# Excerpt — Rulis (1992): the 477-carcinogen potency curve behind the 0.5 ppb threshold

*Alan M. Rulis (FDA), "Threshold of Regulation: Options for Handling Minimal Risk **Situations**," Chapter 14 in
*Food Safety Assessment* (Finley, Robinson & Armstrong eds.), **ACS Symposium Series 484**, ACS, Washington DC,
1992, **pp. 132–139**. DOI **10.1021/bk-1992-0484.ch014**. **Operator-supplied via Taildrop 2026-06-11; held &
OCR-verified** in `papers/lateral/rulis1992_acs484_threshold-of-regulation.pdf` (+`.txt`). Grade
**[CONFIRMED-primary]**. This is the primary derivation the 1995 Threshold of Regulation rule cites as **"Ref.
1"** — i.e. *the* calculation that makes 0.5 ppb a sub-10⁻⁶ number. Flips `_WISHLIST.md` priority-🔴 item.*

## The carcinogen-potency-distribution method (the bell curve, in the author's hand)
Rulis builds the threshold not from a safety factor but from the **statistical distribution of carcinogen
potencies**: plot the potencies (TD₅₀s) of a large carcinogen set as a lognormal distribution, then read off the
dietary concentration at which the *upper-bound* lifetime risk for a randomly-drawn carcinogen falls below a
target. Verified inside:

> "…one corresponding to **343 carcinogens** selected from the original data base compiled by Gold et al. … and
> the other, a more recent one using **477 carcinogens** chosen from an updated Gold et al. database." (p. 135,
> Figure 2.)

The section is headed **"Use of Carcinogen Potencies to Establish a Threshold of Regulation."** Candidate T/R
levels are weighed in ppt–ppb terms (50 ppt as one option; Schwartz's 100 ppt–1 ppb range bounded by analytical
detection at the low end and a >50% "target risk avoidance probability" at the high end; Munro et al.'s 1 ppb,
"possibly as high as 10 to 15 ppb … if adequate data are available to preclude the genotoxicity of the
chemical"). The **477-carcinogen curve** is the one the 1995 rule's preamble describes when it says FDA "plotted
the potencies … as a probability distribution … and found that they formed a bell-shaped distribution curve"
(60 FR at 36583; `sources/FDA_Threshold-of-Regulation_60FR36582_1995.txt`).

## Why it matters
- **It closes the keystone loop with primary on both ends:** Rulis 1992 = the *derivation* (the 477-carcinogen
  potency distribution); the 1995 FR = the *adoption* (0.5 ppb as a sub-"one in a million" level). Both now held.
- It is the **same Rulis** who, in 1987, credited "Frawley in 1967" (register **D5**) — the man who carried
  Frawley's number into the FDA is also the man who recast it as a 10⁻⁶ calculation.
- Note the genotoxicity caveat (Munro): the higher thresholds are conditioned on *precluding* genotoxicity —
  i.e. the method itself concedes that for a genotoxic carcinogen the no-threshold problem (essay §9) reasserts.

**Links:** [[frawley-dossier-project]] · ties to `10` §3.5/§4 (0.5 ppb = a 10⁻⁶ calc), register **D5/D6/H10**,
and `reckoningscience/sections.md` §11. Munro's TTC line is reserved for the later essay (per CLAUDE.md plan).