Compound 1.2.1 having the following general formula: or a salt or solvate thereof wherein: E is selected from O and N(T 3); R 1 is selected from the following general formula: wherein R 11, R 12, R 13, and R 14 are each independently selected from-H, -(C 1 -C 4)alkyl, -(C 2 -C 4)alkenyl, -(C 2 -C 4)alkynyl, -OR 7, -SR 7, -C(halo) 3, -CH(halo) 2, -CH 2 (halo), -CN, -halo, -N 3, -NO 2, -N(R 7) 2, -N(R 7)OH, -C(=O)R 7, -C(=O)N(R 7) 2, -C(=O)OR 7, -OC(=O)R 7, -S(=O)R 7, or -S(=O) 2 R 7; R 12 ', R 13 ', and R 15 ', if present, are each independently selected from -H, or -(C 1 -C 3)alkyl; and R 16 and R 17 are each independently selected from -H, -OH, -(C 1 -C 2)alkyl, -halo, and -C(halo) 3; R2 and R3 are each independently selected from: (a) -halo, -CN, -NO2; or (b) -OT3, -OC(=O)T3; or (c) -C(=O)T3, -C(=O)OT3, -C(=O)N; or (d) -(C1-C3)alkyl, -(C2-C3)alkenyl, -(C2-C3)alkynyl, -(C1-C3)alkoxy, each of which is unsubstituted or substituted with 1 or 2 independently selected R5 groups; each R5 is independently selected from -H, -(C1-C3)alkyl, - alkenyl, - alkynyl, -OR7, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -halo, -N3, -N02, -N 2, -N OH, -C(=O)R7, or-C(=O)OR7; each R7 is independently selected from -H, or -CH3; each T1, T2, and T3 is independently selected from -H or -CH3; and each halo is independently selected from -F, -Cl, -Br, or -I; for use in the treatment of skin irritation. E is selected from O and N(T 3); R 1 is selected from the following general formula: wherein R 11, R 12, R 13, and R 14 are each independently selected from-H, -(C 1 -C 4)alkyl, -(C 2 -C 4)alkenyl, -(C 2 -C 4)alkynyl, -OR 7, -SR 7, -C(halo) 3, -CH(halo) 2, -CH 2 (halo), -CN, -halo, -N 3, -NO 2, -N(R 7) 2, -N(R 7)OH, -C(=O)R 7, -C(=O)N(R 7) 2, -C(=O)OR 7, -OC(=O)R 7, -S(=O)R 7, or -S(=O) 2 R 7; R 12 ', R 13 ', and R 15 ', if present, are each independently selected from -H, or -(C 1 -C 3)alkyl; and R 16 and R 17 are each independently selected from -H, -OH, -(C 1 -C 2)alkyl, -halo, and -C(halo) 3; R 11, R 12, R 13, and R 14 are each independently selected from-H, -(C 1 -C 4)alkyl, -(C 2 -C 4)alkenyl, -(C 2 -C 4)alkynyl, -OR 7, -SR 7, -C(halo) 3, -CH(halo) 2, -CH 2 (halo), -CN, -halo, -N 3, -NO 2, -N(R 7) 2, -N(R 7)OH, -C(=O)R 7, -C(=O)N(R 7) 2, -C(=O)OR 7, -OC(=O)R 7, -S(=O)R 7, or -S(=O) 2 R 7; R 12 ', R 13 ', and R 15 ', if present, are each independently selected from -H, or -(C 1 -C 3)alkyl; and R 16 and R 17 are each independently selected from -H, -OH, -(C 1 -C 2)alkyl, -halo, and -C(halo) 3; R2 and R3 are each independently selected from: (a) -halo, -CN, -NO2; or (b) -OT3, -OC(=O)T3; or (c) -C(=O)T3, -C(=O)OT3, -C(=O)N; or (d) -(C1-C3)alkyl, -(C2-C3)alkenyl, -(C2-C3)alkynyl, -(C1-C3)alkoxy, each of which is unsubstituted or substituted with 1 or 2 independently selected R5 groups; each R5 is independently selected from -H, -(C1-C3)alkyl, - alkenyl, - alkynyl, -OR7, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -halo, -N3, -N02, -N 2, -N OH, -C(=O)R7, or-C(=O)OR7; (a) -halo, -CN, -NO2; or (b) -OT3, -OC(=O)T3; or (c) -C(=O)T3, -C(=O)OT3, -C(=O)N; or (d) -(C1-C3)alkyl, -(C2-C3)alkenyl, -(C2-C3)alkynyl, -(C1-C3)alkoxy, each of which is unsubstituted or substituted with 1 or 2 independently selected R5 groups; each R5 is independently selected from -H, -(C1-C3)alkyl, - alkenyl, - alkynyl, -OR7, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -halo, -N3, -N02, -N 2, -N OH, -C(=O)R7, or-C(=O)OR7; each R7 is independently selected from -H, or -CH3; each T1, T2, and T3 is independently selected from -H or -CH3; and each halo is independently selected from -F, -Cl, -Br, or -I; for use in the treatment of skin irritation.