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

Abstract

We have previously demonstrated a more than 300-fold difference in acute LD50 values for 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) between male Long-Evans (Turku AB; L-E) and Han/Wistar (Kuopio; H/W) rats after intraperitoneal exposure. In the present study, we compared the acute 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 intragastric administration. In agreement with previous data, H/W rats proved to be strikingly resistant to TCDD, since even the highest dose tested, 7200 micrograms/kg, was below the LD50 level for both genders. The corresponding LD50 values for female and male L-E rats were 9.8 and 17.7 micrograms/kg, respectively. A similar strain difference was discovered for PCDD: the LD50 value was > 1620 micrograms/kg for female H/W rats and between 20 and 60 micrograms/kg for female L-E rats. Surprisingly, the acute lethality of HCDD did not follow the same pattern. Female H/W rats turned out to be only about 10 times less susceptible to that congener than female L-E rats (LD50 values 1871 and between 120 and 360 micrograms/kg, respectively). These findings do not support the widely accepted concept that sufficiently high doses of all dioxin congeners will produce the same effects. Either the higher chlorinated dioxins have toxic effects distinct from those of TCDD or the relative contribution of toxic impacts varies among these compounds.

Differential Expression Profiling of the Hepatic Proteome in a Rat Model of Dioxin Resistance

“…A particularly useful tool for studying key mechanisms in dioxin toxicity is indeed the large interstrain difference between TCDD-sensitive Long-Evans (Turku/AB; L-E) and TCDD-resistant H/W rats (12)(13)(14). H/W rats are more than 1000 times more resistant to the acute lethality of TCDD than L-E rats, having oral LD 50 values of Ͼ9600 and 10 g of TCDD/kg of body weight, respectively.…”

Use of 2-Azido-3-[125I]iodo-7,8-dibromodibenzo-p-dioxin as a Probe to Determine the Relative Ligand Affinity of Human versus Mouse Aryl Hydrocarbon Receptor in Cultured Cells

“…There are a number of intra-and interspecies differences in sensitivity to the effects of TCDD (Henck et al, 1981;Chapman and Schiller, 1985;Pohjanvirta et al, 1993). There are also a number of differences in the primary amino acid sequence of the AhR in various species, and it is thought that these differences may be correlated to the susceptibility of a given species to TCDD (Poland et al, 1994;Pohjanvirta et al, 1998;Korkalainen et al, 2000).…”

Genetic Variation in AhR Gene Related to Dioxin Sensitivity in the Japanese Field Mouse, Apodemus speciosus

“…Remarkable differences in sensitivity to TCDD have been reported among species and strains (Bello et al, 2001;Enan et al, 1996;Kleeman et al, 1988;Pohjanvirta et al, 1993;Pohjanvirta and Tuomisto, 1994;Poland and Knutson, 1982). For example, the lethal dose 50 % (LD50) values vary from 1 µg/kg for guinea pig, the most sensitive animal, to >5000 µg/kg for hamster, the most resistant (Poland and Knutson, 1982).…”