OEHHA 2001 — Prop 65 MADL for Cadmium (Oral Route)
Summary
This is the May 2001 California Office of Environmental Health Hazard Assessment document deriving the Proposition 65 Maximum Allowable Daily Level for cadmium by the oral route, at 4.1 µg per day, based on reproductive toxicity. The MADL implements the 1997 Prop 65 listing of cadmium as a reproductive toxicant, which followed the DART Identification Committee’s December 1996 determination on the basis of the companion 1996 hazard identification document. The derivation uses the Ali et al. 1986 rat developmental toxicity study as the most sensitive pivotal study, with a LOEL of 0.706 mg/kg/day that is converted to a NOEL of 0.07 mg/kg/day by dividing by a factor of 10 per California regulation, multiplied by an assumed 58 kg pregnant-woman body weight to yield a NOEL of 4.1 mg/day, and divided by the standard Prop 65 safety factor of 1,000 to produce the MADL of 4.1 µg/day. The MADL applies to the oral route only; the document states that an inhalation MADL is under development, with the current status of that inhalation MADL not addressed in the document and pending verification against current OEHHA publications.
Key numbers
MADL and derivation parameters:
| Parameter | Value |
|---|---|
| MADL (oral) | 4.1 µg/day |
| Effective date of reproductive-toxicity listing | May 1, 1997 |
| MADL document date | May 2001 |
| Pivotal study | Ali et al. 1986, Neurobehav Toxicol Teratol 8:463-468 |
| Pivotal endpoint | Developmental toxicity (decreased pup birthweight, reduced postnatal weight gain, altered locomotor activity) in rats |
| Pivotal exposure | Cadmium acetate in drinking water to pregnant dams throughout gestation |
| LOEL | 0.706 mg/kg/day |
| NOEL (derived from LOEL by dividing by 10 per 22 CCR § 12803(a)(7)) | 0.07 mg/kg/day |
| Assumed pregnant-woman body weight | 58 kg |
| NOEL dose equivalent | 4.1 mg/day |
| Prop 65 safety factor | 1,000 |
| MADL (oral) | 4.1 mg/day ÷ 1,000 = 4.1 µg/day |
Alternative endpoint considered but not controlling (male reproductive toxicity):
| Parameter | Value |
|---|---|
| Pivotal study | Laskey et al. 1980, Environ Res 22:466-475 |
| Endpoint | Reduced epididymal sperm counts in rats exposed to cadmium chloride in drinking water |
| LOEL | 5 ppm |
| NOEL | 1 ppm |
| Reason not controlling | Developmental toxicity was observed at slightly lower exposures, and 22 CCR § 12803(a)(1) directs use of the endpoint with the lowest NOEL |
The 1,000x safety factor applied to NOEL values in the Prop 65 MADL framework represents the statutory “no observable effect” margin under California Health and Safety Code 25249.10: exposure at 1,000 times the MADL is expected to have no observable reproductive effect. This is a statutory safety margin, not an uncertainty factor of the EPA/EFSA type.
Methods (brief)
The derivation follows 22 CCR Sections 12801 and 12803, which prescribe the Proposition 65 MADL calculation procedure for reproductive toxicants. The procedure requires selection of the most sensitive appropriate study, use of the LOEL or NOEL from that study, conversion of LOEL to NOEL by dividing by 10 when only a LOEL is available, conversion to a daily dose by multiplying by the assumed adult body weight (58 kg for pregnant-woman endpoints per California convention, or 70 kg for other reproductive endpoints), and division by 1,000 to produce the MADL. OEHHA updated the literature search conducted for the 1996 hazard identification document before finalizing the MADL in 2001, reviewing additional human and animal studies published in the intervening years; those additional studies are listed in the MADL document’s appendix and did not shift the choice of pivotal study.
Implications
- Certification: the oral MADL of 4.1 µg/day is the California statutory floor. Consumer products sold in California that expose a consumer to more than 4.1 µg/day cadmium orally must carry a Prop 65 warning. HMT&C thresholds that are tighter than the MADL represent a precautionary posture relative to California’s implemented limit; HMT&C thresholds that are looser at the product level would need to confirm no Prop 65 warning trigger via exposure assessment.
- Courses: the LOEL-to-NOEL conversion by dividing by 10, and the 1,000x statutory safety factor, are characteristic Prop 65 procedural elements that are worth teaching alongside the EPA IRIS RfD procedure and the EFSA TWI derivation to show how different regulatory frameworks produce different reference values from overlapping primary literature.
- App: the MADL is a per-day dietary exposure threshold, directly useful for consumer-facing exposure estimates. Because the derivation rests on a developmental endpoint and uses a 58 kg pregnant-woman assumed body weight, the MADL is most sharply applicable to pregnant and potentially-pregnant consumers; the app should weight this threshold accordingly when rendering exposure estimates for users in the women-of-reproductive-age category.
- Microbiome: not addressed in this document.
Provenance notes
License class us-government-work. Two typographical errors in the source document, which this source page does not propagate:
First, the MADL document’s summary line (p. 1) states the pivotal study was “in mice.” The full reference listing on the same document (p. 3, Ali MM, Murthy RC, Chandra SV 1986) is titled “Developmental and long term neurobehavioral toxicity of low level, in utero, cadmium exposure in rats.” The full reference title is correct and indicates rats, not mice; this source page uses rats in the endpoint description. The error in the summary is flagged here and not propagated to the regulation page or the metal page.
Second, the MADL document (p. 1) lists the CAS Registry number for cadmium as “71-43-28.” The correct CAS number for elemental cadmium is 7440-43-9. The number 71-43-2 is the CAS registry number for benzene. This is a typographical error in the source document. Any downstream use of the CAS number from this source page uses the correct value 7440-43-9.
The regulation page notes that an inhalation MADL was indicated as under development as of May 2001, with current status pending verification against current OEHHA publications. The oral MADL at 4.1 µg/day is the value that has been operative in California enforcement since 2001.