|
US$209.00 · In stock
Delivery: <= 3 days. True-PDF full-copy in English will be manually translated and delivered via email.
GB 15193.25-2014: National food safety standard -- Reproductive and developmental toxicity test
Status: Valid
| Standard ID | Contents [version] | USD | STEP2 | [PDF] delivered in | Standard Title (Description) | Status | PDF |
| GB 15193.25-2014 | English | 209 |
Add to Cart
|
3 days [Need to translate]
|
National food safety standard -- Reproductive and developmental toxicity test
| Valid |
GB 15193.25-2014
|
PDF similar to GB 15193.25-2014
Basic data | Standard ID | GB 15193.25-2014 (GB15193.25-2014) | | Description (Translated English) | National food safety standard -- Reproductive and developmental toxicity test | | Sector / Industry | National Standard | | Classification of Chinese Standard | C53 | | Classification of International Standard | 67.020 | | Word Count Estimation | 9,989 | | Date of Issue | 12/1/2014 | | Date of Implementation | 5/1/2015 | | Regulation (derived from) | National Health and Family Planning Committee Announcement 2014 No. 19 | | Issuing agency(ies) | National Health and Family Planning Commission of the People's Republic of China | | Summary | This Standard specifies the reproductive and developmental toxicity tests Basic test methods and technical requirements. This Standard applies to the evaluation of the test substance of reproductive and developmental toxicity. | GB 15193.25-2014: National food safety standard -- Reproductive and developmental 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 reproductive and developmental toxicity test)
Book People's Republic of China National Standard
National Food Safety Standard
Reproductive and developmental toxicity test
(To be issued)
Issued on. 2014-12-01
2015-05-01 implementation
People's Republic of China
National Health and Family Planning Commission released
Book GB 15193.25-2014
National Food Safety Standard
Reproductive and developmental toxicity test
1 Scope
This standard specifies the reproductive and developmental toxicity test basic test methods and technical requirements.
This standard applies to the evaluation of the test substance Reproductive and developmental toxicity.
2 Terms and definitions
2.1 Reproductive toxicity
Damage and harmful effects on male and female reproductive function or capability of future generations. Reproductive toxicity can occur in females during pregnancy, but also
It can occur in pre-pregnancy and lactation. It showed the impact of exogenous chemicals on the reproductive process, such as changes in the reproductive organs and the endocrine system, for
The impact of the cycle and sexual behavior, and 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,
And even death.
2.4 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.
2.5 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.
3 test purposes and principles
The trial included three generations (F0, F1 and F2). F0 and F1 generation of administration of the test substance, reproductive toxicity was observed, F2 generation of developmental toxicity was observed features
Sex. Provide information on the test substance to the female reproductive development and function of male animals. such as gonadal function, mating behavior, pregnancy, childbirth, breast-feeding, broken
Milk and offspring growth and neurobehavioral and so on. The main toxic effects include progeny born after the death of increased growth and development of
Change, functional defects offspring (including neural behavior, physical development) and reproductive abnormalities.
Test Method 4
4.1 test substance
The test substance should first use 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 at the appropriate
Management. The test was incorporated into the feed, drinking water or gavage administration.
4.2 Experimental Animals
4.2.1 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, generally preferred rodent rat, avoid using low reproductive or developmental defects high incidence of strains. For positive
Accurately assess the impact of the test substance on animal reproductive and developmental capacity of animals of both sexes should be used. The selected animal species should be indicated, product
Department, sex, weight and weeks of age. Experiment with sex between an individual animal weight difference does not exceed the average weight of ± 20%. Parental choice
(F0 generation) should be non-parous female Rat, non-pregnant rats.
4.2.2 Number of experimental animals
In order to obtain basic experimental data with statistical requirements, the correct evaluation of the test substance on animal reproductive process development (including the F0 move
Was reproductive, pregnancy and feeding process, first generation (F1 generation) animals from birth to maturity in the process of breast growth and development, as well as son and two
Generation (F2 generation) the animals from birth to weaning growth and development related indicators) may cause toxic effects, the need to ensure that each test substance group and
Control access to at least 20 pregnant rats. Usually at the beginning of the test both sexes in each group needs 30 (F0 generation), follow-up tests
Used to mate the animals of each sex in each group needs 25 (F1 generation) (at least one from each litter male and female, most male and female from each litter
2).
