GB 15193.26-2015 English PDFUS$169.00 · In stock
Delivery: <= 3 days. True-PDF full-copy in English will be manually translated and delivered via email. GB 15193.26-2015: National food safety standard -- Chronic toxicity test Status: Valid
Basic dataStandard ID: GB 15193.26-2015 (GB15193.26-2015)Description (Translated English): National food safety standard -- Chronic toxicity test Sector / Industry: National Standard Classification of Chinese Standard: C53 Classification of International Standard: 07.100 Word Count Estimation: 8,857 Date of Issue: 2015-08-07 Date of Implementation: 2015-10-07 Regulation (derived from): National Food Safety Standard Announcement (2015 No.6) Issuing agency(ies): National Health and Family Planning Commission of the People's Republic of China Summary: This standard specifies the basic test methods and technical requirements for chronic toxicity tests. This standard applies to the assessment of the chronic toxicity of the test substance. GB 15193.26-2015: National food safety standard -- Chronic toxicity test---This is a DRAFT version for illustration, not a final translation. Full copy of true-PDF in English version (including equations, symbols, images, flow-chart, tables, and figures etc.) will be manually/carefully translated upon your order.(National Food Safety Standard chronic toxicity test) National Standards of People's Republic of China National Food Safety Standard Chronic toxicity test Issued on.2015-08-07 2015-10-07 implementation People's Republic of China National Health and Family Planning Commission released National Food Safety Standard Chronic toxicity test 1 ScopeThis standard specifies the basic technical requirements and test methods for chronic toxicity tests. This standard applies to the evaluation of the chronic toxicity of the test substance.2 Terms and definitions2.1 Chronic toxicity Experimental animals after long-term toxic effects of repeated administration of the test substance caused. 2.2 No observed adverse effect level Through animal experiments, the existing technical means and detection index was not observed any of the test substance-related toxic effects maximum dose. 2.3 Minimum observed adverse effect level Under specified conditions, the test substance causing a minimal effect dose animal tissue morphology, function, growth and development, and other harmful effects. 2.4 target organ Organ by the test substance caused significant toxic effects of experimental animals. 2.5 Satellite Group Toxicity of the design and implementation of the additional group of animals, animal handling and feeding conditions and its main research similar to the test medium or Test convalescence observation and testing can also be used to observe and testing does not include other indicators and parameters in the main study.3 test purposes and principlesAnimal experiments to determine the long-term oral chronic toxic effects of repeated administration of the test substance caused understand the test substance dose - response relationship and toxic effects With the target organ, determined not observed adverse effect level (NOAEL) and the minimum observed adverse effect level (LOAEL), the predicted population Chronic exposure to the toxic effects of the test substance and determine the health guidance values provide the basis.4 instruments and reagents4.1 Instruments and equipment Anatomy of commonly used laboratory equipment, animal scales, electronic scales, biological microscope, biochemical analyzer, hematology analyzer, blood coagulation analyzer Instrument, urine analyzers, centrifuges, slicing machines. 4.2 Reagents Formaldehyde, xylene, ethanol, hematoxylin-eosin, paraffin, blood dilution, chemical and biological reagents, analytical reagents coagulation, urinalysis reagent.5 Test methods5.1 test substance The test substance should be used in the original sample, if it can not use the original sample, the test should be treated in accordance with the principles of the test substance for proper disposal. will Test was incorporated into feed, drinking water or gavage administration. 5.2 Experimental Animals 5.2.1 animal selection Experimental animals should be selected in line with national standards and regulations (GB 14923, GB 14922.1, GB 14922.2). First rodents Selected from the rats, rodents, dogs preferred. Recommended-week-old rats 6 weeks to 8 weeks, at the beginning of each test gender differences in animal weight should not exceed ± 20% of average weight. At least 40 the number of animals per group, male and female, should be non-parous female Rat, non-pregnant rats. If you plan to test the mid-sectional Experimental observation of the subject or the end of the recovery period to do (for satellite), should increase the number of animals (n = interim necropsy at least 20, male and female; for satellite communication Often only increased in the control group and high-dose groups of at least 20, male and female). Dogs should be used no more than nine months of age puppies (usually monthly Selected age 4 months to 6 months), at the beginning of each test gender differences in animal weight should not exceed the average weight of ± 20%, the number of animals per group At least eight, male and female, female dogs should be non-parous dog, non-pregnant dogs. If you plan to test the mid or end of the test do necropsy convalescent observation should Increase the number of animals (control and high dose groups each increased by 4, male and female). Sex and number of animals in the control group should be the same group with a test substance. 