
                                            (Oral). 2, 3-dimercaptoproponol (BAL, Dimercaprol) (IM). Penicillamine
                                            (Oral)
                                          •
                                          • Mercury: 2, 3-dimercaptosuccinic acid (Succimer) (Oral). 2, 3-
                                            dimercaptoproponol (BAL, Dimercaprol) (IM). Penicillamine (Oral). N-acetyl-
                                            penicillamine (Oral)
                                          • Arsenic: N-acetyl-penicillamine (Oral). Penicillamine (Oral)
[ ‫ا ر‬




                                          • Fuoride : milk and calcium containing products
                                          •
                                          •
‫ | ]ا‬Pricipales of Dental Toxicology




                                          • CHELATING AGENTS
                                       • Chelation is the formation of a metal ion complex in which the metal ion is
                                       associated with a charged or uncharged electron donor referred to as a ligand.




  4

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Pricipales of dental toxicology

  • 1. Pricipales of Dental Toxicology Iyad Abou Rabii DDS, OMFS, MRes, PhD QASSIM UNIVERSITY
  • 2. Pricipales of Dental Toxicology Iyad Abou Rabii DDS, OMFS, MRes, PhD Dental Toxicology Study of poisons and their effects, particularly on living systems. And Searching for treatments Forensic toxicology (the use of toxicology and other disciplines such as analytical chemistry, pharmacology and clinical chemistry to aid medical or legal investigation of death) Mercury Facts Mercury is the most toxic substance that people are exposed to. • Potential health risks associated with mercury amalgams include: • Mercury inhibits sulfhydryl (-SH) group containing enzymes • Mercury's links to neurological diseases like Alzheimer's disease and autism • Harm to unborn babies • Vulnerability to toxicity, particularly among vulnerable pregnant women and young children • Greater exposure to the effects of mercury due to chewing and drinking beverages • Interaction with other metals and dental materials that increases risks Mercury Types There is three types of Mercury • Inorganic • Organic: Especially in fishes leaving Lakes and rivers are also contaminated when there is a direct discharge of mercury industrial [ ‫ا ر‬ • Mercury vapor. Pharmacodynamics Mercury can pass the skin barrier, blood-brain and the placental barrier and ‫ | ]ا‬Pricipales of Dental Toxicology thus cause devastating effects on the functioning and growth of the brain and the growing foetus. • The most likely routes of exposure are inhalation of inorganic mercury vapour after a spill or during a manufacturing process, or ingestion of methyl mercury from contaminated fish, absorption through skin. • Ditribution • According to Mercury type • Vapor : The most dangerous form absorbed in the lungs and stored in the CNS 1
  • 3. • Oraganic Mercury : Lipophile absorbed in the intestin, most of it excerted with feces • Inorganic : Accumulate in the blood, plasma, and kidney (scereted in the urine) • Mercury plasmatic half-life is about 60-70 days Mecury in dentistry Mercury is a component of the amalgam used for "silver" fillings. The other major ingredients are silver, tin, copper, and zinc. When mixed, these elements bond to form a strong, stable substance. • Mercury vapour from amalgam is the most dangerous form of mercury, most rapidly crossing the blood-brain barrier and mother’s placenta, and ensuring adverse developmental effects at lower levels than other forms. • The mercury-free dentists cite the potential for excess exposure to mercury when removing amalgam fillings as a serious concern for dental practitioners, some of whom have devised various strategies for reducing the amount of mercury exposure for both patients and dental staff during the removal of mercury fillings. Arsenic Arsenic is a poisonous chemical often used in herbicides and pesticides and is classified as a Class 1 carcinogen, meaning it is highly toxic to humans. “arsenic has been linked to cancer of the bladder, lungs, skin, kidney, nasal passages, liver, and prostate”. Other side effects of consuming arsenic can include nausea, vomiting, diarrhea, partial paralysis and blindness. Medical Use of arsenic • Arsphenamine as well as Neosalvarsan was indicated for syphilis but has been superseded by modern antibiotics. • Arsenic trioxide has been used in a variety of ways over the past 500 years, but most commonly in the treatment of cancer. • The US Food and Drug Administration in 2000 approved this compound for the treatment of patients with acute leukemia • It was also used as Fowler's solution in psoriasis.