Claim File c005 — Benzophenone-1 (BP-1, 2,4-Dihydroxybenzophenone)

CAS 131-56-6

Context: BP-1 is the major in-vivo metabolite of BP-3 (oxybenzone) in humans and aquatic organisms, and is also a primary photodegradation product of BP-3. It is also used as an industrial UV absorber (UV-0) in plastics and fragrance/color stabilization. It is not approved as a UV filter for sunscreens in any major jurisdiction. This file documents BP-1 because exposure to BP-1 is intrinsic to BP-3 use, and because BP-1 is more potent biologically than its parent.

Section 1: Identity

• INCI: Benzophenone-1 [C1]
• IUPAC: (2,4-Dihydroxyphenyl)(phenyl)methanone — i.e. 2,4-dihydroxybenzophenone (DHB) [C1]
• Synonyms: BP-1, UV-0, 2,4-DHB, DOB, Uvinul 400, Cyasorb UV-9 (some industrial designations) [C1]
• CAS: 131-56-6 [C1]
• Molecular formula: C13H10O3 [C1]
• Molecular weight: 214.22 g/mol [C1]
• Physical: white-to-pale-yellow crystalline powder; mp 144.5–147 °C; bp ~194 °C / 1 mmHg; density ~0.7 g/mL [C1]
• Solubility: sparingly soluble in water; soluble in alcohols, esters, glacial acetic acid, methyl ethyl ketone; logKow ≈ 2.96 [C1]

Regulatory status

• Use level (when present in cosmetics as colorant/fragrance stabilizer): typically <0.5%. Not used as a UV filter on label. [C2]

Section 2: UV Absorption Spectrum

• λmax #1: ~287 nm (UVB)
• λmax #2: ~325 nm (UVA-II)
• Spectral coverage: ~280–340 nm (UVB + short UVA-II) — comparable to BP-3
• Molar absorption coefficient:
• At ~287 nm in ethanol: ε ≈ 1.6 × 10⁴ M⁻¹·cm⁻¹ [C2]
• At ~325 nm in ethanol: ε ≈ 1.5 × 10⁴ M⁻¹·cm⁻¹ [C2]
• E(1%, 1 cm) at ~287 nm: ≈ 750 (computed) [C3]
• Solvent / pH dependence: like BP-3 the molecule has an ortho-OH/C=O ESIPT motif; the extra 4-OH increases polar-solvent solubility and shifts the bands slightly compared with BP-3. The 4-OH (para to the C=O) is sufficiently acidic (pKa ≈ 7.6) that under cosmetic-pH conditions the molecule sits near the protonation threshold; ionized form is red-shifted.
• Function: efficient UV-absorber/quencher used industrially as plastic stabilizer; photophysics dominated by ESIPT (similar to BP-3) — relatively good non-radiative dissipation.

Section 3: Photodegradation

• BP-1 is itself photostable in plastic-stabilizer service (this is its industrial purpose).
• In aqueous environmental matrices, BP-1 photodegrades with rate constants of similar order to BP-3 (k ≈ 10⁻⁵ s⁻¹ under simulated sunlight). It is a frequently detected transformation product in studies of BP-3 photolysis in surface waters.
• As a photoproduct/metabolite of BP-3:
• Generated by O-demethylation of BP-3
• Found in urine of humans applying BP-3-containing sunscreens (often at concentrations ~1–10% of parent BP-3) [C1]
• Generated in coral and sea anemone tissues from BP-3 (Vuckovic et al. 2022 Science — though those animals primarily form 2-O-glucosides and BP-1 does not feature as strongly)
• Photoproducts of BP-1 itself: further hydroxylated trihydroxybenzophenones (e.g., 2,3,4-trihydroxybenzophenone), ring-opened carboxylic acids in advanced oxidation studies. [C2]

Section 4: Notable issues

4.1 Endocrine activity (the dominant concern)

• More potent than BP-3 in standard estrogenic-activity assays.
• Yeast estrogen screen / E-screen MCF-7 proliferation: BP-1 EC50 in the low µM range (often reported ~0.1–1 µM for half-maximal proliferation), versus BP-3 typically ~5–50 µM in the same assays — i.e. ~10–50× more potent. [C1 — Schlumpf et al. 2001, 2004; Morohoshi et al. 2005]
• Stimulates BG-1 ovarian-cancer cell proliferation via ER-α and induces cyclin D1 — both in vitro and in xenograft mouse models (Park et al. 2013 Toxicology 305:41-48). [C1]
• Also induces epithelial-mesenchymal transition / metastasis-related markers in ER+ cells (Shin et al. 2016) and Wnt/β-catenin activation (Park et al. 2021). [C2]
• In-vivo: uterotrophic activity in immature rodent assay at oral doses (Yamasaki et al. 2003 Toxicol Lett); inhibits placental 3β-HSD activity (steroidogenesis disruption) at micromolar concentrations (Yan et al. 2023). [C1]
• Anti-androgenic activity in AR reporter assays at micromolar concentrations.
• Why it matters for BP-3 users: BP-1 forms in vivo from BP-3, has a longer biological half-life than its parent, and bioaccumulates — meaning topical BP-3 application produces measurable BP-1 internal exposure at potencies higher than the parent compound itself.

4.2 Skin penetration / human exposure

• BP-1 detected in >80–95% of urine samples in U.S. and European biomonitoring studies, almost always co-detected with BP-3. Concentrations typically 10–100× lower than urinary BP-3. [C1 — Calafat 2008, Asimakopoulos 2014]
• Some BP-1 environmental exposure also occurs from food-contact plastics and household dust.

4.3 Aquatic / ecological

• BP-1 is detected in surface waters at low ng/L concentrations; persistence and bioaccumulation potential moderate.
• Aquatic ecotoxicity: zebrafish developmental endpoints, fish steroidogenesis disruption reported at µg/L. Estrogenic activity reproducible across organisms. [C2]

4.4 Allergenicity

• Limited dedicated patch-test data; cross-reactivity with BP-3 expected. Not a top-listed allergen because of low direct application exposure.

4.5 Carcinogenicity / classification

• The closely related parent ketone benzophenone (CAS 119-61-9, not BP-1) is classified by IARC as Group 2B "possibly carcinogenic to humans" (IARC Monograph 101, 2013). BP-1 itself has not been separately classified by IARC. The structure–activity inference and the in-vitro genotoxicity data have led the EU to consider regulatory action on several "BP-x" derivatives under CLP/CMR rules. [C1 — IARC Mono 101]

Confidence

• Identity → C1
• Spectrum λmax / ε → C2
• Endocrine in-vitro potency vs BP-3 → C1
• In-vivo / metabolite role → C1
• Carcinogenicity (parent benzophenone IARC 2B) → C1; BP-1 specifically → C3 (extrapolated)

Key citations

1. Park J et al. Toxicology 2013;305:41-48. doi:10.1016/j.tox.2013.01.003
2. Schlumpf M et al. Environ Health Perspect 2001;109:239-244.
3. Yamasaki K et al. Toxicol Lett 2003;146:111-120.
4. Yan H et al. Toxicol Appl Pharmacol 2023 — placental 3β-HSD inhibition by benzophenone UV filters.
5. Calafat AM et al. Environ Health Perspect 2008;116:893-897.
6. Asimakopoulos AG et al. Sci Total Environ 2014;470-471:1243-1249.
7. Vuckovic D et al. Science 2022;376:644-648. doi:10.1126/science.abn2600
8. IARC Monographs Vol. 101 (2013), Benzophenone — Group 2B.
9. Morohoshi K et al. Food Chem Toxicol 2005;43:555-559.