GB 15193.13-2015 English PDFUS$189.00 · In stock
Delivery: <= 3 days. True-PDF full-copy in English will be manually translated and delivered via email. GB 15193.13-2015: National food safety standard - 90 days oral toxicity test Status: Valid GB 15193.13: Historical versions
Basic dataStandard ID: GB 15193.13-2015 (GB15193.13-2015)Description (Translated English): National food safety standard - 90 days oral toxicity test Sector / Industry: National Standard Classification of Chinese Standard: C53 Classification of International Standard: 7.1 Word Count Estimation: 9,982 Date of Issue: 2015-08-07 Date of Implementation: 2015-10-07 Older Standard (superseded by this standard): GB 15193.13-2003 Regulation (derived from): National Food Safety Standard Announcement 2015 No.6 Issuing agency(ies): National Health and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 GB 15193.13-2015: National food safety standard - 90 days oral 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 90 days oral toxicity test) National Standards of People's Republic of China National Food Safety Standard 90 days oral toxicity test Issued on.2015-08-07 2015-10-07 implementation People's Republic of China National Health and Family Planning Commission released ForewordThis standard replaces GB 15193.13-2003 "30 days and 90 days feeding test." This standard compared with GB 15193.13-2003, the main changes are as follows. --- Standard name was changed to "national food safety standards 90 days oral toxicity test"; --- Modify the "scope"; --- Added "sub-chronic toxicity", "the deleterious effects of the minimum dose observed" Defining and "satellite Unit"; --- Modify the "principle"; --- Added "instruments and reagents" project; --- To increase the "test" project; --- Increasing the processing requirements of the test substance; --- Modify the "animal"; --- Modify the "dose group"; --- Modify the "Procedure"; --- Modify the administration of the test substance in the way; --- Modify the observed indicators; --- Increased body weight and food and water consumption, eye examination, urinalysis, body temperature, ECG content; --- Modify the hematological examination, blood biochemistry, pathology indicators; --- Modify the "data processing"; --- Increase the results of the evaluation content; --- Increasing the project "test report"; --- Added "Interpretation of Results" project. National Food Safety Standard 90 days oral toxicity test1 ScopeThis standard specifies the experimental animals 90 days oral toxicity test methods and requirements for basic tests. This standard applies to the evaluation of the test was sub-chronic toxicity.2 Terms and definitions2.1 Subchronic toxicity Healthy animals in their lifetime does not exceed 10% of the time (usually rats 90d), repeat the test substance after oral exposure caused Kang damage effects. 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 In toxicity studies in the design and implementation of additional group of animals, animal handling and feeding conditions and its main research similar to the test for interim 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 principlesDetermined within 90d oral repeated exposure caused toxic effects of the test substance, understanding the test substance dose - response relationship between target organ toxicity and Reversibility, come 90d orally minimum observed adverse effect level (LOAEL) and not observed adverse effect level (NOAEL), preliminary To determine the safety of the oral test substance, and chronic toxicity test dose, observed indicators, toxicity endpoint selection and was "tentative human health Health guidance values "provide the basis.4 instruments and reagents4.1 Instruments/Devices Anatomy of commonly used laboratory instruments, electronic balance, biological microscope, ophthalmoscope, blood chemistry analyzers, hematology analyzers, coagulation analyzers, urine Liquid analyzers, ECG scanner, centrifuges, pathological machines. 4.2 Reagents Formaldehyde, xylene, ethanol, hematoxylin-eosin, paraffin, thinners blood analyzer, blood chemistry analysis reagents, coagulation analyzer reagents, urine Analytical reagent (or paper) and the like.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 the relevant provisions of GB GB 14922.2 and 14922.1 of. Select has been documented on the test substance sensitive Animal species and strains, usually rodents rats preferred, the preferred non-rodent dogs (usually chosen Beagle dogs). Week-old rats Recommended no more than six weeks, weighing 50g ~ 100g. Start of the test animals of each sex differences in body weight should not exceed ± 20% of the average weight, For not less than 20 animals in each group, male and female; if the medium-term plan to test or observe the end of the trial do observe recovery should increase the number of animals (Control and high dose increased satellite groups of 10, male and female). Dogs usually use 4 months to 6 months, puppies, not more than 9 months, at the beginning of each test gender differences in animal weight should not exceed the average weight of ± 20%, the number of animals in each group at least eight, male and female Half and half; if the test program or test the middle of an autopsy done to observe the end of the recovery period should be increased in the number of animals (control and high dose increased satellite groups 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, rats in the experimental animal room should be at least 3d ~ 5d (dogs 7d ~ 14d) and adaptation to the environment quarantine observation. 5.2.3 Animal Feeding Animal breeding conditions should be consistent with GB 14925, drinking water should be consistent with GB 5749, feed should comply with the relevant provisions of GB 14924. During the test animals free access to water and food, animal recommend caged rat cage can also be components of sex are reared in groups, the number of animal cages (typically less per 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. During the test Each non-animal test should be less than 10% of mortality, dying animal blood biochemical tests should be carried out as far as possible, gross anatomy and disease Histopathological examination, each group of biological samples loss rate should be less than 10%. 