title: Acute inhalation toxicity of ammonia: revisiting the importance of RD50 and LCT01/50 relationships for setting emergency response guideline values.
abstract: This study examined the acute median lethal concentration (LC(50)) and the non-lethal threshold concentration (LC(01)) 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 LC(50) (LC(01)) were 12,303 (10,067) and 4923 (4028) mg/m(3), 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.
authors.affiliation: Global Drug Discovery - Global Early Development/Toxicology, Bayer Pharma AG, D-42096 Wuppertal, Germany. juergen.pauluhn@bayer.com
authors.forename: Jürgen
authors.initials: J
authors.lastname: Pauluhn
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000641:Ammonia / Q000633:toxicity*; D000818:Animals; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D005260:Female; D017408:Guidelines as Topic; D019570:Inhalation Exposure / Q000009:adverse effects*; D007928:Lethal Dose 50; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis; D020711:Threshold Limit Values; D023382:Toxicity Tests, Acute / Q000379:methods* / Q000592:standards
chemical_list: D000393:Air Pollutants; D000641:Ammonia