Template For Subchronic Toxicity Study in Rodents

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Template For Subchronic Toxicity Study in Rodents

Introduction to the Template For Subchronic Toxicity Study in Rodents

March 2004

Toxicology Template Introduction

Identification of Study
Good Laboratory Practice
Executive Summary
Materials and Methods
1. Test Substance
2. Test Substance As Administered
3. Animal Diet
4. Test Animals
5. Experimental Design
6. Body Weight And Feed Intake
7. Cage-Side Observations
8. Opthalmological Examination
9. Hematology
10. Clinical Chemistry
11. Urinalysis
12. Other Tests
13. Necropsy (Interim Sacrifice)
14. Necropsy (Terminal)
15. Gross Pathology Observations
16. Histopathology Observations
17. Statistical Methods
Results
1. Dose Verification
2. Feed Consumption Changes
3. Intake Of Test Substance
4. Feed Efficiency
5. Body Weight Changes
6. Cage-Side Observations
7. Mortality
8. Opthalmological Examination
9. Hematology
10. Clinical Chemistry
11. Urinalysis
12. Other Tests
13. Organ Weights
14. Gross Pathology Changes Observed
15. Histopathology Changes Observed
16. Neurotoxicity
Evaluation And Comment On Study
Summary And Conclusions
1. Brief Summary Of Major Findings From The Study
2. Relationship Between Dose And Incidence/Severity Of Lesions Or Abnormalities
3. Was There A Target Organ?
4. NOEL
References

Subchronic Toxicity Study in Rodents Template

Date of Submission:

Title of Petition or Notification:

Name and Address of Petitioner or Notifier:

I. Identification of Study¹

A. Study File Location:
B. Study Title/Report Number:
C. Name and Address of Testing Facility:
D. Date of Study Report:
E. Dates Study Conducted:
F. Study Objective:
G. Comments:

II. Good Laboratory Practice²

A. Good Laboratory Practice (GLP) Compliance?
B. Quality Assurance (QA) Statement?
C. Availability and Location of Original Data/Specimens/Test Substance:

III. Executive Summary

IV. Materials and Methods

A. Test Substance³

CAS name:
Other name(s):
CAS registry number:
Molecular structure: http://www.⁴ /
Purity:
Impurities:
Stability:
Comments:

B. Test Substance As Administered⁵

Batch/lot number:
Route:
Vehicle used:
Tested adequately for concentration?
Tested for homogeneity?
Tested for stability?
Problems with storage?

C. Animal Diet,

Feed
1. Type:
2. Name:
3. Availability:
4. Analysis for contaminants:
5. Comments:
Water
1. Source:
2. Availability:
3. Analysis for contaminants:
4. Comments:

D. Test Animals⁶

Species/strain/substrain:
Sex:
Age range at initiation of study:
Weight range at initiation of study:
Quarantine/acclimation?
Physical examination times:
Number per cage:
Environmental conditions:
Comments:

E. Experimental Design⁷

1. Targeted dose levels:

Table # [Heading]

test group	conc. in diet (ppm or mg/kg)	dose to animals (mg/kg body-weight/day)	number of males	number of females
Control
Low
Mid
High

2. Total number of animals:
3. Duration of study (including recovery period, if any):
4. Length of exposure to test substance:
5. Were animals randomized?
6. Recovery period:
7. Comments:

F. Body Weight And Feed Intake

1. Parameter examined:

Table # [Heading]

examined	not examined
	Feed Intake* Feed Spillage* Water Intake* Body Weight* Body Weight Changes*

*These parameters are recommended in REDBOOK for subchronic toxicity studies.

2. Comments:(e.g., list frequency)

G. Cage-Side Observations⁸

1. Parameter examined:

Table # [Heading]

examined	not examined
	Appearance* Abnormal Stool* Morbidity* Mortality* Neurotoxicity Screening (Specify parameters), *

*These parameters are recommended in REDBOOK for subchronic toxicity studies. Add additional parameters tested.

