Acute inhalation toxicity of ammonia: Revisiting the importance of RD50 and LCT01/50 relationships for setting emergency response guideline values

This study examined the acute median lethal concentration (LC50) and the non-lethal threshold concentration (LC01) of ammonia in male and female Wistar rats nose-only exposed at exposure durations of either 1 or 4 h. Additional attributes characterizing the acute toxicity of inhaled ammonia were determined during a post-exposure period of 2 weeks. The objective of this study is to further refine the methodology applied to derive Emergency Response Planning Guideline (ERPG) values on potent sensory irritants in a controlled rat bioassay. In the more susceptible male rats the 1- and 4-h LC50 (LC01) were 12,303 (10,067) and 4923 (4028) mg/m3, respectively. At sublethal exposure levels the ventilation of rats was about one third of normal breathing. This change in ventilation and inhalation dosimetry was adjusted for Cxt-dependent lethal endpoints whereas sensory irritation-related phenomena were C-dependently adjusted. In summary, the outcome of this study shows that C- and C × t-dependent causes of toxicity need to be appreciated when extrapolating across species with species-specific inhalation dosimetry. It also appears to be indispensable that each exposure metric must be disentangled when translating C × t-dependent lethality and reflexively-induced, sensation-based C-dependent point of departures. For one hour exposure periods, these PODs were derived to be 1500 and 500 ppm, respectively.