What Are the Different Doxorubicin Side Effects?

[English name] adriamycin [Other names] Doxorubicin, 14-hydroxy daunorubicin, 14-hydroxydaunomycin, Adriamycin, doxorubicin-power, doxorubicin, hydroxy red Bimycin, hydroxyl daunorubicin, doxorubicin, adriamycin, afriamycin, doxorubicin, 14-hydroxydaunomycin, 14-hydroxydaunomycin, etc. Broad antitumor spectrum, suitable for acute leukemia (lymphocytic and granulocyte), malignant lymphoma, breast cancer, bronchial lung cancer (undifferentiated small cell and non-small cell), ovarian cancer, soft tissue sarcoma, osteoblast Tumor, rhabdomyosarcoma, Ewing sarcoma, blastoma, neuroblastoma, bladder cancer, thyroid cancer, prostate cancer, head and neck squamous cell carcinoma, testicular cancer, gastric cancer, liver cancer, etc.

1 Bone marrow hematopoiesis, manifested by platelet and leukopenia.

2 Cardiotoxicity, heart failure may occur in severe cases.

3 Nausea, vomiting,

[Chemical name] (2R, 4S) -4- (3-Amino-2,3,6-trideoxy--L-lyxo-hexopyranosyloxy) -2-hydroxyacetyl-1,2,3,4-tetrahydro-2, 5,12-trihydroxy-7-methoxynaphthacene-6,11-dione

[CA registration number] [23214-92-8]

[Structural formula]

medicine interactions

1. Various bone marrow inhibitors, especially nitrosoureas, high-dose cyclophosphamide or methotrexate, mitomycin, or radiation therapy. If used with the product, the latter amount and total dose should be appropriate Less.

2. If the product is used with streptozotocin, the latter can extend the half-life of the product, so the dose of the former should be reduced.

3. Any drug that may cause liver damage, if used with this product, can increase the liver toxicity of this product; mixed application with heparin, cephalosporin, etc. will easily cause precipitation.

4. This product is cross-resistant to daunorubicin. It is not cross-resistant to methotrexate, fluorouracil, cytarabine, nitrogen mustard, mitomycin, bleomycin, cyclophosphamide, and nitrosourea, and it is not cross-resistant to cyclophosphamide and fluorouracil. , Methotrexate, cisplatin, and nitrosourea drugs have the same degree of synergy.

5. Caution with live virus vaccine during medication.

6. This product can reduce the anticoagulant effect of heparin. ACD and pukamycin used together with this product may cause fatal cardiotoxicity; combined with propranolol, it can strengthen the inhibition of mitochondrial respiratory enzyme activity and increase cardiotoxicity.

[Dosing Instructions]

1. Combined with large doses of cyclophosphamide, the fraction and total amount of this product should be reduced as appropriate.

2. This product is disabled during mediastinal or thoracic radiotherapy. For those who have previously received mediastinal radiation therapy, each dose and total dose of doxorubicin should also be reduced.

3. People who have used sufficient daunorubicin or this product in the past can not use this product again.

4. This product can be used for intraperitoneal administration and bladder perfusion, but not for intrathecal injection.

5. Prevent the product from leaking out of blood vessels. Once it occurs, the local infiltration drug should be drawn as far as possible, and the local immediate injection of 50 to 100 mg of hydrocortisone, or sodium bicarbonate and cold compress.

[Usage and Dosage] Dissolve the sodium chloride injection immediately before use, and the concentration is generally 2mg / ml. Slow intravenous or arterial injection.

1. Usual dose for adults: 50 60mg once, once every 3 4 weeks or 20 30mg per week, for 3 weeks in a row, repeat after 2 3 weeks of discontinuation. Myocardial toxicity, myelosuppression, and gastrointestinal reactions (including oral ulcers) administered in divided doses every week were lighter than those given once every 3 weeks. Children use about half as much as adults. The total dose should not exceed 400 mg / m ^{2 in} terms of body surface area. 30 ~ 40mg can be used in the bladder or chest each time.

