GB 15193.15-2015 English PDFUS$209.00 · In stock
Delivery: <= 3 days. True-PDF full-copy in English will be manually translated and delivered via email. GB 15193.15-2015: National food safety standard -- Genotoxicity test Status: Valid GB 15193.15: Historical versions
Basic dataStandard ID: GB 15193.15-2015 (GB15193.15-2015)Description (Translated English): National food safety standard -- Genotoxicity test Sector / Industry: National Standard Classification of Chinese Standard: C53 Classification of International Standard: 7.1 Word Count Estimation: 10,195 Date of Issue: 2015-08-07 Date of Implementation: 2015-10-07 Older Standard (superseded by this standard): GB 15193.15-2003 Regulation (derived from): National Food Safety Standard Announcement 2015 No.6 Issuing agency(ies): National Health and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 Summary: This standard specifies the test methods and technical requirements for reproductive toxicity tests. This standard applies to the evaluation of the reproductive toxicity of the test substance. GB 15193.15-2015: National food safety standard -- Genotoxicity 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 genotoxicity tests) National Standards of People's Republic of China National Food Safety Standard Reproductive 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 15193.15-2003 "reproduction test." This standard compared with GB 15193.15-2003, the main changes are as follows. --- Standard name was changed to "national food safety standard genotoxicity tests"; --- Added "reproductive toxicity", "developmental toxicity" and "maternal toxicity" terms and definitions; --- Modified "test method", the "experimental animals," "dose and grouping", "Procedure" incorporated "test method"; --- Modify the contents of "test report"; --- Added "explained test" content. National Food Safety Standard Reproductive toxicity test1 ScopeThis standard specifies the technical requirements and test methods for genotoxicity tests. This standard applies to the evaluation of the reproductive toxicity of the test substance.2 Terms and definitions2.1 Reproductive toxicity Damage and harmful effects on male and female reproductive function or capability of future generations. Reproductive toxicity can occur in pregnancy, it can also be made Born in pre-pregnancy and lactation. It showed the impact of exogenous chemicals on the reproductive process, such as changes in the endocrine system and reproductive organs, sexual Affect cycle and sexuality, as well as the impact on fertility and pregnancy outcomes like. 2.2 Developmental Toxicity Individuals prenatal exposure to the test substance, and development before becoming adult (including embryo, fetal and postnatal) harmful effects occur, table Now the development of the organism structural abnormalities, altered growth, dysfunction and death. 2.3 maternal toxicity Effects of test substances cause health damage, direct or indirect parent females pregnant animals, expressed as weight reduction, dysfunction, and signs of poisoning, even death.3 test purposes and principlesWhere the test substance can cause reproductive dysfunction, interfere with the formation of gametes or reproductive cells are damaged, in addition to the results and the impact of a fertilized egg Bed and lead to infertility, can still affect embryogenesis and development, such as embryonic death cause spontaneous abortion, fetal growth retardation and fetal malformation. If maternal adverse effects occur during pregnancy, childbirth and lactation abnormalities can also occur after abnormal fetal postnatal development. Test Method 4 4.1 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. 4.2 Experimental Animals Experimental animals should be selected in line with national standards and regulations. Preferred rats, the choice of 7 weeks to 9 weeks of age, when the start of the test animals Weight difference should not exceed the average weight of ± 20%. Before the test, animals in the experimental animal room should be at least 3d ~ 5d environmental adaptation and seizure Phytophthora observation. Each group should have enough males and females mate, produce about 20 pregnant females. To this end, usually in the beginning of the test both sexes Each group requires parental (F0 generation) 30 rats; continuing tests to mate each rat [first generation (F1 generation), of the second generation (F2 Generation) and a sub-three generations (F3 generation)] need 25 of each sex in each group (male and female from each litter at least one, male and female from each litter up to two). Chosen by the F0 females should be non-producing mouse, non-pregnant rats. Dose group and 4.3 Animals were randomly grouped test was set up at least three of the test substance group and a control group. You should consider the characteristics of the test substance (such as biological metabolic And bioaccumulation characteristics) influence. If the test substance use vehicle control group should be given the maximum use of solvents. If the test substance primer When dropped from animal food intake and utilization, the need to control animals fed experimental animals pairing. Some high test substance Dose of the test substance group design should consider its impact on the balance of nutrients for non-nutrient test substance dose should not exceed 5% of the feed. In a test of physical and biological characteristics of the conditions allowed, the highest dose should be made to the F0 animals significant toxicity, but does not cause Animal deaths; intermediate doses can cause mild toxicity; low dose should not cause the parent and offspring of any animal toxicity (according to The maximum was not observed adverse effect level of 1/30, or human recommended intake of 10 times). 4.4 Experimental animals treated 4.4.1 administered test substance 4.4.1.1 During the test, all animals should be administered the same test substance; at the same time daily administration of the test substance, weekly 7d. Test substances should be administered prior to mating successive generations of rats of both sexes at least 10 weeks, and the test was continued until the end of the test, in which the offspring The males and females after weaning daily administration. Each rat was tested dose administered (administered by the animal weight, mg/kg body weight or g/kg Body weight), the same feed and water. 