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Template for Chronic (1 Year) Dog Toxicity Study Template

Introduction to the Chronic (1 Year) Dog Toxicity Study Template

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Table of Contents

  1. Identification of Study
  2. Good Laboratory Practice
  3. Executive Summary
  4. 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, if any)
    14. NECROPSY (TERMINAL)
    15. GROSS PATHOLOGY OBSERVATIONS
    16. HISTOPATHOLOGY OBSERVATIONS
    17. STATISTICAL METHODS
  5. Results
    1. DOSE VERIFICATION
    2. FEED CONSUMPTION
    3. BODY WEIGHT
    4. INTAKE OF TEST SUBSTANCE
    5. FEED EFFICIENCY
    6. CAGE-SIDE OBSERVATIONS
    7. MORTALITY
    8. OPHTHALMOLOGICAL EXAMINATION
    9. HEMATOLOGY
    10. CLINICAL CHEMISTRY
    11. URINALYSIS
    12. NEUROTOXICITY (IF INDICATED)
    13. OTHER TESTS
    14. ORGAN WEIGHTS
    15. GROSS PATHOLOGY CHANGES OBSERVED
    16. HISTOPATHOLOGY CHANGES OBSERVED
  6. Evaluation and Comments on Study
  7. Summary and Conclusions
    1. BRIEF SUMMARY OF MAJOR FINDINGS FROM THE STUDY
    2. RELATIONSHIP BETWEEN DOSE AND INCIDENCE/SEVERITY OF LESIONS OR ABNORMALITIES
    3. IS THERE A TARGET ORGAN?
    4. NOEL
  8. References

Chronic (1 Year) Toxicity Study in Dogs [1]

Date of Submission:

Title of Petition or Notification:

Name and Address of Petitioner or Notifier:

I. Identification of Study [2] 

A. Study File Location:
B. Study Title/Report Number:
C. Name and Address of Testing Facility:
D. Study Author(s) and/or Study Director(s):
E. Date of Study Report:
F. Dates Study Conducted:
G. Study Objective:
H. Comments:

II. Good Laboratory Practice [3] 

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

III. Executive Summary

KEYWORDS: [4] 

IV. Materials and Methods [5] 

A. TEST substance [6] 

1. CAS name:
2. Other name(s):
3. CAS registry number:
4. Molecular structure: [http://www.chemfinder.com] [7]
5. Purity:
6. Impurities:
7. Stability:
8. Comments:

B. TEST substance AS ADMINISTERED [8] 

1. Batch/Lot Number(s): 
2. Route:
3. Vehicle used:
4. Tested adequately for concentration ? (See Part V-A for calculation)
5. Tested for homogeneity?
6. Tested for stability? [9] 

  • Before treatment period   Yes   No
  • After treatment period   Yes   No
  • After changes to stock   Yes   No
  • (If No, list dates tested for stability  )

7. Problems with storage?  

C. ANIMAL DIET

1. Feed

  1. Type:
  2. Name:
  3. Availability:
  4. Analysis for contaminants:
  5. Comments: (e.g., describe contaminants found)

2. Water

  1. Source:
  2. Availability:
  3. Analysis for contaminants:
  4. Comments: (e.g., describe contaminants found)

D. TEST ANIMALS

1. Species/strain:
2. Sex:
3. Age range at initiation of study:
4. Weight range at initiation of study:
5. Quarantine/acclimation?
6. Physical examination schedule:
7. Number per cage:
8. Environmental conditions (e.g. temperature, humidity, photoperiod, etc.)
9. Comments:

E. EXPERIMENTAL DESIGN [10] 

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: (e.g. dose selection rationale, dosing differences in males and females, etc.)

F. BODY WEIGHT AND FEED INTAKE [11] 

1. Parameter examined:

Table # [Heading]

examined

not examined

  Feed Intake*,
Water Intake*,
Body Weight*,
Body Weight Changes*

*These parameters are recommended in Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for chronic toxicity studies.