4.2.3 Animal Preparation
Before the test, animals in the experimental animal room should be at least 3d ~ 5d acclimatization and quarantine observation, reproductive and developmental toxicity can be carried out
test.
4.2.4 Animal breeding environment
Animal feeding conditions, drinking water, feed should be consistent with GB 14924, the relevant provisions of GB 14925, GB 5749's. Press experimental animals
Single cage or caged by sex, free food and water. When pregnant rats approaching childbirth, in childbirth should be kept separate cages, cage placement made when needed
Nest litter.
Dose group and 4.3
Animals were randomly grouped experimental design was tested at least three groups and one control group. If a solvent is used the test substance, the control group should be given
We use the maximum amount of the solvent. If the test substance causes animal food intake and decreased utilization, then the test and control animals needs
Pair fed animals. High-dose group was designed to test some of the test substance 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 F0 and F1 generation animals significant toxicity, but
Do not cause animal death; intermediate doses can cause mild toxicity; toxicity of low dose should not be any cause parental animals and offspring of anti
should. If the toxicity of the test substance is low, 1000mg/kg bw has not seen the development of the reproductive process have any side effects, then
Limit test may be used, that is no longer considered experimental test substance added another dose group. If the pre-test the effect of high doses of the drug to clear the parent
Role, but had no effect on fertility, it can also be used a limited test.
4.4 Test procedure
4.4.1 The test is administered
4.4.1.1 During the test, all animals should be used in the same manner to give the test substance; such as oral administration of the test substance by gavage frequency per day
1, 7 days a week administration of the test substance. 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, the test substance may be incorporated into the feed, water or oral administration. Preferred incorporation of feed, if that is
Test was added to the feed or drinking 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 can also make use of the test substance carboxymethyl cellulose, starch, etc. dubbed suspended
Liquid or paste and the like. The test substance should now use the existing, data show that except for its storage solution or suspension stabilizer. Should at the same time daily
Gavage once weighed twice weekly intragastric volume weight adjustment. Gavage volume of generally not more than 10mL/kg body weight, such as a water-soluble
When the liquid, the maximum volume of fed up 20mL/kg body weight; as an oily liquid, orally should not exceed the volume of 4mL/kg body weight; each group was given
Consistent volume.
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
5%, while if more than 5% (maximum not more than 10%), the control diet was adjusted nutrient levels (when the test substance no heat or nutrients, and
When you add a proportion of more than 5% in the control group diet should be filled methyl cellulose, incorporated in an amount equivalent to the high dose), dose feed it with nutrients
Level consistent; also depending on the situation to adjust the dose of the test substance feed nutrient levels of nutrients or calories to feed the camp with the control group
Nutrients levels consistent. Unit dosage test substance is ingested per kg body weight of test substance mg (or g) number, i.e., 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) of feed, the incorporation of water is expressed as
mg/mL water. When the test was incorporated into the feed, the need to test substance dose (mg/kg body weight) by animal food intake per 100g of body weight translated into
Feed concentration of the test substance (mg/kg diet).
4.4.2 Test Method
Seven weeks after weaning choice to 9 weeks of the F0 females, males, adapt 3d ~ 5d after the start of administration of the test substance, at least to continue before mating
10 weeks. After mating, the males of the F0 autopsy. In three weeks of mating, pregnancy, during the F1 progeny weaning until the entire test,
The F0 females administration of the test substance daily. F1 generation pups after weaning, administration of the test substance, and has been extended until the F2 generation weaned. During the test root
According metabolism and accumulation characteristics of the test substance, can be adjusted to give a dose (Test procedure Table 1).
