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Claim File c002 — Sulisobenzone (Benzophenone-4, BP-4)

CAS 4065-45-6

Section 1: Identity

INCI name: Benzophenone-4 [C1]
USAN / FDA name: Sulisobenzone [C1]
IUPAC: 5-Benzoyl-4-hydroxy-2-methoxybenzenesulfonic acid [C1]
Synonyms: BP-4, Uvinul MS40, Cyasorb UV-284, Spectra-Sorb UV284, Escalol 577 [C1]
CAS: 4065-45-6 [C1]
EC No.: 223-772-2 [C1]
Molecular formula: C14H12O6S [C1]
Molecular weight: 308.31 g/mol [C1]
Physical: light-tan to off-white crystalline powder, mp ~145 °C [C1]
Solubility: water-soluble (~250 g/L; 1 g/4 mL in some specs) — the sulfonic acid group makes BP-4 hydrophilic; logKow ≈ 0.37 (much lower than BP-3); typically formulated after partial neutralization with NaOH or triethanolamine to give the sulfonate salt Benzophenone-5 (sodium salt). Soluble in alcohols and aqueous-alcoholic vehicles. [C1]
Note: a closely related INCI "Benzophenone-5" denotes the sodium salt of BP-4 (CAS 6628-37-1) — sometimes used interchangeably in formulations. [C1]

Jurisdiction	Status / max concentration
EU Annex VI #22	up to 5% (expressed as acid) [C1]
USA OTC Monograph M020 (sulisobenzone)	up to 10%; FDA 2021 Proposed Order classes as "insufficient data for GRASE" pending additional safety data, similar status as oxybenzone [C1]
Australia (TGA)	Permitted; up to 10% [C2]
Japan	Permitted as quasi-drug filter; commonly limited to 10% [C2]
South Korea (MFDS)	up to 5% [C2]
Hawaii reef bans	Not included in SB2571 (only oxybenzone + octinoxate banned) [C1]
Palau / USVI	Various local sunscreen regulations — BP-4 sometimes covered, sometimes not

Typical use levels: 1–5% in aqueous gel sunscreens, sprays, hair-care UV protection, lip products, and as a photostabilizer in fragrance and color-cosmetic formulations [C2]

λmax #1 (UVB): ~286–290 nm [C2]
λmax #2 (UVA-II): ~324–326 nm [C2]
Spectral coverage: ~260–340 nm — UVB and short UVA-II. Does not extend into long UVA-I (>360 nm). [C1]
Molar absorption coefficient (in water at neutral pH):
At ~286 nm: ε ≈ 1.4–1.6 × 10⁴ M⁻¹·cm⁻¹ [C2]
At ~324 nm: ε ≈ 1.0–1.2 × 10⁴ M⁻¹·cm⁻¹ [C2]
Sodium-salt form (BP-5) shows similar profile, slightly red-shifted in highly alkaline solution
E(1%, 1 cm) at 286 nm: ≈ 450–520 (computed from MW 308 and ε above) [C3]
Solvent / pH dependence: As with all 2-hydroxy-benzophenones, spectrum is governed by the keto-enol equilibrium of the 2-OH/4'-CO motif (intramolecular H-bond → enol form). In aqueous neutral-pH solution the sulfonate is fully ionized but the 2-OH is undissociated (pKa of 2-OH ≈ 9.5–10), so the chromophore behaves like BP-3. At pH > 10, deprotonation of the 2-OH causes a marked red-shift and broadening of the long-wavelength band. [C2]
Functional classification: moderate UVB + weak UVA-II filter, structurally analogous to BP-3 but water-phase soluble, useful where lipid-soluble filters cannot be incorporated (clear gels, leave-on hair products). [C1]

