Teratogenic potency of 2,3,4,7,8-pentachlorodibenzofuran and of three mixtures of polychlorinated dibenzo-p-dioxins and dibenzofurans in mice. Problems with risk assessment using TCDD toxic-equivalency factors.
The potency of 2,3,4,7,8-pentachlorodibenzofuran (P5CDF) and of three defined 2,3,7,8-TCDD-free mixtures of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/PCDFs) to induce cleft palates in NMRI mice was studied. The data were compared with a dose-response curve for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The slope of the dose-response curve for P5CDF was the same as for TCDD. However, application of the International-TCDD-Toxic-Equivalency (I-TE) factor (NATO/CCMS 1988) of 0.5 overestimated the potency of the pentachlorinated congener about 2.5-fold under these experimental conditions, suggesting 0.2 as a TE factor. When assessing the cleft palate frequency on the basis of I-TEs and the weight of the substances, the potencies of the two PCDF mixtures studied were also clearly overestimated. This result was not substantially changed when using the TE factor of 0.2 for P5CDF. For the PCDD mixture studied, the cleft palate-inducing potency found largely agreed with the prediction when applying the I-TE factors. According to our data, the use of TE factors as calculated by the UBA/BGA (1985) or the NATO/CCMS (1988) are both conservative when attempting to assess the cleft palate incidence induced by PCDF mixtures in mice.
Nagao
T
T
Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Germany.
Golor
G
G
Hagenmaier
H
H
Neubert
D
D
D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D002972:Cleft Palate / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D008099:Liver / Q000187:drug effects; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000633:toxicity*; D011108:Polymers / Q000633:toxicity*; D011247:Pregnancy; D012307:Risk Factors; D013723:Teratogens / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects
D001572:Benzofurans; D004338:Drug Combinations; D000072317:Polychlorinated Dibenzodioxins; D011108:Polymers; D013723:Teratogens; C016068:polychlorodibenzofuran; C038890:2,3,4,7,8-pentachlorodibenzofuran