volume 119 | number 5 | May 2011 • Environmental Health Perspectives
Perspectives | Editorial
The National Toxicology Program (NTP) Center for the Evaluation
of Risks to Human Reproduction (CERHR) was established in 1998.
CERHR served as an environmental health resource providing in-
depth scientific assessments of effects on reproduction and develop ment
caused by agents to which humans are exposed. To our knowledge,
CERHR was the only resource of its kind, producing evaluations that
considered toxicity findings in the context of current human exposures
to derive “level-of-concern” conclusions. This qualita tive integration
step is what distinguished CERHR documents from more traditional
hazard evaluations prepared by other agencies.
When CERHR was established, the focus on reproduction and
development was appropriate because of a strong interest in these health
outcomes by the public, regulatory and health agencies, and the scien-
tific community. In addition, a rationale for creating CERHR was the
sense of a lack of uniformity across state and federal agencies in inter-
preting experimental animal studies of reproduction and develop ment.
CERHR was envisioned as a mechanism to apply a consistent strategy
for interpreting these data. Although this need remains, we believe that
the approaches used for CERHR evaluations should also be extended to
other important health outcomes. Many chemicals display more than
one type of toxicity, that is, carcinogens are often immuno toxicants,
and reproductive and developmental toxicants may influence many
endocrine-sensitive systems. A strict focus on reproductive and develop-
mental end points evaluated in the context of current human exposures
may not result in the most health protective levels of concern, and could
be confusing to the public. From a public health perspective, under-
standing the implications of current human exposures should include
consideration of all relevant health effects. Also, the NTP and the
broader toxicology community need to confront the challenging scien-
tific questions involved in utilizing information from the Toxicology in
the 21st Century initiative (Collins et al. 2008). To do this we need a
mechanism to systematically explore linkages between “toxicity path-
ways” and disease outcomes. To provide this, CERHR has spent the last
2 years in transition, laying the groundwork to become a more flexible
scientific analysis program, while continuing to be grounded and recog-
nized as a unique and important public health resource for the interpre-
tation of reproductive and developmental hazards to humans.
This evolution of CERHR is a response to the changing and
increasing demands on both the NTP analysis and research programs.
”What does it mean?” is a question we increasingly want to answer,
as our research and testing tools become more sophisticated and
mechanistically based. A change in CERHR’s scope will also bring its
work more in line with two recent initiatives established within the
NTP that have mandates to address a broad range of health effects
(Bucher 2008). In 2007 the NTP established a biomolecular screen-
ing program to administer its High Throughput Screening (HTS)
Initiative in collaboration with our Tox21 partners (Schmidt 2009).
This program takes advantage of technological advances in molecular
biology and computer science to screen for mechanistic targets or
“toxicity pathways” considered critical to adverse health effects. The
host susceptibility program was also established in 2007 to study the
genetic basis for differences in susceptibility that may lead to a better
understanding of how substances in our environment may be hazard-
ous to some individuals and not to others.
On 11–13 January 2011, CERHR launched its expanded role by
convening a diverse group of experts in toxicology, epidemiology, bio-
informatics, and endocrinology to assess the strength of the literature
linking selected environmental agents and exposures with diabetes and
obesity (NTP 2011). Consideration was given to an array of informa-
tion ranging from epidemiological findings and experimental animal
and mechanistic data to screens of toxicity and disease pathways using
HTS and literature curation methodologies. The use of several new
analysis tools revealed novel linkages between a number of environ-
mental agents and obesity or diabetes. These exciting findings are now
being collated for publication.
To fulfill its mission, the NTP is developing more innovative
and flexible approaches for information and data integration, both
across different programs within the NTP and across the different
types of data that are generated and utilized (i.e., mechanistic or
high throughput; “hypothesis-driven” animal studies of the type
undertaken by National Institute of Environmental Health Sciences
(NIEHS)-funded extramural grantees; and toxicology studies con-
ducted for the purpose of safety assessment). Recent experience
with bisphenol A highlights the public’s confusion and the waste
of scientific resources that can occur when these different types of
scientific literature are developed on parallel, but separate, paths
(Bucher 2009). The evolution of CERHR is an important part of
this information integration effort, and CERHR’s new role calls for a
new name: the Office of Health Assessment and Translation. Under
the leadership of Kristina Thayer, the Office of Health Assessment
and Translation will be the NTP focal point for the thoughtful and
deliberative integration of relevant information of all types in health
assessments for the protection of public health.
