Study on the 90-day Feeding Experimental Background Data of SD Rats for Drug Safety Evaluation

doi:10.12300/j.issn.1674-5817.2024.187

Abstract

Abstract:

Objective To establish background data for a 90-day feeding trial of SD rats to ensure the reliability of research data. Methods Background data from six independent 90-day feeding trials of SD rats conducted by the National Center for Safety Evaluation of Drugs from 2020 to 2023 were summarized. These studies involved a blank control group of 120 SPF-grade 4-week-old SD rats, with an equal number of males and females, which were only given standard full-nutrient pelleted rat feed. After the quarantine period, the animals were observed for an additional 90 days, followed by intraperitoneal injection of Zoletil (50 mg/mL) for anesthesia, blood sampling, euthanasia, and necropsy. By analyzing the data from the blank control group, a relevant background database for SD rats was established. Results Both male and female rats exhibited steady weight gain, with a more pronounced increase in male rats. Within 90 days, the average body weight of male and female rats increased to over 500 g and 300 g, respectively. Three weeks later, the average daily food intake of male rats stabilized at approximately 25~28 g per rat, while that of female rats remained stable at approximately 16~19 g per rat. The food utilization rate of all animals gradually decreased from the first week of the experiment. In the white blood cell (WBC) differential count results, significant differences were observed in the counts of WBCs, neutrophils (Neut), lymphocytes (Lymph), and monocytes (Mono) between males and females (P<0.001). However, there were no significant differences in the percentages of neutrophil (%Neut), lymphocyte (%Lymph), and monocyte (%Mono) between the sexes (P>0.05). The average red blood cell count (RBC), hemoglobin concentration (HGB), hematocrit (HCT), platelet count (PLT), prothrombin time (PT), and activated partial thromboplastin time (APTT) were higher in male animals than in female animals (P<0.05). The average values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CK), lactate dehydrogenase (LDH), glucose (GLU), and triglyceride (TG) in male rats were higher than those in female rats (P<0.05). The urinary pH range for male animals was 5.0 to 8.5, while for female animals it was 6.5 to 9.0. The majority of male animals had a urinary specific gravity lower than 1.020, and the majority of female animals had a urinary specific gravity lower than 1.015. The weights of various organs (excluding the adrenal glands and reproductive organs) in male animals were heavier than those in female animals (P<0.001), while the organ/body weight ratios (excluding the kidneys and reproductive organs) of female animals were higher than those of male animals (P<0.001). Conclusion This study summarizes the background reference ranges for body weight, food intake, hematology, and serum biochemistry indicators in SPF-grade SD rats in the untreated control group from six 90-day feeding trials conducted by the National Center for Safety Evaluation of Drugs. It provides important reference data for related research. By summarizing the background and spontaneous histopathological changes in rats, this study aids in the standardization and normalization of subsequent research, as well as in the evaluation and analysis of abnormal results.

Key words: Drug safety evaluation, SD rats, 90-day feeding study, Hematology, Serum biochemistry, Pathological changes

CLC Number:

Q95-33

QIN Chao,LI Shuangxing,ZHAO Tingting,et al. Study on the 90-day Feeding Experimental Background Data of SD Rats for Drug Safety Evaluation[J]. Laboratory Animal and Comparative Medicine, 2025, 45(4): 439-448. DOI: 10.12300/j.issn.1674-5817.2024.187.

Figures/Tables 6

References 25

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指标 Index	雄性 Male	雌性 Female
WBC C_cell/(10⁹·L^-1)	7.36±4.27	4.82±3.06
%Neut /%	14.10±9.02	14.50±10.58
Neut C_cell/(10⁹·L^-1)	1.04±1.04	0.67±0.53
%Lymph /%	80.30±10.58	80.00±11.96
Lymph C_cell/(10⁹·L^-1)	5.90±3.35	3.89±2.76
%Mono /%	2.30±1.96	2.20±1.37
Mono C_cell/(10⁹·L^-1)	0.17±0.20	0.10±0.08
%Eos /%	1.50±0.98	1.70±1.37
Eos C_cell/(10⁹·L^-1)	0.11±0.08	0.08±0.06
%Baso /%	0.2±0.2	0.1±0.1
Baso C_cell/(10⁹·L^-1)	0.01±0.01	0.01±0.01
RBC C_cell/(10¹²·L^-1)	8.90±0.74	8.05±0.69
HGB ρ/(g·L^-1)	155±14	148±10
HCT /%	50.0±5.0	46.5±5.0
MCV /fL	56.2±4.1	57.7±4.5
MCH m/(pg)	17.4±1.4	18.4±1.2
MCHC ρ/(g·L^-1)	310±31	318±27
PLT C_cell/(10⁹·L^-1)	996±321	939±300
MPV /fL	8.2±3.7	8.3±2.9
%Retic /%	3.24±5.94	2.40±1.43
Retic C_cell/(10⁹·L^-1)	288.5±53.5	191.9±108.6
PT /s	10.7±5.7	8.5±0.8
APTT /s	16.9±5.5	12.8±3.9

