WHAT YOU SHOULD KNOW ABOUT ASBESTOS

The first European Asbestos Forum

Dr. Richard A. LemenAssistant Surgeon General

United States Public Health Service (Ret.)

27th May 2015

Most asbestos comes from open-pit mines using bench drilling techniques.

The term asbestos is traditionally attributed to those forms used

commercially.

Dr. RA Lemen

Non-milled Asbestos

Vein of Asbestos

Serpentine RockDr. RA Lemen

Milled Asbestos

Fibers are separated from the core ore leaving the raw fibers

Dr. RA Lemen

Dry milling is most widely use.

Asbestos Use Dates Back 1000’s of years “In the great civilizations of antiquity, whether in the East, West, or in Europe generally, there was sufficient concentration of the forces of labour to produce the intensest [sic] forms of the maladies classed by Pliny as the “diseases of slaves.”

Some of the most injurious processes known to us now are extremely ancient. To mention but a few:

the textile processes of preparing and weaving asbestos and

flax.”

Adelaide M. Anderson, H.M. Principal Lady Inspector of Factories. Chapter II. Historical Sketch of the development of Legislation for Injurious and Dangerous Industries in England. In: Dangerous Trades, Ed. Thomas Oliver, John Murray, London, 1902.

Dr. RA Lemen

“Asbestos is one of the most marvelous productions of inorganicnature. It is a physical paradox, a mineralogical vegetable,* both fibrous and crystalline,elastic and brittle; a floatingstone, as capable of being carded, spun, and woven, as wool, flax, or silk.”

Occupying the apparent position of a connecting link between themineral and vegetable kingdom, it would appear to possess some ofthe characteristics of both, while being altogether different from either.”

Modern Asbestos Industry Dates to Mid-1800s

R. H. Jones, 1897. Asbestos and Asbestic – Their properties, occurrence, and use.Crosby Lockwood and Son, London, Preface Dr. RA Lemen

Top Asbestos Producers (USGS)

Brazil

Canad

a

China

Kazak

hstan

Russia

0

100,000

200,000

300,000

400,000

500,000

600,000

700,000

800,000

900,000

1,000,000

20112012

www.adao.us

World production of asbestos reached it’s maximum in 1977 of 4.8 x 106 tons (Virta, 2002)

8

Year2000

Is Production & Consumption Decreasing?

Dr. RA Lemen

From: Robert L Virta. Worldwide asbestos supply and consumption trends 1900 to 2000.

China consumes almost all of it’s own asbestosIndia is the largest importer

Brazil exports about ½ it’s asbestosDr. RA Lemen

R. A. Lemen, Ph.D. 10

Ferruginous Bodies > Disease> Background Concentrations > etc.

As Consumption Goes Up Indicators of Human Exposure go

up

Ferruginous Bodies

88% Statistics from Upper Income countries

Time Trends May Indicate Shift Of Disease Burden Slowly Shifting To Countries Using Asbestos Most Recently

Source: Stayner, Welch, Lemen, 2012

AsbestosDiseases

Time

Are Asbestos Diseases Declining?

Emerging Economies

Developed Economies

Dr. RA Lemen

More information is available on the harmful effects of asbestos, and more incontestable epidemiologic and experimental evidence is available on its carcinogenicity, than for any other environmental agent. Dr. Lorenzo Tomatis, Former Director IARC.

Dr. RA Lemen

ASBESTOS-RELATED DISEASESDISEASE ESTABLISHED CAUSAL ASSOCIATION

Asbestosis 1930

Lung Cancer 1949-1955

Mesothelioma 1960-1963

Laryngeal Cancer 2006

Ovarian Cancer 2009

Colorectal reasonably anticipated

Stomach reasonably anticipated

Retroperitoneal fibrosis possibly

Ventilatory impairment unclear overall but restrictive impairment – yes

Large airway obstruction reasonably anticipated [smoking interacts]

Dr. RA Lemen

15

“Asbestos’ effects often appear to be random”

Lung Cancer – 20 -25%

Mesothelioma – 7 -10%

Total Cancers – 35 -40%

Dr. RA Lemen

Vital Statistics“Every death from asbestos-related diseases is avoidable”

Dr. Jakab, WHO Regional Director Europe

Asbestos is one of the most important occupational carcinogens, causing about half of the deaths from occupational cancer (WHO, 2014)Exposures to asbestos occurs through inhalation of fibres (WHO, 2014).

About 125 million people in the World are exposed at the workplace and about 107,000 people die each year from an asbestos-related disease. Worldwide this burden of death is still rising (WHO, 2014).

[Note: this is about to be revised to 194,000]Dr. RA Lemen

Vital Statistics“There is very little time left for that [to eliminate asbestos]”

Dr. Jakab, WHO Regional Director Europe

• 900 million living in Europe potentially Exposed or 1 in 3

• 15,000 deaths per year in Europe• Mesothelioma deaths from just 15 European

countries cost society 1.5 billion euros yearly• 37 of 53 European regional states have banned• 16 European region countries still use asbestos

WHO, 2015 Dr. RA Lemen

Specific Occupations

~ Miscellaneous nonmetallic mineral and stone Products

~ Ship and boat building and repairing

~ Industrial and miscellaneous chemicals

~ Other rubber products, and plastics footwear and belting

ASBESTOSIS most frequently recorded

by industry sector on death certificatesNIOSH

~ Petroleum refining

~ Electric light and power

~ Glass and glass products ~ Construction

~ Railroads

~ Blast furnaces, steelworks, rolling and finishing mills

Dr. RA Lemen

Plumbers, Pipefitter, & Steamfitters Managers and Administrators – No Epidemiology Electricians Carpenters Insulation Workers Laborers, Except Construction Supervisors, Production Occupations – No

