COMPARATIVE ACUTE LETHALITY OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD), 1,2,3,7,8-PENTACHLORODIBENZO-P-DIOXIN AND 1,2,3,4,7,8-HEXACHLORODIBENZO-P-DIOXIN IN THE MOST TCDD-SUSCEPTIBLE AND THE MOST TCDD-RESISTANT RAT STRAIN

We have previously demonstrated a more than 300-fold difference in acu te LD50 values for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) between male Long-Evans (Turku AB; L-E) and Han/Wistar (Kuopio; H/W) rats afte r intraperitoneal exposure. In the present study, we compared the acut e lethality of TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PCDD) and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (HCDD) in these strains by intr agastric administration. In agreement with previous data, H/W rats pro ved to be strikingly resistant to TCDD, since even the highest dose te sted, 7200 mug/kg, was below the LD50 level for both genders. The corr esponding LD50 values for female and male L-E rats were 9.8 and 17.7 m ug/kg, respectively. A similar strain difference was discovered for PC DD: the LD50 value was > 1620 mug/kg for female H/W rats and between 2 0 and 60 mug/kg for female L-E rats. Surprisingly, the acute lethality of HCDD did not follow the same pattern. Female H/W rats turned out t o be only about 10 times less susceptible to that congener than female L-E rats (LD50 values 1871 and between 120 and 360 mug/kg, respective ly). These findings do not support the widely accepted concept that su fficiently high doses of all dioxin congeners will produce the same ef fects. Either the higher chlorinated dioxins have toxic effects distin ct from those of TCDD or the relative contribution of toxic impacts va ries among these compounds.