Derivation of avian dermal LD50 values for dermal exposure models using in vitro percutaneous absorption of [14C]-atrazine through rat, mallard, and northern bobwhite full thickness skin

Highlights: • Estimation of avian dermal LD50s is critical for assessing chemical risk to birds. • Current models generate high dermal exposure estimates. • These models also generate low dermal LD50 estimates. • Empirical dermal absorption data were used for an alternative approach. Understanding dermal exposure is important for higher-tier avian ecological risk assessments. However, dermal exposure and toxicity are often unknown for avifauna. The US EPA's Terrestrial Investigation Model (TIM) uses a method to estimate avian dermal LD50 values (and ultimately dermal exposure) that frequently results in unusually high dermal exposure and low dermal LD50 estimates. This is primarily a result of using organophosphate and carbamate toxicity data to develop the oral-dermal relationship. An estimated dermal LD50 is necessary to generate a dermal route equivalency factor that normalizes potency relative to oral toxicity within the dermal pathway dose equation. In this study, atrazine dermal absorption experiments were conducted with mallard, northern bobwhite, and rat skin. These data were used to derive an avian-mammal dermal route equivalency factor for atrazine and introduce a new approach for estimating dermal LD50 values and ultimately predicting exposure via the TIM dermal pathway. Compared to the default TIM method, this new approach yielded TIM output with lower mean total dose, lower dermal fraction of total dose, greater oral fraction of total dose, and reduced model predicted mortality for atrazine. In addition, the new approach was compared with other methods for estimating avian dermal LD50 values such as those proposed for use with mammalian data and physico-chemical properties and a triazine-specific oral-dermal equation using mammalian LD50 data. The three alternative approaches resulted in output similar to one another and different from the default TIM methods. These results indicate that a dermal route equivalency factor derived from empirical data provides a higher avian dermal LD50 estimate that is consistent with other methods. In addition, the use of this dermal route equivalency factor results in greatly reduced modeled atrazine risk to birds than previously reported in US EPA risk assessments using TIM.