5.2.2 Animal Preparation Before the test, animals in the experimental animal room should be at least 3d ~ 5d (dogs 7d ~ 14d) acclimatization and quarantine observation. 5.2.3 Animal Feeding Animal feeding conditions, drinking water, feed should be in line with national standards and regulations (GB 14925, GB 5749, GB 14924.1, GB 14924.2, GB 14924.3). During the test animals free access to water and food, according to the component group sex feeding cage, cage number of animals (per general Rats with no more than three) shall meet the minimum space required for experimental animals in order not to affect the free movement of animals and the animals were observed for signs appropriate. test During non-animal test each test shall be less than 10% of mortality, dying animal blood biochemical tests should be carried out as far as possible, Gross Anatomy And histopathological examination, each biological samples loss rate should be less than 10%. Dose group and 5.3 5.3.1 Test subjects were set up at least three groups, a negative (vehicle) control group, the control group except that no administration of the test substance, the rest were treated by the same Trial was set. If necessary, additional untreated control group. 5.3.2 should be based on 90 days of high-dose oral toxicity test shall be so determined the animals appear more obvious toxicity in principle, but does not cause too High mortality; low dose does not cause any toxic effects; the dose should be between high-dose and low-dose, toxicity can cause mild to Obtained dose - response relationship, NOAEL and (or) LOAEL. General dose group spacing of 2 to 4 times is appropriate, not more than 10 times. 5.4 test period The trial period for at least 12 months. Any toxic change reversibility satellite group monitored by the test substance caused persistent or delayed for With stop after the observation period to the test substance is not less than 28d, more than 1/3 of the test period. 5.5 Test procedure and outcome measures 5.5.1 The test is administered 5.5.1.1 according to the characteristics of the test substance and test purposes, select the test was incorporated into feed, water or orally administered. If the test was its driving Was palatability, should be given orally. 5.5.1.2 test was orally administered to the test substance is dissolved or suspended in a suitable vehicle, the preferred solvent is water, water-insoluble test substance You can use vegetable oils (such as olive oil, corn oil, etc.), do not dissolve in water or oil test substance may be used as carboxymethyl cellulose, starch, etc. dubbed suspension Or paste like. The test substance should now use the existing, data show that except for its storage solution or suspension stabilizer. Taking into account the use of solvent Media may test substance by the body absorption, distribution, metabolism and accumulation; on the test of physical and chemical properties and toxicity resulting therefrom Impact characteristics; impact on animal food intake or water intake or nutritional status. To ensure that the test substance concentration in vivo stability, daily Same period gavage once (weekly gavage 6d), during the test, weighed twice a week for 4 weeks before 5th week to 13th week weekly weigh 1, then every 4 weeks weighed 1, weight-adjusted volume of gavage. Rodent gavage volume of generally not more than 10mL/kg of body weight, Dog 15mL/kg body weight; as an oily liquid, orally should not exceed the volume of 4mL/kg body weight. Each group was given the volume of the same. 5.5.1.3 incorporated into feed or drinking water test substance administered to the test substance and feed (or water) and mixed well to ensure the stability of the test substance formulation Qualitative and uniformity, without affecting the animal feeding, nutrition and water balance amount of principle. When a small amount of the test substance added to the feed, will be advised After the test was added a small amount of feed mix well, then add a certain amount of feed after mixing, so repeated 3 times to 4 times. Incorporation of the test substance feed Feed ratio generally is less than the mass fraction of 5%, if more than 5% (the maximum should not exceed 10 per cent), adjust the feed nutrient levels in the control group (if When the test was no calories or nutrients, and the addition ratio of more than 5% in the control group diet should be filled methyl cellulose, incorporated in an amount equivalent to high dose Volume), it was tested with each dose group feed nutrient levels remain the same, while additional untreated control group; also depends on the subject matter of heat or camp Develop sub-group dose adjustment of status feed nutrient levels, making it consistent with the control group diet nutrient levels. Test substance dosage unit Per kilogram of body weight is ingested test substance mg (or g) number, namely mg/kg body weight (or g/kg body weight), when the test was incorporated into feed, its agent May also be expressed as amount per unit mg/kg (or g/kg) feed, water is expressed as the incorporation mg/mL water. When the test was incorporated into the feed, the need will be subject to Test substance dose (mg/kg body weight) by animal food intake per 100g of body weight of the test substance converted into feed concentration (mg/kg feed). 