DOSE-RESPONSE REGRESSIONS FOR ALGAL GROWTH AND SIMILAR CONTINUOUS ENDPOINTS: CALCULATION OF EFFECTIVE CONCENTRATIONS
DOSE-RESPONSE REGRESSIONS FOR ALGAL GROWTH AND SIMILAR CONTINUOUS ENDPOINTS: CALCULATION OF EFFECTIVE CONCENTRATIONS
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DOI：
10.1897/08-068r.1
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发表时间：
2009-04-01
影响因子：
4.1
通讯作者：
Nyholm, Niels
中科院分区：
文献类型：
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作者：
Christensen, Erik R.;Kusk, Kresten O.;Nyholm, Niels
我们根据实验得出的中位有效浓度（ec50）和中心点的曲线斜率（50%的抑制），推导出具有95%置信限的probit（对数正态）、威布尔和logistic剂量反应模型的有效浓度方程（EC10）。为了说明，使用绿藻Pseudokirchneriella subcapitata以生长速率作为响应参数来分析封闭淡水藻类分析的数据。选择了四种试验化学品（四乙基溴化铵、肌肉胺、苯腈和4-4-（三氟甲基）苯氧酚）的剂量-响应回归，其代表性斜率范围为50%响应（0.54-2.62）和ec50 （2.20-357 mg/L）。参考ec50和ec10的95%置信限使用probit或Weibull模型，使用具有方差加权和适当逆估计的剂量-反应回归程序对整个数据集进行非线性回归计算。威布尔模型为所有四种化学物质的数据提供了最好的拟合。从我们的推导方程中预测的ec10（95%置信限）相当准确；例如，使用4-4-（三氟甲基）苯氧基苯酚和probit模型，我们得到1.40 (1.22-1.61)mg/L，而非线性回归程序得到1.40 (1.20-1.64)mg/L。该方法的主要优点是EC10或ECx（其中x = 1 - 99）可以从EC20到EC80周围的确定响应中预测，而无需在低或高响应范围内的实验数据。还讨论了藻类生长抑制的EClow，x（预测引起x%抑制的浓度）置信区间的估计问题。较大的置信区间可能是实验误差和缺乏定义良好的参考响应值的结果。
We derive equations for the effective concentration giving 10% inhibition (EC10) with 95% confidence limits for probit (log-normal), Weibull, and logistic dose -responsemodels on the basis of experimentally derived median effective concentrations (EC50s) and the curve slope at the central point (50% inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response regressions for four test chemicals (tetraethylammonium bromide, musculamine, benzonitrile, and 4-4-(trifluoromethyl)phenoxy-phenol) with ranges of representative slopes at 50% response (0.54-2.62) and EC50s (2.20-357 mg/L) were selected. Reference EC50s and EC10s with 95% confidence limits using probit or Weibull models are calculated by nonlinear regression on the whole dataset using a dose - response regression program with variance weighting and proper inverse estimation. The Weibull model provides the best fit to the data for all four chemicals. Predicted EC10s (95% confidence limits) from our derived equations are quite accurate; for example, with 4-4-(trifluoromethyl)phenoxy-phenol and the probit model, we obtain 1.40 (1.22-1.61) mg/L versus 1.40 (1.20-1.64) mg/L obtained from the nonlinear regression program. The main advantage of the approach is that EC10 or ECx (where x = 1 - 99) can be predicted from well-determined responses around EC20 to EC80 without experimental data in the low- or high-response range. Problems with the estimation of confidence interval for EClow,x (concentration predicted to cause x% inhibition) from algal growth inhibition also are addressed. Large confidence intervals may be the result of experimental error and lack of a well-defined reference response value.