. 2022 Feb 19;96(4):1109–1131. doi: 10.1007/s00204-022-03239-9

Table 1.

The Michaelis–Menten parameters including K_M, V_max and intrinsic clearance (Cl_int) calculated as V_max/K_M for formation of metabolites from alkyl-substituted phenanthrenes and phenanthrene in rat and human liver microsomal incubations (Fig. 2)

Parent compound and Metabolites	Structure	Species	K_M (µM)	V_max (pmol/min/mg microsomal protein)	Cl_int (V_max/K_M) µl/min/mg protein
Phenanthrene RT = 8.21 min, λ = 251.1 nm
3,4-Dihydro-phenanthrene-diol RT = 2.13 min, λ = 260.2 nm		Human	22.6 ± 12.7	61.5 ± 6.3	2.7
3,4-Dihydro-phenanthrene-diol RT = 2.13 min, λ = 260.2 nm		Rat	153.7 ± 72.4	10.3 ± 1.8	0.1
3,4-Dihydro-phenanthrene-diol RT = 2.24 min, λ = 237.1 nm		Human	8.1 ± 3.5	6.0 ± 0.3	0.7
3,4-Dihydro-phenanthrene-diol RT = 2.24 min, λ = 237.1 nm		Rat	ND	ND	–
9,10-Dihydro-phenanthene-diol RT = 3.28 min, λ = 231.6 nm		Human	ND	ND	–
9,10-Dihydro-phenanthene-diol RT = 3.28 min, λ = 231.6 nm		Rat	84.2 ± 15.7	9.8 ± 0.6	0.1
9,10-Dihydro-phenanthene-diol RT = 3.38 min, λ = 209.1 nm		Human	32.4 ± 9.0	287.8 ± 17.1	8.9
9,10-Dihydro-phenanthene-diol RT = 3.38 min, λ = 209.1 nm		Rat	121.6 ± 29.1	529.2 ± 43.2	4.4
1,2-Dihydro-phenanthrene-diol RT = 3.57 min, λ = 237.1 nm		Human	25.7 ± 12.6	152.5 ± 14.4	5.9
1,2-Dihydro-phenanthrene-diol RT = 3.57 min, λ = 237.1 nm		Rat	104.3 ± 26.3	79.3 ± 6.5	0.8
3-Phenanthrol RT = 6.02 min, λ = 252.9 nm		Human	ND	ND	–
3-Phenanthrol RT = 6.02 min, λ = 252.9 nm		Rat	103.4 ± 29.5	21.3 ± 2.0	0.2
1-Phenanthrol RT = 6.31 min, λ = 251.7 nm		Human	21.3 ± 5.2	125.2 ± 5.4	5.9
1-Phenanthrol RT = 6.31 min, λ = 251.7 nm		Rat	83.6 ± 43.1	123.9 ± 19.2	1.5
4-Phenanthrol RT = 6.55 min, λ = 245 nm		Human	188.1 ± 104.1	18.0 ± 3.9	0.1
4-Phenanthrol RT = 6.55 min, λ = 245 nm		Rat	145.3 ± 89.8	24.5 ± 5.5	0.2
1-Methylphenanthrene RT = 8.99 min, λ = 255.3 nm
Dihydro-1-methylphenanthrene-diol RT = 2.32 min, λ = 210.4 nm		Human	430.8 ± 134.7	27.5 ± 4.6	0.1
		Rat	ND	ND	–
Dihydro-1-methylphenanthrene-diol RT = 3.43 min, λ = 255.3 nm		Human	ND	ND	–
		Rat	43.7 ± 19.0	4.2 ± 0.4	0.1
Dihydro-1-methylphenanthrene-diol RT = 3.96 min, λ = 260 nm		Human	ND	ND	–
