Chemicals - Test method of reproduction/developmental toxicity screening
Some standard content:
ICS 13. 300; 11. 100
National Standard of the People's Republic of China
GB/T 21766—2008
Chemicals-Test method of reproduction/developmental toxicity screeningIssued on 2008-05-28
Digital Protection
General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of ChinaAdministration of Standardization of the People's Republic of China
Implementation on 2008-08-01
TiKAoNhiKAca-
GB/T 217662008
This standard is equivalent to the Organization for Economic Cooperation and Development (OECD) Chemical Testing Guide No. 421 (1995) & Reproduction/Developmental Toxicity Screening Test (English version).
This standard has been revised for the following editorial reasons:
. The scope section has been added;
The measurement units have been changed to the legal measurement units of my country; the references of OECD have been deleted
Appendix A of this standard is a normative appendix, and Appendix B is an informative appendix. This standard was proposed and submitted by the National Technical Committee for Standardization of Dangerous Chemicals Management (SAC/TC251). The responsible drafting unit of this standard is the Institute of Occupational Health and Poisoning Control, Chinese Center for Disease Control and Prevention. The participating drafting units of this standard are: Ningbo Exit-Entry Inspection and Quarantine Bureau of the People's Republic of China, Tianjin Institute of Inspection and Quarantine Science and Technology, and the main drafters of this standard are: Ma Zhongchun, Sun Jinxiu, Long Zaihao, Hou Fenxia, Chen Xiaoyu, and Lin Zhenxing. I
GB/T21766—2008
OECD Introduction
1. In January 1990, a special expert group discussed the screening method for reproductive toxicity in London and reached a plan for "preliminary reproductive toxicity screening test", which can effectively conduct preliminary evaluation of existing chemical substances. 2. This guide is an updated version of the plan reached at the London meeting. It is the result of the nomination expert meeting on reproductive toxicity screening methods held in Tokyo in October 1992. It is based on the existing high-yield methods used by each member country to detect 3. This guideline is used to design tests to evaluate the effects of chemicals on male and female reproductive functions, such as gonadal function, mating behavior, conception, fetal development and parturition. The information obtained is limited. It is not an alternative method and cannot be used to replace existing guideline methods 414, 415 and 416.
4. This guideline can be used to provide possible reproductive/developmental effects, including early stages of evaluating the toxicological properties of chemicals or chemicals that are subject to differential injection. It can also serve as a set of initial Part of the preliminary screening test to detect existing chemicals with little or no toxicological information, or as a dose range for a more extensive reproductive/developmental study, or all other related studies. 5. This test cannot provide complete information on all aspects of reproduction and development. It can only provide a limited method to detect postnatal manifestations caused by prenatal exposure, or effects that may be induced by postnatal exposure. Due to the relatively small number of group animals, the selection of sexual endpoints, and the short test period, this method cannot provide evidence of no effect. Therefore, although negative results cannot indicate absolute safety for reproduction and development, if the actual exposure level is significantly lower than the observed adverse effect level (NOAEL), this information can ensure a certain degree of safety. Moreover, in the absence of data from other reproductive/developmental toxicity tests, positive results are useful for preliminary hazard assessments and can help determine the necessity and timing of additional tests. 6. This guideline uses oral toxicity. If other exposure routes are used, some modifications are required. 1 Scope
Chemical Reproductive/Developmental Toxicity Screening Test MethodsHiikANikAca
GB/T 21766--2008
This standard specifies the scope, terms and definitions, basic test principles, test methods, test data and reports of chemical reproduction/developmental toxicity screening tests.
This standard is applicable to the screening of teratogenicity, reproduction and growth and developmental toxicity of chemicals. 2 Terms and Definitions
The following terms and definitions apply to this standard. 2.1
Reproduction toxicity Harmful effects on offspring, and (or) damage to male or female (animal) physiological or reproductive functions 2.2
Maternal toxicity Maternal toxicity Direct or indirect harmful effects on female pregnant animals. 2.3
Impairment of fertility Abnormal reproductive function or ability of female or male animals. 2.4
Levelopmentaltoxicity is reproductive toxicity, which refers to the structural (organism defects) or functional abnormalities of the offspring before birth, during the perinatal period and after birth. 2.5
Dose
refers to the amount of the test substance, which is usually expressed in mass (g.mg) or the amount of the test substance given per unit weight of the animal (mg/kg); if the test substance is mixed with any feed for feeding, it can also be expressed in the constant mass fraction of the test substance in the feed (mg/kg). 2.6
Dosage
General term including toxic dose, toxic number and toxic duration. 2.7
Evident toxicity
Clear toxicity after administration of the test sample, which can be used as sufficient evidence for risk assessment. It is expected that with the increase of toxic dose, it can develop into severe poisoning symptoms and even death. 2.8
No-observed-adverse-effect level (NOAEL) The highest dose at which no adverse effects related to exposure are found. 3 Basic principles of the test
The test substance is administered to males and females in multiple dose groups. From the start of the test to the time of sacrifice, the male animals are exposed for at least 4 weeks, that is, at least 2 weeks of exposure in the pre-mating period, and 2 weeks of exposure in the mating period and the post-mating period. As the exposure time of male animals in the pre-mating period is short, it is not enough to evaluate the effect of chemicals on the reproductive system of male animals only by the size of their reproductive capacity. Therefore, pathological histological examination should be carried out to comprehensively evaluate the toxic effects of chemicals on the fertility and sperm formation of male animals.