**The parameters for neurotoxicity screening may include, but are not limited to, the following:

Changes in skin, fur, eyes, mucous membranes, gait, posture, and response to handling,
Occurrence of secretions/excretions or other evidence of autonomic activity such as lacrimation, piloerection, pupil size change, unusual respiratory pattern,
Presence of clonic or tonic seizure,
Stereotype behaviors such as excessive grooming and repetitive circling,
Bizarre behavior such as self-mutilating and walking backwards,
Gross tumor development.

2. Comments: (e.g., list frequency)

H. Opthalmological Examination

Parameter examined:
Comments: (e.g., list frequency)

I. Hematology⁹

Fasting duration prior to blood collection:
When in the study were the blood samples collected?
How were the blood samples drawn?
Dose groups and number of animals tested:
Parameter examined:

Table # [Heading]

measurement related to	examined	not examined
red blood cells		Hematocrit (Hct)* Hemoglobin Conc. (Hb)* Mean Corp. Hb. (MCH)* Mean Corp. Hb. Conc. (MCHC)* Mean Corp. Volume (MCV)* Total Erythrocyte Count (RBC)*
white blood cells		Basophils, Eosinophils* Lymphocytes* Macrophage/Monocytes* Neutrophils* Total Leukocytes (WBC)*
clotting potential		Activated Partial-Thromboplastin Time* Clotting Time* Platelet Count* Prothrombin Time*
others		Bone marrow cytology* Reticulocyte counts*

*These parameters are recommended in REDBOOK for subchronic toxicity studies. Add additional additional parameters tested.

6. Comments:

J.Clinical Chemistry¹⁰

Fasting duration prior to blood collection:
When in the study were the blood samples collected?
How were the blood samples drawn?
Dose groups and number of animals tested:
Parameter examined:

Table # [Heading]

measurement related to	examined	not examined
electrolyte balance		Calcium* Chloride^,* Phosphorus* Potassium^,* Sodium^,*
carbohydrate metabolism		Glucose^,*
liver function: A) hepatocellular (recommend at least 3 out of 5 RED BOOK PARAMETERS ) B) hepatobiliary (recommend at least 3 out of 5 RED BOOK PARAMETERS)		Alanine Aminotransferase (ALT or SGPT)^,* Aspartate Aminotransferase (AST or SGOT)* Glutamate Dehydrogenase* Sorbitol Dehydrogenase* Total Bile Acids*
		Alkaline Phosphatase (ALP)^,* Gamma-Glutamyl Transferase (GGT)^,* Total Bile Acids* Total Bilirubin* 5' Nucleotidase*
kidney function		Creatinine^,* Urea Nitrogen^,*
others (acid/base balance, cholinesterases, hormones, lipids, methemoglobin, and proteins)		Albumin (A)* Globulin (G, calculated) or A/G Ratio* Total Cholesterol* Cholinesterase* Total protein^,* Fasting Triglycerides*

*These parameters are recommended in REDBOOK for subchronic toxicity studies. Add additional additional parameters tested.

** These parameters should generally be given priority when adequate volumes of blood samples can not be obtained from test animals.

6. Comments:

K. Urinalysis¹¹

When were urine samples collected?
Parameter examined:

Table # [Heading]

examined	not examined
	Glucose, Microscopic evaluation for sediment and presence of blood/blood cells, pH, Protein, Specific Gravity, Volume

* These parameters are recommended in REDBOOK for subchronic toxicity studies.

3. Comments :

L. Other Tests¹²

Observations:
Comments:

M. Necropsy (Interim Sacrifice)¹³

Was there an interim sacrifice?
Dose groups and number of animals:
Organs/Tissues weighed:

Table # [Heading]

examined	not examined
	Adrenals, Brain, Epididymides, Heart, Kidneys, Liver, Spleen, Testes, Thyroid/parathyroid, Thymus, Ovaries, Uterus

* These parameters are recommended in REDBOOK for subchronic toxicity studies.

