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© Asian Journal of Pharmacology and Toxicology, 2015.
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Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

Jan 28, 2016

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A test example for LD50 determination for thymoquinone administered intraperitoneally in rats, demonstrates the implementation of interactive computer programs for computing LD50 and other LD values using Finney method (Program 'LD50-mortality-Finney') and Miller-Tainter method (Program 'LD50-mortality-Miller-Tain- ter'), written in MATLAB. Detailed program algorithms and their execution, as well as the differences between them, resulting from differences between the methods, are presented. The Finney method transforms results obtained for mortality (in %) to probit values, where probit values for 0% and 100% mortality depend on the number of experimental animals in the group, and then continues processing. The Miller-Tainter method also transforms mortality results (in %) to probit values, but previously corrects percentage values, relevant to the number of experimental animals, if mortality for the lowest dose is 0% and for the highest dose 100%, the corrected values are changed to probit values, and then continues processesing. In the case of OECD Modifi- cations 420, 423 and 425, once the doses for the determination of LD50 and other LD values are chosen, Litchfield-Wilcoxon statistical program is usually used to estimate these values and their confidence limits. In the test example of thymoquinone given intraperitoneally to rats LD0, LD16, LD50, LD84 and LD100 values obtained by applying the programs “LD50-mortality-Finney”, “LD50-mortality-Miller-Tainter” and those cal- culated by Litchfield-Wilcoxon method were very similar and Fischer's coefficient (F) value showed no statistically significant differences between them (P>0.05).
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Page 2: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.

Page 3: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.

Page 4: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.

Page 5: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.

Page 6: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.

𝑌 = 𝑎 ∗ log 𝑋 + 𝑏

Page 7: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.

𝑉 (log 𝐿𝐷𝑖) = 1

𝑎2 ∗ {1

𝑆𝑛𝑤 +

(log 𝐿𝐷𝑖 −�̅�)2

𝑆𝑛𝑤 (𝑋−�̅�)2 }

𝑆. 𝐸. (log 𝐿𝐷𝑖) = √𝑉 (log 𝐿𝐷𝑖)

𝑆. 𝐸. (𝐿𝐷𝑖) = 𝐿𝐷𝑖 ∗ 2.30 ∗ 𝑆. 𝐸. (log 𝐿𝐷𝑖)

�̅� = 𝑆𝑛𝑤𝑙𝑜𝑔𝑋

𝑆𝑛𝑤

𝑆𝑛𝑤 (𝑋 − �̅�)2 = 𝑆𝑛𝑤𝑙𝑜𝑔𝑋2 − (𝑆𝑛𝑤𝑙𝑜𝑔𝑋)2

𝑆𝑛𝑤

Page 8: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.

Page 9: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.

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𝑌 = 𝑎 ∗ log 𝑋 + 𝑏

Page 13: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.

Page 14: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.

Page 15: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.

Page 16: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.

Page 17: Detailed algorithms of interactive computer programs in MATLAB for the calculation of LD50 and other LD values using methods of Finney, Miller-Tainter and comparison with OECD modifications

© Asian Journal of Pharmacology and Toxicology, 2015.