Litchfield-Wilcoxon method

The Litchfield and Wilcoxon (1949) plotting method was once commonly used. It is certainly a valid method, and it poses no more restrictions on study design than those imposed by the probit method. The Litchfield-Wilcoxon method has become a victim of technology as modem, handheld calculators and the ready availability of simple computer programs have made other methods more convenient to run. 

However, at least one software company has adopted the Litchfield-Wilcoxon method for its acute toxicity protocol package. 

The occurrence of histamine release is also treated as an all-or-none response to permit log-probit plotting. The delayed depressor response plus tachycardia is judged to have or have not occurred after each single bolus injection of the drugs. The percentage of animals responding at each dose level is then determined and the data handled by the Litchfield-Wilcoxon method. 

Parenteral lethality was determined by injecting rabbits of mixed sexes intraperitoneally with 31.6, 63, 126, 252, and 500 /xg/kg of 2,3,7,8-TCDD as a 0.01% corn oil suspension control rabbits were injected with corn oil. The rabbits were housed in individual holding cages and were observed for signs of toxicity for four weeks. The LDso s were calculated by the Weil modification of the Thompson method 14, 15) or by the Litchfield and Wilcoxon method (9). The acute lethality studies were terminated when it was evident that the survivors were not showing signs of toxicity. 

Litchfield JJ, Wilcoxon F. 1949. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 96 99-133. 

Responses to individual doses are given in those cases in which an LD50 could not be calculated. The LD50 for oral administration to rabbits was calculated using the method of Litchfield and Wilcoxon 9) the remaining values were calculated using the Weil modification of the method of Thompson 15). 

NOTE ED50 values determined by the method of Litchfield and Wilcoxon ( 1949). 

Acute Toxicity. The LD50 following oral administration of parathion, either in propylene glycol solutions or in aqueous suspensions of the 15% wettable powder, has been determined for rats, mice, and guinea pigs. The lethal dose was approximated for rabbits and dogs. The results of these experiments are summarized in Table I. Statistical evaluation was by the method of Wilcoxon and Litchfield (11). 

A single bolus injection (200 pL) containing various doses of AmB of different formulations was given intravenously to groups of 10 male CDl mice (Charles River, France), weighing 25 to 30 g. Mouse survival was monitored daily for 30 days and the LD50 was determined by the method of Litchfield and Wilcoxon (27). 

The examples that have been utilized for determining both EDJ0 (in Chapter 6) and LD50 values in this chapter have been based upon visual inspection of graphical data. In actuality, in the pharmaceutical industry acute LDJ0 as well as EDJ0 values are obtained by employing one or more of several statistical formulas/methods (e.g., Litchfield and Wilcoxon). These analyses provide a more accurate determination of the value in question. 

Data analysis is done by the method of Litchfield and Wilcoxon. Mean dose - response curves are plotted on log-probit paper. Best fit to straight lines on these scales is determined by computerized regression. The cumulative ED50 values for vagal and sympathetic inhibition and the cumulative ED95 values for neuromuscular blockade are determined from the lines and 95 % confidence limits are calculated. Differences in potency are considered significant when P < 0.05. 

When sufficient information is available, the preferred method through 1999 utilized probit analyses (Finney 1971 Litchfield and Wilcoxon 1948 and the Number Cruncher Statistical System - Version 5.5) to determine the LCqi and the MLE was used for the LCoi value. 

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