Yun-Ru Ju

Lung cancer risk in relation to traffic-related nano/ultrafine particle-bound PAHs exposure: A preliminary probabilistic assessment

Exposures to carcinogenic polycyclic aromatic hydrocarbons (PAHs) have been linked to human lung cancer. The purpose of this study was to assess lung cancer risk caused by inhalation exposure to nano/ultrafine particle-bound PAHs at the population level in Taiwan appraised with recent published data. A human respiratory tract model was linked with a physiologically based pharmacokinetic model to estimate deposition fraction and internal organic-specific PAHs doses. A probabilistic risk assessment framework was developed to estimate potential lung cancer risk. We reanalyzed particle size distribution, total-PAHs, particle-bound benzo(a)pyrene (B[a]P) and PM concentrations. A dose-response profile describing the relationships between external B[a]P concentration and lung cancer risk response was constructed based on population attributable fraction (PAF). We found that 90% probability lung cancer risks ranged from 10(-5) to 10(-4) for traffic-related nano and ultrafine particle-bound PAHs, indicating a potential lung cancer risk. The particle size-specific PAF-based excess annual lung cancer incidence rate due to PAHs exposure was estimated to be less than 1 per 100,000 population, indicating a mild risk factor for lung cancer. We concluded that probabilistic risk assessment linked PAF for limiting cumulative PAHs emissions to reduce lung cancer risk plays a prominent role in future government risk assessment program.

Assessing human exposure risk to cadmium through inhalation and seafood consumption

The role of cadmium (Cd) bioaccessibility in risk assessment is less well studied. The aim of this study was to assess human health risk to Cd through inhalation and seafood consumption by incorporating bioaccessibility. The relationships between trophically available Cd and bioaccessibility were constructed based on available experimental data. We estimated Cd concentrations in human urine and blood via daily intake from seafood consumption and inhalation based on a physiologically-based pharmacokinetic (PBPK) model. A Hill-based dose-response model was used to assess human renal dysfunction and peripheral arterial disease risks for long-term Cd exposure. Here we showed that fish had higher bioaccessibility (~83.7%) than that of shellfish (~73.2%) for human ingestion. Our results indicated that glomerular and tubular damage among different genders and smokers ranged from 18.03 to 18.18%. Our analysis showed that nonsmokers had 50% probability of peripheral arterial disease level exceeding from 3.28 to 8.80%. Smoking populations had 2-3 folds higher morbidity risk of peripheral arterial disease than those of nonsmokers. Our study concluded that the adverse effects of Cd exposure are exacerbated when high seafood consumption coincides with cigarette smoking. Our work provides a framework that could more accurately address risk dose dependency of Cd hazard.

Bioavailability links mode of action can improve the long-term field risk assessment for tilapia exposed to arsenic.

The objective of this paper was to develop a mechanistic-based framework to explicitly incorporate the factors controlling the bioavailability, toxicodynamics and mode of action to enhance predictive ability of arsenic (As) toxicity to protect the health of farmed tilapia Oreochromis mossambicus. We linked the biotic ligand model and damage assessment model to develop a toxicokinetic model for elucidating the site-specific temporal changes of As bioavailability and to characterize how the fish regulate the metal toxicity. We built a bioavailability-mode of action-based growth toxicity model by linking a bioenergetic growth model and damage assessment model to predict how the As affects on the tilapia growth in the entire life span in site-specific field ecosystems. Here we show that the proposed model well describes the water-chemistry-dependent toxicokinetics and toxicodynamics variations of As to tilapia. We selected two local tilapia farms with different water chemistries located at southwestern Taiwan coast region to implement the proposed algorithm to predict the risk of As exposure. Results indicate that the growth toxicity of O. mossambicus in Taihsi is more sensitive than that in Peimen. We found that the effect of ion competition on the As bioavailability and their ecotoxicological effects on tilapia are more obvious in Taihsi comparing with that in Peimen. We suggested that the proposed bioavailability- and mode of action-based framework can be used to capture the biological response and regulation of tilapia to As exposures. It is applicable for a site-specific and long-term ecotoxicological risk assessment.