2. Combined chemotherapy:

ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine), mainly used for Hodgkin's lymphoma;

CAF (cyclophosphamide, the product and fluorouracil), mainly used for breast cancer;

CAOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), mainly used for malignant lymphoma;

FAM (fluorouracil, the product and mitomycin), mainly used for gastric cancer;

AC (the product and cytarabine), mainly used in adult acute myeloid leukemia;

AOP (the product, vincristine and prednisone), mainly used for the induction of remission of lymphoblastic acute leukemia;

ACP (the product, cyclophosphamide and cisplatin), mainly used for ovarian and bronchial lung cancer, head and neck cancer, bladder cancer, etc .;

CY-VA-DIC (cyclophosphamide, vincristine, this product and dacarbazine), mainly used for soft tissue sarcoma and osteosarcoma;

MACC (methotrexate, this product, cyclophosphamide and cyclohexyl nitrosourea), mainly used for undifferentiated small cell lung cancer or lung adenocarcinoma.

[Formulations and specifications] Doxorubicin for injection: 10mg; 50mg.

Adverse reactions

1. Common hair loss (about 90% of patients), myelosuppression (white blood cells drop to the lowest point about 10 to 14 days after administration, and most gradually return to normal levels within 3 weeks, anemia and thrombocytopenia are rare) Mouth ulcers, loss of appetite, nausea, or even vomiting.

2. A small number of patients may have skin redness or pigmentation in the original radiation field after injection of this product. If the injection fluid overflows, it can cause redness, swelling, pain, or even cellulitis and local necrosis.

3. Leukemia and malignant lymphoma patients when using this product, especially those who use the product for the first time, can cause hyperuricemia due to a large number of destruction of tumor cells, resulting in joint pain or renal function damage.

4. This product has cardiotoxicity, which can cause late-onset severe heart failure, which can sometimes occur after half a year of withdrawal. When there is myocardial damage, rapid heart rate, arrhythmia, conduction block, or jet heart failure can occur. These situations can happen suddenly and there is no sign of abnormality in conventional ECG. Myocardial toxicity is closely related to the cumulative dose. For the total amount of 450 to 550 mg / m ² , the incidence rate is about 1% to 4%. For the total amount of more than 550 mg / m ² , the incidence rate increases significantly, up to 30%. Cardiotoxicity can be exacerbated by the combined use of other drugs. Newer data suggest that high doses of cyclophosphamide and trastuzumab have similar effects.

Contraindications

1. This product can pass through the placenta, which may cause miscarriage. Therefore, it is strictly prohibited to apply it within the first 3 months of pregnancy. After using this product in pregnant women, toxic reactions to the fetus can sometimes appear up to several years later.

2. Disable the product during mediastinal or thoracic radiotherapy.

3. The following conditions should be disabled: white blood cells below 3500 / l or platelets below 50,000 / l in peripheral blood, obvious infection or fever, cachexia, dehydration, electrolyte or acid-base balance disorders, gastrointestinal obstruction, obvious People with jaundice or impaired liver function, patients with decompensated heart and lung function, patients with chickenpox or shingles.

4. Those who are allergic to this product are prohibited. ^[1]

1. This product has carcinogenic effects in animals, and also has potential mutagenic and carcinogenic effects in humans. The product has a significant effect on animal reproductive function, but in humans, its inhibitory effect is greatly reduced in rats.

2. Although there is less renal excretion of this product, red urine can appear within 1 to 2 days after administration, and usually disappears after 2 days. Patients with renal insufficiency should be alert to the appearance of hyperuricemia after using this product; patients with gout, if using this product, the amount of allopurinol should be increased accordingly.

3. Elderly patients, children under 2 years old and patients with existing heart disease should be used with extreme caution.

4. A small number of patients can cause jaundice or other liver dysfunction after administration, and the amount of liver dysfunction should be reduced.

5. Check during medication:

Before and after treatment, measure cardiac function, monitor electrocardiogram, echocardiogram, serum enzymes and other myocardial function tests;

Follow-up examination of peripheral blood (at least once a week) and liver function test;

should always check for oral ulcers, diarrhea and jaundice, advise patients to drink plenty of water to reduce the possibility of hyperuricemia, check serum uric acid or renal function if necessary.

