Oral toxicity of titanium dioxide P25 at repeated dose 28-day and 90-day in rats

Heo, Min Beom; Kwak, Minjeong; An, Kyu Sup; Kim, Hye Jin; Ryu, Hyeon Yeol; Lee, So Min; Song, Kyung Seuk; Kim, In Young; Kwon, Ji-Hwan; Lee, Tae Geol

doi:10.1186/s12989-020-00350-6

Particle and Fibre Toxicology

Table 3 Hematology of rats in repeated-dose 90-day and recovery studies, mean ± SD (number of animals)

From: Oral toxicity of titanium dioxide P25 at repeated dose 28-day and 90-day in rats

Summary of hematological tests from the repeated-dose 90-day study
Sex: Male
Test item	Group(mg/kg/day)
Test item	G1(0)				G2(250)				G3(500)				G4(1000)
WBC¹(K/μL)	6.97	±	1.2	(10)	6.46	±	1.81	(10)	8.1	±	1.39	(10)	7.22	±	1.52	(10)
PMN²(K/μL)	1.58	±	0.55	(10)	1.46	±	0.8	(10)	1.38	±	0.49	(10)	1.34	±	0.34	(10)
EO³(K/μL)	0.11	±	0.03	(10)	0.11	±	0.03	(10)	0.32	±	0.6	(10)	0.11	±	0.03	(10)
BA⁴(K/μL)	0	±	0	(10)	0	±	0	(10)	0	±	0	(10)	0	±	0	(10)
LY⁵(K/μL)	5.04	±	0.86	(10)	4.6	±	1.09	(10)	6.1	±	1.5	(10)	5.52	±	1.26	(10)
MO⁶(K/μL)	0.18	±	0.06	(10)	0.2	±	0.1	(10)	0.21	±	0.07	(10)	0.18	±	0.07	(10)
LUC⁷(K/μL)	0.07	±	0.04	(10)	0.09	±	0.05	(10)	0.09	±	0.04	(10)	0.07	±	0.03	(10)
PMNP⁸(%)	22.3	±	5.5	(10)	21.7	±	6.9	(10)	16.9	±	4.8	(10)	18.8	±	4.4	(10)
EOP⁹(%)	1.6	±	0.5	(10)	1.9	±	0.6	(10)	4.8	±	10.3	(10)	1.5	±	0.5	(10)
BAP¹⁰(%)	0	±	0	(10)	0	±	0	(10)	0	±	0	(10)	0	±	0	(10)
LYP¹¹(%)	72.5	±	5.3	(10)	72.2	±	6.8	(10)	74.5	±	10.1	(10)	76.3	±	4.9	(10)
MOP¹²(%)	2.5	±	0.7	(10)	3	±	1	(10)	2.7	±	0.9	(10)	2.4	±	0.6	(10)
LUP¹³(%)	1	±	0.4	(10)	1.2	±	0.5	(10)	1.2	±	0.7	(10)	1	±	0.4	(10)
RBC¹⁴(M/μL)	8.3	±	0.36	(10)	8.37	±	0.27	(10)	8.31	±	0.37	(10)	8.41	±	0.28	(10)
Hb¹⁵(g/dL)	14.5	±	0.4	(10)	14.6	±	0.5	(10)	14.4	±	0.3	(10)	14.7	±	0.6	(10)
RDW¹⁶(%)	12.7	±	0.6	(10)	12.7	±	0.3	(10)	12.7	±	0.5	(10)	12.6	±	0.6	(10)
HCT¹⁷(%)	43.9	±	1.3	(10)	44.2	±	1.7	(10)	43.4	±	1.3	(10)	44.5	±	1.7	(10)
MCV¹⁸(fL)	52.9	±	1.6	(10)	52.8	±	1.6	(10)	52.3	±	1.6	(10)	52.9	±	1.6	(10)
MCH¹⁹(pg)	17.5	±	0.6	(10)	17.5	±	0.7	(10)	17.4	±	0.6	(10)	17.5	±	0.6	(10)
MCHC²⁰(g/dL)	33	±	0.4	(10)	33.1	±	0.5	(10)	33.2	±	0.4	(10)	33.1	±	0.4	(10)
Reti²¹(%)	2.35	±	0.68	(10)	2.32	±	0.21	(10)	2.21	±	0.39	(10)	2.38	±	0.36	(10)
MetHb²²(%)	2.3	±	0.1	(10)	2.4	±	0.2	(10)	2.3	±	0.4	(10)	2.3	±	0.2	(10)
Heinz²³	0	±	0	(10)	0	±	0	(10)	0	±	0	(10)	0	±	0	(10)