		Rat	17.8 ± 6.7	5.2 ± 0.3	0.3
Dihydro-1-methylphenanthrene-diol RT = 4.35 min, λ = 238.9 nm		Human	25.1 ± 3.3	20.6 ± 0.5	0.8
		Rat	34.3 ± 12.9	16.1 ± 1.3	0.5
Dihydro-1-methylphenanthrene-diol RT = 4.76 min, λ = 254.1 nm		Human	ND	ND	–
		Rat	14.8 ± 4.4	14.0 ± 0.6	0.9
1-(Hydroxymethyl) phennathrene RT = 5.55 min, λ = 254.1 nm		Human	30.5 ± 4.1	475.3 ± 13.2	15.6
1-(Hydroxymethyl) phennathrene RT = 5.55 min, λ = 254.1 nm		Rat	37.4 ± 3.5	1926 ± 40.3	51.5
1-Methylphenanthrol RT = 6.3 min, λ = 252.9 nm		Human	107.5 ± 18.9	14.7 ± 0.8	0.1
1-Methylphenanthrol RT = 6.3 min, λ = 252.9 nm		Rat	ND	ND	–
1-Methylphenanthrol RT = 6.80 min, λ = 258 nm		Human	22.7 ± 6.2	77.3 ± 3.9	3.4
1-Methylphenanthrol RT = 6.80 min, λ = 258 nm		Rat	123.0 ± 22.4	33.1 ± 2.1	0.3
1-Methylphenanthrol RT = 6.92 min, λ = 249.9 nm		Human	ND	ND	–
1-Methylphenanthrol RT = 6.92 min, λ = 249.9 nm		Rat	106.5 ± 21.5	24.0 ± 1.6	0.2
1-Methylphenanthrol RT = 7.00 min, λ = 258 nm		Human	ND	ND	–
1-Methylphenanthrol RT = 7.00 min, λ = 258 nm		Rat	93.4 ± 21.6	17.3 ± 1.2	0.2
1-Methylphenanthrol RT = 7.29 min, λ = 256 nm		Human	ND	ND	–
1-Methylphenanthrol RT = 7.29 min, λ = 256 nm		Rat	150.2 ± 37.6	9.0 ± 0.8	0.1
2-Methylphenanthrene RT = 9.05 min, λ = 252.9 nm
Dihydro-2-methylphenanthrene-diol RT = 3.09 min, λ = 262.1 nm		Human	35.9 ± 11.9	6.4 ± 0.5	0.2
		Rat	ND	ND	–
Dihydro-2-methylphenanthrene-diol RT = 4.26 min, λ = 212.2 nm		Human	ND	ND	–
		Rat	135.8 ± 44.5	23.1 ± 2.7	0.2
Dihydro-2-methylphenanthrene-diol RT = 4.42 min, λ = 243.8 nm		Human	ND	ND	–
		Rat	95.9 ± 46.6	16.2 ± 2.5	0.2
Dihydro-2-methylphenanthrene-diol RT = 4.99 min, λ = 252.9 nm		Human	ND	ND	–
		Rat	141.7 ± 43.3	12..8 ± 1.4	0.1
2-(Hydroxymethyl)-phennathrene RT = 5.59 min, λ = 253.5 nm		Human	21.6 ± 5.9	562.0 ± 27.5	26.0
2-(Hydroxymethyl)-phennathrene RT = 5.59 min, λ = 253.5 nm		Rat	25.8 ± 7.1	2174 ± 115.3	84.3
2-Methylphenanthrol RT = 6.12 min, λ = 262.7 nm		Human	4.9 ± 3.2	16.3 ± 0.8	3.3
2-Methylphenanthrol RT = 6.12 min, λ = 262.7 nm		Rat	NA	90.7 ± 3.8	–
2-Methylphenanthrol RT = 6.98 min, λ = 266.9 nm		Human	ND	ND	-
2-Methylphenanthrol RT = 6.98 min, λ = 266.9 nm		Rat	15.6 ± 4.2	76.0 ± 3.1	4.9