Assessing the effects of pulsed waterborne copper toxicity on life-stage tilapia populations

The impact of environmentally pulsed metal exposure on aquatic organisms is poorly understood experimentally. The purpose of this study was to provide an analysis methodology for assessing the effects of pulsed waterborne copper (Cu) on life-stage tilapia populations. We conducted 10-day exposure experiments to obtain toxicokinetic parameters for larva, juvenile, and adult tilapia exposed to pulsed Cu. We linked threshold damage model and biotic ligand model to assess the survival probability for tilapia populations to pulsed Cu exposure. Here we showed that the change in exposure patterns did change substantially survival rates for each life stage of tilapia. We indicated that an apparent difference in time course of survival probability between pulsed and constant Cu exposures was found in each life stage. We concluded that the life-stage factor needs to be incorporated into studies of species interactions under different disturbance regimes. This study suggested that life-stage-specific toxicokinetic parameters and adequate water chemistry might be important to consider in risk assessment of population survivorship for aquatic species under pulsed exposure scenarios.

Assessing the impact of waterborne and dietborne cadmium toxicity on susceptibility risk for rainbow trout

The purpose of this study was to use a risk-based integrated-scale toxicological model to examine the impact of waterborne and dietborne cadmium (Cd) toxicity on rainbow trout (Oncorhynchus mykiss) susceptibility appraised with recent published data. A probabilistic assessment model was performed to estimate Cd susceptibility risk. The dose-response models were constructed based on two endpoints of % Cd in metabolically active pool (MAP) and susceptibility time that causes 50% effect (ST50). We further constructed an elimination-detoxification-recovery scheme to enhance the model predictive ability. We found a 95% probability of % Cd in gill and liver MAP exceeding 47-49% and it was likely (70% probability) to have exceeded 52-55%, but it was unlikely (30% probability) to have exceeded 56-60%. In contrast to gill and liver, gut had a relative lower Cd susceptibility risk (15-17% Cd in MAP) with a longer ST50. We suggested that the proposed probabilistic risk assessment framework can incorporate the elimination-detoxification-recovery scheme to help government based biomonitoring and bioassessment programs to prevent potential aquatic ecosystems and human health consequences.

Modeling human health risks of airborne endotoxin in homes during the winter and summer seasons

Endotoxin, a component of gram-negative bacterial cell walls, is a pro-inflammatory agent that induces local and systemic inflammatory responses in normal subjects which can contribute to the risk of developing asthma and chronic obstructive lung diseases. A probabilistic approach linking models of exposure, internal dosimetry, and health effects was carried out to quantitatively assess the potential inhalation risk of airborne endotoxin in homes during the winter and summer seasons. Combining empirical data and modeling results, we show that the half-maximum effect of the endotoxin dose (ED50) was estimated to be 707.9 (95% confidence interval (CI): 308.8-1287.0) endotoxin units (EU) for body temperature change, 481.8 (95% CI: 333.2-630.3) EU for elevation of neutrophils, and 1174.5 (95% CI: 816.0-1532.9) EU for elevation of the cytokine, interleukin-6. Our study also suggests that airborne endotoxin in homes may pose potential risks, and a higher risk for elevation of neutrophils and cytokine interleukin-6 appeared in winter season than in summer. Our study offers a risk-management framework for discussion of future studies of human respiratory exposure to airborne endotoxin.

Risk-based probabilistic approach to assess the impact of false mussel invasions on farmed hard clams.

The purpose of this article is to provide a risk-based predictive model to assess the impact of false mussel Mytilopsis sallei invasions on hard clam Meretrix lusoria farms in the southwestern region of Taiwan. The actual spread of invasive false mussel was predicted by using analytical models based on advection-diffusion and gravity models. The proportion of hard clam colonized and infestation by false mussel were used to characterize risk estimates. A mortality model was parameterized to assess hard clam mortality risk characterized by false mussel density and infestation intensity. The published data were reanalyzed to parameterize a predictive threshold model described by a cumulative Weibull distribution function that can be used to estimate the exceeding thresholds of proportion of hard clam colonized and infestation. Results indicated that the infestation thresholds were 2-17 ind clam(-1) for adult hard clams, whereas 4 ind clam(-1) for nursery hard clams. The average colonization thresholds were estimated to be 81-89% for cultivated and nursery hard clam farms, respectively. Our results indicated that false mussel density and infestation, which caused 50% hard clam mortality, were estimated to be 2,812 ind m(-2) and 31 ind clam(-1), respectively. This study further indicated that hard clam farms that are close to the coastal area have at least 50% probability for 43% mortality caused by infestation. This study highlighted that a probabilistic risk-based framework characterized by probability distributions and risk curves is an effective representation of scientific assessments for farmed hard clam in response to the nonnative false mussel invasion.