Table 1 rat reproductive and developmental test program
Test cycle parental (F0) first generation (F1) of the second generation (F2)
1 to Week 10 week administration of the test substance - -
The first 11 weeks to 13 week mating (administration of the test substance) - -
The first 14 weeks to 16 week
Administration of the test substance during pregnancy, pregnancy
After male rats were sacrificed
- -
17 weeks 19 weekend
Administration of the test substance lactation, breast-feeding
After the females were sacrificed
After birth 4d, litter was adjusted to 8
Pups, pups were observed physical development
20 weeks 29 weekend - administration of the test substance -
30 to Week 32 Weekend - mating (administration of the test substance) -
33 weeks 35 Weekend -
Gestational administration of the test substance, the end of pregnancy
Male rats were sacrificed
36 weeks 38 Weekend -
Lactation administration of the test substance, the end of lactation
Female rats were sacrificed
After birth 4d, adjusted to eight young per litter
Rats, pups were observed physical development
The first 39 weeks to the end of the test - -
Offspring observed physical development
Offspring Neurobehavioral detection
4.4.3 Mating
4.4.3.1 Reproductive and developmental toxicity tests available 1.1 (1 male .1 female) or 1.2 (1 male .2 female) mate.
4.4.3.2 each mating, each female shall be from the same group of subjects was randomly selected single male with cage (1.1 mating), paired with cage
Females, males should be marked. All the females during the mating of sperm or vaginal plugs should be checked daily until proven mated date and proof of delivery
As soon as female, male separated after allocation. Vaginal plug or sperm found on the day of conception 0d.
4.4.3.3 Progeny F1 Grand Shushu age 13 weeks before mating. F1 offspring of mating, the same subjects were randomly selected group litter with another litter
Pups 1.1 cross mating to produce offspring F2. Participation mate pups per litter male and female have at least one, and should be randomly rather than by
Weight selection. Not been selected F1 generation of male and female offspring on F2 pups sacrificed at weaning.
4.4.3.4 If after three estrus or two yet to mating success, should be mated females, males apart, not to continue the same cage. Should also be
Infertility animals checked analyze the reasons. Also, it can not successfully mate with animals confirmed through normal reproductive function of animal weight
The new pairing, and when needed genital pathology, examination cycle estrous cycle and spermatogenesis.
4.4.3.5 Because of the toxic effects of the test substance resulted in the number of litters mice unable to meet the test requirements, or observed during the first mating process to be
Suspected changes and results may be parental (F0 generation) or sub-generation rat (F1 generation) second mate. The second time mating is recommended
Unmated female (male) rats have been mated male (female) rats. Second mate Usually after the first mating produced pups weaned
One week.
4.4.4 Standardization pups per litter number
Administration of the test substance and lactation F0 and F1 generation dams pregnancy, were killed after the end of the weaning period. After the F1 generation pups born on the fourth day, the use of
Random manner (rather than weight basis), we will adjust the number of pups per litter, removing excess pups, pups per litter achieve gender and
The number of unity. Litter selected as four males and four females, can also be part of the adjustment based on the actual situation, but not less than litter
Eight pups. F2 generation offspring in the same way to adjust.
5 OUTCOME MEASURES
5.1 pairs of animals to do a comprehensive clinical examination, recording the toxic effects of the test substance produced by physical symptoms, behavioral changes related to, or difficulties in childbirth
Delayed signs and all other indications of toxicity and mortality.
5.2 should be checked during the mating female (F0 and F1 generation) of the vagina and cervix to determine whether the abnormal estrus cycle in females.
5.3 before mating and mating, animal food intake can be recorded once a week, and during pregnancy may be considered daily record. As a test substance by
Incorporation of water give way, it would take a week to calculate the consumption of drinking water. After calving, maternal food intake should also be recorded, and each time choose
Littermate mice were weighed at the same time.
5.4 F0 and F1 generation involvement in reproductive animals should be weighed in the administration of the test was the first day, after weighed once a week, only by
recording.