2-Methylphenanthrol RT = 7.08 min, λ = 260.8 nm		Human	ND	ND	–
2-Methylphenanthrol RT = 7.08 min, λ = 260.8 nm		Rat	39.6 ± 13.3	11.2 ± 0.9	0.3
3-Methylphenanthrene RT = 9.04 min, λ = 252.3 nm
Dihydro-3-methylphenanthrene-diol RT = 4.25 min, λ = 210.4 nm		Human	100.8 ± 20.0	65.0 ± 4.1	0.6
		Rat	312.5 ± 178.2	92.3 ± 25.1	0.3
Dihydro-3-methylphenanthrene-diol RT = 4.42 min, λ = 238.9 nm		Human	71.5 ± 16.2	12.8 ± 0.8	0.2
		Rat	121.5 ± 29.0	20.4 ± 1.7	0.2
3-(Hydroxymethyl)-phenanthrene RT = 5.62 min, λ = 252.9 nm		Human	44.5 ± 6.2	583.8 ± 19.6	13.1
3-(Hydroxymethyl)-phenanthrene RT = 5.62 min, λ = 252.9 nm		Rat	120.2 ± 41.7	2593 ± 305	21.6
3-Methylphennathrol RT = 6.98 min, λ = 252.9 nm		Human	ND	ND	–
3-Methylphennathrol RT = 6.98 min, λ = 252.9 nm		Rat	371.1 ± 476.3	82.6 ± 53.8	0.2
9-Methylphenanthrene RT = 9.02 min, λ = 252.9 nm
3,4-Dihydro-9-methylphenanthrene-diol RT = 2.98 min, λ = 262.1 nm		Human	55.9 ± 23.9	26.1 ± 3.0	0.5
		Rat	ND	ND	–
1,2-Dihydro-9-methylphenanthrene-diol RT = 4.27 min, λ = 238.9 nm		Human	61.8 ± 33.7	15.6 ± 2.4	0.3
		Rat	ND	ND	–
9-(Hydroxymethyl)-phenanthrene RT = 5.6 min, λ = 252.9 nm		Human	35.3 ± 16.3	415.9 ± 43.9	11.8
9-(Hydroxymethyl)-phenanthrene RT = 5.6 min, λ = 252.9 nm		Rat	89.9 ± 42.9	1543 ± 226.6	17.2
9-Methylphenanthrol RT = 6.28 min, λ = 249.9 nm		Human	278.3 ± 145.8	27.8 ± 6.7	0.1
9-Methylphenanthrol RT = 6.28 min, λ = 249.9 nm		Rat	ND	ND	–
9-Methylphenanthrol RT = 6.73 min, λ = 252.9 nm		Human	239.8 ± 235.5	44.9 ± 19.4	0.2
9-Methylphenanthrol RT = 6.73 min, λ = 252.9 nm		Rat	226.2 ± 99.5	27.2 ± 5.1	0.1
9-Methylphenanthrol RT = 6.87 min, λ = 254.7 nm		Human	ND	ND	–
9-Methylphenanthrol RT = 6.87 min, λ = 254.7 nm		Rat	346.4 ± 164.3	124.2 ± 29.2	0.4
9-Methylphenanthrol RT = 7.2 min, 249.9 nm		Human	ND	ND	–
9-Methylphenanthrol RT = 7.2 min, 249.9 nm		Rat	445.7 ± 463.6	41.4 ± 23.4	0.1
9-Methylphenanthrol RT = 7.25 min, λ = 252.9 nm		Human	ND	ND	–
9-Methylphenanthrol RT = 7.25 min, λ = 252.9 nm		Rat	154.4 ± 78.6	10.2 ± 1.9	0.1
2-Ethylphenanthrene, RT = 9.84 min, λ = 253.5 nm
Dihydro-2-ethylphenanthrene-diol RT = 4.6 min, λ = 254.1 nm		Human	ND	ND	–
