title: Determination of concentration-time-mortality relationships versus LC50s according to OECD guideline 403.
abstract: The effect of decreasing the number of animals on the accuracy of estimated concentration-time-mortality relationships and the LC50 values derived from these was investigated by means of simulation methods. Studies of NH3, Cl2, H2S, and COCl2 were made using 5 rats per sex per group. Mortality rates were analysed in 500 new data sets obtained by randomly removing 4 rats/sex/group from the original data sets. It was concluded that the concentration-time-mortality relationship and the LC50 values can be determined over a 5-10-fold time range using one rat/sex/group. The resulting 5 and 95 percentiles compare favourably with the 90% confidence limits when determining a LC50 according to OECD guideline 403. When using concentration-time-mortality relationships, additional information can be obtained which can be used in inhalation hazard risk assessment.
authors.affiliation: TNO-CIVO, AJ Zeist, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Arts
authors.forename: A
authors.initials: A
authors.lastname: Zwart
authors.forename: E D
authors.initials: ED
authors.lastname: Schoen
authors.forename: J M
authors.initials: JM
authors.lastname: Klokman-Houweling
mesh_terms: D000280:Administration, Inhalation; D000641:Ammonia / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D002712:Chlorides / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006285:Health Planning; D006287:Health Planning Guidelines; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000633:toxicity; D008171:Lung Diseases / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D009026:Mortality; D051381:Rats; D011919:Rats, Inbred Strains; D012307:Risk Factors; D013223:Statistics as Topic; D013997:Time Factors
chemical_list: D002712:Chlorides; D000641:Ammonia; D006862:Hydrogen Sulfide