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首页> 外文期刊>Environmental Science & Technology >Examining Uncertainty in In Vitro-In Vivo Extrapolation Applied in Fish Bioconcentration Models
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Examining Uncertainty in In Vitro-In Vivo Extrapolation Applied in Fish Bioconcentration Models

机译：在鱼生物浓缩模型中检查体内体内外推中的不确定性

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摘要

In vitro biotransformation rates were determined for 30 chemicals, mostly fragrance ingredients, using trout liver S9 fractions (RT-S9) and incorporated into in vitro-in vivo extrapolation (IVTVE) models to predict bioconcentration factors (BCFs). Predicted BCFs were compared against empirical BCFs to explore potential major uncertainties involved in the in vitro methods and IVTVE models: (i) in vitro chemical test concentrations; (ⅱ) different gill uptake rate constant calculations (k_1); (ⅲ) protein binding (different calculations and measurement of the fraction of unbound chemical, f_U); (ⅳ) species differences; and (ⅴ) extrahepatic biotransformation. Predicted BCFs were within 0.5 log units for 44% of the chemicals compared to empirical BCFs, whereas 56% were overpredicted by ＞0.5 log units. This trend of overprediction was reduced by alternative k_1, calculations to 32% of chemicals being overpredicted. Moreover, hepatic in vitro rates scaled to whole body biotransformation rates (k_B) were compared against in vivo k_B estimates. In vivo k_B was underestimated for 79% of the chemicals. Neither lowering the test concentration, nor incorporation of new measured f_U values, nor species matching avoided the tendency to overpredict BCFs indicating that further improvements to the IVTVE models are needed or extrahepatic biotransformation plays an underestimated role.
机译：使用鳟鱼肝脏S9级分（RT-S9）测定30种化学物质，主要是香味成分的体外生物转化率，并掺入体内体内外推（IVTVE）模型中以预测生物浓度（BCF）。将预测的BCF与经验BCF进行比较，以探索体外方法和IVTVE模型中涉及的潜在主要不确定性：（i）体外化学试验浓度; （Ⅱ）不同的鳃上速率恒定计算（K_1）; （Ⅲ）蛋白质结合（不同的计算和未结合化学品，F_U的分数）; （ⅳ）物种差异; （Ⅳ）脱毛生物转化。预测的BCF在与经验BCF相比的44％的化学物质中，预测的BCF在0.5个Log单位内，而56％以> 0.5对数单位覆盖。通过替代K_1减少了这种过度规范的这种趋势，计算到32％的化学物质过度。此外，将肝脏的体外速率缩放为全身生物转化率（K_B），与体内K_B估计进行比较。体内K_B低估了79％的化学物质。既不降低测试浓度，也不掺入新的测量的F_U值，也不匹配匹配的倾向，这表明需要进一步改进IVTVE模型或脱胸部生物转化起到低估的作用。

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  • 来源
    《Environmental Science & Technology》 |2020年第15期|9483-9494|共12页
  • 作者

    Heike Laue; Lu Hostettler; Remo P. Badertscher; Karen J. Jenner; Gordon Sanders; Jon A. Arnot; Andreas Natsch;

  • 作者单位

    Givaudan Schweiz AG Fragrances S&T 8310 Kemptthal Switzerland;

    Givaudan Schweiz AG Fragrances S&T 8310 Kemptthal Switzerland;

    Givaudan Schweiz AG Fragrances S&T 8310 Kemptthat Switzerland;

    Givaudan UK Ltd Regulatory Affairs and Product Safety Ashford Kent TN24 OLT United Kingdom;

    Givaudan International SA Regulatory Affairs and Product Safety 1214 Vernier Switzerland;

    ARC Arnot Research and Consulting Toronto Ontario M4M 1W4 Canada;

    Givaudan Schweiz AC Fragrances S&T 8310 Kemptthal Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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