Female animals should be exposed to the poison throughout the test period, at least 2 weeks before mating (equivalent to two complete estrus periods), during mating, pregnancy and at least 4 days after parturition, until the day of sacrifice. After the adaptation period, the length of the test period depends on the status of the female animals, generally 54 days (at least 14 days before mating, 14 days during mating, 22 days during pregnancy, and 4 days during lactation).
During the exposure period, the animal's symptoms of stagnation should be carefully observed every day. Animals that died or were killed during the test should be subjected to gross autopsy. At the end of the test, the surviving animals should also be killed and subjected to gross autopsy. 4 Test Methods
4.1 Experimental Animals
4.1.1 Animal Germplasm
This test method is designed mainly for rats. If other types of animals are used, corresponding modifications need to be made. Animal strains with low fertility or known high rates of developmental defects should not be used. Healthy, unmated and untested animals should be used. The species, strain, sex, weight and age of the experimental animals should be clearly defined. At the beginning of the experiment, the weight difference of the animals should be kept to a minimum, and the weight of each animal should not exceed 20% of the average weight of the same sex. 4.1.2 Housing conditions
The room temperature of the experimental animals should be maintained at 22℃±3℃. Except when the room is cleaned, the room humidity should be controlled at least at 30%~70%, preferably at 50%~60%. Artificial lighting should be used according to a 12-h day/night cycle. Animals should be fed with regular feed and have unlimited drinking water. Some test substances may need to be mixed with tung feed to expose animals, so the choice of animal feed should be considered. Animals can be raised individually or in groups of the same sex, with no more than 5 animals per cage, and the cages should be suitable for animal mating. Pregnant females should be raised in single cages, and nesting materials should be placed at the same time. 4.1.3 Animal preparation
Healthy, young adult animals should be selected and randomly divided into control and exposure groups. The cages should be placed in order to minimize the impact of movement. Animals should be marked one by one and allowed to acclimate to the laboratory environment in the cages for at least 5 days before the start of the experiment.
4.1.4 Administration route and test article preparation
The recommended route of administration of the test article is oral, unless another route of administration is considered more appropriate. When the oral route is chosen, the regurgitation method is usually used; of course, the test article can also be given through food or drinking water. If necessary, the test article needs to be dissolved or suspended in an appropriate excipient. First consider using an aqueous solution/suspension, then an oily solution/emulsion (such as corn oil), and then a solution in another solvent. If the excipient is not water, then its toxicity characteristics must be known. In addition, the stability of the test article in the excipient must be determined. 4.2 Experimental Procedure
4.2.1 Number and Gender of Animals
In order to obtain enough pregnant mice (at least 8 per group) and offspring, and to properly evaluate the effects of the test sample on animal reproduction, pregnancy and nursing, as well as the possible health-damaging effects on the lactation, growth and development of the offspring from conception to 4 days after birth, each test group should have at least 20 animals, half of which are male and half are female.
4.2.2 Dose Design
4.2.2.1 Normally, each test should have at least 3 exposure groups and 1 control group. The exposure dose level can be set based on the results of acute toxicity tests or repeated exposure tests. The control group animals are treated in the same way as the exposure group except that the test substance is not given. If excipients are used in the exposure process of the test substance, the control group should be given the maximum volume of excipients used. 4.2.2.2 The dose selection of the test substance should take into account the existing toxicity and life kinetic data of the test substance itself or related substances. The highest dose set should induce toxic effects in animals, but no animal death or pain should occur. Then set the dose levels in descending order. The principle is to reflect the dose-response relationship and the dose (NOAEL) at the lowest dose. When setting the low dose, a 24-fold group spacing is usually selected. If a fourth dose group is to be added, the group spacing of the fourth dose group can be considered larger (for example, more than 10 times).
4.2.3 Limit test
If the oral (including feed and drinking water) toxicity dose of the test substance reaches 1.000 mg/(kg, d) according to this test method, but no adverse reaction is observed in animals, and the analysis of structurally related compounds also predicts that the test substance is non-toxic, then it is unnecessary to conduct other doses of toxicity tests. However, when human exposure indicates that a higher dose test is required, a limit test should not be conducted. If the test uses other types of exposure methods, such as inhalation or dermal exposure, the maximum exposure concentration or dose can usually be determined by the physicochemical properties of the test sample.
