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Environmental risk assessment (ERA) is critical for protecting life by predicting population responses to contaminants. However, routine toxicity testing often examines only one genotype from surrogate species, potentially leading to inaccurate risk assessments, as natural populations typically consist of genetically diverse individuals. To evaluate the importance of intraspecific variation in translating toxicity testing to natural populations, we quantified the magnitude of phenotypic variation between 20 Daphnia magna clones exposed to two levels of microcystins, a cosmopolitan cyanobacterial toxin. We observed significant genetic variation in survival, growth, and reproduction, which increased under microcystins exposure. Simulations of survival showed that using a single genotype for toxicity tolerance estimates on average failed to produce accurate predictions within the 95% confidence interval over half of the time. Whole genome sequencing of the 20 clones tested for correlations between toxicological responses and genomic divergence, including candidate loci from prior gene expression studies. We found no overall correlations, indicating that clonal variation, rather than variation at candidate genes, predicts population-level responses to toxins. These results highlight the importance of incorporating broad intraspecific genetic variation, without focusing specifically on variation in candidate genes, into ERAs to more reliably predict how local populations will respond to contaminants., (© 2024. The Author(s).)