John William Trevan’s concept of Median Lethal Dose (LD50/LC50) – more misused than used
Introduction Median lethal dose (MLD) has been a controversial subject among biologists and animal ethicists since its inception in 1927 by Trevan. Toxicologists use MLD (LD50) as the first step to assess the toxicity of a substance. Animal ethicists criticize LD50 tests because animals suffer pain,...
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| Format: | Article |
| Language: | English |
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Institute of Rural Health
2021-07-01
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| Series: | Journal of Pre-Clinical and Clinical Research |
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| Online Access: | https://www.jpccr.eu/John-William-Trevan-s-concept-of-Median-Lethal-Dose-LD50-LC50-more-misused-than-used,139588,0,2.html |
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| author | Sadasivan Kalathil Pillai Katsumi Kobayashi Mathews Michael Thomson Mathai Bhavana Sivakumar Parvathy Sadasivan |
| author_facet | Sadasivan Kalathil Pillai Katsumi Kobayashi Mathews Michael Thomson Mathai Bhavana Sivakumar Parvathy Sadasivan |
| author_sort | Sadasivan Kalathil Pillai |
| collection | DOAJ |
| description | Introduction
Median lethal dose (MLD) has been a controversial subject among biologists and animal ethicists since its inception in 1927 by Trevan. Toxicologists use MLD (LD50) as the first step to assess the toxicity of a substance. Animal ethicists criticize LD50 tests because animals suffer pain, and LD50 is irreproducible. The disadvantage of classifying chemicals based on LD50, the importance of the ‘characteristics’ proposed by Trevan, and the ideal mortality range for determining the best estimate of LD50 are also discussed.
Objective
The aim of this review was to understand Trevan’s concept of LD50 and the method of Litchfield and Wilcoxon (L and W), and Finney’s probit analysis for LD50 determination
Materials and method
A literature survey was conducted using Google search and Pubmed. Simulated data set was used for identifying the ideal mortality range for calculating the ‘best estimate’ of LD50.
Brief description of the state of knowledge
After Trevan, the extensively used classical methods for LD50 determination are Finney’s probit analysis and the L and W method. Animal ethicists questioned LD50, because of its irreproducibility. Presently used methods for LD50 tests do not provide information on the dose-response, hence assessing the complete spectrum of toxicity is not possible. However, LD50 is used to classify chemicals.
Conclusions
'The 'characteristic' is more specific than the slope or LD50 of a dose-response curve. LD50 does not manifest the exact nature of the toxicity of a substance; hence, classifying chemicals based on LD50s may have little relevance |
| first_indexed | 2024-04-10T00:25:20Z |
| format | Article |
| id | doaj.art-61bd9db9cd9442ecab086ced5539a264 |
| institution | Directory Open Access Journal |
| issn | 1898-2395 1898-7516 |
| language | English |
| last_indexed | 2024-04-10T00:25:20Z |
| publishDate | 2021-07-01 |
| publisher | Institute of Rural Health |
| record_format | Article |
| series | Journal of Pre-Clinical and Clinical Research |
| spelling | doaj.art-61bd9db9cd9442ecab086ced5539a2642023-03-15T10:41:28ZengInstitute of Rural HealthJournal of Pre-Clinical and Clinical Research1898-23951898-75162021-07-0115313714110.26444/jpccr/139588139588John William Trevan’s concept of Median Lethal Dose (LD50/LC50) – more misused than usedSadasivan Kalathil Pillai0https://orcid.org/0000-0001-9498-1425Katsumi Kobayashi1https://orcid.org/0000-0002-3588-4526Mathews Michael2https://orcid.org/0000-0002-0268-7307Thomson Mathai3https://orcid.org/0000-0003-3505-0203Bhavana Sivakumar4https://orcid.org/0000-0002-9137-8150Parvathy Sadasivan5https://orcid.org/0000-0002-0782-9802International Institute of Biotechnology and Toxicology (IIBAT), Padappai, IndiaEx-Cabinet Secretary Researcher, Food Safety Commission of Japan, Tokyo, JapanTrichinopoly, IndiaTOXINDIA, Maharashta, IndiaSASTRA Deemed University, Thanjavur, IndiaSivavilas, IndiaIntroduction Median lethal dose (MLD) has been a controversial subject among biologists and animal ethicists since its inception in 1927 by Trevan. Toxicologists use MLD (LD50) as the first step to assess the toxicity of a substance. Animal ethicists criticize LD50 tests because animals suffer pain, and LD50 is irreproducible. The disadvantage of classifying chemicals based on LD50, the importance of the ‘characteristics’ proposed by Trevan, and the ideal mortality range for determining the best estimate of LD50 are also discussed. Objective The aim of this review was to understand Trevan’s concept of LD50 and the method of Litchfield and Wilcoxon (L and W), and Finney’s probit analysis for LD50 determination Materials and method A literature survey was conducted using Google search and Pubmed. Simulated data set was used for identifying the ideal mortality range for calculating the ‘best estimate’ of LD50. Brief description of the state of knowledge After Trevan, the extensively used classical methods for LD50 determination are Finney’s probit analysis and the L and W method. Animal ethicists questioned LD50, because of its irreproducibility. Presently used methods for LD50 tests do not provide information on the dose-response, hence assessing the complete spectrum of toxicity is not possible. However, LD50 is used to classify chemicals. Conclusions 'The 'characteristic' is more specific than the slope or LD50 of a dose-response curve. LD50 does not manifest the exact nature of the toxicity of a substance; hence, classifying chemicals based on LD50s may have little relevancehttps://www.jpccr.eu/John-William-Trevan-s-concept-of-Median-Lethal-Dose-LD50-LC50-more-misused-than-used,139588,0,2.htmlld50jw trevanacute toxicitymedian lethal dosemldlitchfield and wicoxon |
| spellingShingle | Sadasivan Kalathil Pillai Katsumi Kobayashi Mathews Michael Thomson Mathai Bhavana Sivakumar Parvathy Sadasivan John William Trevan’s concept of Median Lethal Dose (LD50/LC50) – more misused than used Journal of Pre-Clinical and Clinical Research ld50 jw trevan acute toxicity median lethal dose mld litchfield and wicoxon |
| title | John William Trevan’s concept of Median Lethal Dose (LD50/LC50) – more misused than used |
| title_full | John William Trevan’s concept of Median Lethal Dose (LD50/LC50) – more misused than used |
| title_fullStr | John William Trevan’s concept of Median Lethal Dose (LD50/LC50) – more misused than used |
| title_full_unstemmed | John William Trevan’s concept of Median Lethal Dose (LD50/LC50) – more misused than used |
| title_short | John William Trevan’s concept of Median Lethal Dose (LD50/LC50) – more misused than used |
| title_sort | john william trevan s concept of median lethal dose ld50 lc50 more misused than used |
| topic | ld50 jw trevan acute toxicity median lethal dose mld litchfield and wicoxon |
| url | https://www.jpccr.eu/John-William-Trevan-s-concept-of-Median-Lethal-Dose-LD50-LC50-more-misused-than-used,139588,0,2.html |
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