Table 1.
Characterizations of the treatment of some key uncertainties in relevant authoritative assessments of human health risks from dioxins and in proposals for human tolerable daily intakes
| Assessment | Pivotal effects | Uncertainty factors (UF) used in deriving risk criteria | TDI (TWI)a pg g bw−1 day−1 |
|---|---|---|---|
| WHO (1998)b | Rhesus monkey endometriosis and neurobehaviour; rat male offspring reproduction and immune effects | Mainly pharmacokinetic differences accounted for but not very extensively or explicitly | 1–4 |
| EU/SCF (2000)c | Approximately as above (but with different body burden estimation and dose conversion) | 1–3 (7–21 TWI) | |
| EU/SCF (2001)d | Rat male offspring reproduction; rhesus monkey and rat immune effects omitted) | 10 overall, unspecified | 2 (14 TWI) |
| USEPA (2000a)e | Including carcinogenicity in humans, not a critical endpoint(s); assessment is debatable | Various | 0.06 |
| UK 2001 (2004)f | Rat reproductive development; tumors | LOAEL–NOAELi extrapolation 3 × inter-individual variation in toxicokinetics 3.2 (+half order-of-magnitude due to TEFsj and uncertainties in rat kinetics etc.) | 2, reproduction/development (8, cancer) |
| Germany (2002)g (unofficial) |
More endpoints, species, dosing ages/periods and dioxin-like agents requested | More (empirical) UFs required for pharmacokinetics, LOAEL–NOAEL, dose and animal-human extrapolation, individual variation, additional DLCsk | 1 |
| Japan (2004)h | Rat female reproductive development | 10 LOAEL–NOAEL extrapolation | 4 |
aTDI/TWI tolerable daily or weekly intake, b WHO (1998), based on Gehrs et al. Toxicology 122;3(1997):229–40; Gray et al. Toxicol Appl Pharmacol 146;1(1997a):11–20; Hurst et al. Toxicol Sci 53;2(2000) and 57;2(2000):275–83; Mably et al. Toxicol Appl Pharmacol 114;1(1992):97–107, 108–17, 118–26; Rier et al. Fundam Appl Toxicol 21;4(1993):433–41; Schantz & Bowman, Neurotoxicol Teratol 11;1(1989):13, see also Gaylor and Aylward, Regulat Toxicol Pharmacol 40;1(2004):9–17, cSCF (2000), d SCF (2001), based also on Faqi et al. Toxicol Appl Pharmacol 150;2(1998):383–92; Ohsako et al. Toxicol Sci 66;2(2002):283-92; note that the lowest-dose effects on sperm count of offspring have been found non-reproducible (Foster et al. Environ Health Perspect 118;4(2010):458–64), eUSEPA 2000a, based on Kociba et al. Toxicol Appl Pharmacol 46;2(1978):279–303; fSACN and COT (2004), gUBA unpublished 2002; Gies et al. (2007) (see references), see also Hojo et al. Environ Health Perspect 110;3(2002):247–54 on lowest-dose neurobehavioral effects, and sources in Assmuth and Jalonen (2005) on other putative low-dose effects in humans, hSumida et al. Organohalogen Compds 2005: 2537–9, based also on Gray et al. Toxicol Appl Pharmacol 146;2(1997b):237–44, see also Arima et al. Reproduction 28;4(2009):495–502, iLowest Observed Adverse Effect Level–No Observed Adverse Effect Level, jTCDD (2,3,7.8-Tetrachloro-p-dioxin) Equivalency Factors, Van den Berg et al. (1998) (see references), kDLCs Dioxin-Like Compounds