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Template For Subchronic Toxicity Study in Rodents

Introduction to the Template For Subchronic Toxicity Study in Rodents

March 2004

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 Sacrifice)
   14. Necropsy (Terminal)
   15. Gross Pathology Observations
   16. Histopathology Observations
   17. Statistical Methods
5. 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
6. Evaluation And Comment 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. Was There A Target Organ?
   4. NOEL
8. 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 

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

B.   Test Substance As Administered⁵ 

1. Batch/lot number:
2. Route:      
3. Vehicle used:
4. Tested adequately for concentration?
5. Tested for homogeneity?       
6. Tested for stability?  
7. Problems with storage?         

C.   Animal Diet,

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

D.   Test Animals⁶ 

1. Species/strain/substrain:
2. Sex:
3. Age range at initiation of study:      
4. Weight range at initiation of study:
5. Quarantine/acclimation?    
6. Physical examination times:
7. Number per cage:       
8. Environmental conditions:  
9. Comments:

E.   Experimental Design⁷ 

1. Targeted dose levels:

Table # [Heading]

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]

*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]

*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

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

I. Hematology⁹ 

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]

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

6. Comments:      

J.Clinical Chemistry¹⁰ 

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]

*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 

1. When were urine samples collected?             
2. Parameter examined:

Table # [Heading]

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

3. Comments :

L. Other Tests¹² 

1. Observations:
2. Comments:

M. Necropsy (Interim Sacrifice)¹³ 

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

Table # [Heading]

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

4. Comments:  

N. Necropsy (Terminal)

1. Organs/Tissues weighed:

Table # [Heading]

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

2. Comments:  

O. Gross Pathology Observations

1. Organs/Tissues Examined:
2. Comments:   

P. Histopathology Observations

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

Table # [Heading]

*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]

2. Comments:

V. Results

A.   Dose Verification¹⁴ 

1. Were doses verified?

Table # [Heading]

* Number of measurements (N)

1. Verified by:      
2. Comments:     

B.   Feed Consumption Changes¹⁵ 

1. Observations:
2. Comments:

C.   Intake Of Test Substance¹⁶

1. Observations:

Table # [Heading]

2. Comments:

D.   Feed Efficiency¹⁷ 

1. Was feed efficiency calculated?
2. Comments:  

E.   Body Weight Changes¹⁸ 

1. Observations:
2. Comments:

F.    Cage-Side Observations¹⁹ 

1. Observations:            
2. Comments:     

G.   Mortality²⁰ 

1. Observations:            
2. Comments:     

H. Opthalmological Examination

1. Observations:
2. Comments:

I.      Hematology²¹ 

1. Observations:

Table # [Heading]

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

2. Comments:

J.    Clinical Chemistry²² 

1. Observations:

Table # [Heading]

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

2. Comments:

K.   Urinalysis²³ 

1. Observations:

Table # [Heading]

2. Comments:

L.    Other Tests²⁴ 

1. Observations:
2. Comments:

M.  Organ Weights²⁵ 

1. Observations:

Table # [Heading]

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 

1. Observations:
2. Comments:

O.   Histopathology Changes Observed²⁷ 

1. Observations:

Table # [Heading)

(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]

+ 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

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

VIII. References

(Return to Toxicology Template Introduction)

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