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Para-aminopropiophenone (PAPP) is a potent methaemoglobin (MetHb) forming agent used for the lethal control of exotic carnivores and mustelids. To assess the sensitivity of Australian wildlife to PAPP we developed an in vivo assay that did not use death as an endpoint. Sub-lethal dose-response data were modelled to predict PAPP doses required to achieve an endpoint set at 80% MetHb (MetHb₈₀). The comparative sensitivity of non-target mammals referenced to this endpoint was found to be highly variable, with southern brown bandicoots (Isoodon obesulus) the most sensitive species (MetHb₈₀ = 6.3 mg kg⁻¹) and bush rats (Rattus fuscipes) the most tolerant (MetHb₈₀ = 1035 mg kg⁻¹). Published LD₅₀ estimates were highly correlated with PAPP doses modelled to achieve the MetHb₈₀ endpoint (r² = 0.99, p < 0.001). Most dose-response data for native mammals were collected in the field or in semi-natural enclosures, permitting PAPP and placebo dosed animals to be fitted with tracking transmitters and transponders and released at their point of capture. A protracted morbidity and mortality was observed only in Australian ravens (Corvus coronoides). The combination of sub-lethal dose-response assay and survival data collected in the field provided more relevant information about the actual hazard of pest control agents to non-target wildlife species than laboratory-based lethal-dose bioassays. We discuss the need to replace lethal-dose data with biologically meaningful insights able to define a continuum of toxicological hazards that better serve the needs of conservation and veterinary scientists and wildlife managers. Full article

Para-aminopropiophenone (PAPP) is a methaemoglobin (MetHb) forming compound used for the lethal control of invasive carnivores and mustelids. By measuring the dose-dependent inhibition of O₂ transport arising from the oxidation of haemoglobin (HbFe²⁺) to MetHb (HbFe³⁺), we determined the sensitivity of nine bird species to PAPP. A methaemoglobinaemia absorbance index (MAI) was validated in five common bird species to determine thresholds associated with a 99% probability of survival (ST₉₉) and a 50% probability of mortality (LT₅₀). Dose–response trials in high conservation value birds sought MAI values below the ST₉₉ threshold, projecting the LT₅₀ value and avoiding the need for lethal outcomes. Black-backed gull (LT₅₀ = 1784.7) and eastern rosella (LT₅₀ = 1074 mg kg⁻¹) were the most tolerant species, while brown kiwi (LT₅₀ = 8.4 mg kg⁻¹) and weka (LT₅₀ = 9.3 mg kg⁻¹) were the most sensitive. Takahē were of intermediate acute sensitivity (LT₅₀ = 51 mg kg⁻¹), although protracted impacts on haemoglobin were observed in takahē up to 72 h later and associated with PAPP doses as low as 25.6 mg kg⁻¹. In pukeko (LT₅₀ = 138.4 mg kg⁻¹), protracted declines in haemoglobin 72 h later occurred at doses as low as 29.5 mg kg⁻¹, while at higher doses (253 and 112 mg kg⁻¹), deaths resulted after 4–6 days. Based upon PAPP doses that caused acute and protracted responses, we provide estimates for the lowest observable adverse effect level (LOAEL) and no observable effects level (NOEL) for nine bird species. Full article