PLT²⁴(K/μL)	1053	±	129	(10)	1021	±	192	(10)	1108	±	119	(10)	1067	±	104	(10)
MPV²⁵(fL)	6.7	±	0.6	(10)	6.7	±	0.6	(10)	6.4	±	0.8	(10)	6.7	±	0.3	(10)
Sex: Female
Test item	Group(mg/kg/day)
Test item	G1(0)				G2(250)				G3(500)				G4(1000)
WBC¹(K/μL)	3.54	±	0.53	(10)	4.52	±	1.57	(10)	3.94	±	0.73	(10)	4	±	1.11	(10)
PMN²(K/μL)	0.81	±	0.26	(10)	0.65	±	0.29	(10)	0.45*	±	0.18	(10)	0.64	±	0.3	(10)
EO³(K/μL)	0.06	±	0.02	(10)	0.09	±	0.03	(10)	0.07	±	0.03	(10)	0.07	±	0.03	(10)
BA⁴(K/μL)	0	±	0	(10)	0	±	0	(10)	0	±	0	(10)	0	±	0	(10)
LY⁵(K/μL)	2.57	±	0.61	(10)	3.62	±	1.27	(10)	3.27	±	0.63	(10)	3.15	±	0.97	(10)
MO⁶(K/μL)	0.08	±	0.03	(10)	0.13	±	0.06	(10)	0.11	±	0.04	(10)	0.11	±	0.03	(10)
LUC⁷(K/μL)	0.03	±	0.02	(10)	0.04	±	0.02	(10)	0.05	±	0.01	(10)	0.04	±	0.01	(10)
PMNP⁸(%)	23.4	±	8.8	(10)	14.0**	±	3.7	(10)	11.3**	±	3.9	(10)	16.1**	±	5.8	(10)
EOP⁹(%)	1.7	±	0.6	(10)	2	±	0.5	(10)	1.8	±	0.9	(10)	1.9	±	0.4	(10)
BAP¹⁰(%)	0	±	0	(10)	0	±	0	(10)	0	±	0	(10)	0	±	0	(10)
LYP¹¹(%)	71.8	±	8.7	(10)	80.2**	±	4.4	(10)	83.1**	±	4.5	(10)	78.4**	±	6.2	(10)
MOP¹²(%)	2.3	±	0.7	(10)	2.8	±	0.8	(10)	2.7	±	0.7	(10)	2.7	±	1.1	(10)
LUP¹³(%)	0.9	±	0.4	(10)	1	±	0.4	(10)	1.2	±	0.5	(10)	0.9	±	0.3	(10)
RBC¹⁴(M/μL)	7.61	±	0.28	(10)	7.56	±	0.48	(10)	7.64	±	0.34	(10)	7.6	±	0.31	(10)
Hb¹⁵(g/dL)	14.2	±	0.3	(10)	14.1	±	0.7	(10)	14	±	0.7	(10)	14.3	±	0.5	(10)
RDW¹⁶(%)	11	±	0.4	(10)	10.9	±	0.4	(10)	11	±	0.4	(10)	10.9	±	0.4	(10)
HCT¹⁷(%)	41.7	±	1.1	(10)	41.2	±	1.9	(10)	41.4	±	1.9	(10)	41.8	±	1.6	(10)
MCV¹⁸(fL)	54.9	±	1.6	(10)	54.6	±	1.7	(10)	54.2	±	1.9	(10)	55	±	1.1	(10)
MCH¹⁹(pg)	18.6	±	0.5	(10)	18.6	±	0.6	(10)	18.4	±	0.6	(10)	18.7	±	0.4	(10)
MCHC²⁰(g/dL)	33.9	±	0.6	(10)	34.1	±	0.6	(10)	34	±	0.6	(10)	34.1	±	0.6	(10)
Reti²¹(%)	1.86	±	0.31	(10)	1.96	±	0.25	(10)	2.1	±	0.65	(10)	1.96	±	0.36	(10)
MetHb²²(%)	2.4	±	0.3	(10)	2.4	±	0.2	(10)	2.5	±	0.2	(10)	2.3	±	0.1	(10)
Heinz²³	0	±	0	(10)	0	±	0	(10)	0	±	0	(10)	0	±	0	(10)
PLT²⁴(K/μL)	1005	±	197	(10)	1058	±	104	(10)	1052	±	106	(10)	981	±	161	(10)
MPV²⁵(fL)	7	±	0.5	(10)	7.1	±	0.5	(10)	7.2	±	0.7	(10)	7	±	0.5	(10)
Summary of hematological tests from the recovery study
Test item	Sex: Male								Sex: Female
	Group(mg/kg/day)								Group(mg/kg/day)
	G1(0)				G4(1000)				G1(0)				G4(1000)
WBC¹(K/μL)	6.27	±	1.53	(5)	5.81	±	1.39	(5)	4.04	±	0.91	(5)	3.8	±	0.86	(5)
PMN²(K/μL)	1.4	±	0.57	(5)	0.9	±	0.23	(5)	0.66	±	0.27	(5)	0.54	±	0.16	(5)