The authors declare they have no actual or potential competing financial
John R. Bucher
Linda S. Birnbaum
National Institute of Environmental Health Sciences
National Institutes of Health
Department of Health and Human Services
Research Triangle Park, North Carolina
John R. Bucher is the associate director of the NTP, an interagency
program headquartered at the NIEHS. Along with participating pro-
grams at the National Center for Toxicological Research, Food and Drug
Administration, and laboratories of the National Institute for Occupational
Safety and Health in Morgantown, West Virginia, and Cincinnati,
Ohio, the NTP is the nation’s principal comprehensive toxicology analysis,
research, and testing effort. Bucher holds a Ph.D. in pharmacology from
the University of Iowa, an M.S. in biochemistry from the University of
North Carolina, and a B.A. in biology from Knox College, and he was an
The Office of Health Assessment and
Translation: A Problem-Solving Resource
for the National Toxicology Program
John R. BucherKristina Thayer Linda S. Birnbaum
Environmental Health Perspectives • volume 119 | number 5 | May 2011
Emerging from an agricultural base to more
industrialization, Thailand now faces many
environmental problems, particularly air
pollution, resulting in adverse health conse-
quences. The three major sources of air pollution are vehicular emis-
sions in cities, biomass burning and transboundary haze in rural and
border areas, and industrial discharges in concentrated industrialized
Recent air quality data suggest that particulate matter < 10 µm in
aerodynamic diameter (PM10) is the most important air pollutant in
urban and rural areas. In cities such as Bangkok, air quality monitor-
ing performed by the Pollution Control Department (PCD) for the
past 10 years revealed that the levels of PM10 have exceeded both
annual (50 µg/m3) and 24-hr (120 µg/m3) national standards (PCD
2010). The main source of PM10 in Bangkok is vehicular emissions
(Chuersuwan 2008; Parsons International Ltd. 2001).
In the rural and border areas, most notably Chiangmai, agri-
cultural burning and forest fires, including transboundary haze
from Myanmar, have contributed to high levels of PM10, which
have increased to critical levels since 2006 [250 µg/m3, 300 µg/m3,
175 µg/m3, and 220 µg/m3 in 2006, 2007, 2008, and 2009, respec-
tively (PCD 2010)]. More importantly, many consecutive days of high
PM10 levels resulted in increases in hospital admissions and outpatient
visits (Chiangmai Provincial Public Health Office 2007).
Moreover, the Southeast Asian haze that originated in Indonesia
has continually affected the health of residents of the southern prov-
inces, particularly in 1996 and 1997, where the maximum PM10 levels
reached as high as 314 µg/m3 (PCD 2010). The most severe haze episode
occurred in 1997 and resulted in sharp increases in outpatient visits (26%)
and hospital admissions (33% for all respira-
tory, 36% for pneumonia, 40% for bronchi-
tis/chronic pulmonary obstructive disease, 12%
for asthma) within a period of a few months
(Health Systems Research Institute 1998).
Several studies worldwide have demon-
strated that PM10 is associated with prema-
ture mortality and a wide range of morbidity
outcomes. As part of the Public Health and
Air Pollution in Asia (PAPA) multi cities
study, results for Bangkok showed that each
10-µg/m3 increase in PM10 is associated with a 1.25% increase in
all-cause mortality, which is higher than for the three other participat-
ing cities [0.53% for Hong Kong, 0.26% for Shanghai, and 0.43%
for Wuhan (Wong et al., 2008)] and higher than multi cities studies
conducted in Western countries (Katsouyanni et al. 2001). The higher
effects in Bangkok may be related to high temperatures in Bangkok
throughout the year, higher exposures to air pollution from longer
periods of time spent outdoors, and less availability and use of air-
As a developing country, Thailand strives for a continual eco-
nomic growth. Consequently, expansion of petro chemical plants
rose sharply, particularly, in the coastal province of Rayong, with
> 73 million tons of chemicals used annually (Department of
Industrial Works 2010). Although environmental management has
been instituted, levels of volatile organic compounds (VOCs) con-
tinue to exceed Thailand’s standards (PCD 2010).
Epidemiological studies have been limited, with only sporadic
reports of respiratory symptoms and illnesses after episodic events of
accidental releases from industries. However, a recently completed
large-scale population-based epidemiology study with > 26,000 subjects
indicated that residents who live near the petro chemical industrial estate
have higher risks in adverse pregnancy outcomes, neuro psychological
symptoms, and poor performance on neuro psychological tests (Vichit-
Vadakan et al. 2010). In particular, results show significant excess risk
of preterm birth before < 34 weeks among mothers residing < 4 km
Health Impact from
Air Pollution in Thailand:
Current and Future
NIH Postdoctoral Fellow in biochemistry and environmental toxicology at
Michigan State University. He is a Diplomate of the American Board of
Toxicology and a Fellow of the Collegium Ramazzini.
Kristina A. Thayer, director of the NTP Office of Health Assessment
and Translation, holds a Ph.D. in biological sciences from the University
of Missouri–Columbia. She has been with the NIEHS since 2003, serv-
ing in the NTP Office of Liaison, Policy, and Review and the NIEHS
Office of Risk Assessment Research prior to assuming her current position.
She has authored numerous NTP reports and manuscripts on the toxico-
logical potential of environmental substances.