Photostability: generally regarded as photostable in formulation (similar profile to BP-3 — the ESIPT route dominates de-excitation). Reported losses under simulated solar irradiation are typically <10–15% over standard sunscreen-irradiation protocols. [C2 — Sakkas et al. 2003; Vione 2013]
Aqueous photodegradation kinetics (direct photolysis under simulated sunlight):
k ≈ 5 × 10⁻⁶ – 5 × 10⁻⁵ s⁻¹; half-life in pure water several hours to >1 day
Faster in presence of dissolved organic matter / nitrate (indirect photolysis via •OH) [C2]
Quantum yield (Φ_loss, aqueous): ≈ 10⁻⁴–10⁻³ (low, similar to BP-3) [C2]
Photoproducts (UV/H2O2, UV/persulfate, simulated sunlight studies):
Hydroxylated derivatives, demethylated species, ring-opened products and small carboxylic-acid fragments
Some chlorinated by-products in pool/treated water
Less well characterized than BP-3 photoproducts
Wastewater / environmental: BP-4 is among the most frequently detected sunscreen filters in wastewater effluents and surface waters because of its water solubility and resistance to conventional treatment. Concentrations of 0.1–10 µg/L commonly reported in WWTP effluent; up to ~10 µg/L in receiving rivers. [C1 — Tsui et al. 2014; Ramos et al. 2015]

Lower estrogenic potency than BP-3 in standard yeast-ER and MCF-7 assays: relative potency to E2 reported as ~10⁻⁶ to <10⁻⁷; in some assays BP-4 is inactive at testable concentrations (the sulfonate group reduces membrane permeation and ER binding) [C2 — Kunz & Fent 2006; Molina-Molina 2008]
However, BP-4 has been reported to have weak androgen-receptor antagonism and altered thyroid endpoints in zebrafish at µg/L concentrations [C2 — Zucchi 2011]
SCCS has not produced a dedicated recent opinion specific to BP-4 (assessed as part of historical Annex VI listings)

Very low skin penetration owing to ionic/polar character — in vitro Franz-cell studies typically report <1–2% of applied dose crosses skin within 24 h, vs much higher for BP-3. [C2 — Jiang et al. 1998 Aust J Dermatol; Janjua et al. 2008]
Not included in the FDA Matta JAMA 2019/2020 absorption studies (those were oxybenzone, avobenzone, octocrylene, ecamsule, octinoxate, octisalate, homosalate). No comparable plasma-absorption data exists at this level of rigor for sulisobenzone.
Detected in human urine in biomonitoring studies, generally at lower frequencies and concentrations than BP-3.

BP-4 is a frequent contaminant of coastal waters because of its water solubility — environmental persistence concern is more about exposure ubiquity than acute potency.
Acute toxicity values reported on freshwater organisms (e.g., Daphnia magna 48-h EC50 ~50 mg/L) and zebrafish embryos (LC50 in mg/L range) — orders of magnitude above environmentally measured concentrations. [C2]
Coral planulae studies (Downs and others) have not shown BP-4 to produce the same severity of bleaching/ossification as BP-3 at comparable concentrations, though direct comparative data are limited. BP-4 is not named in the Hawaii SB2571 ban.

BP-4 sensitization is reported but is less common than BP-3 in patch-test populations. May cross-react with other benzophenones.
Photo-contact dermatitis less frequent than for BP-3; the polar sulfonate likely reduces dermal residence time.

Limited published data; no major toxic photoproducts reported analogous to BP-1.

EU Cosmetics Regulation 1223/2009 Annex VI #22 (Benzophenone-4 / Benzophenone-5).
FDA OTC Monograph M020 — Sunscreen Drug Products (sulisobenzone listed at up to 10%).
Kunz PY, Fent K. Aquat Toxicol 2006;79:305-324. doi:10.1016/j.aquatox.2006.06.016
Tsui MM et al. Water Res 2014;67:55-65. doi:10.1016/j.watres.2014.09.013
Sakkas VA et al. J Chromatogr A 2003;1016:211. doi:10.1016/S0021-9673(03)01331-1
Janjua NR et al. J Invest Dermatol 2008;128:2503. doi:10.1038/jid.2008.83
Ramos S et al. J Hazard Mater 2015;306:354. doi:10.1016/j.jhazmat.2015.12.026