6. The cardiotoxicity of doxorubicin mostly occurs 1 to 6 months after discontinuation. Vitamin B6 and coenzyme Q10 should be applied early to reduce its toxicity to the heart.

7. During the medication period, the blood image should be reviewed regularly to avoid bone marrow suppression. ^[1]

Toxicity test data

Numbering	Toxicity type	testing method	Test object	Dosage used	Toxic effect
1	Acute toxicity	Intravenous injection	Humanity	15 mg / kg / D	1. Cardiotoxicity-cardiomyopathy including infarction 2. Gastrointestinal toxicity-nausea, vomiting 3. Skin and accessory toxicity-changes in hair
2	Acute toxicity	Intravenous injection	Humanity	400 ug / kg	1. Gastrointestinal toxicity-Other changes 2. Hematological toxicity-Leukopenia 3. Skin and accessory toxicity-Hair changes
3	Acute toxicity	Intravenous injection	Humanity	380 mg / kg / 31W	1. Cardiotoxicity-cardiomyopathy including infarction 2. Gastrointestinal toxicity-nausea, vomiting 3. Skin and accessory toxicity-changes in hair
4	Acute toxicity	Not reported	Adult male	243 ug / kg	1. Cardiotoxicity-other changes 2. Vascular toxicity-decreased blood pressure regulation
5	Acute toxicity	Intraperitoneal injection	Rat	16 mg / kg	Detailed effects are not reported other than lethal dose
6	Acute toxicity	Intravenous injection	Rat	10510 ug / kg	1. Nutritional and metabolic system toxicity-weight loss or weight loss rate
7	Acute toxicity	Not reported	Rat	7 mg / kg	Detailed effects are not reported other than lethal dose
8	Acute toxicity	oral	Mouse	570 mg / kg	Detailed effects are not reported other than lethal dose
9	Acute toxicity	Intraperitoneal injection	Mouse	10700 ug / kg	Detailed effects are not reported other than lethal dose
10	Acute toxicity	Intravenous injection	Mouse	10 mg / kg	Detailed effects are not reported other than lethal dose
11	Acute toxicity	trachea	Mouse	2400 ug / kg	1. Nutritional and metabolic system toxicity-weight loss or weight loss rate
12	Acute toxicity	Not reported	Mouse	21900 ug / kg	Detailed effects are not reported other than lethal dose
13	Acute toxicity	Intravenous injection	dog	2400 ug / kg	Detailed effects are not reported other than lethal dose
14	Acute toxicity	Intravenous injection	rabbit	5 mg / kg	Detailed effects are not reported other than lethal dose
15	Acute toxicity	Thoracic injection	rabbit	400 ug / kg	1. Cardiotoxicity-other changes 2. Lung, chest or respiratory toxicity-pulmonary interstitial fibrosis, lung disease (including pneumoconiosis) 3. Lung, chest or respiratory toxicity-thickened pleura
16	Acute toxicity	Parenteral	Hamster	3500 ug / kg	1. Carcinogenicity-anti-tumor and anti-cancer activity
17	Acute toxicity	Intraperitoneal injection	mammal	8500 ug / kg	Detailed effects are not reported other than lethal dose
18	Chronic toxicity	Intraperitoneal injection	Rat	15 mg / kg / 3W-I	1. Cardiotoxicity-other changes 2. Hematological toxicity-changes in serum composition (such as TP, bilirubin, cholesterol) 3. Biochemical toxicity-inhibit or induce phosphatase
19	Chronic toxicity	Intraperitoneal injection	Rat	12 mg / kg / 7D-I	1. Cardiotoxicity-changes in conduction velocity 2. Cardiotoxicity-other changes 3. Biochemical toxicity-inhibition or induction of other enzymes
20	Chronic toxicity	Intraperitoneal injection	Rat	21 mg / kg / 8W-I	1. Liver toxicity-decreased liver function 2. Biochemical toxicity-inhibition or dehydrogenase induction