Epidemiology Welders and Cutters Janitors and Cleaners Truck Drivers – No Epidemiology

ASBESTOSIS most frequently reported by Job title on death

certificateNIOSH

Dr. RA Lemen

~ Construction

~ Non-paid worker or non- worker or own home/at home ~ Elementary and secondary schools ~ Industrial and miscellaneous chemicals

~ General government

MESOTHELIOMA most frequently recorded industry sector on death

certificateNIOSH

~ Agricultural production, crops

~ Not specified manufacturing industries

~ Electric light and power

~ Railroads

~ Hospitals

Dr. RA Lemen

~ Managers and Administrators – No Epidemiology

~ Housewife/Homemaker – No Epidemiology (except take-home)

~ Plumbers, Pipefitters, & Steamfitters

~ Janitors and Cleaners

~ Supervisors and Proprietors,

~ Sales Occupations – No Epidemiology.

MESOTHELIOMA most frequent Job title recorded on death

certificateNIOSH

~ Carpenters

~ Teachers, Elementary School

~ Farmers, Except Horticulture – No Epidemiology

~ Electricians

~ Supervisors, Production Occupations – No Epidemiology

~ Truck Drivers – No Epidemiology

Dr. RA Lemen

Lamp Sockets Friction materialsDisk brake pads GasketsGaskets Cement corrugated sheetNon-roofing coatings Cement flat sheetRoof coatings ClothingFloor tiles Pipeline wrapCat Box fill Roofing feltAutomatic transmission componentsvinyl floor tile

Up to 5,000 consumer products contained asbestos

Examples:

From: U.S. Environmental Protection Agency, Feb. 3, 2015 Dr. RA Lemen

ASBESTOS-INDUCED DISEASESHistorical Perspective

Dr. RA Lemen

25

1906 FranceNumerous deaths (@50)reported in a French asbestos textile factory

Auribault, M., 1906. Note sur l’hygiene et la securite des ouvriers dans les filateurset tissages d’amiante. Bull Insp Trav, Paris Vol 14, p. 120 Dr. RA Lemen

Asbestos Textile Weaving Process

26

Charing Cross Hospital LondonDr. Montague Murray Reported a Case of Fatal Lung Disease in a 33Year old Male Textile Worker during Rounds at the Charing Cross Hospital In 1907. The patient had died in 1900.

Patient worked first 10 years in carding Asbestos. He reported he was only survivor of 10 workers he started with, who all died around 30 years of age.

Carding operation

1907

Dr. RA Lemen

ASBESTOS LUNG DISEASE

First x-ray descriptions of asbestos induced Lung disease by Pancoast & Pendergrass In the American Journal of Roentgenology And Radium Therapy

In 1918 the Bulletin of U.S. Labor Statistics –Reports both U.S. & Canadian Insurance Companies would not insure Asbestos WorkersDue to unhealthy conditions in the Industry.

Dr. RA Lemen

1918.

28

Nellie Kershaw1891 -1924

Dr. William Edmund Cooke names the lung disease caused by asbestos – Asbestosis - when Describing the case of this disease in a 33 year old woman named Nellie Kreshaw of Rochdale, England.

Age 12 – worked in a cotton millAge 13 - worked at Garsides asbestos millAge 26 – worker at Turner Brothers Asbestos

in Spinning departmentAge 33 – Died 06:30

14 March 1924

1927

29

Dr. E.R.A. MerewetherFirst Epidemiology Study of Asbestos Workers Conductedin the British Asbestos Textile Industry in 1930finding 28.1 % of 374 workers with Pulmonary Fibrosis (Asbestosis) and after 20 years of exposure 80 %.

The JAMA Reported results of the Merewether & Price Epidemiology Study to American Physicians

1930

Asbestosis

Trends are beginning to peak and level off inWestern Economies

Newly emerging economies trends for asbestosis are climbing, i.e. India’s overall prevalence of asbestosis

was 11.5%

Dr. RA Lemen

31

Cancer & Asbestos1935 Lynch and Smith (1935) in the United States and Gloyne (1935)

in the United Kingdom both associated occupational asbestos exposure with lung cancer.

1936 Reports appeared in the medical literature of lung cancers occurring

in asbestos exposed workers (Egbert and Geiger, 1936 & Gloyne, 1936) .

1938 German physicians began calling lung cancer an occupational disease of asbestos workers (Nordman, 1938).

1939 The UK Inspectorate of Factories report in the 1938 Annual Report

that 12 cases of lung cancer occurred among 103 cases of fatal asbestosis

or 11.6% (HMSO, 1939).

1942 Hueper (1942) in his classic book on cancer discusses asbestos related lung

cancers.

1949 In Factory Inspector’s Report of 1948 reports excess of lung cancer in both

men and women registered to have asbestosis.

Dr. RA Lemen

32

SIR RICHARD DOLLA 1955 study by Doll involved the study of the mortality experience of a cohort of 113 asbestos textile workers employed more than 20 years.

Among this group, there were 11 lung cancer deaths observed compared to only 0.8 expected, when based upon the mortality experience of England and Wales.

Over all studies the RR for lung cancer has varied from 1.0 to 17.6 with an average RR of 9.8.

