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Potential Health Risks from
Exposure to Chrysotile Asbestos
      Dr. Thomas Hesterberg, PhD, MBA
           Consultant in Toxicology
            Littleton, Colorado USA

         Federal Supreme Court of Brazil
                  Brasilia, Brazil
                 31 August 2012
Focus Should be on Potential
       Health Risk of Chrysotile
• Health Risk = Potential Hazard X Exposure
• Most studies of chrysotile
  focus on hazard
• In the 1500s, Paracelsus
  knew that dose determines
  the toxin
• If exposure kept low, there
  is no risk

                                              2
Maintaining Low Chrysotile
           Workplace Exposures
•   Industry workplace limit of 0.1 fibers/cc
•   Engineering controls in work areas
•   Perform cutting in enclosed ventilated areas
•   Maintain housekeeping with frequent cleaning
•   Low exposure (< 0.1 f/cc) => No Health Risk




                                               3
Earlier Animal Inhalation
                Studies of Chrysotile
• Lung cancer observed at very high exposures
   – Exposures were > 1 million fibers/cc
   – This is 10 million times industry exposure limit of 0.1 fiber/cc
• Lung clearance impaired due to overload
   – Other non-toxic particles cause lung disease at these levels
     (carbon black, talc and TiO2)
• These studies only showed effects of lung overload
• Remember: Risk = Hazard X Exposure
   – Low exposures pose no risk to humans

                          Bernstein et al., Crit Rev. Tox., In Press, 2012.
                                                                              4
Inhalation Toxicity Study
                   of Brazilian Chrysotile
• Three month rat inhalation to Brazilian chrysotile
• Exposure to 536 WHO fiber/cc
    – 5000 times the industry workplace limit of 0.1 fiber/cc
• No lung disease was observed at this level
• If no fibrosis at 90 days indicates no cancer in chronic study
        ILSI, Inhalation Toxicology, 17:497–537, 2005
• A much higher exposure level produced only minimal fibrosis
• Risk is avoided if exposure is kept low


                                  Bernstein et al., Inhal. Tox. 18 (5): 1–22, 2006.

                                                                                      5
The Three Ds of Fiber Toxicology

Dose -         Amount reaching the deep lung

Dimension -    Thin fibers deposit in the deep lung; long
               fibers are more toxic

Durability -   Dissolution and breakage; more durable
               fibers are more toxic


                        Hesterberg and Hart., Inhal. Tox., 2001


                                                                  6
Fiber Biopersistence in the Lung
                           Long Fiber (> 20 µm)


                                                         Incongruent Dissolution
 Congruent Dissolution


                                         Transverse Breakage
Complete                                                          Altered Biological
Dissolution              Macrophage                               Reactivity
                         Uptake




                                       Mucociliary Clearance
                                      Intracellular Degradation

                                  Hesterberg and Hart., Inhal. Tox., 2001
                                                                                       7
Asbestos: Structure and Durability



 Chrysotile
                                        Amphibole




                Bernstein and Hoskins, Reg. Tox. and
                Pharm. 45: 252–264 , 2006.
                                                       8
Inhalation Biopersistence Study Protocol
Biopersistence of Amosite and Chrysotile

                  Bernstein and Hoskins, Reg. Tox. and
                  Pharm. 45: 252–264 , 2006.
Inhalation Biopersistence Study
         of Brazilian Chrysotile
• Chrysotile clearance half-time was 1.3 days
• Lower than man-made fibers in IARC Group 3
   – Not classified as carcinogens
• Explains why no disease seen in animals
• And why no disease seen in humans
• Chrysotile can be used safely


                         Bernstein et al., Inhal. Tox. 18 (5): 1–22, 2006.

