. 2014 Oct 2;88(11):2033–2059. doi: 10.1007/s00204-014-1349-9

Table 3.

Clinical pathology parameters in BALF of short-term studies with 5 days and 4 weeks of exposure

Target conc. (mg/m³)	5 days of exposure						4 weeks of exposure
	Control	Ceria NM-212			Ceria NM-211		Control	Ceria NM-212
	0	0.5	5	25	0.5	25	0	0.5	5	25
Measured conc. (mg/m³) + SD	0	0.48 ± 0.0	5.2 ± 1.1	25.6 ± 6.0	0.45 ± 0.1	25.8 ± 1.7	0	0.5 ± 0.2	5.3 ± 0.9	25.9 ± 6.0
BALF cell counts (cn/µL)
Total cells
Time point 1^a	63.73 ± 11.03	69.76 ± 26.15	98.24** ± 16.38	337.35** ± 125.24	71.32 ± 22.69	374.98** ± 77.84	76.42 ± 23.97	75.10 ± 21.51	133.44* ± 48.40	296.90** ± 124.92
Time point 2^b	53.09 ± 13.33	44.20 ± 2.45	43.98 ± 17.70	46.71 ± 8.16	47.01 ± 11.34	81.20 ± 38.87	75.29 ± 14.10	62.23 ± 11.59	97.44 ± 34.23	220.50** ± 105.27
Neutrophils (PMN)
Time point 1^a	0.82 ± 0.80	3.70** ± 2.53	49.19** ± 17.68	272.30** ± 106.62	4.41* ± 3.38	297.21** ± 59.23	0.85 ± 0.35	1.75 ± 1.13	65.66** ± 50.23	222.29** ± 99.25
Time point 2^b	0.69 ± 0.38	1.34 ± 2.01	5.15 ± 9.91	4.63** ± 3.83	2.27** ± 0.56	25.57** ± 33.95	2.44 ± 1.01	2.52 ± 1.37	41.70** ± 22.0	161.69** ± 87.82
Lymphocytes
Time point 1^a	0.22 ± 0.32	0.17 ± 0.22	1.57* ± 0.97	9.20** ± 4.51	0.39 ± 0.34	19.14** ± 15.13	0.55 ± 0.50	0.63 ± 0.74	5.41** ± 3.21	8.93** ± 6.04
Time point 2^b	0.32 ± 0.33	0.11 ± 0.10	0.43 ± 0.31	1.03 ± 0.95	0.51 ± 0.25	2.74** ± 2.17	1.65 ± 1.13	0.77 ± 0.49	7.43* ± 9.02	10.89** ± 3.48
Macrophages
Time point 1^a	62.65 ± 11.56	75.72 ± 15.10	46.83 ± 23.88	51.21 ± 24.76	66.47 ± 22.13	52.99 ± 42.89	74.94 ± 23.79	72.71 ± 21.16	60.25 ± 20.82	59.32 ± 26.28
Time point 2^b	52.05 ± 13.00	42.32 ± 3.66	38.34 ± 11.92	40.93 ± 6.31	44.23 ± 11.53	52.61 ± 15.51	71.14 ± 13.31	58.78 ± 11.04	47.58 ± 16.48	45.17 ± 25.33
Monocytes
Time point 1^a	0.04 ± 0.08	0.00 ± 0.00	0.52* ± 0.37	3.50 ± 1.86**	0.05 ± 0.11	4.40** ± 2.68	0.00 ± 0.00	0.00 ± 0.00	1.65* ± 1.90	3.95* ± 4.65
Time point 2^b	0.00 ± 0.00	0.00 ± 0.00	0.03 ± 0.07	0.07 ± 0.11	0.00 ± 0.00	0.28 ± 0.34	0.06 ± 0.09	0.04 ± 0.08	0.68* ± 0.43	2.46* ± 3.03
Eosinophils
Time point 1^a	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.39 ± 0.54	0.00 ± 0.00	0.00 ± 0.00	0.09 ± 0.12	0.00 ± 0.00	0.00 ± 0.00	0.34 ± 0.49
Time point 2^b	0.03 ± 0.06	0.00 ± 0.00	0.03 ± 0.06	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.12 ± 0.11	0.05 ± 0.11	0.00 ± 0.00
Atypical cells
Time point 1^a	0.00 ± 0.00	0.00 ± 0.00	0.12 ± 0.17	0.76 ± 0.73	0.00 ± 0.00	1.25* ± 0.85	0.00 ± 0.00	0.00 ± 0.00	0.48 ± 0.72	2.07* ± 1.71
Time point 2^b	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.05 ± 0.07	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.29 ± 0.40
Total protein/enzymes
Total protein (mg/L)
Time point 1^a	39 ± 15	47 ± 16	75* ± 23	198** ± 52	44 ± 7	207** ± 54	60 ± 4	83** ± 5	94** ± 21	245** ± 77