twenty one	Chronic toxicity	Intraperitoneal injection	Rat	24 mg / kg / 2W-I	1. Cardiotoxicity-changes in electrocardiogram 2. Hematological toxicity-changes in white blood cell count 3. Chronic disease-related toxicity-death
twenty two	Chronic toxicity	Subcutaneous injection	Rat	24 mg / kg / 12W-I	1. Biochemical toxicity-inhibition or induction of dehydrogenase 2. Biochemical toxicity-inhibition or induction of phosphokinase
twenty three	Chronic toxicity	Intraperitoneal injection	Rat	20 mg / kg / 6W-I	1. Cardiotoxicity-changes in heart weight 2. Endocrine toxicity-other changes 3. Hematological toxicity-changes in white blood cell count
twenty four	Chronic toxicity	Intravenous injection	Rat	12 mg / kg / 3W-I	1. Cardiotoxicity-Cardiomyopathy including infarction 2. Cardiotoxicity-Changes in ECG 3. Nutritional and metabolic system toxicity-Weight loss or rate of weight loss
25	Chronic toxicity	Intravenous injection	Rat	20 mg / kg / 10W-I	1. Cardiotoxicity-cardiomyopathy including infarction 2. Chronic disease-related toxicity-death
26	Chronic toxicity	Intravenous injection	Rat	12 mg / kg / 12W-I	1. Cardiotoxicity pulse rate changes 2. Renal, ureter, and bladder toxicity-changes in renal tubules (including acute renal failure, acute tubular necrosis) 3. Hematological toxicity-changes in red blood cell count
27	Chronic toxicity	Intravenous injection	Rat	12 mg / kg / 52D-I	1. Cardiotoxicity-changes in heart weight 2. Kidney, ureter and bladder toxicity-Changes in bladder weight 3. Biochemical toxicity-Inhibition or induction of catalase
28	Chronic toxicity	Intravenous injection	Rat	12 mg / kg / 6W-I	1. Cardiotoxicity-Other changes 2. Biochemical toxicity-Inhibition or induction of phosphatase 3. Biochemical toxicity-Inhibition or induction of dehydrogenase
29	Chronic toxicity	Intravenous injection	Rat	12500 ug / kg / 5D-I	1. Hematological toxicity-Leukopenia 2. Nutrition and metabolic system toxicity-Weight loss or rate of weight loss
30	Chronic toxicity	Intravenous injection	Rat	7 mg / kg / 7W-I	1. Cardiotoxicity-cardiomyopathy including infarction 2. Nutritional and metabolic system toxicity-weight loss or rate of weight loss 3. Chronic disease-related toxicity-death
31	Chronic toxicity	Intravenous injection	Rat	12 mg / kg / 4W-I	1. Cardiotoxicity-Cardiomyopathy including infarction 2. Cardiotoxicity-Changes in ECG 3. Nutritional and metabolic system toxicity-Weight loss or rate of weight loss
32	Chronic toxicity	Intraperitoneal injection	Mouse	10 mg / kg / 9D-I	1. Hepatotoxicity-decreased liver function 2. Biochemical toxicity-Inhibition of transaminase activity, altered the spatial structure of transaminase 3. Nutrition and metabolic system toxicity-changes in calcium concentration
33	Chronic toxicity	Subcutaneous injection	Mouse	27500 ug / kg / 5D-I	1. Chronic disease-related toxicity-death
34	Chronic toxicity	Intravenous injection	Mouse	22600 ug / kg / 2D-I	1. Chronic disease-related toxicity-death
35	Chronic toxicity	Intravenous injection	Mouse	9 mg / kg / 5D-I	1. Hematological toxicity-abnormal staining of red blood cells or affecting nucleated red blood cells 2. Hematological toxicity-reduced white blood cells 3. Hematological toxicity-changes in red blood cell count
36	Chronic toxicity	Intravenous injection	dog	17500 ug / kg / 36W-I	1. Cardiotoxicity-Arrhythmia 2. Lung, chest or respiratory toxicity-Acute pulmonary edema 3. Skin and accessory toxicity-Hair changes
