Report for 11th International Congress ofToxicology
Tn.Tin.Win.Shwe (NIES)
The 11th International Congress of Toxicology was successfully held inMontreal, Canada from 15th to 19th July, 2007. More than 2000 scientists
coming from more than 75 countries presented their latest researchfindings and discussed recent developments and issues in toxicology. We
met scientists from around the world, renewed old friendship and forgednew professional relationship. The Congress included 35 symposia andmore than 1200 posters covering topic ranging from the latest scientificadvances, global toxicological issues and the challenges unique todeveloping countries. The education program provided an opportunity toenhance our knowledge in new or familiar fields. The Exhibition
introduced new products and services that were interested and attractive
for toxicological research. Among many symposia and posters, we would
like to discuss here some sessions which are related our recent researchwork.
Immunotoxicology: Hypersensitivity and Allergies(1) From chemistry to allergy: To cause sensitization, a compound has topenetrate the skin, where it may be metabolized, and react withepidermal proteins to form new chemical structures that arerecognized as foreign. The way of low-molecular-weight chemicals
can react with skin proteins to form complete antigens and how thesestructures could be recognized by T-cell receptors were discussed.
(2) Mechanism of dendritic cell activation by chemicals: During in vivo
immune responses, the role of antigen-presenting cells is played
primarily by dendritic cells (DC) which acting as initiators of theimmune response. Recently, it has been shown that haptens directly
activate cultured human DCs showing the upregulation of maturation
markers (CD83, CD80, CD86, CD40, and MHCII). Haptens induce thephosphorylation of p38MAPK and c-Jun N-termi9nal kinase andinhibition of p38MAPK is correlated with alteration in phenotypic
indicators of DC maturation suggesting again similarities between
danger signals and haptens for DC activation.
(3) Activation of neutrophils by xenobiotics:in vitro and in vivo aspects ofinflammation: The role of xenobiotics on the cellular physiology ofhuman neutrophils is an area of research that had gained increasing
attention in the past few years. Interactions between humanneutrophils and certain chemicals of environmental concerned werediscussed. In addition, the potent pro-apoptotic activity of the twoanti-cancer agents, Viscum album agglutinin-1 and arsenic trioxide
were discussed in relation with inflammation. Knowing theimportance of neutrophils in the inflammatory process, research
conducted in this field will increase greatly our knowledge ofunderstanding the potential role of xenobiotics in the regulation ofinflammation.
Metals and Neurodegenerative diseases(1) Manganese and neurodegeneration: Occupational exposure tomanganese (Mn) has been associated with the onset of psychologicaland motor symptoms in some individuals, leading to a phenotype
called manganism. Brain Mn accumulation has also been documented
in patients with liver failure, those receiving parenteral nutrition orindividuals with iron (Fe) deficiency. The transport of Mn into thebrain and its molecular/cellular effects in C. elegans and rodents werediscussed and the major attention was directed at the effect of
dietary Fe levels on brain Mn deposition pattern. From these findings,
it has been suggested that any change in dietary Fe levels
exacerbates brain Mn accumulation, and alters normal brain Fe
distribution in multiple discrete brain regions.
(2) Novel multi-model neuroprotective-neurorescue drugs with various
CNS targets for the treatment of Parkinson’s and Alzheimer’s diseases
and amyotrophic lateral sclerosis: New therapeutic strategies in which
drug candidates are designed expressly to act on multiple neural andbiochemical targets for the treatment of cognitive impairment, motor
dysfunction, depression, and neurodegeneration were developed. The
development of single molecular entities that combine two or more of
the following properties: choline esterase inhibition, monoamineoxidase inhibition, iron chelation, neuroprotection, anti-apoptosis,
neurorescue and modulation of components of mitochondrialdependent cell survival proteins were discussed. These bi- or multifunctional compounds could provide greater symptomatic efficacy,
and better utility as potential neuroprotective-neurorescue disease
modifying drugs, because of their ability to modulate mitochondrial
cell survival/death genes and protein and molecular processes that
result in neuronal growth and differentiation.
(3) Chronic effects of mercury and oxidative stress: Hg is a toxic nonessential element to mammals. Methylmercury (MeHg) is an
important public concern, particularly for those regularly consuming
fish or seafood. MeHg is a potent neurotoxin and can cause
permanent injury to mature and developing brain. Literature data
have indicated that in vitro oxidative stress and glutamate play acentral role in MeHg neurotoxicity. The exposure to MeHg during
distinct phase of development alters the glutamatergic system, which
can be related to oxidative stress.
Developing Strategies to understand the effects of air pollution onhuman populations(1) Low-level exposure to benzene is converted to toxic metabolites much
more efficiently than high-level exposures: Although the toxicity ofbenzene has been linked to its metabolism, the dose-related
production of metabolites is not well understood in humans.
According to the investigation of benzene metabolites in urine ofworkers who exposed to benzene in China, indicates that theproduction of toxic metabolites were greater at low exposure levels.
Since cancer risks of benzene exposure are based upon data fromheavily exposed humans and animals, they may underestimate thetrue risks for persons exposed to low levels of benzene.