Time point 2^b	97 ± 122	59 ± 28	51 ± 16	60* ± 9	92 ± 91	82 ± 14	81 ± 23	60 ± 22	98 ± 49	175** ± 98
GGT (nkat/L)
Time point 1^a	20 ± 15	36 ± 20	106** ± 26	125** ± 15	37 ± 26	128** ± 16	37 ± 17	51 ± 11	111** ± 21	149** ± 31
Time point 2^b	30 ± 7	28 ± 17	33 ± 14	61** ± 16	25 ± 10	87** ± 20	42 ± 12	44 ± 20	83** ± 30	123** ± 30
LDH (µkat/L)
Time point 1^a	0.46 ± 0.09	0.58 ± 0.17	0.89** ± 0.25	2.17** ± 0.21	0.67	2.60** ± 0.31	0.51 ± 0.18	0.55 ± 0.15	1.08** ± 0.37	2.28** ± 0.52
Time point 2^b	0.36 ± 0.14	0.47 ± 0.25	0.42 ± 0.04	0.72** ± 0.20	0.58 ± 0.40	1.08** ± 0.32	0.58 ± 0.08	0.50 ± 0.20	0.84* ± 0.22	1.88** ± 1.20
ALP (µkat/L)
Time point 1^a	0.43 ± 0.10	0.53 ± 0.08	1.31** ± 0.53	1.56** ± 0.15	0.55* ± 0.09	1.56** ± 0.35	0.83 ± 0.16	0.84 ± 0.35	1.16** ± 0.10	1.53** ± 0.21
Time point 2^b		1.0	1.5*	1.9**	0.51 ± 0.20	0.87** ± 0.12	0.70 ± 0.09	0.67 ± 0.08	1.05** ± 0.16	1.09** ± 0.25
NAG (nkat/L)
Time point 1^a	46 ± 9	47 ± 11	57 ± 12	74** ± 7	51 ± 19	94** ± 16	45 ± 5	55 ± 15	53* ± 8	86* ± 26
Time point 2^b	41 ± 10	37 ± 12	39 ± 4	46 ± 7	46 ± 7	59* ± 10	47 ± 8	38 ± 6	47 ± 7	71 ± 35
Cell mediators (pg/mL)
MCP-1
Time point 1^a	14.7 ± 0.6	19.1 ± 5.5	101.1** ± 31.3	1,342.9** ± 530.0	17.5* ± 1.6	1,581.0** ± 771.3	14.0 ± 0.0	19.6 ± 11.0	559.4** ± 444.4	3,587.2** ± 281.0
Time point 2^b	48.2 ± 59.1	22.8 ± 12.5	26.7 ± 10.8	144.1* ± 82.8	30.6 ± 26.0	329.2** ± 290.5	17.3 ± 2.6	15.4 ± 3.1	492.5** ± 553.1	1,854.2** ± 1,184.0
CINC-1/IL-8
Time point 1^a	59.8 ± 17.7	83.4* ± 24.6	348.6** ± 185.4	322.4** ± 93.9	88.3* ± 21.1	436.0** ± 228.3	104.2 ± 26.7	103.8 ± 14.0	506.7** ± 195.9	1,190.9** ± 294.9
Time point 2^b	88.3 ± 25.7	87.5 ± 24.7	94.3 ± 35.7	155.1** ± 13.5	99.7 ± 39.4	254.3** ± 70.4	158.8 ± 38.1	133.9 ± 45.3	449.4** ± 226.7	831.0** ± 497.1
M-CSF
Time point 1^a	41 ± 17	52 ± 23	34 ± 25	91** ± 28	61* ± 16	114** ± 48	26 ± 17	22 ± 12	27 ± 18	48 ± 29
Time point 2^b	45 ± 19	48 ± 5	71* ± 13	49 ± 3	51 ± 12	60 ± 24	46 ± 26	55 ± 29	41 ± 14	53 ± 12
Osteopontin
Time point 1^a	172.28 ± 48.04	194.81 ± 131.24	301.40 ± 238.96	849.04** ± 386.44	134.32 ± 82.72	1,116.02** ± 653.35	391.44 ± 187.39	288.80 ± 110.90	755.44* ± 206.21	592.14 ± 336.47
Time point 2^b	320.38 ± 177.64	191.47 ± 116.09	247.44 ± 189.46	495.92 ± 251.93	111.92 ± 80.28	398.72 ± 140.88	337.36 ± 282.91	284.40 ± 292.66	1,003.18* ± 434.20	838.48 ± 529.45

* Statistically significant, p < 0.05

** Statistically significant, p < 0.01; n = 5; SD standard deviation

^aTime point 1: 3 days after the end of exposure (5 days of exposure) and 1 day after the end of exposure (4 weeks of exposure)

^bTime point 2: 24 days after the end of exposure (5 days of exposure) and 35 days after the end of exposure (4 weeks of exposure)