37	Chronic toxicity	Intravenous injection	dog	7250 ug / kg / 5D-I	1. Behavioral toxicity-affects food intake (animals) 2. Gastrointestinal toxicity-excessive exercise, diarrhea 3. Chronic disease-related toxicity-death
38	Chronic toxicity	Intravenous injection	dog	13750 ug / kg / 26W-I	1. Cardiotoxicity-changes in electrocardiogram 2. Vascular toxicity-decreased blood pressure regulation 3. Hematological toxicity-changes in bone marrow
39	Chronic toxicity	Intravenous injection	dog	6250 ug / kg / 18W-I	1. Cardiotoxicity-changes in electrocardiogram
40	Chronic toxicity	Intravenous injection	monkey	23360 ug / kg / 36W-I	1. Cardiotoxicity-Other changes 2. Lung, chest or respiratory toxicity-Acute pulmonary edema 3. Hepatotoxicity-Other changes
41	Chronic toxicity	Intravenous injection	monkey	20800 ug / kg / 5D-I	1. Cardiotoxicity-changes in electrocardiogram 2. Gastrointestinal toxicity-excessive exercise, diarrhea 3. Chronic disease-related toxicity-death
42	Chronic toxicity	Intravenous injection	rabbit	20 mg / kg / 8W-I	1. Cardiotoxicity-changes in cardiac output 2. Vascular toxicity-decreased blood pressure regulation 3. Nutritional and metabolic system toxicity-changes in calcium concentration
43	Chronic toxicity	Intraperitoneal injection	Hamster	27 mg / kg / 3W-I	1. Cardiotoxicity-cardiomyopathy including infarction 2. Skin and accessory toxicity-dermatitis (after systemic exposure) 3. Nutrition and metabolic system toxicity-weight loss or weight loss rate
44	Ocular toxicity	Skin surface	rabbit	15 mg / 24H
45	Mutation toxicity		Salmonella typhimurium	2560 ng / plate
46	Mutation toxicity		Salmonella typhimurium	1 ug / plate
47	Mutation toxicity		Salmonella typhimurium	600 ug / L
48	Mutation toxicity		Salmonella typhimurium	6 ug / plate
49	Mutation toxicity		E.coli	50 mg / L
50	Mutation toxicity		E.coli	10 umol / L
51	Mutation toxicity		E.coli	10 umol / L
52	Mutation toxicity		E.coli	10 umol / L
53	Mutation toxicity		E.coli	1 ug / plate
54	Mutation toxicity		Bacillus subtilis	500 ng / plate
55	Mutation toxicity		Microorganism ed	5 umol / L
56	Mutation toxicity		Microorganism ed	10 umol / L
57	Mutation toxicity	oral	Drosophila melanogaster	1 gm / L
58	Mutation toxicity	Parenteral	Drosophila melanogaster	250 mg / L
59	Mutation toxicity		Saccharomyces cerevisiae	184 umol / L
60	Mutation toxicity		Aspergillus nidulans	100 mg / L
61	Mutation toxicity		Grasshopper cells	250 nmol / L
62	Mutation toxicity		Grasshopper cells	125 nmol / L
63	Mutation toxicity		Non-mammalian testis	1 umol / L
64	Mutation toxicity		Human lymphocyte	20 ug / L
65	Mutation toxicity		Human ovary	10 umol / L
66	Mutation toxicity		Human cells	1250 ug / L
67	Mutation toxicity		Human cells	250 ug / L
68	Mutation toxicity		Human cells	500 nmol / L
69	Mutation toxicity		Human lymphocyte	50 ug / L
70	Mutation toxicity		Human cells	700 nmol / L
71	Mutation toxicity		Human fibroblast	100 umol / L
72	Mutation toxicity		Human fibroblast	500 ug / L
73	Mutation toxicity		Human lymphocyte	100 ug / L
74	Mutation toxicity		Human lymphocyte	1 mg / L
75	Mutation toxicity		Human lymphocyte	10 umol / L
76	Mutation toxicity		Human leukocyte	10 umol / L
77	Mutation toxicity		Hella cells	1 umol / L
78	Mutation toxicity		Human cells	1 umol / L
79	Mutation toxicity		Human cells	10 nmol / L / 2H
80	Mutation toxicity		Human cells	10 nmol / L / 2H
