Introduction to the 2-Generation Reproduction Toxicity Study Template
Toxicology Template Introduction
Table of Contents
- Identification of Study
- Good Laboratory Practice
- Executive Summary
- Materials and Methods
- TEST SUBSTANCE
- TEST SUBSTANCE AS ADMINISTERED
- ANIMAL DIET
- TEST ANIMALS
- EXPERIMENTAL DESIGN
- MATING PROCEDURES
- CULLING PROCEDURES
- PARENTAL BODY WEIGHT AND FEED/WATER INTAKE
- PARENTAL CAGE-SIDE OBSERVATIONS
- PARENTAL REPRODUCTIVE PARAMETERS
- PARENTAL ORGAN WEIGHTS
- PARENTAL GROSS PATHOLOGY OBSERVATIONS
- PARENTAL HISTOPATHOLOGY OBSERVATIONS
- OTHER PARENTAL TESTS
- OFFSPRING OBSERVATIONS/BODY WEIGHT
- OFFSPRING DEVELOPMENTAL ENDPOINTS AND NEUROTOXICITY SCREENING - OPTIONAL
- OFFSPRING IMMUNOTOXICITY - OPTIONAL
- OFFSPRING ORGAN WEIGHTS
- OFFSPRING GROSS PATHOLOGY OBSERVATIONS
- OFFSPRING HISTOPATHOLOGY OBSERVATIONS
- OTHER OFFSPRING TESTS
- STATISTICAL METHODS
- Results
- DOSE VERIFICATION
- PARENTAL FEED/WATER CONSUMPTION CHANGES
- PARENTAL INTAKE OF TEST MATERIAL
- PARENTAL FEED EFFICIENCY
- PARENTAL BODY WEIGHT CHANGES
- PARENTAL ABNORMAL CAGE-SIDE OBSERVATIONS
- PARENTAL MORTALITY
- MATING, FERTILITY, AND REPRODUCTION
- PARENTAL ORGAN WEIGHTS
- PARENTAL GROSS PATHOLOGY CHANGES OBSERVED
- PARENTAL HISTOPATHOLOGY CHANGES OBSERVED
- OTHER PARENTAL TESTS
- OFFSPRING BODY WEIGHT CHANGES
- OFFSPRING OBSERVATIONS
- OFFSRPING MORTALITY
- SEXUAL MATURATION
- ANOGENITAL DISTANCE
- OFFSPRING DEVELOPMENTAL ENDPOINTS AND NEUROTOXICITY - OPTIONAL
- OFFSPRING IMMUNOTOXICITY - OPTIONAL
- OFFSPRING ORGAN WEIGHTS
- OFFSPRING GROSS PATHOLOGY CHANGES OBSERVED
- OFFSPRING HISTOPATHOLOGY CHANGES OBSERVED
- OTHER OFFSPRING TESTS
- Evaluation and Comments on Study
- Summary and Conclusions
- BRIEF SUMMARY OF MAJOR FINDINGS FROM THE STUDY
- RELATIONSHIP BETWEEN DOSE AND INCIDENCE/SEVERITY OF LESIONS OR ABNORMALITIES
- NOEL
- References
Two-Generation Reproduction Toxicity Study [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. Study Author:
D. Name and Address of Testing Facility:
E. Study Initiation Date [3]:
F. Study Completion Date [4]:
G. Study Objective:
H. Comments:
II. Good Laboratory Practice [5]
A. Good Laboratory Practice (GLP) Compliance Statement? [6]
B. Quality Assurance (QA) Statement? [7]
C. Availability and Location of Original Data/Specimens/Test Substance:
D. Describe any changes to the protocol that would affect the quality or integrity of the study:
E. Comments:
III. Executive Summary
IV. Materials and Methods
A. TEST SUBSTANCE [8]
1. CAS name:
2. Other name(s):
3. CAS number:
4. Molecular structure: [9]
5. Purity:
6. Impurities:
7. Stability:
8. Comments:
B. TEST SUBSTANCE AS ADMINISTERED [10]
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 [11]
1. Feed
- Type:
- Name:
- Availability:
- Analysis for contaminants:
- Comments:
2. Water
- Source:
- Availability:
- Analysis for contaminants:
- Comments:
D. TEST ANIMALS [12]
1. Species/strain/substrain:
2. Sex:
3. Age range at initiation of study:
4. Age range at mating:
5. Weight range at initiation of study:
6. Weight range at mating:
7. Quarantine/acclimation?
8. Physical examination times:
9. Number per cage:
10. Environmental conditions:
- Temperature:
- Humidity:
- Air changes:
- Photoperiod:
- Bedding:
11. Comments:
E. EXPERIMENTAL DESIGN [13]
1. Targeted dose levels:
2. Dose Selection Rationale:
3. Dosage Preparation:
Table # [Heading]
| test group- | conc. in diet (ppm or mg/kg) |
dose to animals* (mg/kg body-weight/day) |
number assigned per group | ||
|---|---|---|---|---|---|
| f0 males | f0 females | f0 males | f0 females | ||
| Control | |||||
| Low | |||||
| Mid | |||||
| High | |||||
Table # [Heading]
| test group | conc. in diet (ppm or mg/kg) |
dose to animals* (mg/kg body-weight/day) |
number assigned per group | ||
|---|---|---|---|---|---|
| f1 males | f1 females | f1 males | f1 females | ||
| Control | |||||
| Low | |||||
| Mid | |||||
| High | |||||
4. Total number of parental animals:
5. Duration of study (including recovery period, if any):
6. Length of exposure to test substance:
7. Were animals assigned to test and control groups in a stratified random manner to minimize intergroup weight differences?