Lung Cancer

Dr. RA Lemen

Lung Cancer

The estimated mortality range estimates are 43,000 – 344,000**

deaths annually* Driscoll T et al, 2005. Am J Ind Med, Dec; 48(6): 419-431.

** Estimated based on applying McCormack et al, 2012. BJC, 106, 575-584.

The World Health Organization states the risk ratio (RR) is 6:1 for contacting lung cancer vs.

mesothelioma following chrysotile exposure.****** World Health Organization. Chrysotile Asbestos.

2014. Dr. RA Lemen

15

From: Markowitz S, 2012. Tail of Two Carcinogens: The Legacy of Asbestos and Smoking.Ramazzini Days, October 26-28, Carpi, Italy.

34

Smoking & Lung Cancer Risk With Asbestos Exposure

Non-Smoker

Non-Smoker

Smoker

Smoker

Smoking Status Occupation Relative Risks Cancer Deaths

No Asbestos 1

AsbestosWorker 5.2

No Asbestos 10.3

28.4AsbestosWorker

Asbestos plus smoking raise risk of lung cancer additivelyAsbestosis plus smoking raise lung cancer supra-additively Dr. RA Lemen

15

Asbestos alone raises the risk of lung cancer

35

1. Squamous Cell

3. Adenocarcinoma2. Small (oat) Cell

4. Large Cell

35%

25%

25%

15%

Incidence of Cell Types in Lung Cancers

Dr. RA Lemen

Lung Cancer

While not possible to directly estimate asbestos-related lung cancer estimates between 1 and 8 excess lung cancer cases for each mesothelioma

Source: McCormack et al, 2012. BJC, 106, 575-584Dr. RA Lemen

Mesothelioma and Asbestos“The pathological diagnosis of mesothelioma has been beset by more difficulties than has any

other industrial cancer.” Ian Webster, 1977. Methods by which mesothelioma can be diagnosed. In: Asbestos Symposium, Johannesburg, H.W. Glen (ed.), Department

of Mines, National Institute for Metallurgy, Randburg, SA.

1927 association between mesothelioma and asbestos, however, not publish it until 1955

1934 Gloyne reports on a case of lung cancer with “a few deposits of

growth in the pleura” 1943 Reports of pleural (chest) and peritoneal (abdominal) tumors

associated with asbestos exposures. The first mesothelioma was in a case of asbestosis in Germany. 1947 - 1960

During this time over a dozen more mesothelioma reported

in the worlds scientific literature including two from the Canadian chrysotile mines.

Dr. RA LemenFrom: Lemen, 2012

Dr. RA Lemen

Dr. J.C. Wagner

Fibers end uphere where tumordevelops

33 (22 men, 11 females) cases of mesothelioma occurring between 1956 and 1960 in miners, millers, and transporters of asbestos and of non-mining residents of crocidolite in theN. West Cape Province of S. Africa .

1960

Carried out the first epidemiological study of asbestosWorkers to identify mesothelioma.

Found Mesothelioma, lung cancer and asbestosis in excess in an asbestos manufacturing plant in Ohio.

He identified by Death Certificate 19 lung cancers (3.4: 95% CI = 2.0-5.3); 28 asbestosis; and upon evaluation of death record found 7 mesothelioma, 25 lung cancers and 30 asbestosis cases.

Dr. Thomas F. Mancusco

Phillip-Carey Plant Loveland, OH @ 1968

USPHS Photos

Dr. RA Lemen

1963

Dr. Irving. J. SelikoffFirst to conduct a large scale mortality study of end-product users of asbestos from records of asbestos union members.

Found asbestos end-product Workers were at risk of asbestosis; lung cancer; mesothelioma; and gastrointestinal cancers.

Reocgnized guidance limit was far too High.

Dr. RA Lemen

1964

Dr. RA Lemen

Occupational exposure to all forms of asbestos has resulted in a high incidence of lung cancer, pleural and peritoneal mesothelioma, gastrointestinal tract, & excess of cancers of the larynx.

Mesotheliomas also occur in individuals living in the neighborhood of asbestos factories and crocidolite mines and in household contacts of asbestos workers.

Both cigarette smoking and occupational exposure to asbestos fibres independently increase lung cancer & act in a multiplicative fashion when combined.

The general population may also be exposed to asbestos fibres in air, beverages, drinking-water, food and pharmaceutical and dental preparations & consumer use of asbestos-containing products.

At present, it is not possible to assess whether there is a level of exposure in humans below which an increased risk of cancer would not occur.

IARC

1976

The Lancet EditorialDecember 6, 2008

Mesothelioma mortality in developed countries have increased over the last 20 years, according to high rates of exposure to workers in the 1960s. 125 million people are currently at risk from asbestos and there are about 90,000 asbestos-related deaths per year.

Dr. RA Lemen

Mesothelioma – Estimated 43,000 die annually

Worldwide Age Standardized Mesothelioma Incidence Rates/100,000 for Males, 1998-2002

Dr. RA Lemen

Time trend in age-adjusted mortality rate for pleural and peritoneal mesothelioma, worldwide, 1994-2008

From: Delgermaa et al, 2011. Global mesothelioma deaths reported to the World Health Organization between 1994 and 2008. Bull World Health Org, 89:716-724C.

Dr. RA Lemen

World Asbestos Disease Estimates Mesothelioma

Highest / 100,000

Italian Genoa Province – 5.8West Cape Australia –

4.7Northern Yorkershire – 4.2Northern Ireland – 4.0Scotland – 3.6

U.S. - 0.9 [pleural only]M/F

Mean AgeWorldwide = 4.93.6:1 70.0UK highest = 17.8 5.7:171.3Australia = 16.55.4:1 71.3Italy = 10.3 2.4:171.2

U.S. = 5.04.2:1 72.8

Sources: Stayner, Welch, Lemen, 2013; Delgerman et al, 2011; Bianchi & Bianchi, 2007

Dr. RA Lemen

46

Mesothelioma IncidenceStayner L, Welch LS, Lemen R, 2013

Dr. RA Lemen

Main Asbestos Fiber Types of Commercial Importance

Amosite - Brown Crocidolite-Blue & straight

Anthophyllitebrittle, white fibers

Chrysotile - White fine, silky, flexible

95% of all asbestos 5% of all asbestos consumed

straight, brittle fibers

Tremolite and Actinolite, Anthophyllite is found mainly as a contaminant in other minerals. RALemen

AMPHIBOLESThe Big Three made up about 5% of all asbestos

commercially used

Anthophylite Amosite crocidolite

While its evil cousin Tremolite isblamed as the toxic contaminate of chrysotile and thus makeschrysotile toxic.

TremoliteDr. RA Lemen

Anthophyllite Asbestos Earliest Used Form of Asbestos @2500 b.c.

R. A. Lemen, Ph.D. 50

1965 – Lung fibrosis with short latency

1974 – Lung Ca SMR 3.33 (95% CI: 1.44 - 6.57) No Mesothelioma

1989 – 6/14 mesothelioma reported in Finland with anthophyllite predominate

1994 – 4 mesothelioma among 736 anthophyllite miners

and millers Mined Finland 1915 - 1975 Japan 1883 - 1970

Main uses in cement, insulation, roofing material

First Disease Findings

Amosite Asbestos Asbestos Mines of South Africa

(cummingtonite-grunerite asbestos) First mined @ 1919

1964 – First clinical study - Asbestosis prevalent, few lung cancer, no mesothelioma.

1972 – First Cohort Study – 933 males in New Jersey plant reported 5 mesotheliomas observed (2 pleural; 3 peritoneal)

R. A. Lemen, Ph.D. 51

[Selikoff IJ, Hammond EC, Churg J, 1972. Carcinogenicity of Amosite Asbestos. ArchEnviron Health. 25, Sept., 183-186]

Patterson , NJ

Crocidolite Asbestos First exported @1893 from S. Africa

1960 – First case series of mesothelioma – reported 33 cases (22 males, 11 females; ages 31 to 68) all but one exposed to crocidolite

R. A. Lemen, Ph.D. 52

1988 – First Cohort Study in Australia at Wittenoom –reported high mesothelioma rate

1978 – First epidemiology study of workers of gas mask workers

R Lemen Photo S. Africa 2009

CHRYSOTILE ASBESTOS• FIBERS SEPERATING FROM THE MINERAL

R. A. Lemen, Ph.D. 53

Chrysotile represented over 95% of all asbestos in commercial products.

Chrysotile is the only type of asbestos mined today.

What do we know about the onlyAsbestos type still being Sold?

R. A. Lemen, Ph.D. 54Dr. R

A Lemen

Chrysotile asbestos discovered in Quebec in 1860.

Mining started in 1878.

Canada had world’s first commercial mines.

Canada no longer mines

asbestos.

White Gold Pioneers: Asbestos Mining

• (Asbestos mine at black Lake @ 1890s – White Gold Pioneers: Asbestos Mining: McCord Museum)

Canadian Chrysotile Asbestos Mine at Black Lake @ 1890s McCord Museum. Dr. RA Lemen

Chrysotile production began in Russia as a result of its discover in 1712 in the Ural Mountains (Carroll-Porczynski, 1956).

Russian Asbestos Mine

Russian Asbestos Bagging

Man Standing in Asbestos U.S. Public Health Service Photos - 1994

Russia commands 60% of the world market

Dr. RA Lemen

What happens when we breath in asbestos fibers?

Dr. RA Lemen

Nose Filters out fibers >100µ long

Cilia Clears mucus (and fibers) from lung

Free Alveolar Macrophages (FAMs): Phagocytize fibers within

lung

How does our body react to the presence of asbestos fibers?

Lung Ca

Mesothelioma

Dr. RA LemenAsbestosis

Bio-persistence

Amphiboles are much more bio-persistent in the lung than Chrysotile.

The amphibole contaminate of chrysotile, tremoliteremains in the lung longafter chrysotile has moved into other body areas like the pleura.

Dr. R.A. Lemen

Do All Asbestos Fiber Types React The Same Once Inhaled?

Chrysotile and Bio-persistence

Mesothelial cells have the unique characteristic of engulfing anything, whether a solid, liquid, or gas. Similarly, mesothelial cells phagocytize asbestos fibers. Source: Yamashita et al., 2013. J Clin Biochem Nutr; 53(1): 27-35.,

Dr. RA Lemen

0

5

10

15

20

25

30

35

40

45

50

1

No exp. <0.1 med >1.0 Asbestos Ex-posure in fibers/ml

9.2

17.9

46.3

OR

Rödelsperger et al, 2001. AJIM, 39:262-275

Multiple studies confirm, as exposures continue, relative risk of asbestos-related mesothelioma increase.