4.4.1.2 according to the characteristics of the test substance or test purposes, select the appropriate mode of administration. The preferred feed incorporation, if the test substance added to the feed or drink Water affect animal palatability, oral administration of the test substance should be selected. 4.4.1.3 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 be freshly prepared, our data show that with the exception of their storage solution or suspension stabilizer. Should at the same time daily irrigation Stomach 1, weighed twice weekly gavage volume weight adjustment. Gavage volume of generally not more than 10mL/kg body weight, such as an aqueous solution , The maximum volume of fed up to 20mL/kg body weight; as an oily liquid, orally should not exceed the volume of 4mL/kg body weight; each group was given body Product consistency. 4.4.1.4 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 Of 5%, while if more than 5% (maximum not more than 10%), to adjust the feed nutrient levels in the control group (no heat or if the test substance is a nutritional Time division and 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), feed it with dose group Consistent levels of nutrients, while additional untreated control group; the heat was also a visual test or nutrient status adjusted dose feed Camp The level of nutrients to the control group diet nutrient levels consistent. Test substance dosage units per kilogram of body weight is ingested test substance cents G (or g) number, namely mg/kg body weight (or g/kg body weight), when the test was incorporated into feed dosage unit can also be expressed as mg/kg (or g/kg) of feed, 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 animals Food intake per 100g of body weight of the test substance converted into feed concentration (mg/kg feed). 4.4.2 Mating When each mating, each female is to be a single male with cage (1.1 mating) from the same group of subjects was randomly selected until after the female Plug, or after three estrus or two weeks. Found after vaginal plug should be female, male separately, if after three estrus or two weeks has not been evaluated Mating male and female mice should also be separate, not to continue the same cage. Paired with male and female rat cage should be marked. All the females during the mating period should be checked daily Sperm or vaginal plugs until proven mated so far. Vaginal plug was found the day of conception 0d. It is expected to have been pregnant females should be separated into the breeding cage In pregnant rats labor should provide nesting litter. 4.4.3 Standardization pups per litter number The pups per litter adjusted to four days after birth to the same number (litter 8 - 10), as far as possible within the litter male and female equal to the number, It can also nest inside the female, male, ranging in number, but the number of the sexes among other mouse nest should be the same. Original nest rat should be randomly taken out superfluous, rather than Weight should choose. 4.4.4 Observation Algebra Observation algebraic object varies with the subject, can be used for the generation, second generation, three or more generations observation. If the test was observed in two-generation reproductive test It was significant reproductive offspring, shape or toxic effects, the need for third-generation reproductive toxicity study, further observation reproductive test substance Toxicity. 4.5 generation, second generation and third generation reproductive toxicity test method 4.5.1 generation reproductive toxicity test method Generation reproductive toxicity test is shown in Figure 1.1 a schematic diagram generation reproductive toxicity4.5.2 The two-generation reproductive toxicity test method 4.5.2.1 two-generation reproductive toxicity test is shown in Figure 2. Figure 2 a schematic two-generation reproductive toxicity study 4.5.2.2 F0 generations after weaning, administration of the test substance for 3 months, female - male to mate, the litter size mouse as F1a. After administration of the test is no longer weaning F1a It was observed 3 months. 4.5.2.3 F1a 10d after weaning the F0 mating again, the litter size mouse as F1b, 20 pregnant mice (F0) in five prenatal 2d ~ 3d laparotomy inspection Charles fetuses without deformity; the other five natural childbirth postpartum pups observed situation; for 10 pregnant mice natural childbirth, produced F1b continue to multiply. 4.5.2.4 F1b after weaning, give the test substance containing feed for three months, mating, F2a after weaning fed feed containing no test substances produced, observed 3 months. 4.5.2.5 F2a after weaning 10d will mate again F1b, F2b before production will F1b pregnant rats were divided into two groups, 10 per group, with 4.5.2.3. 4.5.3 Three Generations of reproductive toxicity test method Three Generations of reproductive toxicity test method is shown in Figure 3. Figure 3 a schematic view of the three generations of genotoxicity tests 4.5.4 parental generation, second generation, three generations of breeding experiments 4.5.4.1 parental generation, second generation, three generations of breeding experiments can be carried out with reference to 4.5.2.2,4.5.2.3. 4.5.4.2 according to the situation can multiply more than two litters.5 OUTCOME MEASURES5.1 pairs of animals to do a comprehensive clinical examination, recording general health, all the toxicity and effectiveness of the role of the test substance produced by disease Like, related behavioral changes, signs of difficult or delayed delivery, and all signs of toxicity and mortality, through daily inspection (F0, F1 generation of female) Vagina and cervix, as well as whether the abnormal estrus cycle in females. 5.2 F0, F1 and F2 generations in the administration of the test animals were weighed on the first day, after weighing 2 times a week, it should be conceived dams on day 0, the first 7 days, 14 days and 21 days weighed in lactating rats should also said litter weight. 5.3 before mating and fertile, recording food intake, such as drinking water by the weekly administration of the test substance should be recorded weekly amount of drinking water. 