8. Comments:
F. MATING PROCEDURES [14]
1. Description:
2. Comments:
G. CULLING PROCEDURES [15]
1. Description:
2. Comments:
H. PARENTAL BODY WEIGHT AND FEED/WATER INTAKE [16]
1. Parameters examined (in F0 and F1 animals):
Table # [Heading]
| examined | parameters* | |
|---|---|---|
| f0 parents | f1 parents | |
| Body Weight | ||
| Body Weight Changes | ||
| Feed Intake | ||
| Feed Spillage | ||
| Water Intake | ||
2. Comments: (e.g., list frequency)
I. PARENTAL CAGE-SIDE OBSERVATIONS [17]
1. Parameters examined (in F0 and F1 animals):
Table # [Heading]
| examined | parameters* | |
|---|---|---|
| f0 parents | f1 parents | |
| Appearance | ||
| Abnormal Stool | ||
| Deficiencies in Care** | ||
| Morbidity | ||
| Mortality | ||
| Neurotoxicity Screening (specify parameters)*** | ||
*These parameters are recommended in Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for 2-generation reproduction toxicity studies.
**Deficiencies in care include the following: inadequate construction or cleaning of the nest, pups left scattered and cold, physical abuse of pups, or inadequate lactation or feeding.
***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:
J. PARENTAL REPRODUCTIVE PARAMETERS [18]
1. Reproductive parameters examined (in F0 and F1 animals):
Table # [Heading]
| examined | parameters* | |
|---|---|---|
| f0 parents | f1 parents | |
| Estrous Cycling | ||
| Female Fertility Index | ||
| Gestation Index | ||
| Gestation Length | ||
| Live-born Index | ||
| Number of Primordial Follicles | ||
| Number of Growing Follicles | ||
| Number of Large Corpora Lutea of Lactation from the Post-Lactation Ovary | ||
| Number (Total and Per Liter) of Stillbirths at Day 0 | ||
| Number (Total and Per Liter) of Live Births at Day 0 | ||
| Number of Implantation Sites | ||
| Number of Resorptions (Total, Early, and Late) | ||
| Sperm Count | ||
| Sperm Motility | ||
| Sperm Morphology | ||
* These parameters are recommended in Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for 2-generation reproduction toxicity studies.
2. Indices Formulas:
3. Methods used for Sperm Analysis:
4. Comments:
K. PARENTAL ORGAN WEIGHTS [19]
1. Organs/Tissues weighed (in F0 and F1 animals):
Table # [Heading]
| examined | parameters* | |
|---|---|---|
| f0 parents | f1 parents | |
| Adrenals | ||
| Brain | ||
| Epididymides (single and total weight) | ||
| Kidneys | ||
| Known Target Organs | ||
| Liver | ||
| Ovaries | ||
| Pituitary Gland | ||
| Prostate (ventral and/or dorsal and/or dorsolateral) | ||
| Seminal Vesicles (with coagulating glands) | ||
| Spleen | ||
| Testes (both) | ||
| Thymus | ||
| Uterus | ||
* These parameters are recommended in Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for 2-generation reproduction toxicity studies.
2. Comments:
L. PARENTAL GROSS PATHOLOGY OBSERVATIONS
f0 animals
1. Organs/Tissues Examined:
2. Comments:
f1 animals
1. Organs/Tissues Examined:
2. Comments:
M. PARENTAL HISTOPATHOLOGY OBSERVATIONS [20]
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 (in F0 and F1 animals):
Table # [Heading]
| SYSTEM | examined in f0 parents* |
not examined in f0 parents* |
examined in f1 parents* |
not examined in f1 parents* |
|---|---|---|---|---|
|
digestive
|
Liver, Stomach | Liver, Stomach | ||
|
reticulo- endothelial/hematopoietic
|
Bone Marrow, Lymph Nodes, Peyer's Patch, Spleen, Thymus | Bone Marrow, Lymph Nodes, Peyer's Patch, Spleen, Thymus | ||
|
urogenital
|
Epididymis, Kidneys, Ovaries, Primordial Follicles, Growing Follicles, and Large Corpora Lutea of Lactation from the Post-Lactation Ovary, Prostate, Seminal Vesicle with Coagulating Gland (if present), Testes, Uterus (with oviducts), Vagina | Epididymis, Kidneys, Ovaries, Primordial Follicles, Growing Follicles, and Large Corpora Lutea of Lactation from the Post-Lactation Ovary, Prostate, Seminal Vesicle with Coagulating Gland (if present), Testes, Uterus (with oviducts), Vagina | ||
|
neurologic
|
Brain (at least 3 different levels), Peripheral Nerve Tissue, Spinal Cord (at least 2 different locations) | Brain (at least 3 different levels), Peripheral Nerve Tissue, Spinal Cord (at least 2 different locations) | ||
|
glandular
|
Adrenals, Pituitary Gland, Thymus | Adrenals, Pituitary Gland, Thymus | ||
|
other
|
Target Organs | Target Organs |
* These parameters are recommended in Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for 2-generation reproduction toxicity studies.