4. Comments:

N. Necropsy (Terminal)

1. Organs/Tissues weighed:

Table # [Heading]

examined	not examined
	Adrenals, Brain, Epididymides, Heart, Kidneys, Liver, Spleen, Testes, Thyroid/parathyroid, Thymus, Ovaries, Uterus

*These parameters are recommended in REDBOOK for subchronic toxicity studies. Add additional additional parameters tested.

2. Comments:

O. Gross Pathology Observations

Organs/Tissues Examined:
Comments:

P. Histopathology Observations

Organs/Tissues were collected from which dose groups?
Organs/Tissues were examined from which dose groups?
How were the organs/tissues prepared for histopathology observation?
Organs/Tissues collected:

Table # [Heading]

system	examined	not examined
digestive		Salivary Gland, Esophagus, Stomach, Duodenum, Jejunum, Ileum, Cecum, Colon, Rectum, Gall Bladder (in case of mice), Liver* (middle, left and triangular lobes), Pancreas*
respiratory		Nasal Turbinates, Trachea, Lung* (with main-stem bronchi)
cardiovascular		Aorta, Heart
reticulo- endothelial/ hematopoietic		Bone Marrow* (sternum), Lymph Nodes* (1 related to route of administration, and 1 from a distant location), Spleen, Thymus
urogenital		Kidneys, Ovaries and fallopian tubes, Corpus Uteri, Cervix Uteri, Prostate, Seminal Vesicle* (if present), Testes, Urinary Bladder, Vagina*
neurologic		Brain* (at least 3 different levels), Spinal-Cervical, Spinal-Lumbar, Spinal-Midthoracic, Sciatic Nerve, Harderian Gland* (if present)
glandular		Adrenals, Mammary Glands, Pituitary Glands, Thyroid/Parathyroid Glands, Thymus, Zymbal's Gland (if present)
other		Bone (Femur), Eyes, Skeletal Muscle, Skin, Epididymis*

*These parameters are recommended in REDBOOK for subchronic toxicity studies. Add additional additional parameters tested.

5. Comments:

Q. Statistical Methods

1. Methods of statistical analysis:

Table # [Heading]

methods of statistical analysis	parameters tested

2. Comments:

V. Results

A. Dose Verification¹⁴

1. Were doses verified?

Table # [Heading]

dose group	targeted concentration (ppm or mg/kg)	concentrations found in feed (ppm or mg/kg)	standardDeviation	N*
low
mid
high

* Number of measurements (N)

Verified by:
Comments:

B. Feed Consumption Changes¹⁵

Observations:
Comments:

C. Intake Of Test Substance¹⁶

1. Observations:

Table # [Heading]

dose group	daily dose (mg/kg body-weight/day)
control	0
low
mid
high

2. Comments:

D. Feed Efficiency¹⁷

Was feed efficiency calculated?
Comments:

E. Body Weight Changes¹⁸

Observations:
Comments:

F. Cage-Side Observations¹⁹

Observations:
Comments:

G. Mortality²⁰

Observations:
Comments:

H. Opthalmological Examination

Observations:
Comments:

I. Hematology²¹

1. Observations:

Table # [Heading]

SEX		males	females
DAILY DOSE (mg/kg body-weight/day)		0 CONTROL	0 CONTROL
NUMBER OF ANIMALS
red blood cells
Hematocrit (Hct)	%
Hemoglobin Conc. (Hb)	g/L
Mean Corp. Hb. (MCH)
Mean Corp. Hb. Conc. (MCHC)
Mean Corp. Volume (MCV)	L/L
Total Erythrocyte Count (RBC)	10¹²/L
white blood cells
Basophils
Eosinophils
Lymphocytes	10⁹/L
Macrophage/ Monocytes
Neutrophils	10⁹/L
Total Leukocytes (WBC)	10⁹/L
clotting potential
Activated Partial-Thromboplastin Time
Clotting Time
Platelet Count	10⁹/L
Prothrombin Time
others
Bone marrow cytology
Reticulocyte counts	10¹²/L