81	Mutation toxicity		Human lymphocyte	500 ug / L
82	Mutation toxicity		Human cells	30 nmol / L
83	Mutation toxicity		Human cells	150 ug / L
84	Mutation toxicity		Human cells	150 ug / L
85	Mutation toxicity		Human cells	50 nmol / L
86	Mutation toxicity		Human cells	400 ug / L
87	Mutation toxicity		Human cells	800 ug / L
88	Mutation toxicity		Human cells	1 umol / L
89	Mutation toxicity		Human leukocyte	20 ug / L
90	Mutation toxicity		Human lymphocyte	10 ug / L
91	Mutation toxicity		Human fibroblast	10 ug / L / 1H
92	Mutation toxicity		Human cells	50 nmol / L
93	Mutation toxicity		Human lymphocyte	5 ng / L / 48H
94	Mutation toxicity		Human cells	1 umol / L
95	Mutation toxicity		Human cells	1 umol / L
96	Mutation toxicity	Intraperitoneal injection	Rat	5 mg / kg
97	Mutation toxicity	Parenteral	Rat	1250 ug / kg / 2D (intermittent)
98	Mutation toxicity		Rat cells	1 ug / L
99	Mutation toxicity		Rat fetus	150 ug / L
100	Mutation toxicity		Rat cells	6800 ug / L
101	Mutation toxicity		Rat liver	6100 nmol / L
102	Mutation toxicity		Rat cells	1150 ug / L
103	Mutation toxicity		Rat cells	1 mg / L
104	Mutation toxicity	Intravenous injection	Rat	5 mg / kg / 8H (intermittent)
105	Mutation toxicity		Rat liver	50 nmol
106	Mutation toxicity		Rat liver	2910 pmol / L
107	Mutation toxicity		Rat mammary gland	100 nmol / L
108	Mutation toxicity		Rat mammary gland	10 umol / L
109	Mutation toxicity		Salmonella typhimurium in rats	200 mg / kg
110	Mutation toxicity	Intraperitoneal injection	Rat	2 mg / kg
111	Mutation toxicity	Intraperitoneal injection	Mouse	2 mg / kg / 24H
112	Mutation toxicity		Mouse lymphocyte	5 ug / L
113	Mutation toxicity		Mouse lymphocyte	100 ug / L
114	Mutation toxicity		Mouse fibroblast	1 ug / L
115	Mutation toxicity		Mouse cells	5 umol / L
116	Mutation toxicity		Mouse cells	2 umol / L
117	Mutation toxicity	Intraperitoneal injection	Mouse	5 mg / kg
118	Mutation toxicity		Mouse leukocytes	260 nmol / L
119	Mutation toxicity		Mouse ascites tumor cells	600 ug / kg
120	Mutation toxicity		Mouse cells	4 umol / L
121	Mutation toxicity		Mouse cells	5 ug / L
122	Mutation toxicity		Mouse leukocytes	10 mg / L
123	Mutation toxicity		Mouse mammary gland	400 ug / L
124	Mutation toxicity		Mouse lymphocyte	20 ug / L
125	Mutation toxicity	Intravenous injection	Mouse	15 mg / kg
126	Mutation toxicity		Mouse cells	100 nmol / L
127	Mutation toxicity		Mouse leukocytes	2900 nmol / L
128	Mutation toxicity	Intraperitoneal injection	Mouse	5 mg / kg
129	Mutation toxicity		Mouse leukocytes	10 mg / L
130	Mutation toxicity	Intraperitoneal injection	Mouse	10 mg / kg
131	Mutation toxicity		Mouse cells	150 ug / L
132	Mutation toxicity		Mouse lymphocyte	6600 ug / L
133	Mutation toxicity		Mouse cells	1800 nmol / L
134	Mutation toxicity		Mouse cells	18 umol / L
135	Mutation toxicity		Mouse lymphocyte	5 ug / L
136	Mutation toxicity		Mouse leukocytes	400 ug / L
137	Mutation toxicity	Intraperitoneal injection	Mouse	500 ug / kg
138	Mutation toxicity		Mouse fibroblast	50 ug / L
139	Mutation toxicity	Intravenous injection	Mouse	500 ug / kg
140	Mutation toxicity		Mouse leukocytes	100 ug / L
141	Mutation toxicity	Parenteral	Mouse	5 mg / kg
142	Mutation toxicity	Intraperitoneal injection	Mouse	250 ug / kg
143	Mutation toxicity	Intravenous injection	Mouse	12 mg / kg
144	Mutation toxicity		Mouse ascites tumor cells	5 mg / kg
145	Mutation toxicity		Mouse lymphocyte	3 mg / kg
