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Template for Chronic (1 Year) Dog Toxicity Study Template

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

Return to Toxicology Template Introduction


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 Dogs1

Date of Submission:

Title of Petition or Notification:

Name and Address of Petitioner or Notifier:

I. Identification of Study2 

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 Practice3 

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 Methods5 

A.  TEST substance6 

1.    CAS name:
2.    Other name(s):
3.    CAS registry number:
4.    Molecular structure: http://www.chemfinder.com7 /
 

 

5.    Purity:
6.    Impurities:
7.    Stability:
8.    Comments:
 

B.  TEST substance AS ADMINISTERED8 

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 DESIGN10 

1.    Targeted dose levels:

 

Table # [Heading]

 

test groupconc. in diet(ppm or mg/kg)dose to animals(mg/kg body-weight/day)number of malesnumber 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 INTAKE11 

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 OBSERVATIONS12 

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.      HEMATOLOGY13 

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 toexaminednot 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 CHEMISTRY14 

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 toexaminednot 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.  URINALYSIS15 

1.    When and how were urine samples collected?
2.    Dose groups and number of animals tested:
3.    Parameter examined:
 

 

Table # [Heading]

 

examinednot 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]

 

examinednot 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]

 

examinednot 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]

 

systemexamined 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 analysisparameters tested
  
  
  
  

 

2.    Comments:
 

 

V. Results16 

A.  DOSE VERIFICATION17 

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 GROUPSTARGETED 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 CONSUMPTION18 

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)
SEXmalesfemales
TARGETED DAILY DOSE(mg/kg body-weight/day)0
CONTROL
   0 CONTROL   
NUMBER OF ANIMALS        
WeekXSDXSDXSDXSDXSDXSDXSDXSD
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 WEIGHT19 

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)
SEXmalesfemales
TARGETED DAILY DOSE(mg/kg body-weight/day)0
CONTROL
   0 CONTROL   
NUMBER OF ANIMALS        
WeekXSDXSDXSDXSDXSDXSDXSDXSD
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 SUBSTANCE20 

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)
SEXmalesfemales
TARGETED DAILY DOSE(mg/kg body-weight/day)0
CONTROL
   0 CONTROL   
NUMBER OF ANIMALS        
WeekXSDXSDXSDXSDXSDXSDXSDXSD
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 EFFICIENCY21 

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

 

 F.   CAGE-SIDE OBSERVATIONS22 

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

 

G.  MORTALITY23 

1.    Observations:
2.     Comments:

 

H.  OPHTHALMOLOGICAL EXAMINATION

1.    Observations:
2.     Comments:

 

I.      HEMATOLOGY24 

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)
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 CHEMISTRY25 

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.  URINALYSIS26 

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        
Glucosemmol/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 TESTS28

1.    Observations:
2.    Comments:
 

 

N.  ORGAN WEIGHTS29 

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 Weighta
%        
 EPIDIDYMIDES     
Absolute Weight a
gram    
Per Body Weight a
%    
Per Brain Weighta
%    
 HEART        
Absolute Weight a
gram        
Per Body Weight a
%        
Per Brain Weighta
%        
 KIDNEYS        
Absolute Weight a
gram        
Per Body Weight a
%        
Per Brain Weighta
%        
 LIVER        
Absolute Weight a
gram        
Per Body Weight a
%        
Per Brain Weighta
%        
 SPLEEN        
Absolute Weight a
gram        
Per Body Weight a
%        
Per Brain Weighta
%        
 TESTES     
Absolute Weight a
gram    
Per Body Weight a
%    
Per Brain Weighta
%    
 THYROID and PARATHYROID        
Absolute Weight a
gram        
Per Body Weight a
%        
Per Brain Weighta
%        
 THYMUS        
Absolute Weight a
gram        
Per Body Weight a
%        
Per Brain Weighta
%        
 OVARIES     
Absolute Weight a
gram    
Per Body Weight a
%    
Per Brain Weighta
%    
 UTERUS     
Absolute Weight a
gram    
Per Body Weight a
%    
Per Brain Weighta
%    

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 OBSERVED30 

1.    Observations:
2.    Comments:
 

 

P.    HISTOPATHOLOGY CHANGES OBSERVED31 

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 Study33 

 

 

 

 

 

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.

 

1This 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.

 

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

 

 3Indicate 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

 

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

 

 5Chronic 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.

 

 6Description 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?

 

 7After 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.

 

 8Indicate 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.

 

 9Information 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).

 

 10Provide 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).

 

 11Indicate 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.

 

 12Indicate 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.

 

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

 

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

 

 15Note 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.

 

 16Intermediate 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.

 

 17Note 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.

 

 18Note 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).

 

 19Note 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).

 

 20What 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).

 

 21Note 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.

 

 22List 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).

 

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

 

 24Note 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.

 

 25Note 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.

 

 26Note 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.

 

 29Note 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.

 

 30Note 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.

 

 31See 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.

 

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

 

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

 

 34Summarize 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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