(Specify a method of statistical analysis): * p<0.05, ** p<0.01

2. Comments:

J. Clinical Chemistry²²

1. Observations:

Table # [Heading]

SEX		males	females
DAILY DOSE (mg/kg body-weight/day)		0 CONTROL	0 CONTROL
NUMBER OF ANIMALS
electrolyte balance
Calcium	mmol/L
Chloride	mmol/L
Phosphorus	mmol/L
Potassium	mmol/L
Sodium	mmol/L
carbohydrate metabolism
Glucose	mmol/L
liver function: A) hepatocellular
Alanine Aminotransferase (ALT or SGPT)	U/L
Aspartate Aminotransferase (AST or SGOT)	U/L
Glutamate Dehydrogenase	U/L
Sorbitol Dehydrogenase	U/L
liver function: B) hepatobiliary
Alkaline Phosphatase (ALP)	U/L
Gamma-Glutamyl Transferase (GGT)	U/L
Total Bile Acids	mmol/L
Total Bilirubin	mmol/L
5' Nucleotidase	U/L
kidney function
Creatinine	mmol/L
Urea Nitrogen	mg/dL
others
Albumin (A)	g/L
Globulin (G, calculated)	g/L
A/G Ratio
Total protein	g/L
Total Cholesterol	mmol/L
Fasting Triglycerides	mmol/L
Cholinesterase	U/L

(Specify statistical method of analysis): * p<0.05, ** p<0.01

2. Comments:

K. Urinalysis²³

1. Observations:

Table # [Heading]

SEX		males	females
DAILY DOSE (mg/kg body-weight/day)		0 CONTROL	0 CONTROL
NUMBER OF ANIMALS
Glucose	mmol/L
Microscopic evaluation for sediment and presence of blood/blood cells
pH
Protein	g/L
Specific Gravity
Volume	L/time

2. Comments:

L. Other Tests²⁴

Observations:
Comments:

M. Organ Weights²⁵

1. Observations:

Table # [Heading]

SEX		males	females
DAILY DOSE (mg/kg body-weight/day)		0 CONTROL	0 CONTROL
NUMBER OF ANIMALS
BODY WEIGHT (gram)^a
BRAIN
Absolute Weight^a	gram
Per Body Weight^a	%
ADRENALS
Absolute Weight^a	gram
Per Body Weight^a	%
Per Brain Weight^a	%
EPIDIDYMIDES
Absolute Weight^a	gram
Per Body Weight^a	%
Per Brain Weight^a	%
HEART
Absolute Weight^a	gram
Per Body Weight^a	%
Per Brain Weight^a	%
KIDNEYS
Absolute Weight^a	gram
Per Body Weight^a	%
Per Brain Weight^a	%
LIVER
Absolute Weight^a	gram
Per Body Weight^a	%
Per Brain Weight^a	%
SPLEEN
Absolute Weight^a	gram
Per Body Weight^a	%
Per Brain Weight^a	%
TESTES
Absolute Weight^a	gram
Per Body Weight^a	%
Per Brain Weight^a	%
THYROID and PARATHYROID
Absolute Weight^a	gram
Per Body Weight^a	%
Per Brain Weight^a	%
THYMUS
Absolute Weight^a	gram
Per Body Weight^a	%
Per Brain Weight^a	%
OVARIES
Absolute Weight^a	gram
Per Body Weight^a	%
Per Brain Weight^a	%
UTERUS
Absolute Weight^a	gram
Per Body Weight^a	%
Per Brain Weight^a	%

a: Group means at the end of terminal necropsy are shown.
(Specify methods of statistical analysis): * p<0.05, ** p<0.01

2. Comments:

N. Gross Pathology Changes Observed²⁶

Observations:
Comments:

O. Histopathology Changes Observed²⁷

1. Observations:

Table # [Heading)

