Society for Risk Analysis
New England Chapter
PRESIDENTS (2006-2007)
MICHAEL HUTCHESON
Massachusetts Department of
Environmental Protection, Office of
Research and Standards
P:617 292-5998
F:617-556-1006
michael.hutcheson@state.ma.us
PAST PRESIDENTS
JO ANNE SHATKIN
The Cadmus Group
P:617 673-7161
F: 617 673-7001
jshatkin@cadmusgroup.com
TOM ANGUS
Massachusetts Department of
Environmental Protection, Office of
Research and Standards
P:617 292-5513
F:617-556-1006
Thomas.Angus@state.ma.us
SECRETARY
KAREN VETRANO
TRC Environmental
P. 860-298-6351
F. 860-298-6380
kvetrano@trcsolutions.com
TREASURER
ARLENE LEVIN
Eastern Research Group, Inc.
P. 781-674-7369
F. 781-674-2851
Arlene.Levin@erg.com
WEBMASTER
PAUL LOCKE
Commonwealth of Massachusetts,
Department of Environmental
Protection
P. 617-556-1160
paul.locke@state.ma.us
NEWSLETTER
SUSAN MATKOSKI
AMEC
P. 978-692-9090 x311
F. 978-692-6633
sdmatkoski@comcast.net
susan.matkoski@amec.com
SPONSORS
CDM (Camp Dresser & McKee Inc.)
BENEFACTORS
TRC Environmental
Corporation
Presidents’ Message - August 2006
Dear SRA-New England Members:
Summer has almost gone and autumn is near, as is or next season of meetings. I
am pleased once again to be leading this group for the year and already am
welcoming the opportunity it brings to interact with many of you again more
frequently and to meet new individuals as I plan out this year’s talks. We are
starting out the year on a sound financial footing thanks in large part to the efforts
of previous President Igor Linkov and to the stewardship of Jo Anne Shatkin and
Tom Angus, last years co-Presidents. There is a lot of behind the scenes
organizational effort that goes on to ensure that the seminars take place, so I
would like to thank Jo Anne and Tom for their efforts last year and a stimulating
series of speakers.
We are fortunate to have secured a new meeting location on the MIT Campus.
Our meetings will take place in Building E51–085 (campus map at
http://web.mit.edu/history/www/CampusMapBldg51.html). It is along Memorial
Drive, right across the street from the building where our group met regularly
many years ago, it is convenient to the Kendall Square Red Line T station, and
parking should be available on street or the MIT lots. Many thanks to CDM who
have graciously let us use their conference facilities over the last few years.
We are fortunate to have Dr. Dale Hattis of Clark University as our first speaker
of the year on Wednesday, September 13, 2006. We’ll gather as usual at 4:30 –
5 pm for light refreshments with the talk from 5-6 pm. Many of you are familiar
with Dale as one of the first members of this organization and a long and loyal
participant. He always is innovative and on the leading edge of risk assessment
issues. As you will see from his presentation abstract below, he is once again
providing us with useful and stimulating discussion matter.
Please mark your calendars with the fall meeting dates: 9/13, 10/11, 11/15 and
12/13. I welcome volunteers to give presentations so please don’t hesitate to
contact me or with suggestions for speakers or topics.
I look forward to seeing you on the 13th.
With best wishes,
Michael Hutcheson,
President
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Society for Risk Analysis
New England Chapter
SRA-NE September Seminar
13 September 2006
5:00 P.M.
4:30-5:00 PM Social gathering, light snacks
5:00–6:00 PM Program
Building E51, Room 085, MIT Campus
Cambridge, MA
Dr. Dale Hattis
And Coauthors
N. Rahmioglu, P. Verma, M. Kozlak, and R. Goble
Clark University
Research Professor, George Perkins Marsh Institute
Worcester, Massachusetts
A PRELIMINARY OPERATIONAL CLASSIFICATION SYSTEM FOR NONMUTAGENIC MODES OF ACTION FOR CARCINOGENESIS
Summary: In earlier work we analyzed age-related differences in sensitivity to mutagenic carcinogens. The current project seeks
eventually to create a similar analysis for non-mutagenic modes of action. However “non-mutagenic modes of action” comprise a
diverse set of processes that are likely to contribute to carcinogenesis in ways that could have divergent implications for age-related
changes in susceptibility. Therefore before attempting any quantitative analysis, we believe it is prudent to develop a preliminary
classification system to distinguish groups of modes of action that basic theory might suggest are likely to have different implications
for age-related differences in susceptibility.
The system proposed here is far from the first of its type. However ours has the distinction of being a classification of modes of action
rather than of chemicals themselves. Our variation allows, in principle, for the same chemical to have more than one “mode of action”,
as we think is likely in many cases.
Briefly, our categorization elaborates a classical tripartite division of the overall cancer process:
• Pre-initiator or co-initiator modes of actions [e.g. induction of enzymes that activate parent chemicals to more DNA reactive forms
such as ethanol induction of CYP2E1, increasing susceptibility to vinyl chloride, and expansion of the numbers of potential target stem
cells that are susceptible to transformation (this may be the result of exposure to some endocrine-active agents during gestation)].