5.5 At the end of the test, select the F0 and F1 generation male epididymis, sperm morphology were observed and evaluated the quantity and activity. Can be
Select the control and high dose group of animals to be checked, checking each animal at least 200 sperm. If test results prompted, further
Low dose group of animals to be checked.
5.6 To determine the number of pups per litter, gender, number of stillbirths, live births, and whether there is the appearance of malformations, pups per litter should be as soon as possible after calving female rats
Its inspection. Death of the body stillbirth, offspring during lactation and postnatal day 4 due to the standardization of the nest and killed the pups need, need to be properly
Good save and pathological examination.
5.7 pairs obviously not pregnant animals can be killed after whichever of the uterus using ammonium sulfide staining method to check the number of implantation to confirm whether the embryo in the
Death bed.
5.8 surviving pups after birth that morning, the first 4 days, 7 days, 14 days and 21 days respectively for counting and weighing weight,
And to observe and record the dams and offspring and physiological activity is abnormal.
5.9 in the nest as a unit, check and record all the F1 generation offspring physiological development indicators, recommended to choose before weaning ear isolated, eyes open, Zhang Er, the
Mao, incisor eruption time, and after weaning female vaginal opening and the male testicular descent time. Specific observation time and frequency according to the test
Test used to determine traits of rat strains (Table 2).
Table 2 F1 offsprings physical development index
Physical development index
Observation time and frequency
After weaning weaning after sexual maturity sexual maturity
Weight, clinical manifestations biweekly biweekly once every 1 week
End of the 11th day after the test brain birth weight
Sexual maturation - the right time -
Other development indicators corresponding appropriate time - -
5.10 each test dose group were randomly selected a certain number, a clear mark in F2 pups were related physiological and neurobehavioral development means
Standard on the determination. Physical development, neurobehavioral index detection and the corresponding number of animals shown in Table 3, in which the physiological development index check time
And the frequency with F1 generation pups. Detection neurobehavioral development indicators F2 pups were born after the first 25 days ± 2d and 60 days into the
Row. Cognitive abilities test methods in these two developmental stages used differently, it is recommended to select a targeted and sensitive cognitive tests
method. If there is data suggest that the test substance may affect cognitive ability, need further detects sensory function, motor function,
And a targeted selection of relevant learning and memory testing method according to the literature and the results of previous studies. If there is no mention of such information
For recommended active avoidance test, passive avoidance test and Morris water maze tests as the test methods.
Development Indicators Table 3 F2 offsprings physiological and neurobehavioral
Each test group was selected from each litter
With the number of pups/only
The actual development index
Use the number of pups/only
Male and female male and female
Development Indicators
2020 Determination of the individual capacity of movement
After the 1010 birth 11d, the brain of pups weighed and neuropathological examination
Detailed clinical observation and recording, observe self-activity, sexually mature outlook
Determination of police, motor and sensory function
After the 1010 birth 70d, adult offspring brain weighed and neuropathological examination
10 10 23d after birth onwards, measuring learning and memory ability of pups were
After the 1010 birth 70d, adult offspring brain weighed
21d 112 020 were killed after birth
Combining the characteristics of the test substance to carry out additional clinical testing when necessary 5.11.
Pathological examination 6
6.1 Reproductive toxicity pathology
6.1.1 Gross anatomy
Reproductive and developmental toxicity test, or sacrificed all to death, pups should be subject to gross pathological anatomy, including genitalia observed
Official organs, including the presence or absence of abnormality or structure.
6.1.2 organ weighing
Respond uterus and ovaries, testis and epididymis, prostate, seminal vesicles, brain, liver, kidney, spleen, pituitary, thyroid on the basis of gross anatomy
Vital organs and adrenal glands were weighed and recorded.
6.1.3 Histopathological examination
Mating and for developmental toxicity testing F0 and F1 generation animals retain their ovaries, uterus, cervix, vagina, testis, epididymis, seminal vesicle
Gland, prostate, penis and possible target organs for histopathological examination. It should also determine the number of male sperm whether to change, whether the
Online sperm deformity. Gross anatomy displayed in tissue lesions should be done histopathological examination is recommended for suspected infertility animal reproductive organs do
Histopathological examination.