146	Mutation toxicity		Mouse lymphocyte	5 gm / L
147	Mutation toxicity	Intravenous injection	Mouse	8 mg / kg
148	Mutation toxicity	Intraperitoneal injection	Mouse	3 mg / kg
149	Mutation toxicity		Mouse lymphocyte	5 ug / L
150	Mutation toxicity		Mouse cells	1 mg / kg
151	Mutation toxicity	Intravenous injection	Mouse	6 mg / kg
152	Mutation toxicity		Hamster lung	100 ug / L
153	Mutation toxicity		Hamster Ovary	1 mg / L
154	Mutation toxicity		Hamster cells	5 mg / L
155	Mutation toxicity		Hamster cells	5 mg / L
156	Mutation toxicity		Hamster Ovary	400 ug / L
157	Mutation toxicity		Hamster lung	300 ug / L / 2H
158	Mutation toxicity		Hamster fibroblast	200 nmol / L
159	Mutation toxicity		Hamster Ovary	1 umol / L
160	Mutation toxicity		Hamster lung	300 ug / L / 2H
161	Mutation toxicity		Hamster lung	10 ug / L
162	Mutation toxicity		Hamster Ovary	160 ug / L
163	Mutation toxicity		Hamster fibroblast	20 nmol / L
164	Mutation toxicity		Chicken cells	5 umol / L
165	Mutation toxicity	Intravenous injection	rabbit	1 mg / kg
166	Carcinogenicity	Intravenous injection	Rat	5 mg / kg	1. Carcinogenicity-Carcinogenic (according to RTECS standards) 2. Skin and accessory toxicity-tumor
167	Carcinogenicity	Intravenous injection	Rat	8 mg / kg	1. Carcinogenicity-tumor (according to RTECS standards) 2. Skin and accessory toxicity-tumor
168	Carcinogenicity	Intravenous injection	Rat	10 mg / kg	1. Carcinogenicity-Carcinogenic (according to RTECS standards) 2. Lung, chest or respiratory toxicity-tumor 3. Skin and accessory toxicity-tumor
169	Carcinogenicity	Intravenous injection	Rat	5 mg / kg	1. Carcinogenicity-may be carcinogenic (according to RTECS standards) 2. Skin and accessory toxicity-tumor
170	Carcinogenicity	Intravenous injection	Rat	8 mg / kg	1. Carcinogenicity-Carcinogenic (according to RTECS standards) 2. Skin and accessory toxicity-tumor
171	Carcinogenicity	Intravenous injection	Rat	10 mg / kg	1. Carcinogenicity-Carcinogenic (according to RTECS standards) 2. Skin and accessory toxicity-tumor
172	Carcinogenicity	Intravenous injection	Rat	5 mg / kg	1. Carcinogenicity-Carcinogenic (according to RTECS standards) 2. Skin and accessory toxicity-tumor
173	Carcinogenicity	Intravenous injection	Rat	5 mg / kg	1. Carcinogenicity-may be carcinogenic (according to RTECS standards) 2. Skin and accessory toxicity-tumor
174	Carcinogenicity	Intravenous injection	Rat	2 mg / kg	1. Carcinogenicity-tumor (according to RTECS standards) 2. Skin and accessory toxicity-tumor
175	Reproductive toxicity	Intraperitoneal injection	Rat	8 mg / kg, 6-9 days after conception	1. Reproductive toxicity-abnormal development of the musculoskeletal system
176	Reproductive toxicity	Intraperitoneal injection	Rat	3 mg / kg, 10-12 days after conception	1. Reproductive toxicity-reduced weight gain in newborns
177	Reproductive toxicity	Intraperitoneal injection	Rat	4 mg / kg, 6-9 days after conception	1. Reproductive toxicity-fetal toxicity (such as fetal dysplasia but not death) 2. Reproductive toxicity-abnormal development of the cardiovascular circulatory system 3. Reproductive toxicity-abnormal development of the urinary system
178	Reproductive toxicity	Intraperitoneal injection	Rat	3 mg / kg, 1 day before male mating	1. Reproductive toxicity-abnormal male spermatogenesis (including genetic material, sperm morphology, sperm motility and count) 2. Reproductive toxicity-changes in testis, epididymis, and vas deferens 3. Reproductive toxicity-decline in male fertility