5.4 At the end of the test, according to the experimental design, each generation of male epididymal sperm should be checked for sperm shape, number and activities Ability was evaluated. Sperm motility and sperm morphology, can only check generations male control group and high-dose group of the test substance, each animal Check at least 200 sperm. 5.5 after delivery (lactation 0d) should check the record number of pups per litter, sex, number of stillbirths, live births and the number of visible abnormalities as soon as possible, in Born the day of death, should be checked as far as possible defects and cause of death. Record number of live births, sex and day of birth of an individual born alive Mice weighed, after the first four days of lactation, 7 days, 14 days and 21 days, as well as open the vagina or glans and foreskin separate the end of the trial When pups were weighed. Used for mating weaning of F1 rats, observe and record the vagina or penis foreskin open separate days, observed Sexual maturity. 5.6 At the end of the test all F0, F1 generation of animals weighing organs. the uterus (including cervix and fallopian tube), ovary; testis, epididymis; brain, liver, Kidney, spleen and known target organs. 5.7 end of the trial and all the F0 animals died during the tests shall be as gross anatomy and histopathology were observed in various forms Structural abnormalities and pathological changes, with special attention reproductive organs. If the number of pups per litter enough, F1 generations, F2 generation (and F3 generation) each litter Gender take at least three pups subjected to the same checks. Check organs and tissues should include the uterus, ovaries, testes, epididymis and target organ Organs.6 Data processing and evaluation of results6.1 reproductive index Pregnancy rates are calculated in the formula (1). Pregnancy rate = Number of pregnant animals Mating females number × 100% (1) Pregnancy rates are calculated in the formula (2). Pregnancy rate = Childbirth number of animals live pups Number of pregnant animals × 100% (2) A live born rate calculation see formula (3). A live born rate = The number of pups born alive The total number of pups born × 100% (3) Born survival calculations see formula (4). Born survival = Postpartum 4d offspring survival Live pups at birth number × 100% (4) Breastfeeding survival calculations see formula (5). Breastfeeding survival = The number of pups at weaning survival 21d After surviving pups born 4d number × 100% (5) Sex Ratio calculation see formula (6). Sex Ratio = The number of male offspring after birth Number of female pups after birth (6) 6.2 Data Processing Keep all data and results are summarized in tabular form, the data can be used for statistical table, the table should show experimental animals in each group Was the number, the number of male animals mating, the number of pregnant females, and the emergence of a variety of animal toxicity percent. Statistical data should be Analysis, may be appropriate statistical methods for processing. 6.3 Evaluation Results Compare each test group of animals was whether the control animals breeding index significant differences, in order to assess whether the test substance reproductive toxicity, and To determine its reproductive toxicity was not observed adverse effect level (NOAEL) and the minimum observed adverse effect level (LOAEL). Also According to indicators (such as weight, observed indicators, gross anatomy and histological examination results, etc.) with statistical significance, and further estimate students Role of the characteristics of reproductive toxicity.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 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, sex, origin (supplier name, animal production license number), animal inspection Phytophthora, adaptation, breeding environment (temperature, relative humidity, using experimental animal facility license number), feed sources (supplier name, laboratory animals 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. a) toxicity by sex and dose group were recorded, including reproductive abnormalities, pregnancy and development capabilities; Time or test animals b) test of whether the death of the animal to survive the end of the test; c) the average weight of body weight per litter of pups and pups, as well as post-test single weight of pups; d) any offspring and growth of toxicity and other effects related to reproductive health damage; e) the time and duration of the emergence of a variety of abnormalities observed symptoms; f) parental (F0) and weight data selected for mating the offspring of animals; g) gross anatomy and pathological findings; h) a detailed description of the results of the histopathological examination; i) statistical processing of results. 7.9 Test Conclusions. The tested substance reproductive toxicity characteristics, dose-response relationship, and reproductive toxicity NOAEL derived and (or) LOAEL Conclusions. Explanation 8 trial Reproductive toxicity test animals orally repeated exposure to the male and female reproductive function impairment test substance produced and future generations have Harmful effects and the dose - effect and dose - response relationship information derived LOAEL and NOAEL. The test results should be combined with sub-chronic Test, teratogenicity test, toxicokinetics test results and other comprehensive interpretation. Due to the existence of species differences in animals and humans, so extrapolated results The people there are some limitations, but can also provide valuable information for determining the initial population exposure level. ......Tips & Frequently Asked Questions:Question 1: How long will the true-PDF of GB 15193.15-2015_English be delivered?Answer: Upon your order, we will start to translate GB 15193.15-2015_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 15193.15-2015_English with my colleagues?Answer: Yes. The purchased PDF of GB 15193.15-2015_English will be deemed to be sold to your employer/organization who actually pays for it, including your colleagues and your employer's intranet.Question 3: Does the price include tax/VAT?Answer: Yes. 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