Toxicological assessment of epinephrine and norepinephrine by analog approach

Epinephrine and norepinephrine have been used in the management of anaphylactic reactions and cardiac resuscitation, along with treatment of asthma and glaucoma extensively, but their toxicological profiles are not yet completed. Based on this circumstance, various toxicological endpoints of epinephrine and norepinephrine were explored. Since there is a paucity of some endpoints' data, readacross was applied to fill the data gaps using analog approach. Along with structural similarity, biological and mechanistic plausibility were also considered in analog selection. The similarity justification and supporting experimental data were provided for uncertainty evaluation. Short term repeated dose toxicity values as NOAEL and LOAEL belonging to epinephrine were used to estimate the repeated dose toxicity of norepinephrine. The in vivo and in vitro mutagenicity tests were considered representative of genotoxicity. Both chemicals are showed to be non-genotoxic. They are experimentally reported to cause developmental and reproductive toxicity. For the carcinogenicity endpoint, a conclusion could not be reached because similar compounds were seen to show conflicting results.