(2) Using the workplace as a window to study the role of diesel andgasoline engine emissions in lung cancer development: Motor engine
emissions represent a major environmental health issue. Associations
between diesel and gasoline exhausts and lung cancer wereinvestigated by population base case control study, and found that
there was on evidence of excess risks of lung cancer with exposure togasoline exhaust. For diesel engine emissions, results differed bycontrol group used especially at high concentration levels.
(3) Polymorphism and effect of air pollution: Genetic polymorphism
induced by the air pollution has been associated with increased risk ofdevelopment of cancer and asthma. In addition, this polymorphism
has been linked to an altered level of biomarker of exposure toambient air pollutants. In development of asthma, it has beenreported that deficiencies in either GSTM1 or GSTT1 increases therisk, but mostly in the high exposure group. Integration of
information of genetic constitution and proper exposure assessment
may provide new information on the adverse health effect of ambient
air pollution in genetic susceptible populations.
(4) Air pollution and asthma:Lessons from animal models: While allergen
exposure is a major risk factor for asthma, especially in children,
exposure to air pollution exacerbate asthma symptoms and may evenbe capable of causing asthma. Studies from animal models confirm
that exposure to many components of air pollution can cause airway
inflammation and airway hyperresponsiveness and can also prime thelungs of sensitized animals to respond more vigorously to allergeninhalation. Studies using inbred mouse strains and knockout mice
have also provided important clues about both the mechanistic basis
for the pulmonary effects of air pollution, as well as genetic
susceptibility, and have proved predictive for understanding humandisease.
Environmental exposure and children’s health(1) Developmental neurotoxicity of industrial chemicals:
Neurodevelopmental disorders such as autism, attention deficit
disorder, mental retardation, and cerebral palsy are comm0on, costly
and can cause lifelong disability. Their causes are mostly unknown. A
few industrial chemicals (e.g., lead, methylmercury, polychlorinatedbiphenyls (PCBs), arsenic, and toluene) are recognized causes ofneuro-developmental disorders and subclinical brain dysfunction.
Exposure to these chemical during early fetal development can cause
brain injury at dose much lower that those affecting adult brainfunction. The toxic effects of such chemicals in the developing humanbrain are not known and they are not regulated to protect children.
New, precautionary approaches that recognize the uniquevulnerability of the developing brain are needed for testing andcontrol of chemicals.
(2) Exposure to urban air pollution in Bangkok school children: Potential
health effects: Urban air pollution resulting from traffic congestion is amajor problem in many Asian mega cities such as Bangkok. This typeof pollution contains a number of carcinogenic compounds, includingpolycyclic aromatic hydrocarbons (PAHs), benzene and 1,3 butadiene.
Bangkok school children were exposed to total PAHs at levels morethan 6-folds higher than those in the rural area. In addition, DNAdamage levels were significantly higher while DNA repair capacity wassignificantly reduced in urban school children. It is apparent thatchildren living in major cities may have increased risk of thedevelopment of diseases due to exposure to carcinogenic substancesin air pollution.
(3) Insecticide exposure during pregnancy and effects on fetal growthand child mental, motor and behavioural development: Residential
pesticide use is widespread in the U. S. but data are limited on use
during pregnancy. The organophosphates chlorpyrifos and diazinon
and the carbamate propoxur were found in 99%-100% of 48 h
personal air samples collected from mothers and repeat two-week
integrated indoor air samples from a subset of homes. These three
insecticides were found in 29%-55% of blood samples collected fromthe mothers and newborns at delivery. The more highly exposed
newborns were also significantly more likely by age 3 to have early
indicators of attentional disorder, attention deficit hyperactivity
disorder and pervasive personality disorder by parental report on theChild behavior Checklist.
Overview for 11th ICTRegarding Continuing Education (CE) Lectures, most of the lecturers
were recognized for their novel findings and concepts. Among CE lectures,
CE 2; Development and interpretation of toxicokinetic data for risk on
safety assessments and CE 4; Drug induced immunostimulation and its
relevance to immunotoxicity attracted for attendants.
Regarding symposia and poster sections, toxicologists from various
countries presented various points of view such as developmental toxicity,
genotoxicity, hepatotoxicity, immunotoxicity, neurotoxicity, toxicity in maleand female reproductive systems, cardiotoxicity, and nanotoxicity. In thisyear, most of the toxicologists gave attention to developmental toxicity
and child’s health.
From 11th ICT, we have learned(1) Toxicants and their risks(2) Mechanism and cell signaling pathway in toxicity(3) Commonly unaware risk to children living in susceptible areas (e.g.,
mercury, lead, diesel exhaust particles)(4) Rules and regulations are needed to control toxic effects and relevant
preventive measures and(5) Modified and newly designed experimental apparatus provided byexhibitors.
In addition, we had a chance to make warmly friendship between
toxicologists from many countries. However, there are limited reports forthe effect of indoor air toxic chemicals like toluene on pulmonary system,
nervous system and behavioral system. Furthermore, presentations for invivo experimental animal model were also limited in this congress. Finally,
registration fee was very expensive for scientist who wanted to participate
from developing countries.