A human PBPK/PD model to assess arsenic exposure risk through farmed tilapia consumption.

The purpose of this study was to develop a biologically based risk assessment model for human health through consumption of arsenic (As) contaminated farmed tilapia (Oreochromis mossambicus) from blackfoot disease (BFD)-endemic area in Taiwan for estimating the consumption advice. We linked a physiologically based pharmacokinetic (PBPK) and a pharmacodynamic (PD) model to account for the exposure and dose-response profiles of As in human. Risk analysis indicates that consumption of farmed tilapia poses no significant threat from As-induced lung and bladder cancers. The predicted risk-based median consumption advice was no more than 5-17 meals month(-1) (or 2-6 g day(-1)).

Presenting characteristics of trisomy 8 as the primary cytogenetic abnormality associated with childhood acute lymphoblastic leukemia. A Pediatric Oncology Group (POG) Study (8600/8493).

Although trisomy 8 is the single most common numerical abnormality in acute myeloid leukemia (AML), relatively few cases with acute lymphoblastic leukemia (ALL) and trisomy 8 have been reported. We report the clinical and laboratory features of seven children with ALL and trisomy 8 as the sole cytogenetic abnormality and review nine similar cases from the literature. Among the children studied by the Pediatric Oncology Group (POG) with newly diagnosed ALL, only 0.3% had trisomy 8 as the sole abnormality. Four of our patients had T-cell ALL and three had early pre-B ALL. Presenting clinical features were typical for the respective immunophenotypes. Six of the seven children achieved complete remission. Our study suggest that trisomy 8 is an infrequent, recurring abnormality among children with ALL, which appears to be associated with a T-cell immunophenotype.

Assessment of human health risks for arsenic bioaccumulation in tilapia (Oreochromis mossambicus) and large-scale mullet (Liza macrolepis) from blackfoot disease area in Taiwan.

This paper carries out probabilistic risk analysis methods to quantify arsenic (As) bioaccumulation in cultured fish of tilapia (Orechromis mossambicus) and large-scale mullet (Liza macrolepis) at blackfoot disease (BFD) area in Taiwan and to assess the range of exposures for the people who eat the contaminated fish. The models implemented include a probabilistic bioaccumulation model to account for As accumulation in fish and a human health exposure and risk model that accounts for hazard quotient and lifetime risk for humans consuming contaminated fish. Results demonstrate that the ninety-fifth percentile of hazard quotient for inorganic As ranged from 0.77-2.35 for Taipei city residents with fish consumption rates of 10-70 g/d, whereas it ranged 1.86-6.09 for subsistence fishers in the BFD area with 48-143 g/d, consumption rates. The highest ninety-fifth percentile of potential health risk for inorganic As ranged from 1.92 x 10(-4)-5.25 x 10(-4) for Taipei city residents eating tilapia harvested from Hsuehchia fish farms, with consumption rates of 10-70 g/d, whereas for subsistence fishers it was 7.36 x 10(-4)-1.12 x 10(-3) with 48-143 g/d consumption rates. These findings indicate that As exposure poses risks to residents and subsistence fishers, yet these results occur under highly conservative conditions. We calculate the maximum allowable inorganic As residues associated to a standard unit risk, resulting in the maximum target residues, are 0.0019-0.0175 and 0.0023-0.0053 microg/g dry weight for tilapia and large-scale mullet, respectively, with consumption rates of 70-10 g/d, or 0.0009-0.0029 and 0.0011-0.0013 microg/g dry weight for consumption rates of 169-48 g/d.

Organ-specific toxicokinetics and dose-response of arsenic in tilapia Oreochromis mossambicus.

We appraised organ-specific toxicokinetics and dose responses of arsenic burdens in tilapia Oreochromis mossambicus. We kinetically linked an Area-under-the-curve (AUC)-based acute toxicity model and a pharmacodynamic model to derive dose-response relationships between equilibrium organ-specific arsenic concentrations and mortality effects. The AUC-based acute toxicity model was also used to derive organ-specific internal effect concentration (IEC)-time-response relationships, which can also be applied to predict a time-mortality profile. We conducted a 7-day exposure experiment to obtain toxicokinetic parameters, whereas the AUC-based acute toxicity model was verified with LC50(t) data obtained from a 7-day acute toxicity bioassay. Our results demonstrated that 96-hour LC50 and incipient LC50 for tilapia exposed to arsenic are 28.68 (95% confidence interval to 24.92 to 32.44) and 25.55 mg L(-1), respectively. Dose-response relationships followed the Hill equation, which could be expressed as organ-specific bioconcentration factors and incipient LC50. Organ-specific dose-response relationships showed that muscle, gill, and liver have a relatively steep sigmoid dose-response profile in that IEC50 were 26.6, 62.5, and 78.5 microg g(-1) dry wt (dw), respectively. Organ-specific arsenic internal lethal burdens were the highest in the gill and the lowest in the muscle in waterborne-exposed tilapia. The IEC and target-organ concentrations derived in this study can be used in site-specific risk assessment.