Comparing lethal dose ratios using probit regression with arbitrary slopes

Abstract Background Evaluating the toxicity or effectiveness of two or more toxicants in a specific population often requires specialized statistical software to calculate and compare median lethal doses (LD50s). Tests for equality of LD50s using probit regression with parallel slopes have been impl...

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Main Authors: Chengfeng Lei, Xiulian Sun
Format: Article
Language:English
Published: BMC 2018-10-01
Series:BMC Pharmacology and Toxicology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40360-018-0250-1
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author Chengfeng Lei
Xiulian Sun
author_facet Chengfeng Lei
Xiulian Sun
author_sort Chengfeng Lei
collection DOAJ
description Abstract Background Evaluating the toxicity or effectiveness of two or more toxicants in a specific population often requires specialized statistical software to calculate and compare median lethal doses (LD50s). Tests for equality of LD50s using probit regression with parallel slopes have been implemented in many software packages, while tests for cases of arbitrary slopes are not generally available. Methods In this study, we established probit-log(dose) regression models and solved them by the maximum likelihood method using Microsoft Excel. The z- and χ 2-tests were used to assess significance and goodness of fit to the probit regression models, respectively. We calculated the lethal doses (LDs) of the toxicants at different significance levels and their 95% confidence limits (CLs) based on an accurate estimation of log(LD) variances. We further calculated lethal dose ratios and their 95% CLs for two examples without assuming parallel slopes following the method described by Robertson, et al., 2017. Results We selected representative toxicology datasets from the literature as case studies. For datasets without natural responses in the control group, the slopes, intercepts, χ 2 statistics and LDs calculated using our method were identical to those calculated using Polo-Plus and SPSS software, and the 95% CLs of the lethal dose ratios between toxicants were close to those calculated using Polo-Plus. For datasets that included natural responses in the control group, our results were also close to those calculated using Polo-Plus and SPSS. Conclusion This procedure yielded accurate estimates of lethal doses and 95% CLs at different significance levels as well as the lethal dose ratios and 95% CLs between two examples. The procedure could be used to assess differences in the toxicities of two examples without the assumption of parallelism between probit-log(dose) regression lines.
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spelling doaj.art-ad989f6da0a945d2b7d8a0c10d3d70082022-12-21T22:21:13ZengBMCBMC Pharmacology and Toxicology2050-65112018-10-0119111010.1186/s40360-018-0250-1Comparing lethal dose ratios using probit regression with arbitrary slopesChengfeng Lei0Xiulian Sun1Wuhan Institute of Virology, Chinese Academy of SciencesWuhan Institute of Virology, Chinese Academy of SciencesAbstract Background Evaluating the toxicity or effectiveness of two or more toxicants in a specific population often requires specialized statistical software to calculate and compare median lethal doses (LD50s). Tests for equality of LD50s using probit regression with parallel slopes have been implemented in many software packages, while tests for cases of arbitrary slopes are not generally available. Methods In this study, we established probit-log(dose) regression models and solved them by the maximum likelihood method using Microsoft Excel. The z- and χ 2-tests were used to assess significance and goodness of fit to the probit regression models, respectively. We calculated the lethal doses (LDs) of the toxicants at different significance levels and their 95% confidence limits (CLs) based on an accurate estimation of log(LD) variances. We further calculated lethal dose ratios and their 95% CLs for two examples without assuming parallel slopes following the method described by Robertson, et al., 2017. Results We selected representative toxicology datasets from the literature as case studies. For datasets without natural responses in the control group, the slopes, intercepts, χ 2 statistics and LDs calculated using our method were identical to those calculated using Polo-Plus and SPSS software, and the 95% CLs of the lethal dose ratios between toxicants were close to those calculated using Polo-Plus. For datasets that included natural responses in the control group, our results were also close to those calculated using Polo-Plus and SPSS. Conclusion This procedure yielded accurate estimates of lethal doses and 95% CLs at different significance levels as well as the lethal dose ratios and 95% CLs between two examples. The procedure could be used to assess differences in the toxicities of two examples without the assumption of parallelism between probit-log(dose) regression lines.http://link.springer.com/article/10.1186/s40360-018-0250-1ToxicityProbit regressionLethal dose ratioMaximum likelihood
spellingShingle Chengfeng Lei
Xiulian Sun
Comparing lethal dose ratios using probit regression with arbitrary slopes
BMC Pharmacology and Toxicology
Toxicity
Probit regression
Lethal dose ratio
Maximum likelihood
title Comparing lethal dose ratios using probit regression with arbitrary slopes
title_full Comparing lethal dose ratios using probit regression with arbitrary slopes
title_fullStr Comparing lethal dose ratios using probit regression with arbitrary slopes
title_full_unstemmed Comparing lethal dose ratios using probit regression with arbitrary slopes
title_short Comparing lethal dose ratios using probit regression with arbitrary slopes
title_sort comparing lethal dose ratios using probit regression with arbitrary slopes
topic Toxicity
Probit regression
Lethal dose ratio
Maximum likelihood
url http://link.springer.com/article/10.1186/s40360-018-0250-1
work_keys_str_mv AT chengfenglei comparinglethaldoseratiosusingprobitregressionwitharbitraryslopes
AT xiuliansun comparinglethaldoseratiosusingprobitregressionwitharbitraryslopes