4.2.4 Exposure
4.2.4.1 The animals should be exposed continuously, once a day. When the exposure is by gavage, the dose should be completed in a single dose using a stomach tube or suitable cannula. The maximum volume of liquid test substance for a single gavage exposure depends on the size of the test animal. Except for water-soluble substances, the gavage volume can be 2nL/100g, and other solutions should not exceed 1mL/100g. Except for irritant or corrosive test substances that require higher concentrations, the gavage volume of different exposure doses can be maintained by adjusting the test substance concentration. 4.2.4.2 If the test substance is exposed through feed or drinking water, ensure that the addition of the test substance does not disrupt the nutritional balance of the feed or drinking water. When the test substance is administered through feed, a constant mass fraction (mg/kg) or a constant dose based on the animal's body weight may be used. Other methods must be explained. When administering via oral administration, the animals should be administered at the same time each day, and the dose should be adjusted at least weekly to maintain a constant dose of the test substance according to the animal's body temperature. 4.2.5 Test Procedures
4.2.5.1 After the animals have completed an adaptation period of at least 5 days, both male and female animals should be administered for at least 2 weeks before mating. The test schedule should be arranged after the animals have reached sexual maturity. The time of sexual maturity of rats of different strains in different experimental spaces may vary slightly, such as SD rats at 10 weeks of age and Wistar rats at 12 weeks of age. Female rats with offspring should be killed on the 4th day after delivery. The day of birth (that is, when delivery is completed) is defined as 0 days after birth. Female rats that show no signs of mating should be killed 24 to 26 days after the last day of mating. Female and male rats should continue to be administered during the mating period. Males should continue to be exposed to the poison after the mating period has ended, until a total of at least 28 days of exposure has been completed. Males are then killed or, if deemed appropriate, retained and exposed for further mating. 4.2.5.2 Parent females should be exposed to the poison daily during pregnancy until (including) the 3rd day after the birth of the pups or the day of killing. For studies involving inhalation or dermal exposure, exposure should be continued until at least (including) the 19th day of pregnancy. 4.2.5.3 See Appendix A for a diagram of the experimental schedule.
4.2.6 Animal mating
Animals should normally be mated in a 1:1 (1 female to 1 male) pattern in the experiment. This is excepted in the case of accidental female mortality. A female should be housed with the same male and female until conception or 2 weeks. The female vagina should be checked every morning for the presence of sperm or plugs. The day when sperm or plugs are detected is defined as day 0 of pregnancy. If pregnancy has not occurred after two weeks of mating, the infertile female mice can be re-mated with other male mice in the same group that have been confirmed to be fertile. 4.2.7 Observation
4.2.7.1 During the test, general clinical observations should be carried out at least once a day. If poisoning symptoms are found, the number of observations should be increased. The observation time should be fixed every day and should be selected at the peak period when sexual signs may appear after exposure. Record relevant behavioral changes, symptoms of dystocia or delayed labor and all toxic reactions, including mortality. Also record the time, degree and duration of these toxic symptoms. 4.2.7.2 The gestation period of the animals should be recorded (calculated from the 0th day of conception). After the animals give birth, the sex of each case of pups and the number of dead fetuses, live fetuses, low-weight mice (significantly smaller than the pups of the control group) and the deformities should be determined as soon as possible. 4.2.7.3 The live pups should be counted and sexed, and the litter weight should be weighed within 24 hours after delivery (day 0 or day 1 after delivery) and on day 4 after delivery. In addition to observing the behavior of the parent animals, any abnormal behavior of the offspring animals should also be recorded. 4.2.8 Body weight and food/water consumption
4.2.8.1 Female and male mice should be weighed on the first day of exposure, at least once a week thereafter, and once again at the end of the test. During gestation, female mice should be weighed on days 0, 7, 14, and 20 of gestation, within 24 hours of parturition (day 0 or 1 postpartum) and on day 4 postpartum. Individual data for each adult animal should be included in the report. 4.2.8.2 The feed consumption of animals should be measured at least weekly before mating, during gestation, and during lactation. It is optional to test the feed consumption of animals during the mating period. When the test substance is exposed through drinking water, the water consumption of animals during these periods should also be measured. 4.2.9 Pathological examination
4.2.9.1 Gross dissection examination
4.2.9.1.1 When adult animals are killed or die during the experiment, they should be immediately examined visually for any deformities or pathological changes. Particular attention should be paid to the tissues and organs of the reproductive system. The days of implantation should be recorded. Counting the number of corpora lutea is strongly recommended. 4.2.9.1.2 Weigh the testicles and epididymis of all parent male mice. 4.2.9.1.3 The dead fetuses and pups killed 4 days after birth should be carefully examined for deformities. 4.2.9.1.4 Preserve the ovaries, testicles, epididymis, accessory organs and all organ specimens with visible lesions from all parent animals. Avoid using formalin fixation for routine examination of the testicles and epididymis. It is recommended to use Bouin fixative. 4.2.9.2 Histopathological examination
First, conduct a detailed histological examination of the ovaries, testicles, and epididymis of the animals in the high-dose group and the control group (with special emphasis on the stage of spermatogenesis and the cell structure of the testicular interstitium). If necessary, other preserved tissues can also be examined. When histopathological changes are found in the high-dose group, the animals in the other dose groups should be examined. 5 Experimental data and report
5.1 Data
5.1.1 The data of each animal should be recorded separately and the test results should be tabulated. The table should show the number of experimental animals in each group, the number of animals that died during the experiment, the number of animals killed due to humane reasons, the number of animals mated, the number of animals pregnant, various toxic reactions and the percentage of animals that showed them. Describe in detail the observed toxic symptoms, including the time of onset, duration and degree, pathological histological changes and related storage data of mice. The summary report form in Appendix B is very useful. 5.1.2 Due to the limitation of the study scale, it is difficult to ensure the complete accuracy of the statistical analysis of the differences in the multiple endpoints in the test, especially the reproductive endpoints. The selected statistical method should be suitable for the distribution of the variables studied, and the statistical method should be determined before the test. Since the sample size of this test is small, it is helpful to analyze the results of this test if there are historical control data (such as litter size). 5.2 Evaluation of results
5.2.1 The test results should be evaluated based on the observed toxic effects, gross anatomical and pathological histological examination results. The evaluation content includes the relationship between the dose of the test substance and the appearance and disappearance of malformations, incidence and severity, as well as general damage, target organ determination, infertility, clinical malformations, affected reproductive and litter function, weight changes, mortality and other toxic effects. 5.2.2 When evaluating the reproductive function of male mice, due to the short exposure time of male mice, the histopathological examination of the testis and epididymis must be considered together with their fertility data.
