Comparison of the up-and-down, conventional LD50, and fixed-dose acute toxicity procedures.
The up-and-down procedure (UDP), fixed-dose procedure (FDP) and conventional LD50 tests were compared to determine their consistency in chemical hazard classification for acute oral toxicity according to the European Economic Community (EEC) system. There was consistent classification for 23 out of 25 cases between the UDP and the conventional LD50 results, in 16 out of 20 cases between the FDP and the conventional LD50, and in seven out of 10 cases between the UDP and the FDP. The UDP needed only between six and 10 animals of one sex (fewer than either the LD50 or the FDP). Available literature indicates that the sexes are usually similar in their acute toxicity responses and that of females are often more sensitive than males when acute toxicity differences do exist, thus obviating the need for both sexes to be tested in most cases. Unlike the FDP, the UDP also estimates an LD50, thus providing data directly applicable to all current hazard classification systems based on acute oral toxicity.
Lipnick
R L
RL
US Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Washington, DC 20460.
Cotruvo
J A
JA
Hill
R N
RN
Bruce
R D
RD
Stitzel
K A
KA
Walker
A P
AP
Chu
I
I
Goddard
M
M
Segal
L
L
Springer
J A
JA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005062:European Union; D005260:Female; D015386:Hazardous Substances / Q000009:adverse effects / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D016016:Proportional Hazards Models; D051381:Rats; D017751:Safety Management; D012727:Sex Characteristics; D018675:Toxicity Tests / Q000592:standards*
D015386:Hazardous Substances