	NUMBER OF ANIMALS WITH, GROSS, NON-NEOPLASTIC, OR NEOPLASTIC LESIONS
SEX	males	females
DAILY DOSE (MG/KG BODY-WEIGHT/DAY)	0 CONTROL	0 CONTROL
NUMBER OF ANIMALS EXAMINED
*DIGESTIVE SYSTEM*
ORGAN/TISSUE ^#
GROSS LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION

NEOPLASTIC LESIONS
NEOPLASTIC LESIONS
NEOPLASTIC LESIONS

*RESPIRATORY SYSTEM*
ORGAN/TISSUE ^#
GROSS LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION

NEOPLASTIC LESIONS
NEOPLASTIC LESIONS
NEOPLASTIC LESIONS

*CARDIOVASCULAR SYSTEM*
ORGAN/TISSUE ^#
GROSS LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION

NEOPLASTIC LESIONS
NEOPLASTIC LESIONS
NEOPLASTIC LESIONS

*RETICULO-ENDOTHELIAL /HEMATOPOIETIC SYSTEM*
ORGAN/TISSUE ^#
GROSS LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION

NEOPLASTIC LESIONS
NEOPLASTIC LESIONS
NEOPLASTIC LESIONS

*UROGENITAL SYSTEM*
ORGAN/TISSUE ^#
GROSS LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION

NEOPLASTIC LESIONS
NEOPLASTIC LESIONS
NEOPLASTIC LESIONS

*GLANDULAR SYSTEM*
ORGAN/TISSUE ^#
GROSS LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION

NEOPLASTIC LESIONS
NEOPLASTIC LESIONS
NEOPLASTIC LESIONS

(Specify methods of statistical analysis): * p<0.05, ** p<0.01
# Organs/tissues listed under section IV.P.
In general, data at end of dosing period can be shown; however, if there were additional noteworthy findings at earlier timepoints, these should be included. Note severity of lesions as needed.

2. Comments:

P. Neurotoxicity²⁸

1. Observations:

Table # [Heading]

	NUMBER OF ANIMALS
SEX	males	females
DAILY DOSE (MG/KG BODY-WEIGHT/DAY)	0 CONTROL	0 CONTROL
NUMBER OF ANIMALS EXAMINED
*OBSERVATIONS OF NERVOUS SYSTEM TOXICITY ⁺*
OBSERVATION
OBSERVATION
OBSERVATION

*GROSS- AND HISTO-PATHOLOGY CHANGES IN THE NEUROLOGIC SYSTEM ^#*
ORGAN/TISSUE
GROSS LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION
NON-NEOPLASTIC LESION

NEOPLASTIC LESIONS
NEOPLASTIC LESIONS
NEOPLASTIC LESIONS

+ See under section IV.G for the types of observation for nervous system toxicity: List noteworthy findings. If additional parameters (other than those in the Template) showed noteworthy changes, these should be added to the tables. In general, include data at the end of the dosing period. However, if one observes additional noteworthy findings at earlier timepoints, these should be included. Footnotes should be used as needed to provide additional information about the tests or the results. Note the severity of the abnormal observations using the following scales; + Mild, ++ Moderate, and +++ Marked or other scales, as appropriate.
# Organs/tissues listed under section IV.P

2. Comments:

VI. Evaluation and Comment on Study²⁹

VII. Summary and Conclusions³⁰

A. Brief Summary Of Major Findings From The Study

B. Relationship Between Dose And Incidence/Severity Of Lesions Or Abnormalities

C. Was There A Target Organ?

D. NOEL

Was there a no observed effect level?
Comments:

VIII. References

End Notes

This section includes some comments that are only relevant when using the Word template.

¹Make note of: study file location (Volume, pages), study title/report #, testing facility name, publication dates of study, study objective, and comments, if needed.

²Indicate Yes or No for the Questions A and B. However, please elaborate on the type of GLP compliance (USFDA, OECD, etc.) or make other notations.

³Description of the test substance should be given, including purity, any possible contaminants or impurities, and any potential properties of the test substance that could have affected its integrity. Are there factors that might have affected the actual administered dose, as opposed to the intended dose?