5.3 Test report
The test report must include the following information:
5. 3.1 Test substance
a) Physical properties and relevant physicochemical properties;
b) Name and identification code.
5. 3.2 Formulator
If it is not water, the reason for the choice should be stated. 5.3.3 Experimental animals
a) Type/strain;
b) Number, age, sex;
c) Source, housing conditions, food, etc.;
Individual weight at the beginning of the test.
5.3.4 Test conditions
a) Principles of dose selection;
Detailed description of test substance preparation, concentration, stability and uniformity of sample preparation;c)
Detailed description of test substance exposure:
Convert test substance concentration in feed/drinking water into actual dose [tmg/(kg·d)] as needed; Detailed description of feed and water quality.
5.3.5 Results
Weight/weight change;
Feed consumption, water consumption;
Toxic effect data according to sex and dose, including fertility, pregnancy and other toxic symptoms; gestation period;
Toxic or other effects on reproduction, offspring, postnatal growth, etc.; Clinically observed phenomena, severity and duration (whether reversible); number of survivors, number of abortions;
Number of surviving mice with visible abnormalities, number of dwarfed mice; time of animal death during the experiment;
Litter size and litter size when the number of implantations and corpora lutea are recorded; data on body and organ weights of parent animals at the time of sacrifice; results of gross anatomical examination,
Detailed description of the results of microscopic examination of male rat genitals and other tissues;rn)
Abortion data (if available):
Statistical treatment of results.
5.3.6 Discussion of results
5.3.7 Conclusion
5.3.8 Interpretation of results
-TKAONT KAca-
GB/T 21766--2008
This test can evaluate the tropism of animals on reproduction/growth and development after repeated exposure to a test sample. It can provide a basis for further reproductive toxicity tests.
GB/T21766—2008
Appendix A
(Normative Appendix)
Reproduction/developmental toxicity screening test schedule
A,1 Reproduction/developmental toxicity screening test schedule (maximum test period based on 14-day mating period), see Table A.1. Table A.1 Reproductive/developmental toxicity screening test schedule Male rat/mating
Pre-mating period (14 d)
Test start
Mating period (up to 14 d)
Pregnant female rat
Extended decoction (optional)
Non-pregnant rat
Gestation period (approximately 22 d)
Dissected male
(at least 4 weeks of infection period)
Lactation period (4 d)
Postpartum 4 Dissected male rats and pups (optional)
Appendix B
(Informative Appendix)
Reproduction/developmental test effect summary report table
B. 1 Reproduction/developmental test effect summary report, see Table B. 1..Table B, 1 Summary Report of Effects of Reproduction/Development Experiments Observation
Specific Quantity (Unit)
Number of Initial Pairs
Number of Female Rats that Have Been Mated
Number of Rats that Have Been Pregnant
Number of Animals that Have Been Pregnant within 1 to 5 Days of Mating
Number of Animals that Have Been Pregnant within 6 to 14 Days of Mating
Number of Animals with Pregnancy = 22 Days
Number of Animals with Pregnancy ≥ 23 Days
Number of Female Rats that Have Given Birth
Number of Female Rats with Surviving Pups
Average Number of Corpora Lutea of Female Rats
Number of Nymphs of Female Rats
Average Number of Pups Per Female Rats at Birth
Average Number of Pups Living 4 Days after Birth
Average Sex Ratio of Pups at Birth
4 Days after Birth Average sex ratio of offspring
Average weight of offspring per litter at birth
Average weight of offspring per litter 4 days after birth
Average weight of offspring per litter at birth
Average weight of offspring per litter d after birth
Deformed mice
Number of mothers who did not give birth to deformed offspring
Number of mothers who gave birth to 1 deformed offspring
Number of mothers who gave birth to 2 deformed offspring
Offspring loss
Number of mothers with absorbed fetuses
Number of mothers with 1 absorbed fetus
Number of mothers with 2 absorbed fetuses
Number of mothers with ≥3 absorbed fetuses
Dose 2
-TYKAONIKAca-
GB/T 21766—2008
GB/T 21766—2008
Dose (unit)
Number of mothers with 0 dead fetuses
Number of mothers with 1 dead fetus
Number of mothers with 2 dead fetuses
Number of mothers with ≥3 dead fetuses before death
Number of mothers still alive 4 days after giving birth
Number of mice with 1 dead fetus 4 days after giving birth
Number of mothers with 2 dead fetuses
Number of mothers with ≥3 dead fetuses 4 days after giving birth
GB/T 21766-2008
Table B.1 (continued)
Copyright table Any infringement will be investigated
Book number: 155066-1-32175
800299
People's Republic of China
National standard
Chemicals
Reproduction/developmental inactivity screening test method
GB/T 21766—2008
Published and distributed by China Standard Promotion Publishing House
No. 16, Sanlihebei Street, Fuxingmenwai, Beijing
Postal code: 100045
Website stop spc. net. cn
Tel: 6852394668517548
Printed by Zhongyin Standard Press, Huangdao Printing Co., Ltd. Distributed by Xinhua Bookstores in various places
Format 880×1230
First edition in July 2008
Printing sheet 0.75
Number of units 18,000
First printing in July 2008
Book number: 155066·1-32173 Price 14,00 yuan Replaced by our publishing center
If there is any printing error
Copyright reserved
Infringement will be investigated
Report phone: (010)68533533
-TYKAONIKAca=1 Test substance
a) Physical properties and relevant physicochemical properties;
b) Name and identification code.