                                                                             11
Correlation of Results from
   Biopersistence and Inhalation Toxicity
                          Biopersistence                  Inhalation Toxicity
Fiber                     Half-Life (Days)              Fibrosis       Tumors
Crocidolite                   817                        +               +
Amosite                       418                        +               +
MMVF32                         79                        +               +
RCF1                           55                        +               +
MMVF33                         49                        +               -
MMVF21                         67                        +               -
                                    Not Classified as
MMVF10 (Fiber glass)           37 Carcinogen by IARC     -               -
MMVF 10.1 (Fiber glass)        14.5                      -               -
X607                            9.8 Cancer Label not     -               -
MMVF11 (Fiber glass)            9    Required in EU      -               -
MMVF22 (Mineral wool)           9                        -               -
MMVF34 (Mineral wool)           6                        -               -
Chrysotile (Brazilian)          1.3                      -               -

                                                                                   12
                                         Hesterberg and Hart., Inhal. Tox., 2001
Potential Chrysotile Substitutes
 International Agency for Research on Cancer (IARC)
• Examined chrysotile substitutes in 2005
• IARC did not indicate whether potential substitutes
  would actually work in chrysotile applications
• Unlike chrysotile, most of the 13 substitutes had very
  little toxicology information
• Little or no human studies on substitutes
• In Brazil, a combination of polypropylene and
  cellulose fibers are proposed substitutes

                           WHO Workshop on Chrysotile
                           Substitutes, Lyon, France, 2005.
                                                              13
Cellulose Fiber Health Effects

• Lung disease in rats and hamsters
• Biopersistent: clearance > 1000 days
   – Compared to 1.3 days for chrysotile asbestos
• Excess lung cancer in paper mill workers
• Excess deaths from chronic obstructive pulmonary
  disease and asthma in paper mill workers
• Not recommended as chrysotile substitute

                          National Toxicology Program, Toxicology
                          Report Series, No. 74, 2006.
                                                                    14
Polypropylene Fiber
                   Inhalation Toxicity
• Inhalation toxicity study of polypropylene fibers
• Exposures up to 48 fibers/cc
   – Compared to 536 fibers/cc in chrysotile study
• Increase in reversible lung disease
• Levels of fibers in the lung increased with time
• Biopersistence: no lung clearance of fibers after 30 days
• Not recommended as a chrysotile substitute


                                 Hesterberg et al., Fund. Appl. Tox.
                                 19:358-366, 1992.
                                                                       15
Conclusions
•   Chrysotile not toxic at non-overload levels
•   Chrysotile clears from the lung within days
•   Risk = Hazard X Exposure
•   No risk identified below workplace limit (0.1 f/cc)
•   Chrysotile substitutes not adequately tested
•   Chrysotile can be used safely



                                                      16

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STF - Audiência Pública do Amianto - 31/08/2012 - Supremo Tribunal Federal