A probabilistic approach to quantitatively assess the inhalation risk for airborne endotoxin in cotton textile workers

Endotoxin, a component of gram-negative bacterial cell walls, is a proinflammatory agent that induces local and systemic inflammatory responses in normal subjects which can contribute to the risk of developing asthma and chronic obstructive lung diseases. A probabilistic approach linking models of exposure, internal dosimetry, and health effects were carried out to quantitatively assess the potential inhalation risk of airborne endotoxin for workers in cotton textile plants. Combining empirical data and modeling results, we show that the half-maximum effects of the endotoxin dose (ED50) were estimated to be 3.3 x 10(5) (95% confidence interval (CI): 1.9-14.7 x 10(5)) endotoxin units (EU) for the blood C-reactive protein (CRP) concentration, 1.1 x 10(5) (95% CI: 0.6-1.7 x 10(5))EU for the blood polymorphonuclear neutrophil (PMN) count, and 1.5 x 10(5) (95% CI: 0.4-2.5 x 10(5))EU for the sputum PMN count. Our study offers a risk-management framework for discussing future establishment of limits for respiratory exposure to airborne endotoxin for workers in cotton textile plants.

Determination and assessment of phthalate esters content in sediments from Kaohsiung Harbor, Taiwan

Phthalate esters (PAEs) are known organic endocrine disruptors. The distribution of 10 PAEs in sediments of Kaohsiung Harbor of Taiwan was studied using organic solvents extraction and quantified by gas chromatography/mass spectrometry. The average concentration of total PAEs (ΣPAEs) in the sediment was 8713±11,454ng/g dw with di-(2-ethylhexyl) phthalate (DEHP) (3630ng/g-dw) and diisononyl phthalate (DiNP) (3497ng/g dw) being the major species, which constitutes of 41.7% and 40.1% of ΣPAEs. PAEs concentration was relatively high near the river mouths, especially in Love River mouth, and diminished toward the harbor. Based on the sediment quality guidelines developed from previous studies, several of the observed PAE levels exceeded the Maximum Contaminant Level, especially for DEHP and thus may cause adverse effect in aquatic organisms.

Subcellular partitioning links BLM‐based toxicokinetics for assessing cadmium toxicity to rainbow trout

The purpose of this article was to develop an integrated‐scale toxicological model to investigate the impact of cadmium (Cd) toxicity on rainbow trout (Oncorhynchus mykiss) based on recent published experimental data. This model was generated from three different types of functional relationship: biotic ligand model (BLM), damage assessment model (DAM), and subcellular partitioning model (SPM), both of key toxicological determinants involved and of functional connections between them. Toxicokinetic parameters of uptake rate constant (k1) and elimination rate constant (k2) in gill, liver, and subcellular fractions were derived. A negative correlation between gill binding fraction of Cd and bioaccumulation factor was found. Detoxifying ability (% detoxified in liver metabolically detoxified pool (MDP)) and k2 were negatively correlated, indicating that increasing % detoxified in MDP can compensate for lower k2. This finding suggests a potential tradeoff between the abilities of elimination and detoxification for Cd. Yet, compensation between the ability to eliminate Cd and the ability to recover Cd‐induced damage was not found. However, changes in k2 and recovery rate constant (kr) can shift the dynamics of Cd susceptibility probability. This analysis implicates that once k2 is determined experimentally, the values of kr and % detoxified in MDP can be predicted by the proposed k2−kr and k2−% detoxified relationships. This study suggests that the mechanistic linking of BLM‐based DAM and SPM can incorporate the organ‐ and cell‐scale exposure experimental data to investigate the mechanisms of ecophysiological response for aquatic organisms exposed to metal stressors.