5. 3. 2 Formulation
If it is not water, explain the reason for the choice. 5.3.3 Experimental animals
a) Type/strain;
b) Number, age, sex;
c) Source, living conditions, food, etc.;
Individual weight at the beginning of the test.
5.3.4 Experimental conditions
a) Principles of dose selection;
Detailed description of test substance preparation, concentration, stability and uniformity of sample preparation;
Detailed description of test substance exposure:
Convert the test substance concentration in feed/drinking water into actual dose [tmg/(kg·d)] as needed; Detailed description of feed and water quality.
5.3.5 Results
Weight/weight change;
Feed consumption, water consumption;
Toxic effect data according to sex and dose, including fertility, pregnancy and other toxic symptoms; gestation period;
Toxic or other effects on reproduction, offspring, postnatal growth, etc.; Clinically observed phenomena, severity and duration (whether reversible); number of survivors, number of abortions;
Number of surviving mice with visible abnormalities, number of dwarfed mice; time of animal death during the experiment;
Litter size and litter size when the number of implantations and corpora lutea are recorded; data on body and organ weights of parent animals at the time of sacrifice; results of gross anatomical examination,
Detailed description of the results of microscopic examination of male rat genitals and other tissues;rn)
Abortion data (if available):
Statistical treatment of results.
5.3.6 Discussion of results
5.3.7 Conclusion
5.3.8 Interpretation of results
-TKAONT KAca-
GB/T 21766--2008
This test can evaluate the tropism of animals on reproduction/growth and development after repeated exposure to a test sample. It can provide a basis for further reproductive toxicity tests.
GB/T21766—2008
Appendix A
(Normative Appendix)
Reproduction/developmental toxicity screening test schedule
A,1 Reproduction/developmental toxicity screening test schedule (maximum test period based on 14-day mating period), see Table A.1. Table A.1 Reproductive/developmental toxicity screening test schedule Male rat/mating
Pre-mating period (14 d)
Test start
Mating period (up to 14 d)
Pregnant female rat
Extended decoction (optional)
Non-pregnant rat
Gestation period (approximately 22 d)
Dissected male
(at least 4 weeks of infection period)
Lactation period (4 d)
Postpartum 4 Dissected male rats and pups (optional)
Appendix B
(Informative Appendix)
Reproduction/developmental test effect summary report table
B. 1 Reproduction/developmental test effect summary report, see Table B. 1..Table B, 1 Summary Report of Effects of Reproduction/Development Experiments Observation
Specific Quantity (Unit)
Number of Initial Pairs
Number of Female Rats that Have Been Mated
Number of Rats that Have Been Pregnant
Number of Animals that Have Been Pregnant within 1 to 5 Days of Mating
Number of Animals that Have Been Pregnant within 6 to 14 Days of Mating
Number of Animals with Pregnancy = 22 Days
Number of Animals with Pregnancy ≥ 23 Days
Number of Female Rats that Have Given Birth
Number of Female Rats with Surviving Pups
Average Number of Corpora Lutea of Female Rats
Number of Nymphs of Female Rats
Average Number of Pups Per Female Rats at Birth
Average Number of Pups Living 4 Days after Birth
Average Sex Ratio of Pups at Birth
4 Days after Birth Average sex ratio of offspring
Average weight of offspring per litter at birth
Average weight of offspring per litter 4 days after birth
Average weight of offspring per litter at birth
Average weight of offspring per litter d after birth
Deformed mice
Number of mothers who did not give birth to deformed offspring
Number of mothers who gave birth to 1 deformed offspring
Number of mothers who gave birth to 2 deformed offspring
Offspring loss
Number of mothers with absorbed fetuses
Number of mothers with 1 absorbed fetus
Number of mothers with 2 absorbed fetuses
Number of mothers with ≥3 absorbed fetuses
Dose 2
-TYKAONIKAca-
GB/T 21766—2008
GB/T 21766—2008
Dose (unit)
Number of mothers with 0 dead fetuses
Number of mothers with 1 dead fetus
Number of mothers with 2 dead fetuses
Number of mothers with ≥3 dead fetuses before death
Number of mothers still alive 4 days after giving birth
Number of mice with 1 dead fetus 4 days after giving birth
Number of mothers with 2 dead fetuses
Number of mothers with ≥3 dead fetuses 4 days after giving birth
GB/T 21766-2008
Table B.1 (continued)
Copyright table Any infringement will be investigated
Book number: 155066-1-32175
800299
People's Republic of China
National standard
Chemicals
Reproduction/developmental inactivity screening test method
GB/T 21766—2008
Published and distributed by China Standard Promotion Publishing House
No. 16, Sanlihebei Street, Fuxingmenwai, Beijing
Postal code: 100045
Website stop spc. net. cn
Tel: 6852394668517548
Printed by Zhongyin Standard Press, Huangdao Printing Co., Ltd. Distributed by Xinhua Bookstores in various places
Format 880×1230
First edition in July 2008
Printing sheet 0.75
Number of units 18,000
First printing in July 2008
Book number: 155066·1-32173 Price 14,00 yuan Replaced by our publishing center
If there is any printing error
Copyright reserved
Infringement will be investigated
Report phone: (010)68533533
-TYKAONIKAca=1 Test substance
a) Physical properties and relevant physicochemical properties;
b) Name and identification code.