  • 1. Potential Health Risks from Exposure to Chrysotile Asbestos Dr. Thomas Hesterberg, PhD, MBA Consultant in Toxicology Littleton, Colorado USA Federal Supreme Court of Brazil Brasilia, Brazil 31 August 2012
  • 2. Focus Should be on Potential Health Risk of Chrysotile • Health Risk = Potential Hazard X Exposure • Most studies of chrysotile focus on hazard • In the 1500s, Paracelsus knew that dose determines the toxin • If exposure kept low, there is no risk 2
  • 3. Maintaining Low Chrysotile Workplace Exposures • Industry workplace limit of 0.1 fibers/cc • Engineering controls in work areas • Perform cutting in enclosed ventilated areas • Maintain housekeeping with frequent cleaning • Low exposure (< 0.1 f/cc) => No Health Risk 3
  • 4. Earlier Animal Inhalation Studies of Chrysotile • Lung cancer observed at very high exposures – Exposures were > 1 million fibers/cc – This is 10 million times industry exposure limit of 0.1 fiber/cc • Lung clearance impaired due to overload – Other non-toxic particles cause lung disease at these levels (carbon black, talc and TiO2) • These studies only showed effects of lung overload • Remember: Risk = Hazard X Exposure – Low exposures pose no risk to humans Bernstein et al., Crit Rev. Tox., In Press, 2012. 4
  • 5. Inhalation Toxicity Study of Brazilian Chrysotile • Three month rat inhalation to Brazilian chrysotile • Exposure to 536 WHO fiber/cc – 5000 times the industry workplace limit of 0.1 fiber/cc • No lung disease was observed at this level • If no fibrosis at 90 days indicates no cancer in chronic study ILSI, Inhalation Toxicology, 17:497–537, 2005 • A much higher exposure level produced only minimal fibrosis • Risk is avoided if exposure is kept low Bernstein et al., Inhal. Tox. 18 (5): 1–22, 2006. 5
  • 6. The Three Ds of Fiber Toxicology Dose - Amount reaching the deep lung Dimension - Thin fibers deposit in the deep lung; long fibers are more toxic Durability - Dissolution and breakage; more durable fibers are more toxic Hesterberg and Hart., Inhal. Tox., 2001 6
  • 7. Fiber Biopersistence in the Lung Long Fiber (> 20 µm) Incongruent Dissolution Congruent Dissolution Transverse Breakage Complete Altered Biological Dissolution Macrophage Reactivity Uptake Mucociliary Clearance Intracellular Degradation Hesterberg and Hart., Inhal. Tox., 2001 7
  • 8. Asbestos: Structure and Durability Chrysotile Amphibole Bernstein and Hoskins, Reg. Tox. and Pharm. 45: 252–264 , 2006. 8
  • 10. Biopersistence of Amosite and Chrysotile Bernstein and Hoskins, Reg. Tox. and Pharm. 45: 252–264 , 2006.
  • 11. Inhalation Biopersistence Study of Brazilian Chrysotile • Chrysotile clearance half-time was 1.3 days • Lower than man-made fibers in IARC Group 3 – Not classified as carcinogens • Explains why no disease seen in animals • And why no disease seen in humans • Chrysotile can be used safely Bernstein et al., Inhal. Tox. 18 (5): 1–22, 2006. 11
  • 12. Correlation of Results from Biopersistence and Inhalation Toxicity Biopersistence Inhalation Toxicity Fiber Half-Life (Days) Fibrosis Tumors Crocidolite 817 + + Amosite 418 + + MMVF32 79 + + RCF1 55 + + MMVF33 49 + - MMVF21 67 + - Not Classified as MMVF10 (Fiber glass) 37 Carcinogen by IARC - - MMVF 10.1 (Fiber glass) 14.5 - - X607 9.8 Cancer Label not - - MMVF11 (Fiber glass) 9 Required in EU - - MMVF22 (Mineral wool) 9 - - MMVF34 (Mineral wool) 6 - - Chrysotile (Brazilian) 1.3 - - 12 Hesterberg and Hart., Inhal. Tox., 2001
  • 13. Potential Chrysotile Substitutes International Agency for Research on Cancer (IARC) • Examined chrysotile substitutes in 2005 • IARC did not indicate whether potential substitutes would actually work in chrysotile applications • Unlike chrysotile, most of the 13 substitutes had very little toxicology information • Little or no human studies on substitutes • In Brazil, a combination of polypropylene and cellulose fibers are proposed substitutes WHO Workshop on Chrysotile Substitutes, Lyon, France, 2005. 13
  • 14. Cellulose Fiber Health Effects • Lung disease in rats and hamsters • Biopersistent: clearance > 1000 days – Compared to 1.3 days for chrysotile asbestos • Excess lung cancer in paper mill workers • Excess deaths from chronic obstructive pulmonary disease and asthma in paper mill workers • Not recommended as chrysotile substitute National Toxicology Program, Toxicology Report Series, No. 74, 2006. 14
  • 15. Polypropylene Fiber Inhalation Toxicity • Inhalation toxicity study of polypropylene fibers • Exposures up to 48 fibers/cc – Compared to 536 fibers/cc in chrysotile study • Increase in reversible lung disease • Levels of fibers in the lung increased with time • Biopersistence: no lung clearance of fibers after 30 days • Not recommended as a chrysotile substitute Hesterberg et al., Fund. Appl. Tox. 19:358-366, 1992. 15
  • 16. Conclusions • Chrysotile not toxic at non-overload levels • Chrysotile clears from the lung within days • Risk = Hazard X Exposure • No risk identified below workplace limit (0.1 f/cc) • Chrysotile substitutes not adequately tested • Chrysotile can be used safely 16