2. Comments: (e.g., list frequency; control vs. treatment group measurements)

G. CAGE-SIDE OBSERVATIONS [12] 

1. Parameter examined:

Table # [Heading]

examined

not examined

  Appearance*,
Abnormal Stool*,
Morbidity*,
Mortality*,
Neurotoxicity Screening (Specify parameters)**

*These parameters are recommended in Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for chronic toxicity studies.

** 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,
  • autonomic activity such as lacrimation, piloerection, pupil size change, unusual respiratory pattern,
  • Presence of clonic or tonic seizure,
  • Stereotypic behaviors such as excessive grooming and repetitive circling,
  • Bizarre behavior such as self-mutilation and walking backwards,
  • Gross tumor development.

2.   Comments: (e.g., list frequency)

H.  OPTHALMOLOGICAL EXAMINATION

1. Parameter examined: 2. Comments:

I.   HEMATOLOGY [13] 

1. Fasting duration prior to blood collection:
2. When during the study (dates, times) were the blood samples collected? .
3. How were the blood samples drawn?
4. Dose groups and number of animals tested: 5. 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 Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for chronic toxicity studies.

6. Comments:

J.   CLINICAL CHEMISTRY [14] 

1. Fasting duration prior to blood collection:
2. When in the study were the blood samples collected?
3. How were the blood samples drawn?
4. Dose groups and number of animals tested: 5. 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)

B) hepatobiliary (recommend at least 3 out of 5)
  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 Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for chronic toxicity studies.

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

6. Comments:

K. URINALYSIS [15] 

1. When and how were urine samples collected?
2. Dose groups and number of animals tested:
3. 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 Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for chronic toxicity studies.

4. Comments:

L.   OTHER TESTS

1. Observations: 2. Comments:

M. NECROPSY (INTERIM, if any)

1. Organs weighed:

Table # [Heading]

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

* These parameters are recommended in Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for chronic toxicity studies.

2. Comments: (e.g., note scheduled or unscheduled necropsy)
 

N. NECROPSY (TERMINAL)

1. Organs weighed:

Table # [Heading]

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

* These parameters are recommended in Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for chronic toxicity studies.

2.   Comments:

O. GROSS PATHOLOGY OBSERVATIONS

1. Organs/Tissues examined: 2. Comments:

P.   HISTOPATHOLOGY OBSERVATIONS

1. Organs were collected from which dose groups?
2. Organs were examined from which dose groups?
3. How were the organs/tissues prepared for histopathology observation?
4. Organs/tissues collected:  

Table # [Heading]

system examined  not examined
digestive
  Salivary Gland*, Esophagus*, Stomach*, Duodenum*, Jejunum*, Ileum*, Cecum*, Colon*, Rectum*, Gall Bladder*, 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*, Urinary Bladder*; As applicable: fallopian tubes*, Corpus Uteri*, Cervix Uteri*, Vagina*, Prostate*, Seminal Vesicle*, Testes*  
  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*
other
  Bone (Femur)*, Eyes*, Skeletal Muscle*, Skin*, Epididymis*

* These parameters are recommended in Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for chronic toxicity studies.

5. Comments:  

Q. STATISTICAL METHODS

1. Methods of statistical analysis:  

Table # [Heading]

methods of statistical analysis parameters tested
   
   
   
   

2. Comments:  

V. Results [16] 

A. DOSE VERIFICATION [17] 

1. Were doses verified?

We suggest using an Excel file to calculate the Means and Standard Deviations (SD). (Optional): A sample Excel file (calculation.xls) is provided.