[ • Recently new research has been done in locating tumours using arsenic-74 (a positron emitter). • Arsenic is used in dentistry as gel in order to produce the necrosis of the pulp before endodontic therapy, in that case intensive car soul be taken to prevent its leakage [ ‫ا ر‬ Lead Lead is a toxic element existed in the dental clinic (amalgam fillings, Xray ‫ | ]ا‬Pricipales of Dental Toxicology shields, Xray films), once in the body lead can • Inhibit heme biosynthesis Heme is the essential structural component of hemoglobin, myoglobin and cytochromes. • Binds to sulfhydryl groups (-SH groups) of proteins (including a lot of important metabolic enzymes) Pharmacodynamique Absorbtion • Skin: alkyl lead compounds, because of lipid solubility (methyl and tetraethyl lead) 2
  • 4. • Inhalation: up to 90% depending upon particle size • GI: adults 5 to 10%, children 40% Distribution Initially carried in red cells and distributed to soft tissues (kidney and liver); redistributed to bone, teeth and hair mostly as a phosphate salt. Rates of absorption and distribution are greatly influenced by dietary intake and body stores of phosphate, calcium and iron relative to lead • high PO4, Pb storage in bone • high Vitamin D, Pb storage in soft tissue • low PO4, Pb sequestered in soft tissue • high Ca++, Pb sequestered in soft tissue • Half life in blood 30-60 days, bone 20-30 years Source of exposure # GI - paint, pottery,amalgam # Inhalation - metal fumes, amalgam dust # Skin -tetraethyl lead in gasoline Fluoride as Toxic material Fuorosis Fluorosis occurs when teeth are developing. • The most critical ages are from 0 to 6 years. After 8 years, risk of fluorosis is essentially past. • During the critical ages F intake in excess of 0.1mg/kg body weight/day can lead to fluorosis. • This is roughly 1mg/day for a 1 to 2 year old or 1.5 to 2 mg for a 5 year old. • • Remember that all forms of F intake comprise the daily consumption. • This includes • water intake (up to 1.5mg/day) • Foods (0.3 to 1.0mg) and especially significant in young children • Swallowed toothpaste. Children under 2 years swallow 50% of toothpaste during tooth brushing and at 5years, 25%, both of which may amount to 1mg F/day. [ ‫ا ر‬ Probable toxic dose (PTD) PTD is 5 mg F/kg body weight. ‫ | ]ا‬Pricipales of Dental Toxicology For a 20 kg 5 to 6 year old this would be 100 mg for a 10 kg 2 year old, 50 mg. F content of dental products or treatments may exceed these values for young children. For example, a gel tray containing 5 ml of APF contains 61.5mg F (F is absorbed more quickly when in acidic form.), 100ml of 0.2 or 0.4% F mouth rinse contains 91 or 97mg F and a tube of fluoridated toothpaste contains as much as 230mg F. Best Practice of luoride administration 3
  • 5. Current clinical recommendations for preventive F measures are 1) to determine total F intake per day from all sources in order to assess over or under F exposure 2) determine caries risk 3) institute a regimen commensurate with individual caries risk status which emphasizes bioavailability of post-eruptive topical F (e.g. regular use of F dentifrice and other home products if indicated) 4) administer professional topical F treatments, the timing of which should also be gauged to caries risk (This may not be needed in low risk individuals) and 5) administer systemic topical F if indicated. (The latter is currently under review. Present Academy of Pediatric Dentistry recommendations are presented below. Toxicological management in dentistry Prevention 1. Consider all sources of exposure 2. Best practice 3. Management of Dental wastes Dignosis 1. History of exposure 2. Biological fluids analysis (blood mercury, whole blood lead level, arsenic blood and urinary levels) Treatment Remove from exposure • Chelating agents • 1.Lead: Calcium disodium EDTA (IV). 2, 3-dimercaptosuccinic acid (Succimer) (Oral). 2, 3-dimercaptoproponol (BAL, Dimercaprol) (IM). Penicillamine (Oral) • • Mercury: 2, 3-dimercaptosuccinic acid (Succimer) (Oral). 2, 3- dimercaptoproponol (BAL, Dimercaprol) (IM). Penicillamine (Oral). N-acetyl- penicillamine (Oral) • Arsenic: N-acetyl-penicillamine (Oral). Penicillamine (Oral) [ ‫ا ر‬ • Fuoride : milk and calcium containing products • • ‫ | ]ا‬Pricipales of Dental Toxicology • CHELATING AGENTS • Chelation is the formation of a metal ion complex in which the metal ion is associated with a charged or uncharged electron donor referred to as a ligand. 4