POLYCHLORINATED DIBENZODIOXINS (PCDDs), POLYCHLORINATED DIBENZOFURANS (PCDFs), AND COPLANAR POLYCHLORINATED BIPHENYLS (PCBs)

General Information


Synonyms: COPLANAR POLYCHLORINATED BIPHENYLS (PCBs), PCDDs, PCDFs, POLYCHLORINATED DIBENZODIOXINS (PCDDs), POLYCHLORINATED DIBENZOFURANS (PCDFs)
Functional Class:
  • Food Contaminant
    • CONTAMINANT

Evaluations


Evaluation year: 2002
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: TRS 909-JECFA 57/121
Tox Monograph: FAS 48-JECFA 57/451
Estimated exposure

Best estimate: 7-160 (PCDD+PCDF) / 7-150 (coplanar PCBs) pg/kg bw/month

Toxicological study
Pivotal Study: Determination of LOEL for TCDD (Faqi et al., 1998): Pregnant Wistar rats Wistar rats (Faqi et al., 1998). Pregnant Wistar rats received an initial subcutaneous loading dose of [14C]TCDD at 25, 60 or 300 ng/kg bw 2 weeks before mating and were then given a subcutaneous weekly maintenance dose of TCDD at 5, 12 or 60 ng/kg bw. Effects on male reproduction were studied on postnatal days 70 and 170. Reported effects in offspring at the lowest dose: Decreased daily sperm production, number of sperm, sperm transit rate; increased number of abnormal sperm; increased mounting and intromission latencies. Determination of NOEL for TCDD (Ohsako et al., 2001): Pregnant Holtzman rats (6/group) were given a single oral dose of TCDD at 0, 12.5, 50, 200 or 800 ng/kg bw on day 15 of gestation, and the male offspring were assessed for reproductive development on postnatal days 49 and 120. At postnatal day 120, anogenital distance was significantly reduced at > 50 ng/kg bw (maximum decrease, about 18%) & ventral prostate weights were significantly reduced at 200 and 800 ng/kg bw, by 27% and 39%, respectively. Maternal body burden LOELs and NOELs for effects on male rat offspring of 25 ng/kg bw and 13 ng/kg bw, respectively, 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 body burdens at steady-state based on a toxicokinetic model that assumed 1st-order kinetics at low-doses & incorporated the estimated value for absorption & systemic half-life in humans of 50% and 7.6 years.
Animal specie: Wistar rats (Faqi et al, 1998); Holtzman rats (Ohsako, 2001)
Effect: Maternal body-burden effects on male offspring
NOEL: 12.5 ng/kg bw (Ohsako et al., 2001); none (Faqi et al., 1998)
LOEL: 25 ng/kg bw (Ohsako et al., 2001)
PTMI: 70 pg/kg bw/month; applied to intake of PCDDs, PCDFs and coplanar PCBs.
Point of departure: EHMI: 630 pg/kg (LOEL value) & 330 pg/kg (NOEL value)