[OR = Odds Ratio]

Dr. RA Lemen

Where Does Mesothelioma OccurPleural Mesothelioma

Mesothelioma developsin the two layers of thepleura

Tumor then spreads to coversthe lung in a thick sack that squeezes and suffocates as it grows

Remaining Lung

Dr. R.A. Lemen

Where Does Mesothelioma OccurPeritoneal Mesothelioma

Dr. R.A. Lemen

So Is Exposure to Chrysotile Safe?

Dr. RA Lemen

65

FACTSToxicology and epidemiology

supportChrysotile

withincreased risk Cancer

[Stayner, Dankovic , Lemen. AJPH. 1996 Feb;86(2):179-86.]

Dr. RA Lemen

In human lung tissue, amosite fibers were greatest in number followed by chrysotile, crocidolite, tremolite/actinolite, and anthophyllite.

BUT

In mesothelial tissues, chrysotile fibers were 30.3 times more common than amphiboles.

Suzuki & Yuen, 2002 Asbestos fibers contributing to the induction of human malignant mesothelioma. Ann N Y Acad Sci. Dec;982:160-76.

Dr. R.A. Lemen

FACTS

CHRYSOTILE –Early Medical Findings

Dr. Cartier, mining company doctor, reported two cases of pleural mesothelioma, one with minimal asbestosis; the other with no asbestosis, among 4,000 asbestos workers seen at the Thetford International Clinic in Quebec.

R. A. Lemen, Ph.D.

67 Mesothelioma

1952

[Cartier P, 1952. Abstract of discussion. Arch Ind Hyg Occup Med: 5; 262]

R. A. Lemen, Ph.D.

From Cartier P, 1955. Some clinical observations of asbestosis in miners and mill workers. Arch Indust Health. 11: 204-207.

CHRYSOTILE Early Medical Findings

Cartier, reported among the 4000 workers between 1945 and 1953 – 128 with asbestosis

Thetford Mine Mill

1955

R. A. Lemen, Ph.D.

69

CHRYSOTILE - early Medical

Findings

Thetford medical officer informs a visiting British industry physician that he had observed 126 workers

with pleural plaques and that 93% of them had signs of asbestosis.

The communication was kept confidential.[From Greenberg M, 2005.

1963

CHRYSOTILE Early Medical Findings

Rossiter reported a high prevalence of various abnormal

radiological changes among miner and

millers from Thetford-Mines.

70

R. A. Lemen, Ph.D.

1972

R. A. Lemen, Ph.D.

71

Results of an epidemiological study of an 1891-1920 birth cohort of

Quebec chrysotile miners in Canada published.

Excess mortality was found in the Canadian miners.

CHRYSOTILE - Early Epidemiology

From: Nayebzabeh et al. 2001.

1980

Canadian Miners

R. A. Lemen, Ph.D.

72

Follow-up of the original study found the SMR of lung cancer rose from 1.25 to 1.39, and deaths from mesothelioma also increased.

FromNayebzabeh et al. 2001.

CHRYSOTILE-Early

Epidemiology

1993

Thetford-Mines (Québec)]

  

International Labour OrganizationCHEMICAL DATA SAFETY CARDS

Asbestos, chrysotile ICSC: 0014 White asbestos Serpentine chrysotile CAS No:2001-29-5 RTECS No: CI6478500 UN No: 2590 EC No: 650-013-00-6 Mg3Si2H4O6 / Mg3(Si2O5)(OH)4

Molecular mass: 554IPCS

InternationalProgramme onChemical Safety Prepared in the context of cooperation between the International Programme on Chemical Safety and the European Commission © IPCS 2004

R. A. Lemen, Ph.D.73

What Is The Scientific Consensus About the One Asbestos Fiber Type Still Mined & Sold?

International Labour OrganizationCHEMICAL DATA SAFETY CARDS

Effects of long-term or repeated exposure -

The substance may have effects on the lungs, resulting in pulmonary fibrosis and mesothelioma. This substance is carcinogenic to humans.

The recommendations on this Card also apply to other forms of asbestos.

Avibest C, 7-450 asbestos, Calidria RG 144, Calidria RG 600, Calidria RG 100, Hooker no.1 chrysotile asbestos, K 6-30, Plastibest 20, RG 600, 5RO4, Sylodex, Cassiar AK, Cassiar A 65, Fritmag, P 3-50 and P 4-20 are trade names.International programme on chemical Safety Prepared in the context of cooperation between the International Programme on Chemical Safety and the European Commission

© IPCS 2004R. A. Lemen, Ph.D.

74

International Labour OrganizationCHEMICAL DATA SAFETY CARDS

These findings along with the results of the experimental studies leave no doubt that the scientific evidence supports the carcinogenicity of chrysotile alone in the induction of mesothelioma

The debate, as it applies to human exposure to pure chrysotile containing products is academic, at best, as there appear to be few if any pure chrysotile deposits unequivocally identified or reported in the scientific literature

Nor have any products purported to contain only chrysotile been conclusively shown to contain uncontaminated pure chrysotile.

R. A. Lemen, Ph.D.75

International Labour OrganizationCHEMICAL DATA SAFETY CARDS

However, if and when such deposits or products are identified, the fact remains that chrysotile alone can cause mesothelioma, as demonstrated in this lecture, when applying the existing scientific knowledge into the parameters of the Hill Causation Model

The exact potency of chrysotile, per dose to cause mesothelioma, when compared to the amphiboles, remains controversial and has been discussed in various other papers (Stayner et al, 1976; Hodgson JT & Darnton A., 2000; Landrigan et al, 1999 & IPCS, 1998)

However, even when potency, on a dose by dose basis, is considered the fact remains that chrysotile is capable

ofcausing mesothelioma and that no safe dose has beenidentified below which a risk of developing mesotheliomaexists. R. A. Lemen, Ph.D.