5. 3. 2 Formulation
If it is not water, explain the reason for the choice. 5.3.3 Experimental animals
a) Type/strain;
b) Number, age, sex;
c) Source, living conditions, food, etc.;
Individual weight at the beginning of the test.
5.3.4 Experimental conditions
a) Principles of dose selection;
Detailed description of test substance preparation, concentration, stability and uniformity of sample preparation;
Detailed description of test substance exposure:
Convert the test substance concentration in feed/drinking water into actual dose [tmg/(kg·d)] as needed; Detailed description of feed and water quality.
5.3.5 Results
Weight/weight change;
Feed consumption, water consumption;
Toxic effect data according to sex and dose, including fertility, pregnancy and other toxic symptoms; gestation period;
Toxic or other effects on reproduction, offspring, postnatal growth, etc.; Clinically observed phenomena, severity and duration (whether reversible); number of survivors, number of abortions;
Number of surviving mice with visible abnormalities, number of dwarfed mice; time of animal death during the experiment;
Litter size and litter size when the number of implantations and corpora lutea are recorded; data on body and organ weights of parent animals at the time of sacrifice; results of gross anatomical examination,
Detailed description of the results of microscopic examination of male rat genitals and other tissues;rn)
Abortion data (if available):
Statistical treatment of results.
5.3.6 Discussion of results
5.3.7 Conclusion
5.3.8 Interpretation of results
-TKAONT KAca-
GB/T 21766--2008
This test can evaluate the tropism of animals on reproduction/growth and development after repeated exposure to a test sample. It can provide a basis for further reproductive toxicity tests.
GB/T21766—2008
Appendix A
(Normative Appendix)
Reproduction/developmental toxicity screening test schedule
A,1 Reproduction/developmental toxicity screening test schedule (maximum test period based on 14-day mating period), see Table A.1. Table A.1 Reproductive/developmental toxicity screening test schedule Male rat/mating
Pre-mating period (14 d)www.bzxz.net
Test start
Mating period (up to 14 d)
Pregnant female rat
Extended decoction (optional)
Non-pregnant rat
Gestation period (approximately 22 d)
Dissected male
(at least 4 weeks of infection period)
Lactation period (4 d)
Postpartum 4 Dissected male rats and pups (optional)
Appendix B
(Informative Appendix)
Reproduction/developmental test effect summary report table
B. 1 Reproduction/developmental test effect summary report, see Table B. 1..Table B, 1 Summary Report of Effects of Reproduction/Development Experiments Observation
Specific Quantity (Unit)
Number of Initial Pairs
Number of Female Rats that Have Been Mated
Number of Rats that Have Been Pregnant
Number of Animals that Have Been Pregnant within 1 to 5 Days of Mating
Number of Animals that Have Been Pregnant within 6 to 14 Days of Mating
Number of Animals with Pregnancy = 22 Days
Number of Animals with Pregnancy ≥ 23 Days
Number of Female Rats that Have Given Birth
Number of Female Rats with Surviving Pups
Average Number of Corpora Lutea of Female Rats
Number of Nymphs of Female Rats
Average Number of Pups Per Female Rats at Birth
Average Number of Pups Living 4 Days after Birth
Average Sex Ratio of Pups at Birth
4 Days after Birth Average sex ratio of offspring
Average weight of offspring per litter at birth
Average weight of offspring per litter 4 days after birth
Average weight of offspring per litter at birth
Average weight of offspring per litter d after birth
Deformed mice
Number of mothers who did not give birth to deformed offspring
Number of mothers who gave birth to 1 deformed offspring
Number of mothers who gave birth to 2 deformed offspring
Offspring loss
Number of mothers with absorbed fetuses
Number of mothers with 1 absorbed fetus
Number of mothers with 2 absorbed fetuses
Number of mothers with ≥3 absorbed fetuses
Dose 2
-TYKAONIKAca-
GB/T 21766—2008
GB/T 21766—2008
Dose (unit)
Number of mothers with 0 dead fetuses
Number of mothers with 1 dead fetus
Number of mothers with 2 dead fetuses
Number of mothers with ≥3 dead fetuses before death
Number of mothers still alive 4 days after giving birth
Number of mice with 1 dead fetus 4 days after giving birth
Number of mothers with 2 dead fetuses
Number of mothers with ≥3 dead fetuses 4 days after giving birth
GB/T 21766-2008
Table B.1 (continued)
Copyright table Any infringement will be investigated
Book number: 155066-1-32175
800299
People's Republic of China
National standard
Chemicals
Reproduction/developmental inactivity screening test method
