Table 3. Overview on the Skin Sensitization Profile (Human and LLNA) of 15 Aromatic Aldehydes in Comparison with Their Analytically Proven Reactivity Profile.

compound	no	LLNA potency class	skin sensitization profilea	reaction chemistry profile
chloratranol	F3	strong	LLNA EC3 = 0.4%, pEC3 = 2.67	(1) low Gly-pNA imine stability (log K < 2, Table 1)
				(2) lowest imine decomposition rates (k–1pseudo < 0.005 min–1, Table 1)
				(3) cross-linking of protein structures (Scheme 8)
			human potency class 1	(4) adduct stabilization through imine-enaminone tautomerisation11
				(5) high lysine reactivity at pH 7.511 (Table 2)
				(6) high cysteine-SH reactivity39
atranol	F2	strong	LLNA EC3 = 0.6%, pEC3 = 2.40	(1) low Gly-pNA imine stability (log K < 2, Table 1)
				(2) lowest imine decomposition rates (k–1pseudo < 0.004 min–1, Table 1)
				(3) cross-linking of protein structures (Scheme 8, Natsch & Emter 201732)
			human potency class 1	(4) adduct stabilization through imine-enaminone tautomerization11
				(5) high lysine reactivity at pH 7.511 (Table 2)
				(6) high cysteine-SH reactivity39
2-bromo-5-hydroxy benzaldehyde	E4	moderate	LLNA EC3 = 2.6%, pEC3 = 1.89	(1) medium Gly-pNA imine stability (log K > 2, Table 1)
				(2) no lysine reactivity at pH 7.511 (Table 2)
				(3) SNAr-type adduct formation with cysteine-SH (Scheme 10)
4-chlorobenzaldehyde	D2	weak/non	LLNA EC3 > 10%, pEC3 < 1.15	(1) low Gly-pNA imine stability (log K < 2, Table 1)
				(2) moderate lysine reactivity at pH 7.511 (Table 2)
4-isopropyl benzaldehyde	B1	weak/non	LLNA EC3 > 10%, pEC3 <1.17	(1) very low Gly-pNA imine stability (log K < 1, Table 1)
				(2) low lysine reactivity at pH 7.511 (Table 2)
4-methyl benzaldehyde	A4	weak/non	LLNA EC3 > 10% (0.69%)	(1) very low Gly-pNA imine stability (log K < 1, Table 1)
			pEC3 <1.08 (2.24)	(2) very low lysine reactivity at pH 7.511 (Table 2)
6-methoxy naphthalene carbaldehyde	F1	weak/non	LLNA EC3 > 20%, pEC3 <1.17	(1) low Gly-pNA imine stability (log K < 2, Table 1)
				(2) no lysine reactivity at pH 7.511 (Table 2)
benzaldehyde	A1	weak/non	LLNA EC3 > 25%, pEC3 < 0.63	(1) low Gly-pNA imine stability (log K < 2, Table 1)
			human potency class 5	(2) very low lysine reactivity at pH 7.511 (Table 2)
			LOEL 2760 μg/cm2
			NOEL 590 μg/cm2
4-hydroxy benzaldehyde	B4	weak/non	LLNA EC3 > 25%, pEC3 < 0.69	(1) very low Gly-pNA imine stability (log K < 0, Table 1)
				(2) no lysine reactivity at pH 7.511 (Table 2)
4-methoxy benzaldehyde	C3	weak/non	LLNA EC3 > 25%, pEC3 < 0.74	(1) very low Gly-pNA imine stability (log K < 1, Table 1)
			LOEL 4724 μg/cm2	(2) no lysine reactivity at pH 7.511 (Table 2)
			NOEL-HRIPT 3543 μg/cm2
			NOEL-HPT 6900 μg/cm2
4-nitro benzaldehyde	D1	weak/non	LLNA EC3 > 50%, pEC3 < 0.48	(1) medium Gly-pNA imine stability (log K > 2, Table 1)
				(2) no lysine reactivity at pH 7.511 (Table 2)
vanillin	D3	weak/non	LLNA EC3 > 50%, pEC3 < 0.48	(1) very low Gly-pNA imine stability (log K < 0, Table 1)
			human potency class 5	(2) very low lysine reactivity at pH 7.511 (Table 2)
			NOEL 1181 μg/cm2
ethyl vanillin	D4	weak/non	LLNA EC3 > 50%, pEC3 < 0.52	(1) very low Gly-pNA imine stability (log K < 0, Table 1)
				(2) very low lysine reactivity at pH 7.511 (Table 2)
3-chloro-4-methoxy benzaldehyde	E3	weak/non	LLNA EC3 > 65%, pEC3 < 0.42	(1) very low Gly-pNA imine stability (log K < 1, Table 1)
				(2) very low lysine reactivity at pH 7.511 (Table 2)
2-hydroxy benzaldehyde	B2	--	positive in human tests	(1) very low Gly-pNA adduct stability (log K < 1, Table 1)
				(2) moderate lysine reactivity at pH 7.511 (Table 2)

^aSkin sensitization profiles taken from the literature.^11,12