Journal of Toxicology

Research Article

A Toxicological Evaluation of Methylliberine (Dynamine®)

Table 6

Results of the hematological evaluation in the 90-day study.


Group (mg/kg bw/day)		WBC	NEU	LYM	MONO	EOS	BASO	RBC	HGB	HCT	MCV	MCH	MCHC	PLT	RET	PT	APTT
Group (mg/kg bw/day)		[×10⁹/L]	[%]	[%]	[%]	[%]	[%]	[×10¹²/L]	[g/L]	[L/L]	[fL]	[pg]	[g/L]	[×10⁹/L]	[%]	[sec]	[sec]
Main study groups

Male
0 (Control)	Mean	7.01	17.76	78.20	2.14	1.31	0.08	9.35	160.0	0.49	51.94	17.09	329.4	907.8	1.67	10.44	13.54
	SD	1.51	7.28	7.59	0.66	0.36	0.06	0.41	6.9	0.02	1.01	0.40	3.5	78.7	0.29	0.21	1.13
75	Mean	7.67	20.32	74.96	2.81	1.10	0.08	9.02	162.3	0.49	54.05	18.02	333.5	849.4	2.23	10.46	14.39
	SD	1.32	3.01	3.67	0.66	0.47	0.06	0.46	4.1	0.02	1.18	0.56	7.5	104.0	0.29	0.25	1.05
	SS
112	Mean	8.58	25.13	69.95	2.86	1.30	0.08	9.00	165.00	0.50	55.27	18.36	332.30	896.20	2.74	10.10	13.91
	SD	2.19	15.45	15.92	0.69	0.52	0.04	0.30	3.23	0.01	1.67	0.61	3.83	75.65	0.52	0.24	1.52
	SS
150	Mean	9.22	29.51	65.60	2.81	1.42	0.09	9.09	168.50	0.51	55.79	18.55	332.50	882.80	2.73	10.12	13.62
	SD	2.83	12.06	14.00	0.74	1.81	0.07	0.45	6.10	0.02	2.38	0.82	4.14	121.32	0.37	0.16	1.63
	SS
187	Mean	9.08	26.57	69.04	3.00	0.77	0.11	9.01	168.50	0.52	57.27	18.71	327.00	896.70	3.15	10.27	15.17
	SD	1.99	3.61	3.81	0.50	0.20	0.03	0.30	4.33	0.02	1.31	0.43	4.45	115.59	0.30	0.26	0.87
	SS
225	Mean	7.89	31.96	63.34	3.04	0.94	0.09	9.07	170.10	0.52	57.35	18.81	327.90	933.90	3.27	10.23	15.17
	SD	2.39	9.43	10.88	1.20	0.42	0.03	0.53	6.69	0.02	2.36	0.83	5.95	84.10	0.32	0.21	1.46
	SS
Test for significance		NS			NS		NS	NS	DN	DN	DN	DN	NS	NS	DN	DN	DN
Historical control Range		4.3–10.6	10-3–35.7	60.1–86.5	1.2–6.7	0.7–2.8	0.0–0.2	8.1–9.9	145.0–183.0	0.4–0.5	49.9–60.2	16.3–20.7	315.0–361.0	339.0–1062.0	1.2–2.3	10.0–11.2	10.2–15.6