76

Scientific and Governmental Agencies conclude all commercial types of asbestos cause Mesothelioma

WHO EPA

Surgeon General of the United States

World Trade Organization

National Academy of Science

Rr. RA Lemen

IS POLITICAL

NOT SCIENTIFIC

R. A. Lemen,.

78

CHRYSOTILE ASBESTOS CONTROVERSYOVER MESOTHELIOMA

Science is the Art of Disproving Hypotheses

Dr. RA Lemen

White Swan Hypothesis:

Chrysotile does not cause mesothelioma

Dr. RA Lemen

The White Swan Hypothesis:Chrysotile does not cause mesothelioma

Studies that conclude that exposure to chrysotile causes mesothelioma

Is disproved by the finding of Black Swans:

Dr. RA Lemen

82Lenters et al, 2011. A meta-analysis of asbestos and lung cancer: is better quality exposure assessment associated with steeper slopes of the exposure-response relationships? Env Health Perspect, Nov; 119(11); 1547-1555.

Potency Between Amphiboles &

Chrysotile “Potency differences for predominantly chrysotile versus amphibole asbestos-exposed cohorts become difficult to ascertain when meta-analyses are restricted to [in] studies with fewer exposure assessment limitations.”

Dr. RA Lemen

Arguments

regarding

Chrysotile Asbestos

are driven by

Economics

not ScienceDr. RA Lemen

73

Header Goes HereGraham W. Gibbs and Geoffrey Berry

Chapter 4. Epidemiology and Risk Assessment2008

`EPIDEMIOLOGY AND RISK ASSESSMENT 107

replaced by acetone clearing. When modern quality control methods and sample density rules were introduced, the fiber concentration became 3200 f/mL.

Host and Environmental Considerations

The third category of parameter influencing risk estimates includes smoking, as well as other host and environmental variables. Selikoff et al. (1968) first reported a synergis tic effect between asbestos and smoking in the causation of LC, and this observation was confirmed by Berry et al. (1972). In a later follow-up Berry et al. (1985) found that "overall nonsmokers have a RR of LC due to asbestos exposure 1.8 times that of smokers." More recently, Liddell (2001a) concluded, "the RR of LC from asbestos exposure is about twice as high in nonsmokers as in smokers." His conclusion was not without controversy since in another review, Lee (2001) stated, "asbestos exposure multiplies risk of LC by a similar factor in nonsmokers and smokers." The work of Liddell (2001a) was extended by Berry and Liddell (2004) who concluded, "The excess RR for LC from asbestos exposure is about three times higher in nonsmokers than in smokers," and "If interactions are pres ent the RR from exposure changes only slightly between light and heavy smokers, but is higher (in the former than the latter). The RR estimated from epidemiological studies of a mixed population of nonsmokers and smokers applies to smokers." In some areas, radon in homes is elevated. While debated, radon and radon daughters are now established carcinogens (Darby et aI., 1998). This factor has not been generally taken into account in asbestos risk estimations. The effect of not taking confounding, or modifying factors into account could lead to either an underestimation or an overestimation of the risk ascribed to asbestos, but an overestimation of risk is more likely, since in practice coexposures tend to correlate positively.

_ Thresholds of Risk

There are levels of exposure below which asbestosis resulting from exposure does not occur, but estimates of thresholds differ. It is debated whether there is a threshold below which there is no increase in risk of LC and MM (Browne and Gibbs, 1998). A lin ear dose-response relationship between RR and exposure is often used as "a widely accepted and scientifically reasonable compromise rather than an established scientific principle" (HEI-AR, 1991). Hodgson and Darnton (2000) noted that "direct statistical confirmation of a threshold from human data is virtually impossible," and used a non threshold model. Browne (2001) criticized these authors, while Liddell (2001b), noted, "nonlinearity is extremely difficult to detect epidemiologically, especially at low levels of exposure." While it might seem prudent for regulators to assume a linear risk through zero in the absence of proven evidence, it is argued that such an assumption is contrary to what is known about the interaction of asbestos with the respiratory tract. For example, not all fibers in the air are inhaled or penetrate into the lung. It is necessary for fibers to get to the pleura to cause disease, some fibers dissolve and are eliminated and the majority deposit proximally in the respiratory tract. Fibers are coated by biological fluids that may serve to protect the lung. There are DNA repair mechanisms that provide protection in the event genetic damage occurs. Taken together, it is highly improbable that there is a finite risk at close to zero exposure and it seems reasonable to conclude that thresholds exist.

It is necessary for fibers to get to the pleura to cause disease . . .

Even the Scientists That Negate the Role of Chrysotile

Have to Admit:

Dr. R.A. Lemen

Chrysotile Asbestos

Obscure the Facts

Create Doubt Chrysotyle producers

Dr. R.A. Lemen

However

In a profit-driven frenzy, the asbestos alchemists peddle their toxic wares to ill-informed governments and consumers. But blow away their smoke, remove their mirrors, and the truth emerges for all to see:

All forms of asbestos are deadly, there is no safe concentration of exposure identified, industry propaganda is unreliable and the continued to use of chrysotile is unconscionable.