EO³(K/μL)	0.06	±	0.03	(5)	0.07	±	0.02	(5)	0.06	±	0.02	(5)	0.06	±	0.02	(5)
BA⁴(K/μL)	0	±	0	(5)	0	±	0	(5)	0	±	0	(5)	0	±	0	(5)
LY⁵(K/μL)	4.64	±	1.06	(5)	4.66	±	1.37	(5)	3.13	±	0.7	(5)	3.05	±	0.81	(5)
MO⁶(K/μL)	0.12	±	0.08	(5)	0.13	±	0.04	(5)	0.12	±	0.03	(5)	0.1	±	0.02	(5)
LUC⁷(K/μL)	0.05	±	0.02	(5)	0.05	±	0.02	(5)	0.07	±	0.04	(5)	0.04	±	0.01	(5)
PMNP⁸(%)	22	±	6.2	(5)	16.2	±	5.4	(5)	16.1	±	4.3	(5)	14.5	±	4.2	(5)
EOP⁹(%)	0.9	±	0.6	(5)	1.3	±	0.4	(5)	1.4	±	0.3	(5)	1.7	±	0.4	(5)
BAP¹⁰(%)	0	±	0	(5)	0	±	0.1	(5)	0	±	0	(5)	0	±	0	(5)
LYP¹¹(%)	74.4	±	5.3	(5)	79.4	±	5.7	(5)	77.6	±	4.4	(5)	79.9	±	4.2	(5)
MOP¹²(%)	1.9	±	1	(5)	2.2	±	0.7	(5)	3	±	0.4	(5)	2.8	±	0.7	(5)
LUP¹³(%)	0.8	±	0.2	(5)	0.8	±	0.2	(5)	1.9	±	1.1	(5)	1	±	0.3	(5)
RBC¹⁴(M/μL)	8.72	±	0.41	(5)	8.38	±	0.28	(5)	7.78	±	0.63	(5)	7.75	±	0.34	(5)
Hb¹⁵(g/dL)	14.7	±	0.7	(5)	14.7	±	0.5	(5)	14.2	±	0.7	(5)	14.1	±	0.5	(5)
RDW¹⁶(%)	13.3	±	1.3	(5)	13	±	0.5	(5)	11.4	±	0.2	(5)	11.3	±	0.4	(5)
HCT¹⁷(%)	45.1	±	1.8	(5)	45.1	±	1.6	(5)	42.6	±	2.2	(5)	42.3	±	1.6	(5)
MCV¹⁸(fL)	51.8	±	1.3	(5)	53.8	±	2.1	(5)	54.8	±	2.8	(5)	54.6	±	1.9	(5)
MCH¹⁹(pg)	16.9	±	0.6	(5)	17.5	±	0.7	(5)	18.3	±	1	(5)	18.3	±	0.6	(5)
MCHC²⁰(g/dL)	32.7	±	0.5	(5)	32.6	±	0.2	(5)	33.5	±	0.3	(5)	33.4	±	0.2	(5)
Reti²¹(%)	2.39	±	0.5	(5)	2.48	±	0.86	(5)	1.96	±	0.29	(5)	1.86	±	0.15	(5)
MetHb²²(%)	1.7	±	0.8	(5)	2.1	±	0.9	(5)	1.2	±	0.8	(5)	1.8	±	0.8	(5)
Heinz²³	0	±	0	(5)	0	±	0	(5)	0	±	0	(5)	0	±	0	(5)
PLT²⁴(K/μL)	1091	±	52	(5)	1116	±	133	(5)	902	±	237	(5)	1068	±	186	(5)
MPV²⁵(fL)	8.2	±	0.4	(5)	8.3	±	0.2	(5)	6.6	±	1.2	(5)	6.5	±	1	(5)

1: White blood cell, 2: Neutrophil, 3: Eosinophil, 4: Basophil, 5: Lymphocyte, 6: Monocyte, 7: Large unstained cell, 8: Percent of neutrophil, 9: Percent of eosinophil, 10: Percent of basophil, 11: Percent of lymphocyte, 12: Percent of monocyte, 13: Percent of large unstained cell, 14: Red blood cell, 15: Hemoglobin, 16: Red cell distribution width, 17: Hematocrit, 18: Mean corpuscular volume, 19: Mean corpuscular hemoglobin, 20: Mean corpuscular hemoglobin concentration, 21: Reticulocyte, 22: Methemoglobin, 23: Heinz body, 24: Platelet, 25: Mean platelet volume
*: Significant difference compared with the vehicle control group, P < 0.05
**: Significant difference compared with the vehicle control group, P < 0.01

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