• Promoter modes of action [e.g. increases in the replication rate or decreases in the death/differentiation rate of “initiated” relative to
normal stem cells. This can take the form of a reduction in the growth suppression exerted by normal neighboring cells on initiated
cells via the transfer of inhibitors via “gap junctions”].
• Progressor modes of action, [e.g. facilitation of the growth/spread of fully transformed cells--by inhibition of normal suppressors of
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Society for Risk Analysis
New England Chapter
angiogenesis, inhibition of growth repression; or impairment of immune surveillance].
Theory suggests early-life relative susceptibility for the first of these groups, and late-life relative susceptibility for the third and
probably also the second group [for example, the PPAR-alpha ligand WY-14,643 has a much stronger carcinogenic promotion effect
for rat liver when given to older (15-20 month) rats than when given to younger (2-7 month) animals]. In addition, we propose to add a
fourth group:
• Inherently multi-phase modes of action. Tentatively we include in this category generic mitogenic stimuli including the regenerative
proliferation that occurs following gross cell killing. This is because the enhanced replication of stem cells needed for tissue
replenishment is likely to both increase the number of mutations created for all mutagenic transitions in a multi-stage cancer process,
and allow the expression of any relative growth advantage attributable to intrinsic characteristics of cells with “initiating” mutations.
We think it is a favorable time to elaborate this system in part because several relatively new experimental tools have become available
that can help rule in or rule out specific processes as contributors to specific carcinogenic responses. These include
• “Knockout” mice derived from a congenic “wild type” mouse that has identical genes except for a normal copy of the one removed or
inactivated. These have recently been used to establish the role of gap junction inhibition in liver cancer promotion by phenobarbital
but not by the “peroxisome proliferator” Wy-14,643.
• A variety of initiation-promotion-progression model systems that can be used to probe the age-dependent sequence of actions of
specific agents in tumorigenesis in liver, skin, intestinal epithelium, and mammary tissue. The value of these is enhanced by
sophisticated modeling of the induction and growth of initiated clones. This sometimes yields unexpected results such has the findings
of enhanced or prolonged initiation by tetrachloro-dibenzo-dioxin and phenobarbital. Likely mechanisms for such phenomena involve
changes in the efficiency with which apoptosis is triggered following DNA damage following exposure to classical mutagenic agents.
Overall there is considerable reason for optimism that newer insights into the molecular biology of cancer will lead to improved risk
assessment modeling of the contributions of chemicals to carcinogenesis via different and sometimes multiple modes of action at
different stages of the life cycle.
Biography: Dale Hattis is Research Professor with the George Perkins Marsh Institute at Clark University. For the past thirty years he
has been engaged in the development and application of methodology to assess the health, ecological, and economic impacts of
regulatory actions. His work has focused on approaches to incorporate interindividual variability data and quantitative mechanistic
information into risk assessments for both cancer and non-cancer endpoints. Recent research has explored age-related differences in
sensitivity to carcinogensis and other effects, a taxonomy of different non-mutagenic modes of action for carcinogenesis with likely
differential implications for age-related sensitivity, PBPK modeling of acrylamide dose in rats and humans, and mechanism-based dose
response modeling of carcinogenic effects from ionizing radiation. He is a leader in efforts to replace the current system of uncertainty
factors with distributions based on empirical observations. He is a member of the Environmental Health Committee of the EPA Science
Advisory Board, and for several years he has served as a member of the Food Quality Protection Act Science Review Board. He has
recently been chosen to be the president-elect of the Dose Response Specialty Group of the Society for Risk Analysis. He has also
served as a member of the National Research Council Committee on Estimating the Health-Risk-Reduction Benefits of Proposed Air
Pollution Regulations. He has been a councilor and is a Fellow of the Society for Risk Analysis, and serves on the editorial board of its
journal, Risk Analysis. He holds a Ph.D. in Genetics from Stanford University and a B.A. in biochemistry from the University of
California at Berkeley.
*****************************************************************************************
POSITIONS (one this month)
Please note that the job-posting fee for this newsletter is $100 for recruiters/commercial and $50 for government
and nonprofit organizations. Please make your payment to Arlene Levin, NE-SRA Treasurer at Eastern Research
Group. Inc. 110 Hartwell Street, Lexington, MA 02421
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Society for Risk Analysis
New England Chapter
Risk Assessment Positions Available for Toxicologists and Exposure Scientists - Minnesota
Department of Health, August, 2006
Use your knowledge, skills, and experience to improve public health. Your work will include
investigating environmental hazards in Minnesota, improving risk assessment methods and practice,
and developing state air and water standards for public health protection. You will join a state program
that is involved in state, regional, and national environmental health science research and
consultation. Challenges that face Minnesota risk assessors include: integrating new exposure and
toxicological techniques, such as biomonitoring and genomics, into risk assessment
practice; investigating the toxicology of emerging environmental hazards, such as
perfluorochemicals; and incorporating early and late life considerations of toxicity and exposure into
risk assessment methods.