Table # [Heading]

DOSE GROUPS TARGETED DAILY DOSE(mg/kg body-weight/day) targeted concentration in feed(ppm or mg/kg) concentrations found in feed(ppm or mg/kg)  standardDeviation  N* 
LOW          
MID          
HIGH          

* Number of measurements (N)

2. Verified by:
3. Comments:  

B. FEED CONSUMPTION [18] 

1. Observations: We suggest using an Excel file to calculate the Means and Standard Deviations (SD).

Table # [Heading]

  Weekly Summary of daily feed consumption (mean gram of feed consumed/day)
SEX males females
TARGETED DAILY DOSE(mg/kg body-weight/day) 0
CONTROL
      0 CONTROL      
NUMBER OF ANIMALS                
Week X SD X SD X SD X SD X SD X SD X SD X SD
0                                
1                                
2                                
3                                
4                                
5                                
6                                
7                                
8                                
9                                
10                                
11                                
12                                
13                                
14                                
15                                
16                                
17                                
18                                
19                                
20                                
21                                
22                                
23                                
24                                
25                                
26                                
27                                
28                                
29                                
30                                
31                                
32                                
33                                
34                                
35                                
36                                
37                                
38                                
39                                
40                                
41                                
42                                
43                                
44                                
45                                
46                                
47                                
48                                
49                                
50                                
51                                
52                                

X: Mean, SD: Standard Deviation

2. Comments:  

C. BODY WEIGHT [19] 

1. Observations: We suggest using an Excel file to calculate the Means and Standard Deviations (SD).

Table # [Heading]

  Weekly Summary of body weights (mean kg body weight/day)
SEX males females
TARGETED DAILY DOSE(mg/kg body-weight/day) 0
CONTROL
      0 CONTROL      
NUMBER OF ANIMALS                
Week X SD X SD X SD X SD X SD X SD X SD X SD
0                                
1                                
2                                
3                                
4                                
5                                
6                                
7                                
8                                
9                                
10                                
11                                
12                                
13                                
14                                
15                                
16                                
17                                
18                                
19                                
20                                
21                                
22                                
23                                
24                                
25                                
26                                
27                                
28                                
29                                
30                                
31                                
32                                
33                                
34                                
35                                
36                                
37                                
38                                
39                                
40                                
41                                
42                                
43                                
44                                
45                                
46                                
47                                
48                                
49                                
50                                
51                                
52                                

X: Mean, SD: Standard Deviation

2. Comments:  

D. INTAKE OF TEST SUBSTANCE [20] 

1. Observations: We suggest using an Excel file to calculate the Means and Standard Deviations (SD).

Table # [Heading]

  Weekly Summary of daily intake of test material (mg/kg body-weight/day)
SEX males females
TARGETED DAILY DOSE(mg/kg body-weight/day) 0
CONTROL
      0 CONTROL      
NUMBER OF ANIMALS                
Week X SD X SD X SD X SD X SD X SD X SD X SD
0                                
1                                
2                                
3                                
4                                
5                                
6                                
7                                
8                                
9                                
10                                
11                                
12                                
13                                
14                                
15                                
16                                
17                                
18                                
19                                
20                                
21                                
22                                
23                                
24                                
25                                
26                                
27                                
28                                
29                                
30                                
31                                
32                                
33                                
34                                
35                                
36                                
37                                
38                                
39                                
40                                
41                                
42                                
43                                
44                                
45                                
46                                
47                                
48                                
49                                
50                                
51                                
52                                

X: Mean, SD: Standard Deviation

2. Comments:  

E. FEED EFFICIENCY [21] 

1. Was feed efficiency calculated?
2. Comments: (e.g., groups, time periods) 

 F. CAGE-SIDE OBSERVATIONS [22] 

1. Appearance:
2. Abnormal Stool:
3. Morbidit:
4. Signs of Neurotoxicity:
5. Comments:  

G. MORTALITY [23] 

1. Observations:
2. Comments:

H.  OPHTHALMOLOGICAL EXAMINATION

1. Observations:
2. Comments:

I.   HEMATOLOGY [24] 

1. Observations: (n.b.; include dates and times of blood sampling and alter table as necessary)  

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)
10 [12]/L
               
white blood cells                
Basophils
                 
Eosinophils
                 
Lymphocytes
10 [9]/L                
Macrophage/Monocytes
                 
Neutrophils
10 [9]/L                
Total Leukocytes (WBC)
10 [9]/L                
clotting potential                
Activated Partial-Thromboplastin Time
                 