In addition to the first pair of stuffed animals at the highest dose of the test substance and control groups, and autopsy specimens were found to have abnormal histopathology
an examination. As the highest dose of the test substance group found no significant pathological changes, other specimens were tested dose group can no longer be pathological
an examination. Conversely, if the highest dose group tested was found to significant pathological changes, other dose groups related to the test substance should also be made into a specimen
Step inspection.
6.2 neurodevelopmental toxicity pathology
In the F2 pups first 11 days and 70 days after birth, were neuropathological examination related to pups. May be affected by high dose
Check the test substance and control groups, such as the discovery of significant neuropathological changes, before proceeding, check the low-dose group of the test substance. nerve
Developmental toxicity observed pathological recommend the olfactory bulb, cortex, hippocampus, basal ganglia, thalamus, hypothalamus, midbrain, brain stem and cerebellum
organization.
7 Data processing and evaluation of results
7.1 Data Processing
All data and results are summarized in tabular form, the data can be used for statistical table, the table should be displayed for each group of experimental animals
Number, the number of male animals mating, the number of pregnant females, and the emergence of a variety of animal toxicity percent. Reproductive, physical development index number
It should be based on the statistical units of the nest. Developmental neurotoxicity and pathology inspection results should be an appropriate method of statistical analysis. Metering funding
Material variance analysis, were compared between the plurality of test and control groups, the distribution of classified data using Fisher's exact test, chi-square seized
Test, rank sum test, ranked data using Ridit analysis, rank sum test and so on.
7.2 Evaluation Results
Compare each test group of animals was whether the control animals observed indicators and pathological findings were significant differences, in order to assess the test
Was whether the reproductive and developmental toxicity, reproductive and developmental toxicity and determine its minimum observed adverse effect level (LOAEL) and not observed deleterious
Dose (NOAEL). While also indicators of significant differences (such as weight, physiological indicators, gross anatomy and histopathology according to appear
Test results, etc.), to further assess the role of reproductive and developmental toxicity characteristics.
8 Test Report
8.1 Name of test, the test unit name and contact details, report number.
8.2 Test Requester name and contact information, sample acceptance date.
8.3 Test start and end dates, test project manager, technical director of the test unit, date of issue.
8.4 test summary.
8.5 test substance. name, lot number, dosage form, the state (including organoleptic, properties, package integrity, identification), the number of pre-treatment method, solvent.
8.6 Experimental animals. species, strain, level, quantity, weight, sex, origin (supplier name, animal production license number), animals
Quarantine, adaptation, breeding environment (temperature, relative humidity, using experimental animal facility license number), feed sources (supplier name, experiment
Animal feed production license number).
8.7 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.
8.8 Test results.
a) toxicity test substance by sex and group were recorded, including reproductive abnormalities, pregnancy and development capabilities;
b) time during the test or experimental animals, animal deaths to the end of the trial whether survival;
c) the average weight of body weight per litter of pups and pups, as well as post-test single body weight of pups;
d) any reproduction, offspring and their toxic effects and other health damage growth and development;
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 o...
Tips & Frequently Asked Questions:Question 1: How long will the true-PDF of GB 15193.25-2014_English be delivered?Answer: Upon your order, we will start to translate GB 15193.25-2014_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 15193.25-2014_English with my colleagues?Answer: Yes. The purchased PDF of GB 15193.25-2014_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. Our tax invoice, downloaded/delivered in 9 seconds, includes all tax/VAT and complies with 100+ countries' tax regulations (tax exempted in 100+ countries) -- See Avoidance of Double Taxation Agreements (DTAs): List of DTAs signed between Singapore and 100+ countriesQuestion 4: Do you accept my currency other than USD?Answer: Yes. If you need your currency to be printed on the invoice, please write an email to [email protected]. In 2 working-hours, we will create a special link for you to pay in any currencies. Otherwise, follow the normal steps: Add to Cart -- Checkout -- Select your currency to pay.
|