|
CFSAN/Office of Food Additive Safety
April 2005
Date of Submission:
Title of Petition or Notification:
Name and Address of Petitioner or Notifier:
KEYWORDS: 4
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:
1. Feed
2. Water
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.)
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)
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:
2. Comments: (e.g., list frequency)
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:
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
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:
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)
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:
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:
Table # [Heading]
methods of statistical analysis | parameters tested |
---|---|
2. Comments:
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:
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 | ||||||||||||||||
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51 | ||||||||||||||||
52 |
X: Mean, SD: Standard Deviation
2. Comments:
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 | ||||||||||||||||
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51 | ||||||||||||||||
52 |
X: Mean, SD: Standard Deviation
2. Comments:
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 | ||||||||||||||||
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52 |
X: Mean, SD: Standard Deviation
2. Comments:
1. Observations:
2. Comments:
1. Observations:
2. Comments:
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:
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:
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:
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.
1. Observations:
2. Comments:
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:
1. Observations:
2. Comments:
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 |
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NON-NEOPLASTIC LESION |
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NON-NEOPLASTIC LESION |
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NEOPLASTIC LESIONS |
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NEOPLASTIC LESIONS |
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NEOPLASTIC LESIONS |
# See Section IV.O for the list of organs or tissues.
2. Comments:
1. Was
there a no observed effect level?
2. Comments:
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.