5.3 dose 5.3.1 Packet The experiment included at least three doses of the test substance group, a negative (vehicle) control group, if necessary, additional untreated control group. If you need to test the medium-term To observe the blood biochemical parameters, or the end of the trial do an autopsy recovery observed in the control and high dose for an additional satellite group. In addition to the control group not given the test Matter, the rest were treated with the test substance dose group. 5.3.2 Design of dose High doses of the principle 5.3.2.1 should make some animals appear more obvious toxicity, but does not cause death; low dose should not have any concept of Observed toxic effects (equivalent NOAEL), and higher than the actual human exposure levels; dose ranging between, there may be mild toxic effect It should be to derive NOAEL and (or) LOAEL. Group spacing generally declining doses 2 to 4 times with appropriate, such doses total span of the test substance Too large set dose can be added. The reference design test dose acute toxicity LD50 dose 28-day oral toxicity test dose and human RNI Amount. 5.3.2.2 LD50 test substance can be determined, 28-day oral toxicity test of the NOAEL or LOAEL as 90 days oral toxicity test The highest dose group; or 5% ~ 15% LD50 as the highest dose group, the percentage of LD50 select the main reference LD50 dose response Slope of the curve. Then this dose group consists of several doses, the lowest dose group at least three times the recommended human intake. 5.3.2.3 not seek LD50 test substance, the test dose should be possible to cover the expected intake of 100 times the human dose, without affecting animals Under the premise of feeding and nutritional balance should try to improve dose and high dose group, the recommended intake for human subjects was large, high-dose group also To give the maximum amount by design. 5.4 Test procedure and outcome measures 5.4.1 The test is administered 5.4.1.1 according to the characteristics of the test substance or 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. The test substance should be administered continuously 90d. 5.4.1.2 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 can also make use of the test substance carboxymethyl cellulose, starch, etc. dubbed suspended Liquid or paste and the like. The test substance should be freshly prepared, our data show that with the exception of their storage solution or suspension stabilizer. To ensure that the test was moving Stability within the object of concentration, the same period gavage once daily (weekly gavage 6d). During the test, the first four weeks weighed twice a week, after Weighed once a week, weight-adjusted volume of gavage. Gavage volume of generally not more than 10mL/kg body weight, such as aqueous solution, the maximum filling Rat Gastric volume up to 20mL/kg body weight of the dog 15mL/kg body weight; the case of an oily liquid, the volume should not exceed gavage 4mL/kg body Weight; each group was given a consistent volume. 5.4.1.3 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, nutritional balance and water intake to the principle of the test substance incorporated into feed ratio is generally less than the mass fraction 5%, (maximum not more than 10%), the adjustable control diet nutrient levels (when the test substance no heat or nutrient if more than 5% And when the addition ratio of more than 5% in the control group diet should be filled methyl cellulose, incorporated in an amount equivalent to the high dose), dose it with nutritional Hormone levels consistent, while additional untreated control group; also depends on the subject matter of heat or nutrient status nutrient feed dose adjustment Level, so that the control diet was consistent levels of nutrients. Test substance dosage units 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 dosage unit can be expressed as mg/kg (or g/kg) feed Materials, the incorporation of water is expressed as mg/mL of water. When the test was incorporated into the feed, the need to test substance dose (mg/kg body weight) by an animal per 100g Food Intake and Weight converted into animal feed test concentration (mg/kg feed), usually 90 days oral toxicity tests in rats daily food intake by weight 8% conversion. 5.4.2 General Clinical Observation Observation period 90d, assuming that the recovery observed after administration of the test animals should stop was to continue to observe 28d, to observe the test substances toxic Reversibility, persistence and delayed effects. Usually observed at least once daily during the clinical manifestations of animal testing and record animals poisoning Signs, and the extent and duration of death. Observation includes hair, skin, eyes, mucous membranes, secretions, excretions, respiratory system, nervous System, autonomic activity (eg. lacrimation, piloerection reaction, pupil size, unusual respiratory) and behavior (eg. gait, posture, response to treatment, there is No tonic or clonic activity, stereotyped reactions, abnormal behavior, etc.). Of weak constitution animals should be isolated, dying and dead animals should be Anatomy. 5.4.3 Body weight and food intake, and water consumption Weekly record weight, food consumption, food utilization calculation; at the end of the test, calculated animal weight gain, total food intake, total food use rate. The test was administered in drinking water, it should be recorded daily water intake. As the test was administered by incorporation of feed or water shall be calculated and reported for each test substance The actual dose administered dose. 5.4.4 eye examination Before the test and during the test, at least for the high-dose group and the control group were eye examination (cornea, lens, conjunctiva, rainbow Film), canine check with sodium fluorescein, if found in the high dose group animals ocular changes, to deal with all animals to be checked. 