# Excerpt — the origin of the 10⁻⁶ "one in a million" acceptable cancer risk *Two firsthand/expert histories of how regulators built a round number to stand in for a threshold that, for genotoxic carcinogens, does not exist. Both held locally and OCR-verified. Source PDFs: `papers/lateral/rodricks2019_risk-assessment-came-to-washington.pdf`, `papers/lateral/crump2018_doseresponse_VSD-history.pdf`. Grade **[CONFIRMED-primary]** (Rodricks is a participant memoir).* ## Rodricks (2019), *Dose-Response* 17(1) — "When Risk Assessment Came to Washington: A Look Back" Joseph V. Rodricks was an FDA scientist present at the creation. On the 1962 **DES Proviso** to the Delaney Clause (a carcinogenic animal drug allowed if "no residue" is found), and what happened when detection outran "zero": > "Mantel's risk target was 1 in 100 million, and the calculated doses corresponding to that excess lifetime > risk he labeled 'virtually safe.'" > "Hutt proposed that 'safe doses' for carcinogens such as DES could be defined as those associated with > lifetime risk levels of less than **1 in 1 million**, when these risks were estimated using a linear, > no-threshold model (several publications had demonstrated that the Mantel–Bryan approach could not be counted > on to place an upper bound on risk at low doses but that a linear, no threshold model could)." → The 10⁻⁶ number entered U.S. law through FDA General Counsel **Peter Barton Hutt**, after "extensive discussions" with Rodricks and others — a deliberately chosen round number, two orders of magnitude *up* from Mantel's already-arbitrary 10⁻⁸. It is the carcinogen-side de minimis, grown inside the Delaney statute. ## Crump (2018), *Dose-Response* 16(4) — "Cancer Risk Assessment and the Biostatistical Revolution of the 1970s" Kenny Crump on the conceptual break that made a "no-effect level" impossible for genotoxic carcinogens — the exact void the essay's §9 names: > "In the 1970s there came a realization that cancer could develop from a mutation in a single cell and > consequently it was unlikely that a threshold existed for substances that could cause such mutations, and > that risk could increase linearly with exposure." Crump documents the **Mantel-Bryan (1961)** log-probit "virtually safe dose" procedure (his Fig. 1) and notes the method "apparently was never used by a regulatory" agency in that form — the math was a placeholder that the agencies replaced, but the round-number *target* survived. ## The earlier / INDIRECT root (operator's question, 2026-06-11) — the 10⁻⁶ branch grows off the factor-of-100 trunk Rodricks states, firsthand, what the 10⁻⁶ method was built to **replace** — and it is the first essay's number, run by Frawley's own FDA mentors. **[CONFIRMED-primary]:** > Leo Friedman (FDA) "told me that the method for establishing safe levels for most chemicals, devised by his > predecessor at the FDA, **Arnold Lehman, and another FDA toxicologist, O. Garth Fitzhugh**, was based on a > widely accepted view … that the toxic properties of most chemicals expressed themselves only after a > **threshold** dose … The **Lehman–Fitzhugh approach, published in the 1949 to 1955 period, relied upon the > application of what were then called 'safety factors.'**" - **Shared root.** The carcinogen-side de minimis (10⁻⁶) and Frawley's food-additive de minimis (0.1 ppm, built on the 100-fold margin) are **two branches off the same Lehman–Fitzhugh trunk** — and Lehman ran the FDA Division of Pharmacology where Frawley worked, while **Fitzhugh (with Nelson) was Frawley's own co-author.** Crump confirms the split: "Prior to around 1960, risk assessment for all adverse health effects, **including cancer**, were carried out in a similar manner" (the NOAEL-safety-factor approach); the 10⁻⁶ branch separated only with the 1970s single-cell/no-threshold realization. **[CONFIRMED-primary]** (Crump). - **The indirect (radiation) source of the no-threshold logic.** Rodricks: the threshold-free view came from "a **community of experts working in the areas of chemical and radiation carcinogenesis** … their notions of thresholds, reversibility, and dose–response were radically different from those of the traditional toxicologists." He names **Arthur Upton (NCI director, "a giant in the area of radiation risk")**, **Umberto Saffiotti**, and **Marvin Schneiderman**. The single-hit model Mantel & Bryan lean on traces to radiation target theory (**Lea, *Actions of Radiations on Living Cells*, 1946**, their ref 12). So the no-threshold premise under 10⁻⁶ was **imported from radiation protection**, not grown inside food toxicology. **[CONFIRMED- primary]** for the named connection; the radiation-protection primaries themselves are not held. - **The indirect root, now partly nailed** (acquisition targets, `05` §C7 / `_WISHLIST.md` §🔵): **(a)** ✓ **HELD — Lehman & Fitzhugh (1954), "100-Fold Margin of Safety"** (operator Taildrop 2026-06-11, register **H16**) — the shared trunk; it concedes the ×100 is "a good target but not an absolute yardstick … no scientific or mathematical means by which we can arrive at an absolute value." Still wanted: **(b)** a radiation-protection primary — NBS Handbook 59 / NCRP Rep. 17 (1954, "maximum permissible dose"; free on archive.org) and/or **Lea 1946** (single-hit); **(c)** **Crump (1976)**, the "linearized multistage model" Rodricks says EPA adopted (the method bridge from Mantel-Bryan to the modern linear default); **(d)** the other **~5 papers in Friedman's "thin folder"** that seeded the FDA's move — Rodricks names only Mantel-Bryan; the rest are uncatalogued. **Links:** [[frawley-dossier-project]] · pairs with `MantelBryan_1961_virtually-safe-dose_excerpt.md` and `Kelly_1991_myth-of-10-6_excerpt.md` · ties to `reckoningscience/sections.md` §1 (the ignorance factor / factor of 100), §9 (no-threshold void), §11 (the 1995 rule, whose 0.5 ppb is a sub-10⁻⁶ calc — `sources/FDA_Threshold-of-Regulation_60FR36582_1995.txt`), and `10` §3.5. Still-wishlisted primaries: Mantel & Bryan 1961 (the original 10⁻⁸); the FDA SOM Federal Register pages; Kelly 1991 (the "no scientific basis" survey). See `papers/lateral/_WISHLIST.md`.