179	Reproductive toxicity	Intraperitoneal injection	Rat	4200 ug / kg, 7-13 days after conception	1. Reproductive toxicity-abnormal development of the musculoskeletal system 2. Reproductive toxicity-physical changes in newborns
180	Reproductive toxicity	Intraperitoneal injection	Rat	2 mg / kg, 3 days after female conception	1. Reproductive toxicity-increased mortality before embryo implantation 2. Reproductive toxicity-increased mortality after implantation 3. Reproductive toxicity-abnormal development of the musculoskeletal system
181	Reproductive toxicity	Intraperitoneal injection	Rat	8 mg / kg, 9-12 days after conception	1. Reproductive toxicity-fetal toxicity (such as fetal dysplasia but not death) 2. Reproductive toxicity-abnormal development of the musculoskeletal system
182	Reproductive toxicity	Intravenous injection	Rat	500 ug / kg, male mating 1 day ago	1. Reproductive toxicity-abnormal male spermatogenesis (including genetic material, sperm morphology, sperm motility and count)
183	Reproductive toxicity	Intravenous injection	Rat	10 mg / kg, male mated 1 day ago	1. Reproductive toxicity-changes in testis, epididymis, and vas deferens
184	Reproductive toxicity	Intravenous injection	Rat	3 mg / kg, 1 day before male mating	1. Reproductive toxicity-abnormal male spermatogenesis (including genetic material, sperm morphology, sperm motility and count) 2. Reproductive toxicity-changes in testis, epididymis, and vas deferens
185	Reproductive toxicity	Intravenous injection	Rat	8 mg / kg, male mated 1 day ago	1. Reproductive toxicity-abnormal male spermatogenesis (including genetic material, sperm morphology, sperm motility and count)
186	Reproductive toxicity	Intravenous injection	Rat	8 mg / kg, male mated 1 day ago	1. Reproductive toxicity-abnormal male spermatogenesis (including genetic material, sperm morphology, sperm motility and count)
187	Reproductive toxicity	Parenteral	Rat	61336 ug / kg, male mating 56 days ago	1. Reproductive toxicity-abnormal male spermatogenesis (including genetic material, sperm morphology, sperm motility and count)
188	Reproductive toxicity	Not reported	Rat	4500 ug / kg, 10-12 days after conception	1. Reproductive toxicity-abnormal development of the urinary system 2. Reproductive toxicity-Reduced weight gain in the newborn 3. Reproductive toxicity-affects the behavior of the newborn
189	Reproductive toxicity	Intravenous injection	Mouse	2 mg / kg, male mated 1 day ago	1. Reproductive toxicity-abnormal male spermatogenesis (including genetic material, sperm morphology, sperm motility and count)
190	Reproductive toxicity	Intravenous injection	Mouse	7 mg / kg, 7-13 days after conception	1. Reproductive toxicity-embryo or fetal death 2. Reproductive toxicity-abnormal development of the musculoskeletal system
191	Reproductive toxicity	Intravenous injection	Mouse	700 ug / kg, 7-13 days after conception	1. Reproductive toxicity-physical changes in newborns
192	Reproductive toxicity	Intravenous injection	Mouse	4200 ug / kg, 7-13 days after conception	1. Reproductive toxicity-fetal toxicity (such as fetal dysplasia but not death)
193	Reproductive toxicity	Intravenous injection	rabbit	7800 ug / kg, 6-18 days after conception	1. Reproductive toxicity-abortion

Material toxicity reference: ^[2-162]