From: Lemen RA, 2008. Smoke and Mirrors: Chrysotile asbestos is good for your – Illusion and confusion but not fact. In: India’s Asbestos Time Bomb, Eds. David Allen and Laurie Kazan-Allen, IBAS, London, September.

Dr. RA Lemen

Low Dose Exposure How Low Does It go!!!!

Asbestos

&

MesotheliomaAre Low and Background Exposures

Safe?

Dr. RA Lemen

Background Exposures

do not cause Mesothelioma

Background Exposures

have not been proven to cause

Mesothelioma

Rather

Dr. RA Lemen

What We Do Know AboutBackground Exposures

+

Background Exposures

Occupational Exposures

=Increased

Risk(total dose)

Dr. RA Lemen

91

The Helsinki Consensus Report on Diagnosis and Attribution

Scand J Work Environ Health 1997; 23: 311 – 318

The following points need to be considered in the assessment

Mesothelioma can occur in cases with low asbestos

exposure.

However

Very low background environmental exposures carry

low risk.

Dr. RA Lemen

92

Non-Mutagenic AgentsFor non-mutagenic agents it is assumed there is some

level that is incapable of causing harm otherwise known as a threshold.

casesThreshold

exposure

Number of cases

Dr. RA Lemen

Most oncogenes are mutations . . .

The existing evidence suggests that asbestos fiber-induced carcinogenicity involves both mutagenic and nonmutagenic mechanisms or both.

From: Huang SXL et al, 2011. Role of Mutagenicity in asbestos fiber-induced carcinogenicity and other diseases. J Toxicol Environ Health, Part B. 14: 179-245.

Dr. RA Lemen

Conclusions on thresholds for non-mutagenic agents

cannot be applied for mutagenic agents.

Asbestos Causes Mutations

Dr. RA Lemen

{Dose

Response

The more someone is exposed, the greater the risk

Linear Models of Dose Response have been around for years and are generally accepted (NRC, 1984)

Mesothelioma is caused by asbestos fibers reaching the pleura – the location of target cells for mesothelioma

Richard A. Lemen, Ph.D.Assistant Surgeon GeneralUSPHS (Ret.)

Dr. RA Lemen

{Dose

Response

Exposure

Dis

ease

Linear Dose Model

Dr. RA Lemen

Non-Linear Dose Response Curve

LOW DOSE THRESHOLD

HIGH DOSELOW DOSE

NUMBER OF CASES OF DISEASE

EXPOSuRE

UnknownSusceptible

?

Dr. RA Lemen

The Higher the Exposure the Shorter the Latency

The Lower the Exposure the Longer the Latency

DoseFiber/yrs

Latency in Years0 10 20 30 40 50+

25

1000

2000

Dr. RA Lemen

The data for the most heavily exposed people as well as those for the groups with the lowest exposures are exactly the same as would be expected, if an inverse correlation exists between the intensity of exposure to asbestos and the duration of latency period.”Bianchi, Latency periods in asbestos-related mesothelioma of the pleura, European Journal of Cancer Prevention, VOL. 6, 1997, p. 164, Supp. Ex. 17

Each Exposure Shortens The Latency Period For Mesothelioma

“Latency time was also dependent on exposure, varying from 29.6 years for insulators (with the highest exposure) to 51.7 in women with domestic exposure.”

Hillerdal, Mesothelioma: cases associated with non-occupational and low dose exposures, Occup Environ Med 1999; 56: 505-513, p.509

Dr. RA Lemen

{

Low Dose Exposure

You do not need to be exposed to a lot of asbestos to get mesothelioma.

Chrysotileasbestos

Dr. RA Lemen

{

Low Dose Exposure

Richard A. Lemen, Ph.D.Assistant Surgeon GeneralUSPHS (Ret.)

In a person with multiple exposures to asbestos, ALL of them contributed to increase the risk of developing mesothelioma.

+

=

+

=

+

Dr. RA Lemen

Low Dose Exposure

Richard A. Lemen, Ph.D.Assistant Surgeon GeneralUSPHS (Ret.)

You cannot isolate any particular exposure to asbestos and hold it HARMLESS in the causation of mesothelioma.

+

+

=

+

Dr. RA Lemen

103

Mesothelioma has occurred following short term asbestos exposures of only a few weeks, and can result from very low levels of exposure.

Dr. RA Lemen

Documented cases of asbestos-related diseases have occurred when the only apparent exposure has been shaking and laundering of the clothing of an exposed worker.

Take-home exposures

AmphiboleAsbestos

Dr. RA Lemen

105

Dr. RA Lemen

United States Occupational Standard For Asbestos Does Not Eliminate Risk

Department of Labor, Occupational Safety and Health Administration, 29 CFR Parts 1910, 1915 and 1926, Occupational Exposure to Asbestos, Final Rule, Federal Register, Vol. 59, No. 153, August 10, 1994

The 0.1 f/cm3 level leaves a remaining significant risk.

3-4/1,000

Dr. RA Lemen

106

Lifetime Risk of Mesothelioma at Low Cumulative Doses of Asbestos

0.0004 fibers/cm3 (Median Dose) X 73 years lifetime exposure

= 0.0292 f/cc/years of exposure

(9 per million lifetime risk)

Breslow, L, (Chair), et al., 1984. Asbestiform Fibers –Nonoccupational Health Risks, National Academy of Sciences; Table 7-2.: 212 .