The Minnesota Department of Health has three open positions:
1) Research Scientist 3. Toxicologist or epidemiologist with laboratory experience in inhalation
toxicology to develop risk assessment methods for air contaminants and evaluate inhalation toxicity
studies. The position will consult with other scientists on environmental reviews and support the
development of human health-based standards for air and water contaminants. A Ph.D. level of
training or experience is preferred and a Master's degree plus experience is a requirement.
2) Environmental Research Scientist. Toxicologist or exposure scientist with experience or training in
risk assessment to develop human health-based standards for air and water contaminants. A Ph.D.
level of training or experience is preferred and a Master's degree plus experience is a requirement.
3) Research Scientist 2. Scientist with training in toxicology, exposure science, and risk assessment
to support the Department's work in developing human health-based standards for air and water
contaminants. A Master's degree plus experience is a requirement.
The State of Minnesota offers excellent health and retirement benefits, flexible work hours, and
rewarding careers.
The positions are posted at http://www.doer.state.mn.us/employment.htm (search for "research scientist").
Contact Pamela Shubat, Ph.D., Health Risk Assessment, Pamela.shubat@health.state.mn.us, 651-2014925, for detailed position descriptions or for more information about research scientist positions in
health risk assessment at the Minnesota Department of Health. Postings note that the Applicatin
Deadline is August 31, 2006. Flexibility in meeting the application deadline should be discussed with
Pam Shubat.
* * * * * * * * * * * * *
Pamela Shubat, Ph.D., Supervisor
Health Risk Assessment Unit
Division of Environmental Health
Minnesota Department of Health
625 N. Robert St.
St. Paul, MN 55155-2538
Telephone: (651) 201-4925
Fax: (651) 201-4606
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Society for Risk Analysis
New England Chapter
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DIRECTIONS TO MIT: Building E51, Cambridge, MA 02139, 617-452-6000.
From I-93 (north of Boston): Take Route 93 South into Boston. Take Exit 26A North 28 (Leverett
Circle, Cambridge). Once on exit, keep left & follow signs for Storrow Drive. At bottom of ramp, take
left at the lights. Go straight through next set of lights onto Storrow Drive West & get in the left lane.
Exit at government Center/Kendall Sq. exit. Take a right and drive across the bridge into Cambridge—
watch carefully to take the sharp right at the bottom of the bridge that will curve you around and onto
Memorial Drive West. Follow Memorial Drive for one block and take a right onto Wadsworth Street.
From I-93 (south of Boston): Take Route 93 North into Boston. Take Exit 26 (Storrow
Drive/Cambridge - Somerville). Once on exit, stay in the left lane & follow through the tunnel &
onto Storrow Drive. Get in the left lane. Exit at government Center/Kendall Sq. exit. Take a right
and drive across the bridge into Cambridge—watch carefully to take the sharp right at the bottom
of the bridge that will curve you around and onto Memorial Drive West. Follow Memorial Drive
for one block and take a right onto Wadsworth Street.
From Mass Turnpike (I-90): Follow I-90 east to the Cambridge/Brighton exit (exit 18). Following the
signs to Cambridge, cross the River Street Bridge, and take a sharp right onto Memorial Drive heading
east. Follow Memorial Drive for 2 miles - you’ll pass the Hyatt Hotel, the MIT dorms, go under an
underpass and then the campus with it’s domed buildings. After the underpass, get in the left lane and take
a left at the first stoplight onto Wadsworth Street (sign says Kendall Square).
Local: Driving from the Central Artery (Boston): From I-93 North, take the exit marked “Storrow
Drive West.” Storrow Drive follows the Boston side of the Charles River and MIT is on the Cambridge
side of the Charles. Stay in the left lane to take the Longfellow Bridge exit ramp on your left. Take a right
and drive across the bridge into Cambridge—watch carefully to take the sharp right at the bottom of the
bridge that will curve you around and onto Memorial Drive West. Follow Memorial Drive for one block
and take a right onto Wadsworth Street.
From the T:
Red Line The T stop that is closest to MIT is the Kendall Square/MIT stop, on the Red Line.
Green Line: If you are coming from the Green line, change to the Red Line at Park Street, heading towards
Alewife.
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Society for Risk Analysis
New England Chapter
Blue Line & Airport: From Logan International Airport, take the shuttle bus to the airport Subway stop, then
take the Blue Line inbound to Government Center. Change to the Green line Inbound to Park, then take the Red
line (towards Alewife) to Kendall.
Orange Line: Change from the Orange Line to the Red Line (towards Alewife) at Downtown Crossing.
Directions to the Building from the T:: To arrive at Building E51, exit the Kendall T (or the Marriott Hotel) on
Main Street, and walk toward the Charles River. Turn right onto Wadsworth Street (a FleetBoston Bank is on the
corner). Building E51 is one block in on the corner of Wadsworth and Amherst Streets. The entrance is at 2
Amherst. Enter through the revolving doors.
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