5.5.2 General observations Observed at least daily during the test 1 5.5.2.1 General clinical manifestations of animals, and animals recorded signs of poisoning, the extent and duration Room and death. Observation includes hair, skin, eyes, mucous membranes, secretions, excretions, respiratory system, nervous system, autonomic activity (eg. Tears, vertical hair response, pupil size, unusual respiratory) and behavior (such as gait, posture, response to treatment, with or without tonic or clonic live Moving, rigid reactions, abnormal behavior, etc.). 5.5.2.2 If tumorigenesis, tumor record time, location, size, shape, and so developments. 5.5.2.3 for the dying and dead animals should be dissected and recorded as accurately as possible the time of death. 5.5.3 body weight, food intake and water intake During the 13 weeks before the test animals were recorded weekly body weight, food and water intake (when the test substance when administered by drinking water), then every 4 weeks; Test when selecting dogs were recorded weekly body weight, food and water intake (when the test substance when administered by drinking water). At the end of the test, calculated animals Weight gain, total food intake, food utilization (the first 3 months, rodents), total food utilization (non-rodent), the total test substance intake. 5.5.4 eye examination Before the test, the animals eye examination (cornea, conjunctiva, iris). At the end of the test, high dose group and control group animals eye Ministry inspection, if found that high-dose group were ocular changes, to deal with the other group of animals to be checked. 5.5.5 Hematology 5.5.5.1 Tests for three months, at the end of the first six months and 12 months and a test (test period of 12 months or more), each at least check Check each 10 male and female animals, each inspection should be possible to use the same animal; when choosing dog tested first nine months increased test this time point. If the dose level of 90 days after oral toxicity tests did not show any considerable and hematological changes, the test may not be the first three-month inspection. 5.5.5.2 Check indicators white blood cell count and classification (at least three categories), red blood cell count, platelet count, hemoglobin concentration, erythrocyte Hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), coagulation Blood zymogen time (PT), activated partial thromboplastin time (APTT) and the like. If the impact on the hematopoietic system, should be added to the measured reticulocyte count And the number of bone marrow smear cytology. 5.5.6 blood biochemical examination 5.5.6.1 5.5.5.1 by time and the number of animals will be specified. If 90 days after oral toxicity test dosage levels considerably and did not show any blood Biochemical indicators of change, the test may not be the first three-month inspection. Blood should be before the animals were fasted overnight. 5.5.6.2 Check indicators include electrolyte balance, carbohydrate, fat and protein metabolism, liver (cells, bile duct) and other aspects of renal function. Comprising at least alanine Aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl peptidase (GGT), urea (Urea), creatinine (Cr), blood glucose (Glu), total protein (TP), albumin (Alb), total cholesterol (TC), triglyceride (TG), calcium, chlorine, potassium, Sodium, total bilirubin, etc., can be detected phosphorus, uric acid (UA), if necessary, total bile acid (TBA), globulin, cholinesterase, sorbitol dehydrogenase, high-speed rail Hemoglobin, specific hormones and other indicators. 5.5.7 Urine 5.5.7.1 Tests for three months, at the end of the first six months and 12 months and a test (test period of 12 months) for all animals Conduct urine tests; the choice of dogs tested, adding this time testing for nine months. If 90 days oral toxicity test dose of water Quite flat and did not show any abnormal urine test result, the test may not be the first three-month inspection. 5.5.7.2 inspection items including appearance, urine protein, relative density, pH, glucose and occult blood, etc., if the expected toxic reaction indications, should be increased in urine Urine microscopy, cell analysis and other relevant items, such as fluid examination. 5.5.8 body temperature, ECG Dogs before the test, the test at 3 months, at the end of the first six months and 12 months and a test (test period of 12 months or more) should be Body temperature, ECG. 5.5.9 pathology 5.5.9.1 Gross anatomy All animals, including death or dying during the test and sacrificed animals were sacrificed and the expiration of the test animals were dissected and should Visually comprehensive system, including surface, cranial, thoracic and abdominal cavity and its organs, and weighing the brain, heart, liver, kidney, spleen, uterus, ovary, testis Absolute weight pills, epididymis, thymus, adrenal glands, and calculate the relative weight of the [Dirty/body ratio and (or) Dirty/brain ratio], if necessary, should choose another Organs, such as thyroid (including parathyroid), prostate. 