5.4.5 Hematology Mid-term test rats (satellite group), end of the trial, the end of the recovery period (satellite group) hematological parameters were measured; dogs before the test, the test period (45d), end of the trial, the end of the recovery period (satellite group) hematological parameters were measured. Recommended indicators for the white blood cell count and classification (at least three When classification), red blood cell count, hemoglobin concentration, hematocrit, platelet count, prothrombin time (PT), activated partial thromboplastin Room (APTT) and the like. If the impact on the blood system, should be added to measure reticulocytes, bone marrow smear cytology. 5.4.6 Blood biochemical tests Mid-term test rats (satellite group), end of the trial, the end of the recovery period (satellite group) blood biochemical parameters were measured; dogs before the test, the test period Room (45d), end of the trial, the end of the recovery period (satellite group) blood biochemical tests should be fasting blood. Determination of indicators should include electrolysis Mass 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), chlorine, potassium, sodium targets. If necessary, it can detect calcium, phosphorus, uric acid (UA), total bile acid (TBA), cholinesterase, sorbitol dehydrogenase, methemoglobin, hormones and other indicators. It should be based on the test substance as toxic With the characteristics or the structure-activity relationship between the increase in test content. 5.4.7 Urine In the mid-term test in rats (satellite group), end of the test, urine routine examination carried out recovery end (for satellite), the dogs before the test, the test period Room (45d), end of the trial, the end of the recovery period (satellite group) urine routine examination. Including appearance, urine protein, density, pH, glucose and Occult blood and so on. If the expected toxic reaction indications, should increase the relevant items such as urine sediment microscopy, cell analysis. 5.4.8 body temperature, ECG Dogs before the test, the test period (45d), end of the trial, the end of the recovery period (satellite group) should be body temperature, ECG. 5.4.9 pathology 5.4.9.1 Gross anatomy End of the test must be carried out in general inspection of all animals convalescent end (for satellite), the body surface including, cranial, thoracic and abdominal cavity and its organs, Absolute weight and said the brain, heart, thymus, adrenal gland, liver, kidney, spleen, testes, epididymis, uterus, ovary, calculate the relative weight of the [Dirty/body weight ratio and (Or) dirty/brain ratio]. 5.4.9.2 Histopathological examination You can be of the highest dose group and the control group of animals following organ histopathology, detection of disease and then to the lower dose group phase Organs and tissues should be checked. Detecting organs include brain, pituitary, thyroid, thymus, lung, heart, liver, spleen, kidney, adrenal, stomach, twelve Duodenum, jejunum, ileum, colon, rectum, pancreas, mesenteric lymph nodes, ovaries, uterus, testis, epididymis, prostate and bladder. Necessary, to add test Spinal cord (cervical, thoracic, lumbar), esophagus, salivary gland, cervical lymph node, trachea, arteries, seminal vesicles and coagulating gland, cervix, vagina, breast, bone and bone marrow, Sciatic nerve and muscle, skin, eye and other tissues and organs. Lesions or suspected lesions visible histopathological examination. Histopathological examination should be reported histopathological lesions given photo. 5.4.10 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 Keep all data and results are summarized in tabular form, listing the number of animals in each group before the experiment, the animals die during the test and the number of deaths Dead time, the number of animal toxicity appears, listing seen toxicities, including the time of occurrence of toxic effects, duration and extent. The count The amount of information given by the mean, standard deviation, and number of animals. Animal body weight, food intake, water intake (the test was administered in drinking water), food utilization, blood Fluid examination, blood biochemical examination, urinalysis, electrocardiogram, organ weight, dirty/body ratio and (or) dirty/brain ratio, pathology and other results should be Appropriate methods of statistical analysis. Generally, the measurement data using variance analysis, the mean ratio between the plurality of test group and control group Comparing, sorting data using Fisher exact distribution test, chi-square test, rank sum test, ranked data using Ridit analysis, rank sum test and so on. 6.2 Evaluation Results Clinical observation should, growth and development, blood tests, urine test, blood biochemical tests, ECG, gross anatomy, organ weight and Dirty/body ratio and (or) dirty/brain ratio, histopathological examination and other results, combined with the results of comprehensive statistical analysis to determine the toxicity of the test substance Role of the characteristics, extent, target organs, dose - response, the dose - response relationship, such as satellite recovery group is provided, but also to determine the effect of the test substance may be toxic Reversibility. Obtained 90 days oral toxicity LOAEL and (or) NOAEL, dose chronic toxicity testing on the basis of comprehensive analysis, Observe the selection of indicators to provide evidence.7 Test 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 subs......Tips & Frequently Asked Questions:Question 1: How long will the true-PDF of GB 15193.13-2015_English be delivered?Answer: Upon your order, we will start to translate GB 15193.13-2015_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 15193.13-2015_English with my colleagues?Answer: Yes. 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