⁴After you put a blinking cursor on the http address, (CTRL +) left-click once to follow the link and wait. Enter a chemical name, CAS Number, or molecular formula inside the search window and click 'search' button. Right-click inside the molecular structure and select 'copy' submenu. Return to your document and put the cursor underneath item #4 (molecular structure). Right click to open up the menu options and select 'paste' submenu. You can drag the structure to any position you want and resize. If preferred, use other methods of depicting the molecular structure.

⁵Indicate how the test substance was administered and whether any vehicle was used to dissolve/suspend the test substance (e.g., dissolved in corn oil and mixed into the feed). Also note if there was adequate testing for concentration and homogeneity (appropriate tests with replicates) and whether there were stability tests done. Was the strength of the test material checked over the period and under the conditions that the feed mix, test article in vehicle, etc., would be stored?

⁶Note anything that might have affected the study. Use the comments to indicate other factors that might have impacted the study.

⁷Provide adequate details. Use the comments to indicate additional information about the experimental design. To change the table, place cursor in the row or column that you wish to modify, then from the 'Table' menu, use 'Select Row' or 'Select Column' to highlight the row or column that you wish to change, and use the 'delete' or 'insert' functions to make your changes.

⁸Indicate the measurements or observations that were made by highlighting the parameter and dragging the term into the 'Examined' side. Those parameters not examined will remain in the 'Not Examined' side. Use the comments to indicate when observations were made and any other notable fact.

⁹Drag and drop to indicate parameters that were examined. Use comments to indicate other important information.

¹⁰Drag and drop to indicate parameters that were examined. Use comments to indicate other important information.

¹¹Note when urine was collected for testing, the groups that were affected, and drag and drop the parameters that were tested. Make comments on anything considered significant or treatment-related.

¹²If other tests were conducted, make note of the endpoints considered significant or treatment-related.

¹³If there was an interim sacrifice (e.g., at 30 or 60 days), make notes on which groups were affected, and the number and sex of the animals that were tested.

¹⁴Note whether there was a verification of the doses being administered (by what analytical methodology and in which laboratory). Was this done more than once? Were there adequate data to calculate the actual dose that was administered?

¹⁵Note any statistically or biologically significant feed consumption changes. Note feed consumption changes that were not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend.

¹⁶Considering the level of feed intake and the level of test substance in the feed, what was the dose actually being delivered to the animals?

¹⁷Note when feed efficiency was determined; if any changes were observed; if feed efficiency was calculated for all groups or only selected groups; and if calculations were made per group, per cage, or per animal.

¹⁸Note any statistically or biologically significant body weight changes. Also note body weight changes that are not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend. You may wish to insert graphs or tables in this section.

¹⁹List significant, dose-related abnormal cage-side observations. For neurotoxicological observations, also use a Table in Section V. P. (see Section IV. G. for parameters).

²⁰For each animal with an unscheduled death, note the group, date of death, and any observations, including lesions observed at necropsy.

²¹Note findings that were statistically or biologically treatment-related. Also note changes that were not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend. The comment section is available to explain data findings, if needed.

²²Note findings that were statistically or biologically treatment-related. Also note changes that were not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend. The comment section is available to explain data findings, if needed.

²³Note findings that were statistically or biologically treatment-related. Also note changes that were not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend. The comment section is available to explain data findings, if needed.

²⁴When other tests were conducted, make note of the tests and any significant treatment-related effects.

²⁵Note findings that were statistically or biologically treatment-related. Also note changes that were not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend. The comment section is available to explain data findings, if needed.

²⁶Note findings that were statistically or biologically treatment-related. Also note changes that were not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend. The type of lesion should be noted. The comment section is available to explain data findings, if needed. Also note the findings in Histopathology Section V.O. below.

²⁷Note findings that were statistically or biologically treatment-related. Also note changes that were not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend. The type of lesion should be noted. The comment section is available to explain data findings, if needed.

²⁸Provide summary tables of all positive effects. In addition, provide an explicit statement as to whether or not the test substance may represent a potential neurotoxic hazard.