Clotting Time
                 
Platelet Count
10 [9]/L                
Prothrombin Time
                 
others                
Bone marrow cytology
                 
Reticulocyte counts
10 [12]/L                
                     

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

2. Comments:  

J.   CLINICAL CHEMISTRY [25] 

1. Observations: (n.b.; include dates and times of clinical chemistry sampling and alter table as necessary)

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 Amino-transferase (ALT or SGPT)
U/L                
Aspartate Amino-transferase (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. URINALYSIS [26] 

1. Observations: (n.b.; include dates and times of urine sampling and alter table as necessary) 

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.   NEUROTOXICITY (IF INDICATED) [27] 

1. Observations: (n.b.; include dates and times of neurotox screening and alter table as necessary)

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, data at the end of dosing period can be shown; however, if there were additional noteworthy findings at earlier time points, 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.O.

M. OTHER TESTS [28]

1. Observations:
2. Comments:  

N. ORGAN WEIGHTS [29] 

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:  

O. GROSS PATHOLOGY CHANGES OBSERVED [30] 

1. Observations:
2. Comments:  

P.   HISTOPATHOLOGY CHANGES OBSERVED [31] 

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
               
                 
NEUROLOGIC SYSTEM [32]                 
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
               

[# ]See Section IV.O for the list of organs or tissues.

2. Comments:  

VI. Evaluation and Comment on Study [33] 

VII. Summary and Conclusions [34] 

A. BRIEF SUMMARY OF MAJOR FINDINGS FROM THE STUDY

B. RELATIONSHIP BETWEEN DOSE AND INCIDENCE/SEVERITY OF LESIONS OR ABNORMALITIES

C. IS THERE A TARGET ORGAN?

D. NOEL

1. Was there a no observed effect level?
2. Comments:  

VIII. References


End Notes

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

[1]This Template is set up for submitting data from typical chronic dog studies. The sections are adjustable; if you find you need more space for a larger group of animals, you can add them to the section. If you have a smaller group of animals, you can delete the unneeded sections. The same applies to sections on feed mixtures and data for levels of test substances in feed. 

[2]Make note of: Study location (Volume, pages), Study title/Report #, Testing facility, publication dates and comments, if needed. 

[3]Indicate Yes or No for questions A and B. However, you may want to elaborate on the type of GLP compliance (USFDA, OECD, etc.) or make other notations 

[4]Please include keywords that may be helpful for indexing and accessing study reports from electronic archives. 

[5]Chronic studies often include treatment groups that will be terminated before completion of the study. Intermediate or interim sampling protocols should be included and noted. Scheduled or unscheduled necropsies should be clearly stated. 

[6]Description of the test substance should be given, including purity, any possible contaminants or impurities, any properties of the test substance that could affect its integrity. Are there factors that could affect the actual administered dose, as opposed to the intended dose? 

[7]After 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, the reviewer is free to use other methods of depicting the molecular structure. 

[8]Indicate how the test substance was given and whether any vehicle was used to dissolve or 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 and whether stability tests were 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? Note anything that was not normal or routine. 

[9]Information about methods used for testing stability. A brief description may be helpful to clarify how often stability of test articles was tested (e.g., was stability tested for each dilution made from the stock solution). 

[10]Provide 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. For major changes, it may be easiest to create a new table and paste it into the template (e.g. if doses differ in male and female treatments). 

[11]Indicate the measurements 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. 

[12]Indicate 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. 

[13]Drag and drop to indicate the parameters that were examined. Use comments to indicate other important information. 

[14]Drag and drop to indicate parameters that were examined. Use comments to indicate other important information. 

