Quantitative comparison of the results obtained by the multiple-dose guinea pig maximization test and the non-radioactive murine local lymph-node assay for various biocides.
We compared the results of the multiple-dose guinea pig maximization test (GPMT) and the non-radioactive murine local lymph-node assay (LLNA) for various biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results in the LLNA. In the GPMT, the minimum first induction doses ranged over four orders (0.00005-0.5%), while elicitation-threshold doses, which were evaluated using an optimally sensitized group of animals in the multiple-dose studies, ranged over five orders (0.00006-2.8%). In the LLNA, minimum induction doses ranged over more than three orders (0.01-30%). With respect to 13 biocides that were positive in both the GPMT and the LLNA, results were quantitatively compared. When compared after conversion to corresponding area doses (microg/cm), the minimum doses required to elicit skin reaction in guinea pigs were always lower than that for induction in mice with all biocides. Correlation between minimum induction doses from the GPMT and the LLNA seemed poor (r=0.57), while that between minimum induction doses in the LLNA and elicitation-threshold doses in the GPMT was relatively good (r=0.73). The results suggest the possibility to estimate human elicitation-threshold doses, which are definitely lacking in the process of risk assessment for skin-sensitizers, from the data of the LLNA.
Yamano
Tetsuo
T
Osaka City Institute of Public Health and Environmental Sciences, 8-34 Tojo-cho, Tennoji-ku, Osaka 543-0026, Japan. tetsuo.yamano@iphes.city.osaka.jp
Shimizu
Mitsuru
M
Noda
Tsutomu
T
D000287:Administration, Topical; D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007271:Injections, Intradermal; D023441:Local Lymph Node Assay; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000473:pathology*; D015262:Xenobiotics / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
D000963:Antimetabolites; D015262:Xenobiotics; D001973:Bromodeoxyuridine