Female
0 (Control)	Mean	4.91	21.03	74.11	2.52	1.89	0.08	8.41	154.6	0.46	55.16	18.39	333.6	886.7	1.73	9.91	13.35
	SD	1.72	13.74	14.85	0.67	0.96	0.06	0.27	4.6	0.01	1.14	0.44	5.5	174.7	0.36	0.21	1.28
75	Mean	5.98	17.53	78.14	2.64	1.14	0.07	8.12	150.8	0.46	56.85	18.59	327.2	905.8	2.55	9.93	15.15
	SD	1.65	4.21	3.88	0.76	0.59	0.05	0.35	4.9	0.02	1.32	0.74	8.0	104.7	0.40	0.37	1.17
	SS
112	Mean	6.27	18.41	77.83	2.37	0.91	0.07	8.22	152.1	0.46	55.47	18.52	333.6	947.7	2.84	9.88	15.19
	SD	1.80	5.20	5.12	0.52	0.16	0.05	0.41	8.7	0.02	0.84	0.58	8.0	97.7	0.38	0.09	1.11
	SS
150	Mean	7.24	22.44	73.93	2.50	0.61	0.06	8.14	153.4	0.46	57.08	18.86	330.4	927.5	3.04	9.85	14.37
	SD	1.18	4.07	3.92	0.31	0.10	0.05	0.31	3.7	0.01	1.13	0.50	4.8	115.8	0.42	0.20	1.28
	SS
187	Mean	7.39	22.00	74.21	2.58	0.60	0.10	8.19	151.4	0.46	56.60	18.52	327.2	967.4	3.27	9.80	13.67
(^†)	SD	1.48	7.11	7.31	0.84	0.14	0.00	0.46	9.2	0.02	1.88	0.59	5.7	100.8	0.39	0.22	1.46
	SS
225	Mean	7.53	25.68	70.03	2.96	0.74	0.06	8.21	153.4	0.46	56.37	18.72	332.0	1013.4	3.15	9.85	14.14
	SD	1.49	12.34	13.37	0.96	0.40	0.05	0.36	5.7	0.01	1.49	0.68	5.3	94.2	0.53	0.13	0.91
	SS
Test for significance		DN			NS		NS	NS	NS	NS	DN	NS	DN	NS	DN	NS	DN
Historical control range		1.5–9.2	7.6–50.2	43.7–88.7	1.0–5.0	0.8–3.7	0.0–0.2	7.4–10.1	141.0–175.0	0.4–0.5	50.1–57.7	17.2–20.1	319.0–365.0	450.0–1127.0	1.2–3.6	9.5–10.5	11.1–16.1
Recovery groups
Male
0 (Control)	Mean	7.30	18.02	76.32	3.06	1.90	0.12	8.88	156.40	0.48	53.32	17.60	330.2	786.4	1.63	10.68	12.22
	SD	2.26	4.50	3.98	1.83	1.08	0.04	0.39	7.92	0.02	0.83	0.23	8.0	155.9	0.21	0.20	1.19
225	Mean	7.88	19.98	75.06	3.04	1.28	0.12	8.56	159.20	0.50	57.80	18.62	321.8	758.6	2.47	10.70	12.96
	SD	0.63	5.23	5.70	0.88	0.33	0.04	0.27	3.70	0.02	1.24	0.40	2.2	119.5	0.30	0.22	0.54
	SS
Test for significance		NS	NS	NS	NS	NS	NS	NS	NS	NS			NS	NS		NS	NS
Female
0 (Control)	Mean	4.20	25.48	68.94	2.52	2.62	0.08	8.68	155.20	0.48	54.82	17.88	326.0	740.4	2.22	10.10	13.14
	SD	1.41	5.24	4.70	0.47	2.06	0.08	0.34	4.92	0.02	0.95	0.41	7.9	169.5	0.20	0.33	1.06
225	Mean	5.18	20.80	75.42	2.08	1.16	0.08	8.69	156.60	0.48	54.92	18.04	328.4	863.0	1.78	10.12	14.32
	SD	1.06	5.56	5.42	0.46	0.18	0.04	0.45	4.98	0.02	1.40	0.51	4.3	145.6	0.38	0.13	0.57
Test for significance		NS	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS

Abbreviations: APTT, activated partial thromboplastin time; BASO, basophil granulocytes; DN, Duncan’s multiple range test; EOS, eosinophil granulocytes; HCT, hematocrit; HGB, hemoglobin; LYM, lymphocyte; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglogin; MCHC, mean corpuscular hemoglobin concentration; MONO, monocyte; NEU, neutrophil granulocytes; NS, not significant; PLT, platelet count; PT prothrombin time; RBC, red blood cell (erythrocyte); RET, reticulocyte; SD, standard deviation; SS, statistically significant compared to control; -test versus control; , Mann-Whitney -test versus control; WBC, white blood cell. ^†Main group females at 187 mg/kg bw/day (; one animal died at collection due to over anesthesia). , .