²⁹Give your evaluation of the study: what was done well; what the problems were; did the study accomplish what it was supposed to do?

³⁰Summarize the key findings from the study. Was there a dose-effect relationship? Were target organs identified? Was a NOEL achieved for each significant effect/observation? What was the NOEL? The whole study should be summarized in this section.

Some of the internet links may have been changed in this document. Guidance documents can be found in the guidance are of the Food section of www.

(Return to Toxicology Template Introduction)

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Template For Subchronic Toxicity Study in Rodents

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Template For Subchronic Toxicity Study in Rodents

Introduction to the Template For Subchronic Toxicity Study in Rodents

Table Of Contents

Subchronic Toxicity Study in Rodents Template

I. Identification of Study1

A. Study File Location: B. Study Title/Report Number: C. Name and Address of Testing Facility: D. Date of Study Report: E. Dates Study Conducted: F. Study Objective: G. Comments:

II. Good Laboratory Practice2

A. Good Laboratory Practice (GLP) Compliance? B. Quality Assurance (QA) Statement? C. Availability and Location of Original Data/Specimens/Test Substance:

III. Executive Summary

IV. Materials and Methods

A. Test Substance3

B. Test Substance As Administered5

C. Animal Diet,

D. Test Animals6

E. Experimental Design7

F. Body Weight And Feed Intake

G. Cage-Side Observations8

H. Opthalmological Examination

I. Hematology9

measurement related to

J.Clinical Chemistry10

measurement related to

K. Urinalysis11

L. Other Tests12

M. Necropsy (Interim Sacrifice)13

N. Necropsy (Terminal)

O. Gross Pathology Observations

P. Histopathology Observations

Q. Statistical Methods

V. Results

A. Dose Verification14

B. Feed Consumption Changes15

C. Intake Of Test Substance16

D. Feed Efficiency17

E. Body Weight Changes18

F. Cage-Side Observations19

G. Mortality20

H. Opthalmological Examination

I. Hematology21

J. Clinical Chemistry22

K. Urinalysis23

L. Other Tests24

M. Organ Weights25

N. Gross Pathology Changes Observed26

O. Histopathology Changes Observed27

P. Neurotoxicity28

VI. Evaluation and Comment on Study29

VII. Summary and Conclusions30

A. Brief Summary Of Major Findings From The Study

B. Relationship Between Dose And Incidence/Severity Of Lesions Or Abnormalities

C. Was There A Target Organ?

D. NOEL

VIII. References

End Notes

I. Identification of Study¹

A. Study File Location:
B. Study Title/Report Number:
C. Name and Address of Testing Facility:
D. Date of Study Report:
E. Dates Study Conducted:
F. Study Objective:
G. Comments:

II. Good Laboratory Practice²

A. Good Laboratory Practice (GLP) Compliance?
B. Quality Assurance (QA) Statement?
C. Availability and Location of Original Data/Specimens/Test Substance:

A. Test Substance³

B. Test Substance As Administered⁵

D. Test Animals⁶

E. Experimental Design⁷

G. Cage-Side Observations⁸

I. Hematology⁹

measurement
related to

J.Clinical Chemistry¹⁰

K. Urinalysis¹¹

L. Other Tests¹²

M. Necropsy (Interim Sacrifice)¹³

A. Dose Verification¹⁴

B. Feed Consumption Changes¹⁵

C. Intake Of Test Substance¹⁶

D. Feed Efficiency¹⁷

E. Body Weight Changes¹⁸

F. Cage-Side Observations¹⁹

G. Mortality²⁰

I. Hematology²¹

J. Clinical Chemistry²²

K. Urinalysis²³

L. Other Tests²⁴

M. Organ Weights²⁵

N. Gross Pathology Changes Observed²⁶

O. Histopathology Changes Observed²⁷

P. Neurotoxicity²⁸

VI. Evaluation and Comment on Study²⁹

VII. Summary and Conclusions³⁰