GB/T 21766—2008
Published and distributed by China Standard Promotion Publishing House
No. 16, Sanlihebei Street, Fuxingmenwai, Beijing
Postal code: 100045
Website stop spc. net. cn
Tel: 6852394668517548
Printed by Zhongyin Standard Press, Huangdao Printing Co., Ltd. Distributed by Xinhua Bookstores in various places
Format 880×1230
First edition in July 2008
Printing sheet 0.75
Number of units 18,000
First printing in July 2008
Book number: 155066·1-32173 Price 14,00 yuan Replaced by our publishing center
If there is any printing error
Copyright reserved
Infringement will be investigated
Report phone: (010)68533533
-TYKAONIKAca=8 Interpretation of results
-TKAONT KAca-
GB/T 21766--2008
This test can evaluate the tropism of animals on reproduction/growth and development after repeated contact with a test sample. It can provide a basis for further reproductive toxicity tests.
GB/T21766—2008
Appendix A
(Normative Appendix)
Reproduction/developmental toxicity screening test schedule
A,1 Reproduction/developmental toxicity screening test schedule (maximum test period based on 14d mating period), see Table A.1. Table A.1 Reproductive/developmental toxicity screening test schedule Male rat/mating
Pre-mating period (14 d)
Test start
Mating period (up to 14 d)
Pregnant female rat
Extended decoction (optional)
Non-pregnant rat
Gestation period (approximately 22 d)
Dissected male
(at least 4 weeks of infection period)
Lactation period (4 d)
Postpartum 4 Dissected male rats and pups (optional)
Appendix B
(Informative Appendix)
Reproduction/developmental test effect summary report table
B. 1 Reproduction/developmental test effect summary report, see Table B. 1..Table B, 1 Summary Report of Effects of Reproduction/Development Experiments Observation
Specific Quantity (Unit)
Number of Initial Pairs
Number of Female Rats that Have Been Mated
Number of Rats that Have Been Pregnant
Number of Animals that Have Been Pregnant within 1 to 5 Days of Mating
Number of Animals that Have Been Pregnant within 6 to 14 Days of Mating
Number of Animals with Pregnancy = 22 Days
Number of Animals with Pregnancy ≥ 23 Days
Number of Female Rats that Have Given Birth
Number of Female Rats with Surviving Pups
Average Number of Corpora Lutea of Female Rats
Number of Nymphs of Female Rats
Average Number of Pups Per Female Rats at Birth
Average Number of Pups Living 4 Days after Birth
Average Sex Ratio of Pups at Birth
4 Days after Birth Average sex ratio of offspring
Average weight of offspring per litter at birth
Average weight of offspring per litter 4 days after birth
Average weight of offspring per litter at birth
Average weight of offspring per litter d after birth
Deformed mice
Number of mothers who did not give birth to deformed offspring
Number of mothers who gave birth to 1 deformed offspring
Number of mothers who gave birth to 2 deformed offspring
Offspring loss
Number of mothers with absorbed fetuses
Number of mothers with 1 absorbed fetus
Number of mothers with 2 absorbed fetuses
Number of mothers with ≥3 absorbed fetuses
Dose 2
-TYKAONIKAca-
GB/T 21766—2008
GB/T 21766—2008
Dose (unit)
Number of mothers with 0 dead fetuses
Number of mothers with 1 dead fetus
Number of mothers with 2 dead fetuses
Number of mothers with ≥3 dead fetuses before death
Number of mothers still alive 4 days after giving birth
Number of mice with 1 dead fetus 4 days after giving birth
Number of mothers with 2 dead fetuses
Number of mothers with ≥3 dead fetuses 4 days after giving birth
GB/T 21766-2008
Table B.1 (continued)
Copyright table Any infringement will be investigated
Book number: 155066-1-32175
800299
People's Republic of China
National standard
Chemicals
Reproduction/developmental inactivity screening test method
GB/T 21766—2008
Published and distributed by China Standard Promotion Publishing House
No. 16, Sanlihebei Street, Fuxingmenwai, Beijing
Postal code: 100045
Website stop spc. net. cn
Tel: 6852394668517548
Printed by Zhongyin Standard Press, Huangdao Printing Co., Ltd. Distributed by Xinhua Bookstores in various places
Format 880×1230
First edition in July 2008
Printing sheet 0.75
Number of units 18,000
First printing in July 2008
Book number: 155066·1-32173 Price 14,00 yuan Replaced by our publishing center
If there is any printing error
Copyright reserved
Infringement will be investigated
Report phone: (010)68533533
-TYKAONIKAca=8 Interpretation of results
-TKAONT KAca-
GB/T 21766--2008
This test can evaluate the tropism of animals on reproduction/growth and development after repeated contact with a test sample. It can provide a basis for further reproductive toxicity tests.
