EPA IRIS — Cadmium Oral Reference Doses
The EPA Integrated Risk Information System chemical assessment for cadmium provides two route-specific oral reference doses that reflect the different absorption efficiency of cadmium in water versus food matrices (EPA IRIS Cd 1989). Both values were last revised October 1, 1989 and remain in force (EPA IRIS Cd 1989).
| Parameter | Water RfD | Food RfD |
|---|---|---|
| Oral RfD | 5 × 10⁻⁴ mg/kg/day | 1 × 10⁻³ mg/kg/day |
| Daily equivalent (µg/kg/day) | 0.5 | 1.0 |
| NOAEL | 5 × 10⁻³ mg/kg/day | 1 × 10⁻² mg/kg/day |
| Composite uncertainty factor | 10 | 10 |
| Critical effect | Significant proteinuria | Significant proteinuria |
| EPA confidence | High | High |
| Last revised | 1989-10-01 | 1989-10-01 |
Critical effect and derivation
The critical endpoint is significant proteinuria, indicating renal tubular dysfunction, the same canonical cadmium endpoint that anchors the EFSA 2009 tolerable weekly intake and the ATSDR 2012 chronic oral Minimal Risk Level. The route-specific RfD distinction is a methodological feature unique to the EPA approach: cadmium absorption from drinking water is approximately twofold higher than from food matrices, so equivalent body burden protection requires a tighter water RfD than food RfD (EPA IRIS Cd 1989).
The composite uncertainty factor of 10 reflects EPA’s standard approach for human variability when the critical effect is observed in human chronic-exposure cohort studies (occupational and environmentally exposed populations), reducing the need for animal-to-human extrapolation factors (EPA IRIS Cd 1989). The “high confidence” classification reflects both the strength of the underlying epidemiological evidence and the consistency across studies (EPA IRIS Cd 1989).
Status of the 1999 reassessment draft
A 1999 EPA external review draft for cadmium (EPA/635/R-99/000-something), retained in raw/reports/EPA_IRIS_Cadmium_ToxicologicalReview.pdf, proposed a reassessment that was never finalized. The 1989 RfD values therefore remain the operative US federal reference (EPA IRIS Cd 1989). The 1999 draft is documented separately in the synthesis page as a historical document worth ingesting in a future wave because it demonstrates EPA reviewed and chose not to adopt a revision, which is part of the defensibility record.
Comparison to other reference values
| Body / Jurisdiction | Value (original units) | Daily equivalent (µg/kg b.w./day) | Ratio to ATSDR chronic oral MRL | Source |
|---|---|---|---|---|
| ATSDR chronic oral MRL (US, 2012) | 0.1 µg/kg/day | 0.1 | 1 | ATSDR 2012 |
| EFSA TWI (EU, 2009) | 2.5 µg/kg b.w./week | ≈ 0.36 | 3.6x | EFSA Cd 2009 |
| JECFA PTMI (international, 2010) | 25 µg/kg b.w./month | ≈ 0.83 | 8.3x | JECFA 73rd 2010 |
| EPA IRIS oral RfD, food (US, 1989) | 1 × 10⁻³ mg/kg/day | 1.0 | 10x | EPA IRIS Cd 1989 |
| EPA IRIS oral RfD, water (US, 1989) | 5 × 10⁻⁴ mg/kg/day | 0.5 | 5x | EPA IRIS Cd 1989 |
The EPA IRIS food RfD is the most permissive of the four major dietary cadmium reference values when expressed on a daily per-body-weight basis (EPA IRIS Cd 1989). The 1989 vintage of the assessment, contrasted with the more recent ATSDR (2012) and EFSA (2009) values, partly explains the divergence.
Sources
- EPA IRIS Cd 1989 — EPA IRIS Chemical Assessment Summary, Cadmium (CASRN 7440-43-9), last revised October 1, 1989.