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Toxicities derived from anti-tumor screening data
Abstract:
A recent study published by the National Academy of Sciences emphasized an acute shortage of data on the toxic effects of chemicals in man and animals. This shortage makes risk assessment difficult and impacts seriously on the development of a sound environmental policy. The National Cancer Institute, in its search for effective anti-cancer agents, has determined quantitative as well as qualitative toxicities for a large number of chemicals. Probit analysis was used to derive lethalities (LD50s) from data obtained in the process of testing anti-cancer agents in mice. These data were compared with those derived from testing those same agents in normal mice and it was found that a correlation exists between the two toxicities. Toxicities derived from NCI testing in normal animals were compared with published values and a similar correlation was found. LD50s were derived for all compounds tested in normal mice as well as those tested in mice bearing L1210 and P388 lymphocytic leukemias. Over 32,000 LD50s were derived for 22,597 unique compounds.
Insights
This study addresses the critical lack of chemical toxicity data by generating over 32,000 lethal dose 50 (LD50) values. These findings aid in chemical risk assessment and environmental policy development.
Area of Science:
- Toxicology
- Environmental Health
- Pharmacology
Background:
- A significant data gap exists regarding the toxic effects of chemicals in humans and animals, hindering accurate risk assessment and sound environmental policy.
- The National Cancer Institute (NCI) has generated extensive toxicity data during its search for anti-cancer agents.
- Establishing reliable toxicity data is crucial for regulatory and public health initiatives.
Purpose of the Study:
- To address the shortage of chemical toxicity data by deriving and compiling lethal dose 50 (LD50) values.
- To validate toxicity data by comparing NCI-derived values with published data and testing in different animal models.
- To provide a comprehensive dataset of LD50 values for a large number of unique chemical compounds.
Main Methods:
- Utilized probit analysis to calculate LD50 values from toxicity data obtained during anti-cancer agent testing in mice.
- Compared toxicity data from mice bearing specific leukemias (L1210 and P388) with data from normal mice.
- Validated NCI-derived toxicity values by comparing them with previously published toxicity data.
Main Results:
- A strong correlation was observed between toxicities determined in mice bearing leukemias and those in normal mice.
- NCI-derived toxicities in normal animals showed a similar correlation with published toxicity values.
- Over 32,000 LD50 values were successfully derived for 22,597 unique chemical compounds.
Conclusions:
- The study successfully generated a substantial database of LD50 values, significantly contributing to the understanding of chemical toxicities.
- The findings support the utility of NCI's toxicity testing data for broader risk assessment applications.
- This comprehensive dataset provides valuable information for environmental policy, chemical safety, and drug development.