GB/T21766—2008
Appendix A
(Normative Appendix)
Reproduction/developmental toxicity screening test schedule
A,1 Reproduction/developmental toxicity screening test schedule (maximum test period based on 14d mating period), see Table A.1. Table A.1 Reproductive/developmental toxicity screening test schedule Male rat/mating
Pre-mating period (14 d)
Test start
Mating period (up to 14 d)
Pregnant female rat
Extended decoction (optional)
Non-pregnant rat
Gestation period (approximately 22 d)
Dissected male
(at least 4 weeks of infection period)
Lactation period (4 d)
Postpartum 4 Dissected male rats and pups (optional)
Appendix B
(Informative Appendix)
Reproduction/developmental test effect summary report table
B. 1 Reproduction/developmental test effect summary report, see Table B. 1..Table B, 1 Summary Report of Effects of Reproduction/Development Experiments Observation
Specific Quantity (Unit)
Number of Initial Pairs
Number of Female Rats that Have Been Mated
Number of Rats that Have Been Pregnant
Number of Animals that Have Been Pregnant within 1 to 5 Days of Mating
Number of Animals that Have Been Pregnant within 6 to 14 Days of Mating
Number of Animals with Pregnancy = 22 Days
Number of Animals with Pregnancy ≥ 23 Days
Number of Female Rats that Have Given Birth
Number of Female Rats with Surviving Pups
Average Number of Corpora Lutea of Female Rats
Number of Nymphs of Female Rats
Average Number of Pups Per Female Rats at Birth
Average Number of Pups Living 4 Days after Birth
Average Sex Ratio of Pups at Birth
4 Days after Birth Average sex ratio of offspring
Average weight of offspring per litter at birth
Average weight of offspring per litter 4 days after birth
Average weight of offspring per litter at birth
Average weight of offspring per litter d after birth
Deformed mice
Number of mothers who did not give birth to deformed offspring
Number of mothers who gave birth to 1 deformed offspring
Number of mothers who gave birth to 2 deformed offspring
Offspring loss
Number of mothers with absorbed fetuses
Number of mothers with 1 absorbed fetus
Number of mothers with 2 absorbed fetuses
Number of mothers with ≥3 absorbed fetuses
Dose 2
-TYKAONIKAca-
GB/T 21766—2008
GB/T 21766—2008
Dose (unit)
Number of mothers with 0 dead fetuses
Number of mothers with 1 dead fetus
Number of mothers with 2 dead fetuses
Number of mothers with ≥3 dead fetuses before death
Number of mothers still alive 4 days after giving birth
Number of mice with 1 dead fetus 4 days after giving birth
Number of mothers with 2 dead fetuses
Number of mothers with ≥3 dead fetuses 4 days after giving birth
GB/T 21766-2008
Table B.1 (continued)
Copyright table Any infringement will be investigated
Book number: 155066-1-32175
800299
People's Republic of China
National standard
Chemicals
Reproduction/developmental inactivity screening test method
GB/T 21766—2008
Published and distributed by China Standard Promotion Publishing House
No. 16, Sanlihebei Street, Fuxingmenwai, Beijing
Postal code: 100045
Website stop spc. net. cn
Tel: 6852394668517548
Printed by Zhongyin Standard Press, Huangdao Printing Co., Ltd. Distributed by Xinhua Bookstores in various places
Format 880×1230
First edition in July 2008
Printing sheet 0.75
Number of units 18,000
First printing in July 2008
Book number: 155066·1-32173 Price 14,00 yuan Replaced by our publishing center
If there is any printing error
Copyright reserved
Infringement will be investigated
Report phone: (010)68533533
-TYKAONIKAca=cn
Tel: 6852394668517548
Printed by Zhongyin Standard Press, Huangdao Printing Co., Ltd. Distributed by Xinhua Bookstores in various places
Format 880×1230
First edition in July 2008
Printing sheet 0.75
Number of units 18,000
First printing in July 2008
Book number: 155066·1-32173 Price 14,00 yuan Replaced by our publishing center
If there is any printing error
Copyright reserved
Infringement will be investigated
Report phone: (010)68533533
-TYKAONIKAca=cn
Tel: 6852394668517548
Printed by Zhongyin Standard Press, Huangdao Printing Co., Ltd. Distributed by Xinhua Bookstores in various places
Format 880×1230
First edition in July 2008
Printing sheet 0.75
Number of units 18,000
First printing in July 2008
Book number: 155066·1-32173 Price 14,00 yuan Replaced by our publishing center
If there is any printing error
Copyright reserved
Infringement will be investigated
Report phone: (010)68533533
-TYKAONIKAca=
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