Quantitative differentiation of toxicity contributions and predicted global risk of fipronil and its transformation products to aquatic invertebrates

Biotransformation often alters chemical toxicity, yet its impacts on risk assessment are hardly quantified due to the challenges in acquiring internal exposure-based thresholds for chemicals that are readily metabolizable. Here, we integrated toxic unit and toxicokinetics to quantitatively assess toxicity contributions and potential risk of both parent compound and transformation products (TPs) to aquatic organisms, using fipronil (FIP) as a representative toxicant. In aquatic invertebrates Chironomus dilutus and Hyalella azteca, approximately 90 % of FIP was transformed to fipronil sulfone (SUL). FIP and SUL exhibited similar intrinsic toxicity to these organisms, which was contrary to conventional perception that SUL was more toxic than FIP. However, biotransformation was still important in risk assessment because the TP had 10-fold slower depuration rate than FIP. The amphipod H. azteca was found to be as sensitive to FIPs as the insect C. dilutus, which was previously considered ten times more sensitive based on external thresholds. This discrepancy has led to overlooking the toxicity of FIP to H. azteca in regional risk assessments. Lastly, we predicted the lethal risk of FIPs in global surface water. When using external thresholds for prediction, FIPs in 3.4 % of the water samples were lethally toxic to H. azteca, and the percentage of water samples at risk increased to 14 % when internal thresholds were used and SUF dominated the risk. This study presents an improved method for quantifying aquatic risk of readily metabolized toxicants. Our findings underscore the urgency of considering TPs in water quality assessments, especially for sensitive species that are at risk in the environment.