		Rat	25.3 ± 23.2	33.9 ± 11.8	1.3
Dihydro-2-ethylphenanthrene-diol RT = 5.16 min, λ = 276.6 nm		Human	108.3 ± 56.2	18.4 ± 3.2	0.2
		Rat	ND	ND	–
Dihydro-2-ethylphenanthrene-diol RT = 5.29 min, λ = 241.9 nm		Human	132.0 ± 49.6	22.1 ± 3.0	0.2
		Rat	181.7 ± 38.3	42.9 ± 3.5	0.2
2-(1-Hydroxyethyl)-phenanthrene RT = 6.21 min, λ = 253.5 nm		Human	96.5 ± 31.7	468.8 ± 50.3	4.9
		Rat	105.4 ± 27.4	3149.0 ± 266.1	29.9
2-Ethylphenanthrol RT = 7.57 min, λ = 255.3 nm		Human	ND	ND	–
2-Ethylphenanthrol RT = 7.57 min, λ = 255.3 nm		Rat	223.6 ± 100.8	16.5 ± 3.1	0.1
2-Ethylphenanthrol RT = 7.74 min, λ = 254.1 nm		Human	ND	ND	–
2-Ethylphenanthrol RT = 7.74 min, λ = 254.1 nm		Rat	233.3 ± 89.7	16.6 ± 2.7	0.1
2-Ethylphenanthrol RT = 7.89 min, λ = 254.1 nm		Human	ND	ND	–
2-Ethylphenanthrol RT = 7.89 min, λ = 254.1 nm		Rat	133.2 ± 76.4	11.8 ± 2.4	0.1
RT = 9.38 min, λ = 267.6 nm	Unknown	Human	205.0 ± 85.7	37.2 ± 6.5	0.2
RT = 9.38 min, λ = 267.6 nm	Unknown	Rat	95.4 ± 30.5	238.0 ± 23.9	2.5
9-Ethylphenanthrene RT = 9.71 min, λ = 252.9 nm
Dihydro-9-ethylphenanthrene-diol RT = 3.81 min, λ = 263.3 nm		Human	104.6 ± 17.3	15.2 ± 0.8	0.1
		Rat	117.7 ± 59.9	12.0 ± 2.1	0.1
Dihydro-9-ethylphenanthrene-diol RT = 3.88 min, λ = 262.1 nm		Human	59.1 ± 12.4	23.5 ± 1.4	0.4
		Rat	ND	ND	–
9-(2-Hydroxyethyl)-phenanthrene RT = 6.00 min, λ = 253.5 nm		Human	22.6 ± 6.4	61.4 ± 3.3	2.7
		Rat	72.9 ± 15.2	37.0 ± 2.26	0.5
9-(1-Hydroxyethyl)-phenanthrene RT = 6.20 min, λ = 252.9 nm		Human	122.2 ± 22.5	267.7 ± 17.4	2.2
		Rat	138.2 ± 15.2	1206 ± 47.9	8.7
9-Ethylphenanthrol RT = 7.42 min, λ = 252.9 nm		Human	159.9 ± 34.9	12.8 ± 1.1	0.1
9-Ethylphenanthrol RT = 7.42 min, λ = 252.9 nm		Rat	91.6 ± 30.2	29.7 ± 3.1	0.3
9-Ethylphenanthrol RT = 7.58 min, λ = 254.1 nm		Human	244.7 ± 52.6	29.1 ± 2.8	0.1
9-Ethylphenanthrol RT = 7.58 min, λ = 254.1 nm		Rat	321.4 ± 70.5	56.6 ± 1.8	0.2
9-Ethylphenanthrol RT = 7.93 min, λ = 250.5 nm		Human	ND	ND	–
9-Ethylphenanthrol RT = 7.93 min, λ = 250.5 nm		Rat	90.3 ± 23.1	22.8 ± 1.8	0.3
RT = 9.35 min, λ = 256.6 nm	Unknown	Human	ND	ND	–
RT = 9.35 min, λ = 256.6 nm	Unknown	Rat	169.0 ± 51.7	52.7 ± 6.2	0.3
