California Proposition 65 — Cadmium Listing and Maximum Allowable Daily Level
Cadmium is listed under California’s Safe Drinking Water and Toxic Enforcement Act of 1986 (Proposition 65) under two separate findings: as a carcinogen (listing pre-dating this wiki’s ingest corpus, with a separately derived No Significant Risk Level that is not yet ingested) and as a reproductive toxicant (listing effective May 1, 1997, following the Developmental and Reproductive Toxicant Identification Committee’s December 4, 1996 determination) (OEHHA 1996). This page covers the reproductive-toxicity listing and its implementing Maximum Allowable Daily Level of 4.1 µg/day oral (OEHHA 2001). The carcinogen listing and its NSRL are covered in a separate regulation page pending ingest of the underlying OEHHA documents.
Reproductive-toxicity listing
California Health and Safety Code 25249.5 et seq. requires the state to publish a list of chemicals known to the state to cause cancer or reproductive toxicity. For reproductive toxicity, the “state’s qualified experts” are the members of the Developmental and Reproductive Toxicant Identification Committee, a committee of the Office of Environmental Health Hazard Assessment’s Science Advisory Board (22 CCR 12301) (OEHHA 1996).
The DART ID Committee selected cadmium for evaluation at its May 12, 1995 public meeting and requested that OEHHA staff prepare a review of the scientific evidence on the chemical’s reproductive toxicity. OEHHA’s Reproductive and Cancer Hazard Assessment Section produced the hazard identification document “Evidence on the Developmental and Reproductive Toxicity of Cadmium” (OEHHA 1996), which was released in draft for public and Committee review on October 4, 1996. At its December 4, 1996 meeting the Committee determined that cadmium had been clearly shown through scientifically valid testing according to generally accepted principles to cause developmental and male reproductive toxicity. The reproductive-toxicity listing took effect May 1, 1997 (OEHHA 1996).
MADL value
MADL parameters from OEHHA 2001:
| Parameter | Value |
|---|---|
| MADL (oral) | 4.1 µg/day |
| Listing effective date | May 1, 1997 |
| MADL document date | May 2001 |
| Controlling endpoint | Developmental toxicity (reduced pup birthweight, reduced postnatal weight gain, altered locomotor activity) |
| Controlling study | Ali et al. 1986 (rats, cadmium acetate in drinking water during gestation) |
| Statutory safety factor | 1,000 |
The MADL for inhalation was noted in the 2001 document as under development (OEHHA 2001); its current status has not been verified against current OEHHA publications and is pending as an action item.
Derivation
The MADL was derived following 22 CCR Sections 12801 and 12803, the procedure prescribed in California regulation for Proposition 65 MADL development (OEHHA 2001). The pivotal study was Ali et al. 1986, which reported a LOEL of 0.706 mg/kg/day for developmental effects in rats exposed in utero to cadmium acetate in drinking water; no NOEL was identified in the study, so the LOEL was converted to a NOEL by dividing by 10 per 22 CCR § 12803(a)(7), yielding a NOEL of 0.07 mg/kg/day. This NOEL was multiplied by the assumed pregnant-woman body weight of 58 kg to produce a daily NOEL dose of 4.1 mg/day. The MADL was then calculated by dividing by the statutory safety factor of 1,000 per 22 CCR § 12801(b)(1), producing the final MADL of 4.1 µg/day (OEHHA 2001).
The male reproductive toxicity endpoint was considered as an alternative basis using Laskey et al. 1980 (NOEL 1 ppm for reduced epididymal sperm counts) (OEHHA 2001). That endpoint was not controlling because the developmental endpoint was more sensitive, and 22 CCR § 12803(a)(1) directs use of the endpoint with the lowest NOEL when multiple reproductive effects support the listing.
Statutory meaning of the MADL
Under California Health and Safety Code 25249.10, exposure at 1,000 times the MADL is the level at which no observable reproductive effect is expected (OEHHA 2001). The MADL itself is therefore the 1,000x safety-adjusted threshold below which a business is not required to provide a Proposition 65 warning for reproductive toxicity for cadmium exposure by the oral route. A consumer product that would expose a consumer to more than 4.1 µg/day cadmium by the oral route must carry a Prop 65 warning unless the business can demonstrate by other means that the exposure does not exceed the MADL (OEHHA 2001).
The MADL is not a food safety threshold in the EFSA TWI or EPA RfD sense. It is a product-labeling trigger derived through a statutory formula that differs from dose-response reference-value methodology used by other agencies. Comparing the MADL directly to a weekly or monthly TWI or to an RfD requires understanding the different regulatory functions each value plays.
Carcinogen listing (separate)
Cadmium is also listed under Proposition 65 as a carcinogen, through a separate Committee determination that predates the reproductive-toxicity listing (OEHHA 1996). The carcinogen listing has its own No Significant Risk Level derived independently through the Prop 65 cancer pathway. Neither the carcinogen listing nor the NSRL is ingested yet; both are flagged for a future ingest wave and are not covered by this page’s MADL value.
Comparison to other reference values
Pending full batch completion. The MADL is per-day exposure denominated in micrograms; the EFSA TWI is per-kilogram-body-weight-per-week; the JECFA PTMI is per-kilogram-body-weight-per-month; the EPA IRIS RfD is per-kilogram-body-weight-per-day. Direct numeric comparison requires translation through assumed body weight and averaging window, and the underlying endpoints differ (EFSA and EPA anchor on renal tubular dysfunction; OEHHA MADL anchors on developmental toxicity; JECFA and ATSDR to be determined on ingest). This comparison will be populated once all reference values are in the wiki.
Sources
- OEHHA 1996 — OEHHA, October 1996. Evidence on the Developmental and Reproductive Toxicity of Cadmium (hazard identification document underlying the 1997 listing).
- OEHHA 2001 — OEHHA, May 2001. Proposition 65 Maximum Allowable Daily Level (MADL) for Reproductive Toxicity for Cadmium (Oral Route).
Pending: OEHHA documents underlying the separate Proposition 65 carcinogen listing for cadmium and the corresponding No Significant Risk Level; the 2001-plus inhalation MADL if completed.