Transcript arsenic3 - Harvard University Department of Physics

Chronic Arsenic
Poisoning at Low Doses:
Some recent epidemiological
findings and implications for
arsenic exposure
Lecture at
London School of
Tropical Medicine and Hygienc
12.45 pm, Thursday December 6th 2001
by
Richard Wilson
Mallinckrodt Research Professor of
Physics
Harvard University
Problems with NAS
report (2001)
Uses Taiwan ecological data
as a basis
Straight line to the national
incidence
Ignores all other data
Data in tables, in graphs
and in text are different
“it is wise to compare the
results of the assessment
with the real world”
(2 pages out of 188)
ARSENIC
Metal
Molecular weight 74.92
Melting Point 8170C
Specific Gravity 5.73
Many compounds and minerals
• Arsenic has been used for over
3000 years
• As2O3 ARSENLITE
• by roasting As2S or FeAsS
• As2S3 ORPIMENT
• PbHAsO4 SHULTENITE
• KH(ASO2)2 Fowler’s Solution
• CH3AsO(ON2)2
• CH3AsO(OH)ONa
• Pesticides with various names
Common Sources
Non-Ferrous Smelters
Coal Burning
Cotton Gins
Cigarette smoke
Early Information
(pre 1986)
Acutely Toxic
to Rodents and People
Used as Medicine
Fowler’s solution 1% in alcohol
Cure for Syphilis
(recent) cure for leukemia
Early Information
(pre 1986) contd.
1888 Skin lesions and Cancers
1897 Lung cancer from pesticides
1920s lung cancer from smelters
1950s angiosarcoma from
pesticides
BUT
no cancers in rodents
Early Misconception
(pre 1986)
Rodents dont get cancer,
therefore people wont
Inhalation a special case
with non-linearity
(but Zeise and I contested that)
Preliminary warning
• TSENG et al found skin Tumors
in TAIWAN
• BUT
• They appeared to follow a
threshold relationship.
THE GREAT
SURPRIZE
In 1986 C J Chen
And collaborators reported
internal cancers in the same area
of Taiwan
IGNORED FOR 5 YEARS!
Why?
Only a Chinese study
(as bad as the Russians?)
1990 Allan Smith
1991 Byrd,Lamm Wilson
took him seriously
THE GREAT
SURPRIZE
The internal cancers seemed to be
linear with dose and the risk is
huge.
BUT:
An ecological study
and
Only in one location and there
might be another cause
THE VINDICATION
CHILE
ARGENTINE
INNER MONGOLIA
BANGLADESH
WEST BENGAL
NO PREVIOUS STUDY
INCONSISTENT
LOW DOSE LINARITY
the regulatory default
• Crump Guess and Peto of 1975
CRITICAL ISSUES
FOR LINEARITY
• The POLLUTANT ACTS
• in the same way as
• WHATEVER ELSE
INFLUENCES THE
• CANCER RATE
• CANCERS CAUSED BY
• THE POLLUTANT
• ARE INDISTINGUISHABLE
FROM OTHER CANCERS
THE ARGUMENTS APPLY
TO
ANY CARCINOGEN
e.g
ARSENIC
Arsenic risk
• Skin lesions may be unique
• There may be a threshold at
• 50 -150 ppb
• (Data from Taiwan and also
from Inner Mongolia)
• BUT
• Internal cancers may be
different
Toxicologists like
Thresholds
• Few (if any) toxicologists
address the Peto argument.
• ?? Threshold for bladder cancer
and not for lung cancer??
• ED01 data on 2 DAA
• linear for liver
• threshold for bladder
• anticarcarcinogen for others
• WHY IS THERE SO MUCH
CANCER IF EVERYTHING
HAS A THRESHOLD?
Many Legislators still
want
< 1 in a million!
Where does this leave regulation
of arsenic?
Limits should be 5 ppt!
(not practical)
Arsenic risk
• For internal cancers
• At 500 ppb Measured Risk
• (Chile) is 10%
• If linear,
• risk is one in a million
• at 5 parts per trillion!!
• “background” is about
• 2 parts per billion
MY CONCLUSION
(REPEAT OF 20 YEARS AGO)
IT IS NOT POSSIBLE
TO REGULATE A
ONE IN A MILLION
LIFETIME RISK
CONSISTENTLY
• ATTEMPTS TO DO SO
• ARE
• ARBITRARY
• and
• CAPRICIOUS
How should we dispose
of ARSENIC? (contd)
EPA says that Arsenic need not be
put in a secure landfill.
BUT
If the proposed EPA regulations
for Yucca Mountain are applied
No water system in USA and
not much agricultural land
would be in compliance.
Can One Prove a
threshold?
MAYBE
if one focusses on the right
question:
Similarity to
Asbestos
Benzene
Can One Prove a
threshold? (2)
MEREWEATHER”S
QUESTION (1937)
Is it ASBESTOS or is it the
ASBESTOSIS that is
caused by asbestos that
causes the lung cancers?
If the former LNT is likely
If the latter LNT is less
likely
Can One Prove a
threshold? (3)
There semes to be a
threshold for
SKIN LESIONS
(should be studied further)
Are lung cancers more or
less likely if there are skin
lesions?
(Allan Smith may tell us)
Can One Prove a
threshold? (4)
Are the lung cancers really
indistinguishable from
background cancers?
If NOT Peto’s argument
does not apply
Try DNA matching on lung
tumor samples.
Similarly for asbestos cancers, radiation
leukemias etc.