0.002 fibers/cm3 (High Dose) X 73 years lifetime exposure

= 0.146 f/cc/years of exposure

(46 per million lifetime risk)

Dr. RA Lemen

Iwatsubo Case Control Study on Dose-Response at Low Levels

Asbestos Cases ControlsOR 95% CI

ExposureIntermittent

<0.5 6698 1.1 (0.8-1.7) .05-0.99 19 8

4.0 (1.7-9.7) 1-99.9 48 21

4.0 (2.2-7.2) ≥ 10 17 5

5.9 (2.1-16.7)

Continuous

<0.5 11 111.9 (0.8-4.8)

0.5-0.99 10 44.6 (1.4-15.4)

1-9.99 32 69.2 (3.7-23.1)

≥ 10 32 5 11.3 (4.1-30.7)

Am J Epidemiol Vol. 148, No. 2, 1998 Dr. RA Lemen

cases controls OR 95% CICumulative exposure up to end of observation (fiber years)

not exposed 1167 1>0-0.15 14 12

7.9 2.1-30.00.15-1.5 38 25

21.9 5.7-83.81.5-15 4616 47.1 11.5-19.3>15 16 5

45.4 8.1-257

Cumulative exposures up to 10 years before end of observationnot exposed 1167 1>0-0.15 15 13

7.9 2.1=29.50.15-1.5 39 24

24.0 6.2-93.01.5-15 4516 51.8 12.4-216>15 15 5

42.6 7.3-249

Cumulative exposure up to 20 years before end of observationnot exposed 1468 1>0-0.15 15 13

9.2 2.4-35.0>0.15-1.5 44 24

20.5 5.8-72.6>1.5-15 40 16

32.2 8.5-122>15 12 4

43.8 7.1-269

Rödelsperger et al, 2001. AJIM, 39:262-275

Mesothelioma & Exposure – German Hospital-Based Case-Contorl Study

Dr. RA Lemen

109

kk

Asbestos and Man-Made Vitreous Fibers as Risk Factors for Diffuse Malignant Mesothelioma: Results From a German Hospital-Based Case-Control Study, Claus Rodelsperger, DSC, Karl-Heinz Jockel, PhD, Hermann Pohlabeln, MSC, Wolfgang Romer, MA, and Hans-Joachim Woitowitz, MD, American Journal of Industrial Medicine 39: 262-275 (2001)

…our results confirm the previously reported

observation of a distinct dose-response relationship even at levels of cumulative exposure below 1 fiber year.

(p. 262)

Conclusion of German Study

Dr. RA Lemen

Initial vs. Continuous Exposure

Asbestos is a complete carcinogen,

Which means

It can both initiate and promote cancer

Therefore

Persistence exposure after initial exposure can not be discounted or irrelevant.

Tomatis et al, 2007. Int J Occup Environ Health, 13:64-69; Governa et al, 1999. J Toxicol Environ Health A, Nov. 12, 58(5): 279-287.

111

In Conclusion - Asbestos Diseases Are Not Declining in

Most Parts of the World?

Age-adjusted rates of death are increasing in most Industrialized countries, but is now slowing in a few.

They are still rising in Europe and dramatically increasing in Japan.

Little data in developing World. However, it may be too soon to see an increase in many of the countries due to the long latency of the Asbestos-induced cancers.

Asbestos and Asbestos-related diseases remain a global health problem.

Dr. RA LemenDelgermaa et al., 2011 & Lemen, 2012

In Conclusion -Is Production and Consumption Decreasing?

Chrysotile is the only form being commercially exploited

Use decreased by Bans and Regulations have severely restricted exposures in those with them

Brazil, China, Kazakhstan, and Russia still exploit chrysotile’s use

Consumption Increasing in developing countries Dr. RA Lemen

113

Chrysotile is not SafeEvidence currently suggest a lower risk for

mesothelioma than from equal doses of amphiboles, but as better exposure data

becomes available this difference becomes less.

Asbestosis and lung cancer risks are similar.

There is no form of safe asbestos.Dr. RA Lemen

In Conclusion –

114

In Conclusion -Have High Exposures Been Eliminated?

High exposures still occur in developed countries

Very high exposures in

developing world, although

data is limited

Dr. RA Lemen

In Conclusion - Iceland first banned asbestos in 1983, now more than

50 countries have bannedThe pace of bans has slowed over the past decade with some withdrawing their bans and other have

extended the timeframe for implementation.This is an indication of the success of

the pro-chrysotile lobby

9 of 10 of the most populous countries, all major past or present users of Asbestos have yet to

adopt bans.

World coverage of asbestos bans remains low.Dr. RA Lemen

116

What Should We Expect for the Future?

After bans enacted asbestos-related diseases will

begin to decrease after 10-20 years,

However,

They will never be eliminated entirely until all asbestos is eliminated or under control.

With greater consumption of asbestos in developing countries asbestos-related

diseaseswill increase if exposures are not

eliminated.

In Conclusion -

Dr. RA Lemen

Quote From: Marty S. Kanarek, 2011. Mesothelioma from chrysotile asbestos: Update. AEP, 21(9): 688-699, September.

117

“Thus, it is reasonable to assume that the total numbers of cases that are documented

Is just the tip of the iceberg

of a potential world-wide environmental cancer epidemic of mesothelioma from

asbestos, including chrysotile asbestos”

Dr. RA Lemen

Dr. RA Lemen

What must we do?To make a world-wide ban a reality --Dr. RA Lemen