Minimizing Experimental Testing on Fish for Legacy Pharmaceuticals

There was no regulatory requirement for ecotoxicological testing of human pharmaceuticals authorized before 2006, and many of these have little or no data available to assess their environmental risk. Motivated by animal welfare considerations, we developed a decision tree to minimize in vivo fish t...

Full description

Saved in:
Bibliographic Details
Published inEnvironmental science & technology Vol. 57; no. 4; pp. 1721 - 1730
Main Authors Coors, Anja, Brown, A. Ross, Maynard, Samuel K., Nimrod Perkins, Alison, Owen, Stewart, Tyler, Charles R.
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 31.01.2023
Subjects
Algae
Animal welfare
Animals
Biocompatibility
Daphnia
Decision trees
Ecotoxicology
Ecotoxicology and Public Health
Environmental Monitoring
Environmental protection
Environmental risk
Fish
Fishes
In vivo methods and tests
Pharmaceutical Preparations
Pharmaceuticals
Quotients
Risk Assessment
Toxicity
Toxicity testing
Water Pollutants, Chemical - analysis
Water Pollutants, Chemical - toxicity
vertebrate testing
animal welfare
fish plasma model
ecotoxicity
environmental risk assessment
Online AccessGet full text

Cover

More Information
Summary:There was no regulatory requirement for ecotoxicological testing of human pharmaceuticals authorized before 2006, and many of these have little or no data available to assess their environmental risk. Motivated by animal welfare considerations, we developed a decision tree to minimize in vivo fish testing for such legacy active pharmaceutical ingredients (APIs). The minimum no observed effect concentration (NOECmin, the lowest NOEC from chronic Daphnia and algal toxicity studies), the theoretical therapeutic water concentration (TWC, calculated using the fish plasma model), and the predicted environmental concentration (PEC) were used to derive API risk quotients (PEC/NOECmin and PEC/TWC). Based on a verification data set of 96 APIs, we show that by setting a threshold value of 0.001 for both risk quotients, the need for in vivo fish testing could potentially be reduced by around 35% without lowering the level of environmental protection. Hence, for most APIs, applying an assessment factor of 1000 (equivalent to the threshold of 0.001) to NOECmin substituted reliably for NOECfish, and TWC acted as an effective safety net for the others. In silico and in vitro data and mammalian toxicity data may further support the final decision on the need for fish testing.
ISSN:0013-936X
1520-5851
DOI:10.1021/acs.est.2c07222