指标 Index	雄性 Male	雌性 Female
WBC C_cell/(10⁹·L^-1)	7.36±4.27	4.82±3.06
%Neut /%	14.10±9.02	14.50±10.58
Neut C_cell/(10⁹·L^-1)	1.04±1.04	0.67±0.53
%Lymph /%	80.30±10.58	80.00±11.96
Lymph C_cell/(10⁹·L^-1)	5.90±3.35	3.89±2.76
%Mono /%	2.30±1.96	2.20±1.37
Mono C_cell/(10⁹·L^-1)	0.17±0.20	0.10±0.08
%Eos /%	1.50±0.98	1.70±1.37
Eos C_cell/(10⁹·L^-1)	0.11±0.08	0.08±0.06
%Baso /%	0.2±0.2	0.1±0.1
Baso C_cell/(10⁹·L^-1)	0.01±0.01	0.01±0.01
RBC C_cell/(10¹²·L^-1)	8.90±0.74	8.05±0.69
HGB ρ/(g·L^-1)	155±14	148±10
HCT /%	50.0±5.0	46.5±5.0
MCV /fL	56.2±4.1	57.7±4.5
MCH m/(pg)	17.4±1.4	18.4±1.2
MCHC ρ/(g·L^-1)	310±31	318±27
PLT C_cell/(10⁹·L^-1)	996±321	939±300
MPV /fL	8.2±3.7	8.3±2.9
%Retic /%	3.24±5.94	2.40±1.43
Retic C_cell/(10⁹·L^-1)	288.5±53.5	191.9±108.6
PT /s	10.7±5.7	8.5±0.8
APTT /s	16.9±5.5	12.8±3.9

指标 Index	雄性 Male	雌性 Female
ALT z/(U·L^-1)	37±18	28±16
AST z/(U·L^-1)	128±35	107±37
ALP z/(U·L^-1)	104±45	53±27
CK z/(U·L^-1)	747±494	634±439
LDH z/(U·L^-1)	1 240±735	1 072±672
GGT z/(U·L^-1)	4.52±1.84	2.43±0.88
TBIL c/(μmol·L^-1)	2.61±0.76	3.16±1.31
UREA c/(mmol·L^-1)	6.10±2.35	6.20±2.35
CRE c/(μmol·L^-1)	30±8	34±8
GLU c/(mmol·L^-1)	7.80±3.02	6.92±1.41
CHO c/(mmol·L^-1)	1.80±0.82	1.97±0.98
TG c/(mmol·L^-1)	0.68±0.53	0.56±0.51
TP ρ/(g·L^-1)	64.3±10.2	69.0±11.4
ALB ρ/(g·L^-1)	40.8±12.0	48.5±15.3
A/G	1.81±0.88	2.51±1.45
K⁺c/(mmol·L^-1)	5.04±0.61	4.61±0.61
Na⁺c/(mmol·L^-1)	144.1±3.3	143.1±2.5
Cl^-c/(mmol·L^-1)	102.9±4.3	103.4±5.3

指标 Index	雄性 Male	雌性 Female
ALT z/(U·L^-1)	37±18	28±16
AST z/(U·L^-1)	128±35	107±37
ALP z/(U·L^-1)	104±45	53±27
CK z/(U·L^-1)	747±494	634±439
LDH z/(U·L^-1)	1 240±735	1 072±672
GGT z/(U·L^-1)	4.52±1.84	2.43±0.88
TBIL c/(μmol·L^-1)	2.61±0.76	3.16±1.31
UREA c/(mmol·L^-1)	6.10±2.35	6.20±2.35
CRE c/(μmol·L^-1)	30±8	34±8
GLU c/(mmol·L^-1)	7.80±3.02	6.92±1.41
CHO c/(mmol·L^-1)	1.80±0.82	1.97±0.98
TG c/(mmol·L^-1)	0.68±0.53	0.56±0.51
TP ρ/(g·L^-1)	64.3±10.2	69.0±11.4
ALB ρ/(g·L^-1)	40.8±12.0	48.5±15.3
A/G	1.81±0.88	2.51±1.45
K⁺c/(mmol·L^-1)	5.04±0.61	4.61±0.61
Na⁺c/(mmol·L^-1)	144.1±3.3	143.1±2.5
Cl^-c/(mmol·L^-1)	102.9±4.3	103.4±5.3

性别 Gender	葡萄糖 Glucose	蛋白质 Protein	胆红素 Bilirubin	尿胆原 Urobilinogen	酸碱值 pH	尿比重 Urine specific gravity	隐血 Occult blood	酮体 Ketones	亚硝酸盐 Nitrite	白细胞 WBC C_cell/(10⁹·L^-1)
雄性 Male	-: 60/60	-: 1/60	-: 59/60	NORMAL: 41/60	5.0: 2/60	<1.005: 18/60	-: 41/60	-: 22/60	-: 60/60	-: 9/60
		+-: 13/60	1+: 1/60	1+: 15/60	5.5: 1/60	1.010: 18/60	+-: 15/60	+-: 27/60		25: 15/60
		1+: 24/60		2+: 4/60	6.0: 1/60	1.015: 10/60	1+: 3/60	1+: 11/60		75: 26/60
		2+: 20/60			6.5: 7/60	1.020: 11/60	2+: 1/60			250: 9/60
		3+: 2/60			7.0: 6/60	1.025: 2/60				500: 1/60
					7.5: 3/60	>1.030: 1/60
					8.0: 23/60
					8.5: 17/60
雌性 Female	-: 60/60	-: 29/60	-: 60/60	NORMAL: 50/60	6.5: 2/60	<1.005: 23/60	-: 55/60	-: 50/60	-: 60/60	-: 41/60
		+-: 17/60		1+: 7/60	7.0: 6/60	1.010: 19/60	+-: 2/60	+-: 8/60		25: 10/60
		1+: 11/60		2+: 2/60	7.5: 3/60	1.015: 15/60	1+: 1/60	1+: 2/60		75: 7/60
		2+: 3/60		3+: 1/60	8.0: 22/60	1.020: 3/60	2+: 1/60			250: 2/10
					8.5: 26/60		3+: 1/60
					9.0: 1/60