5.5.9.2 Histopathological examination 5.5.9.2.1 histopathological examination of principles. a) may be on the high-dose group and the control group were all preserved organs and tissues fixed for histopathological examination; b) found that high-dose group after lesions of the lower dose group corresponding organ and tissue for histopathological examination; c) death or dying during the test and sacrificed animals to deal with all the tissues and organs preserved for histopathological examination; d) The gross anatomy macroscopic examination of diseased organs and tissue for histopathological examination; e) a pair of organs such as kidney, adrenal gland, organ sides should be examined histopathologically. 5.5.9.2.2 saved should be fixed for histopathological examination of organs and tissues including the salivary glands, esophagus, stomach, duodenum, jejunum, ileum, Cecum, colon, rectum, liver, pancreas, gall bladder (non-rodent), brain (including brain, cerebellum and brain stem), pituitary gland, sciatic nerve, spinal cord (Cervical, thoracic and lumbar), ocular (eye examination found abnormal, non-rodent), optic nerve (non-rodent), adrenal, parathyroid, Thyroid, thymus, trachea, lung, aorta, heart, bone marrow, lymph nodes, spleen, kidney, bladder, prostate, testis, epididymis, uterus, ovary, breast Glands. Necessary, to add measured seminal vesicles and coagulating gland, lacrimal glands (rodents), Ringer gland (rodents), turbinate, cervix, fallopian Tubes, vagina, bone, muscle, skin and eye (rodents) and other tissues and organs. Histopathological examination report should, given the pathological lesions Histological picture. 5.5.10 Other indicators If necessary, depending on the nature of the test substance and toxicity observed, add other indicators (such as neurotoxicity, immunotoxicity, endocrine toxicity Indicators).6 Data processing and evaluation of results6.1 Data Processing 6.1.1 store all data and results are summarized in tabular form, listing the number of animals in each group before the start of the test, the animals die during the test Number of death and time of death, the number of animals appear toxicity, toxicity seen described, including the emergence of time toxic effects, duration and degree. 6.1.2 animal body weight, food intake, water intake (the test was administered via drinking water), food utilization, hematological, blood biochemistry, urine Check the index, organ weight, dirty/body ratio and (or) Dirty/brain ratio, gross and histopathology examination results were statistically analyzed. one Like the case of the measurement data using analysis of variance, performed the test substance were compared between each dose group and control group, using Fisher's classified information Indeed distribution test, chi-square test, rank sum test, ranked data using Ridit analysis, rank sum test and so on. 6.2 Evaluation Results Results of the evaluation should include the performance of the test substance chronic toxicity, the dose - response relationship, the target organ, reversibility, chronic toxicity draw the appropriate NOAEL and (or) LOAEL.7 Report7.1 Name of test, the test unit name and contact details, report number. 7.2 Test Requester name and contact information, sample acceptance date. 7.3 Test start and end dates, test project manager, technical director of the test unit, date of issue. 7.4 test summary. 7.5 test substance. name, lot number, dosage form, the state (including organoleptic, properties, package integrity, identification), the number of pre-treatment method, solvent. 7.6 Experimental animals. species, strain, level, quantity, weight, weeks of age, gender, origin (supplier name, animal production license number), Animal quarantine, adaptation, breeding environment (temperature, relative humidity, using experimental animal facility license number), feed sources (supplier name, Animal feed production license number). 7.7 Test method. the test group, the number of animals in each group, according to dose selection, route of administration and duration of the test substance, observed indicators, statistical methods. 7.8 Test Results. The animal growth activity, toxicity characteristics (including the presence of time and outcome), weight gain, food intake, water intake (The test was administered via drinking water), food utilization, clinical observation (signs of toxicity, extent, duration, survival), eye examination, blood Fluid examination, blood biochemical examination, urinalysis, electrocardiogram, gross anatomy, organ weight......Tips & Frequently Asked Questions:Question 1: How long will the true-PDF of GB 15193.26-2015_English be delivered?Answer: Upon your order, we will start to translate GB 15193.26-2015_English as soon as possible, and keep you informed of the progress. The lead time is typically 1 ~ 3 working days. The lengthier the document the longer the lead time.Question 2: Can I share the purchased PDF of GB 15193.26-2015_English with my colleagues?Answer: Yes. 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