10-Methyl-9-ethylphenanthrene RT = 10.19 min, λ = 255.3 nm
Dihydro-10-methyl-9-ethylphenanthrene-diol RT = 4.29 min, λ = 266.3 nm		Human	141.8 ± 83.7	7.2 ± 1.7	0.1
		Rat	253.1 ± 223.1	6.4 ± 2.7	0.0
Dihydro-10-methyl-9-ethylphenanthrene-diol RT = 4.34 min, λ = 266.3		Human	102.1 ± 70.3	10.5 ± 2.5	0.1
		Rat	73.7 ± 45.0	8.09 ± 1.6	0.1
9-(2-Hydroxyethyl)-10-methylphenanthrene RT = 6.5 min, λ = 255.3 nm		Human	24.7 ± 16.5	12.9 ± 1.8	0.5
		Rat	88.4 ± 39.2	21.0 ± 3.1	0.2
9-(1-Hydroxyethyl)-10-methylphenanthrene RT = 6.65 min, λ = 256 nm		Human	192.4 ± 106.8	187.1 ± 45.2	1.0
		Rat	114.3 ± 4.5	630.2 ± 81.4	5.5
9-Ethyl-10-(1-hydroxymethyl)-phenanthrene RT = 6.90 min, λ = 256 nm		Human	118.2 ± 65.0	85.9 ± 17.4	0.7
		Rat	98.9 ± 38.5	85.8 ± 11.6	0.9
9-Ethyl-10-methylphenanthrol RT = 7.82 min, λ = 255.3 nm		Human	ND	ND	–
9-Ethyl-10-methylphenanthrol RT = 7.82 min, λ = 255.3 nm		Rat	94.4 ± 41.4	65.6 ± 9.8	0.7
9-Ethyl-10-methylphenanthrol RT = 8.3 min, λ = 252.3 nm		Human	ND	ND	–
9-Ethyl-10-methylphenanthrol RT = 8.3 min, λ = 252.3 nm		Rat	219.8 ± 126.8	29.4 ± 7.7	0.1
1-N-hexylphenanthrene RT = 12.60 min, λ = 256 nm
1-Hydroxyhexyl-phenanthrene RT = 8.45 min, λ = 256 nm		Human	67.9 ± 20.0	48.3 ± 6.1	0.7
1-Hydroxyhexyl-phenanthrene RT = 8.45 min, λ = 256 nm		Rat	35.8 ± 18.1	103.4 ± 18.1	2.9
1-Hydroxyhexyl-phenanthrene RT = 8.58 min, λ = 256 nm		Human	ND	ND	–
1-Hydroxyhexyl-phenanthrene RT = 8.58 min, λ = 256 nm		Rat	42.2 ± 10.9	54.8 ± 5.2	1.3
1-Hydroxyhexyl-phenanthrene RT = 8.82 min, λ = 256 nm		Human	51.7 ± 14.2	44.2 ± 4.8	0.9
1-Hydroxyhexyl-phenanthrene RT = 8.82 min, λ = 256 nm		Rat	26.6 ± 6.0	25.6 ± 1.8	1.0
1-Hydroxyhexyl-phenanthrene RT = 9.13 min, λ = 256 nm		Human	ND	ND	–
1-Hydroxyhexyl-phenanthrene RT = 9.13 min, λ = 256 nm		Rat	33.1 ± 7.3	11.7 ± 0.9	0.4
1-N-dodecylphenanthrene RT = 16.62 min, λ = 302.5 nm
NM	NA	Human	NA	NA	NA
NM	NA	Rat	NA	NA	NA

The retention time (RT) and wavelength (λ) used to identify and quantify the metabolites by UPLC–UV analysis are also presented. Results are shown as mean ± standard error of the mean (SEM) from three independent microsomal incubations

ND not detected, NM no metabolism, NA not applicable