Linda S. Birnbaum, director of the NIEHS and the NTP, over sees
a budget that funds multidisciplinary biomedical research programs and
prevention and intervention efforts that encompass training, educa tion,
technology transfer, and community outreach. She recently received an
honorary Doctor of Science from the University of Rochester, the distin-
guished alumna award from the University of Illinois, and was elected
to the Institute of Medicine. She is the author of > 700 peer-reviewed
publica tions, book chapters, abstracts, and reports. Birnbaum received
her M.S. and Ph.D. in microbiology from the University of Illinois,
Urbana. A board-certified toxicologist, she has served as a federal scientist
for 31 years, 19 with the U.S. EPA Office of Research and Development,
preceded by 10 years at the NIEHS as a senior staff fellow, a principal
investigator, a research micro biologist, and a group leader for the insti-
tute’s Chemical Disposition Group.
Bucher JR. 2008. NTP: new initiatives, new alignment. Environ Health Perspect 116:A14–A15.
Bucher JR. 2009. Bisphenol A: where to now? Environ Health Perspect 117:A96–A97.
Collins FS, Gray GM, Bucher JR. 2008. Toxicology. Transforming environmental health protec-
tion. Science 319:906–907.
NTP (National Toxicology Program). 2011. NTP Workshop: Role of Environmental Chemicals
in the Development of Diabetes and Obesity. Available: http://ntp.niehs.nih.gov/go/36433
[accssed 8 April 2011].
Schmidt CW. (2009) Tox 21: new dimensions of toxicity testing. Environ Health Perspect
from the industrial estate [odds ratio (OR) = 3.34; 95% confidence Download full-text
interval (CI), 1.18–9.47]; non significant increased risks were found
for all pregnancy outcomes (OR = 1.60; 95% CI, 0.87–2.93), preterm
birth before 37 weeks (OR = 1.68; 95% CI, 0.85–3.30), low birth
weight (OR = 1.42; 95% CI, 0.52–3.78), and small for gestational age
(OR = 1.24; 95% CI, 0.31–4.90. Generally, the excess risk decreases
with increased distances.
Obtaining sustainable development that balances environmental
conservation and the well‑being of the population remains a challenge
for Thailand. In national strategies for development, policy makers often
rely only on economic information fbecause of the lack of empirical
data on health, social, and environmental impacts from develop mental
policies and projects. Fostering and strengthening epidemiological
research in Thailand not only provides the necessary perspective for
policy develop ment but contributes to the larger body of knowledge in
environ mental health.
The authors declare they have no actual or potential competing financial
Faculty of Public Health, Thammasat University
Rangsit, Pathumthani, Thailand
Nuntavarn Vichit-Vadakan currently serves as the dean of the Faculty
of Public Health, Thammasat University. She continues to participate in
numerous important environmental epidemiological studies as the principal
investigator. Results of her studies have led to policy development, such as
the setting of Thailand’s national standard for PM2.5.
Nitaya Vajanapoom has a Ph.D. in epidemiology from the University
of North Carolina and is an environmental epidemiologist at Thammasat
University in Bangkok. Her studies on the health effects of air pollu-
tion include the PAPA project and a 5-year population-based study that
examined the health effects of air pollution from a lignite power plant and
petro chemical industrial estate in Thailand.
Chiangmai Provincial Public Health Office. 2007. Report of Out-patients According to 21 Groups
of Causes and Report of In-patients According to 75 Groups of Causes from Health Service
Units, Ministry of Public Health [in Thai]. Available: http://www.chiangmaihealth.com/ict/stat.
php [accessed 10 September 2010].
Chuersuwan N, Nimrat S, Lekphet S, Kerdkumrai T. 2008. Levels and major sources of PM2.5 and
PM10 in Bangkok Metropolitan Region. Environ Int 34:671–677.
Department of Industrial Works. 2010. Industrial Chemicals Data [in Thai]. Available: http://www.
diw.go.th/diw_web/html/versionthai/data/chem-map/ [accessed 10 September 2010].
Health Systems Research Institute. 1998. Health and Environmental Impacts from the 1997 Asean
Haze in Southern Thailand [in Thai]. Bangkok:Desire Co. Ltd.
Katsouyanni K, Touloumi G, Samoli E, Gryparis A, Le Tertre A, Monopolis Y, et al. 2001.
Confounding and effect modification in the short-term effects of ambient particles on total
mortality: results from 29 European cities within the APHEA2 project. Epidemiol 12(5):521–531.
Parsons International Ltd. 2001. Final Report for the Bangkok Air Quality Management Project.
Bangkok:Bangkok Metropolitan Administration.
PCD (Pollution Control Department), Ministry of Natural Resources and Environment. 2010.
Annual Air Quality [in Thai]. Available: http://aqnis.pcd.go.th [accessed 10 September 2010].
Vichit-Vadakan N, Vajanapoom N, Channarong P. 2010. Residents Living Near Petro Chemical
Industries and Their Health Outcomes [in Thai]. Bangkok:Thailand Research Fund.
Wong CM, Vichit-Vadakan N, Kan H, Qian Z. 2008. Public health and air pollution in Asia (PAPA):
a multicity study of short-term effects of air pollution on mortality. Environ Health Perspect
volume 119 | number 5 | May 2011 • Environmental Health Perspectives
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