[15]Note when urines were collected for testing, the groups that were tested, and drag and drop the parameters that were tested. Make comments on anything significant. 

[16]Intermediate or interim data points should be included and noted. Scheduled or unscheduled necropsies should be clearly noted. Footnotes may be useful in tables to describe any changes in sample size that may be due to planned or unplanned deviation in animal number. Tables can be expanded or modified to include scheduled interim data collection. 

[17]Note here whether there was a check or verification of the doses being administered (by what analytical methodology and in which laboratory). If the test substance was mixed in the feed, provide a statement in the study report verifying, for example, that a 100 ppm feed mixture was analyzed to contain 100 E 5 ppm, or 100 E 10 ppm of the test substance? Was this done more than once? Were there adequate data to permit the calculation of the actual dose administered?

We suggest using an Excel file to calculate the Means and Standard Deviations (SD). (Optional): Download the Excel file named 'calculation.xls' to your computer. This Excel file contains four sheets named: Dose verification, Body Wt, Feed Consumption, and Intake of test substance. Each sheet can be accessed by clicking the name tab that appears on the lower left-hand side of the Excel file. 

[18]Note any statistically or biologically significant feed consumption changes. You may also want to note feed consumption changes that were not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend. You may wish to insert graphs or use a table as provided in this section or delete it if not needed. To use the optional Excel file (calculation.xls) click the 'Feed Consumption' tab on the lower left-hand side of the file) to calculate the Means and Standard Deviations (SD). 

[19]Note any statistically or biologically significant body weight changes. You may also want to note body weight changes that were not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend. You may wish to insert additional graphs or tables (e.g. body weight change per unit time), and/or use a table as provided in this section or delete it if not needed. To use the optional Excel file, (calculation.xls) click the 'Body Weight' tab on the lower left-hand side of the file) to calculate the Means and Standard Deviations (SD). 

[20]What was the level of intake of feed and the level of test substance in the feed was, what was the dose actually being delivered to the animals? You may wish to use a table as provided in this section or delete it if not needed. To use the optional Excel file (calculation.xls), click the 'Intake of Test Substance' tab on the lower left-hand side of the file to calculate the Means and Standard Deviations (SD). 

[21]Note in this section if 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 or per animal. 

[22]List significant, dose-related abnormal cage-side observations reported. Also, use a Table in Section V. L. to note any significant, dose-related abnormal neurotoxicological observations (see Section IV. G for a list of neurotox parameters). 

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

[24]Note findings that were statistically or biologically treatment-related. You may also want to 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. 

[25]Note findings that were statistically or biologically treatment-related. You may also want to 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. 

[26]Note findings that were statistically or biologically treatment-related. You may also want to 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. 

[27] If indicated, list treatment-related findings in the nervous system that were noted under results sections V. F: Abnormal cage-side observations, V. O: Gross pathological changes, and V.P: Histopathological changes. Provide a statement whether or not the test substance presents a potential neurotoxicity hazard. If no neurotoxicity is indicated, this section may be omitted or deleted. 

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

[29]Note findings that were statistically or biologically treatment-related. You may also want to 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. 

[30]Note findings that were statistically or biologically treatment-related. You may also want to 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, use a Table at the next histopathology section to note any findings. 

[31]See section IV.O for the list of organs or tissues.

This table should serve as a summary of the comprehensive histopathology report. Footnotes (or addenda) can be added to describe critical findings or individual observations that should be noted. Complex histopathology findings may not be transferable to this summary table.

Note findings that were statistically or biologically treatment-related. You may also want to note changes that were not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend. Note treatment-related findings in the nervous system in this section, if not already noted in Section V. L. The type of lesion should be noted. The comment section is available to explain data findings, if needed.

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. 

[32]If this information has already been entered in section V.L., delete the relevant rows in this table to prevent duplication of neurologic system entries. 

[33]Give your comments on the study: what was done well; what the problems were; did the study accomplish what it was supposed to do? 

[34]Summarize 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.

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