POLYCHLORINATED DIBENZOFURANS (PCDFs)

Comments:

The Committee evaluated the PCDDs, PCDFs and coplanar PCBs for which toxic equivalency factors (TEFs) for mammals have been derived by WHO (Ahlborg et al., 1994). The subset of PCDDs and PCDFs considered in this assessment comprises those with chlorine substitutions at the 2, 3, 7 and 8 positions. TCDD is one of the most potent toxins known. 1,2,3,7,8-Pentachlorodibenzodioxin is of a similar potency, while the other members of the subset are 10–10 000 times less toxic. The 12 PCBs included in this assessment have either one or no chlorine substitutions in the ortho positions & have dioxin-like toxicity of 10–100 000 less than that of TCDD. As carcinogenicity due to TCDD was not linked to mutagenicity or DNA binding and occurred at higher levels than other toxic effects, the Committee concluded that establishing a tolerable intake based on non-cancer effects would also address carcinogenic risk. The Committee considered adverse effects on the reproductive tracts of prenatally-exposed male rats to be the critical endpoint for risk assessment. The maternal LOEL (Faqi et al., 1998) and NOEL (Ohsako et al., 2001) values of 25 ng/kg bw and 13 ng/kg bw, respectively, from the pivotal studies were converted to equivalent human monthly intake (EHMI) values of 630 pg/kg & 330 pg/kg by addition of 3 ng/kg bw to account for background body burden levels and calculation of the equivalent human body burdens at steady-state, based on assumed 1st-order kinetics at low-doses, 50% oral absorption & systemic half-life in humans of 7.6 years. To the EHMI values, the Committee applied total safety factors of 9.6 and 3.2, respectively, to account for intraspecies variation (3.2) & use of a LOEL instead of a NOEL (3). From the resultant range of PTMIs of 40–100 pg/kg bw per month, the Committee chose the mid-point, 70 pg/kg bw per month, as the PTMI to be applied to intake of PCDDs, PCDFs and coplanar PCBs expressed as TEFs. The Committee explored the theoretical effects of various maximum regulatory limits on compliance and on long-term average reduction of intake. The Committee concluded that, in view of the half-lives of these compounds in humans, setting regulatory limits on the basis of the PTMI would have no discernible effect on body burdens for several years.

Intake:

Range of TEFs of PCDDs and PCDFs: 7–68 pg/kg bw/month (median, GEMS estimate), 33–42 pg/kg bw/month (median, national data), 81–100 pg/kg bw/month (90th percentile, national data), & 15–160 pg/kg bw/month (90th-percentile, GEMS estimate). Coplanar PCBs: 7–57 pg/kg bw/month (median, GEMS estimate), 19–150 pg/kg bw/ month (90th percentile, GEMS estimate), 9–47 pg/kg bw/month (median, national data), & 25–130 pg/kg bw/month (90th percentile, national data).

Tolerable Intake:

PTMI 70 pg/kg bw/month, applied to intake of PCDDs, PCDFs and coplanar PCBs.

Meeting:

57

Report: 

Tox Monograph: