A dose-response curve for Yusho syndrome

Abstract

Analysis of rice oil consumption by a subgroup of Yusho patients and recent measurements on the composition of the oil they consumed suggest that the median dose (ED 50) of polychlorodibenzofurans (PCDFs) causing “severe” symptoms was about 68 μg/kg body mass (range: 45–104 μg/kg.) (The oil consumption was estimated ex post facto in a 1968 survey of the group's eating and cooking habits.) While most authorities now agree that the PCDFs present in the contaminated rice oil caused the Yusho syndrome, this ED 50 estimate is rendered somewhat uncertain by the fact that cocontaminant polychloroquaterphenyls (PCQs) and -biphenyls (PCBs), both present at about 100 times greater concentration, may either augment or diminish the PCDF toxicity by an unknown amount. Nevertheless, the ED 50 value quoted is consistent with what is known about the dose-response for induction of chloracne by 2,3,7,8-tetrachlorodibenzodioxin (TCDD). This finding implies that single doses of about 1 2 μg PCDF/kg body wt will cause no adverse effects in humans. Using Poiger's estimate of the clearance rate for TCDD in humans ( t 1 2 = ∼2100 days ) as a measure of the time to equilibrium for chronic ingestion, we conclude that a daily intake of 1.50 × 10 −4 μg PCDF/kg body mass (150 pg/kg/day) would cause no adverse effects and would represent a health-conservative basis for environmental standards. This value exceeds by 50 to 100 times the estimated present intake by North Americans of PCDFs from environmental sources (ca. 1–3 pg/kg/day).