5. Comments:
N. OTHER PARENTAL TESTS [21]
1. Observations:
2. Comments:
O. OFFSPRING OBSERVATIONS/BODY WEIGHT [22]
1. Parameters examined (in F1 and F2 offspring):[23]
Table # [Heading]
| observations | examined in f1 offspring* |
not examined in f1 offspring* |
examined in f2 offspring* |
not examined in f2 offspring* |
|---|---|---|---|---|
|
cage-side
|
Appearance Gross Anomalies Morbidity Mortality |
Appearance Gross Anomalies Morbidity Mortality |
||
|
other
|
Litter Size (Total; Day 0, 4, 7, 14, 21) Litter Weight (Day 0, 4, 7, 14, 21) Pup Body Weight and Sex (Day 0, 4, 7, 14, 21) Sex Ratio (Day 0, 4, 7, 14, 21) Viability Index (Day 0-4, 4-7, 7-14, 14-21) Weaning Index |
Litter Size (Total; Day 0, 4, 7, 14, 21) Litter Weight (Day 0, 4, 7, 14, 21) Pup Body Weight and Sex (Day 0, 4, 7, 14, 21) Sex Ratio (Day 0, 4, 7, 14, 21) Viability Index (Day 0-4, 4-7, 7-14, 14-21) Weaning Index |
*These parameters are recommended in Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for 2-generation reproduction toxicity studies.
2. Offspring Indices:
3. Sexual Maturation (in F1 offspring only):
4. Anogenital Distance (in F2 offspring only)[24] :
5. Comments: (e.g., list frequency)
P. OFFSPRING DEVELOPMENTAL ENDPOINTS AND NEUROTOXICITY SCREENING - OPTIONAL [25]
1. Parameters examined (in F1 and F2 offspring):
Table # [Heading]
| observations | examined in f1 offspring |
not examined in f1 offspring |
examined in f2 offspring |
not examined in f2 offspring |
|---|---|---|---|---|
|
developmental endpoints
|
Detachment of Pinna Eye OpeningTooth Eruption |
Detachment of Pinna Eye OpeningTooth Eruption |
||
|
gross neurotoxicity screening
|
Pupil Reflex Startle Reflex Surface and/or Mid-air ReflexVibrissae Placing |
Pupil Reflex Startle Reflex Surface and/or Mid-air ReflexVibrissae Placing |
2. Comments: (e.g., list frequency)
Q. OFFSPRING IMMUNOTOXICITY - OPTIONAL [26]
1. Parameters examined:
Table # [Heading]
| measurement related to | examined in f1 offspring |
not examined in f1 offspring |
examined inf2 offspring | not examined inf2 offspring |
|---|---|---|---|---|
|
white blood cells
|
Basophils Eosinophils Lymphocytes Macrophage/Monocytes Neutrophils Total Leukocytes (WBC) |
Basophils Eosinophils Lymphocytes Macrophage/Monocytes Neutrophils Total Leukocytes (WBC) |
||
|
organs/tissues(weight changes)
|
Lymph Nodes Peyer's Patch Spleen Thymus |
Lymph Nodes Peyer's Patch Spleen Thymus |
||
|
others
|
Acute Phase Protein Albumin Albumin-to-Globulin Ratio Bone marrow cytology Electrophoretic Analysis of Serum Proteins Globulin Immunoglobulin G Immunostaining of Spleen and Lymph Nodes for B and T Cells Total Serum Protein |
Acute Phase Protein Albumin Albumin-to-Globulin Ratio Bone marrow cytology Electrophoretic Analysis of Serum Proteins Globulin Immunoglobulin G Immunostaining of Spleen and Lymph Nodes for B and T Cells Total Serum Protein |
2. Fasting duration prior to blood collection:
3. When in the study were the blood samples collected?
4. How were the blood samples drawn?
5. Comments:
R. OFFSPRING ORGAN WEIGHTS [27]
1. Organs/Tissues weighed:
Table # [Heading]
| examined | parameters* | |
|---|---|---|
| f1 offspring | f2 offspring | |
| Brain | ||
| Spleen | ||
| Thymus | ||
*These parameters are recommended in Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for 2-generation reproduction toxicity studies.
2. Comments:
S. OFFSPRING GROSS PATHOLOGY OBSERVATIONS
f1 offspring
1. Organs/Tissues Examined:
2. Comments:
f2 offspring
1. Organs/Tissues Examined:
2. Comments:
T. OFFSPRING HISTOPATHOLOGY OBSERVATIONS [28]
f1 offspring
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:
5. Comments:
f2 offspring
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:
5. Comments:
U. OTHER OFFSPRING TESTS [29]
1. Observations:
2. Comments:
V. STATISTICAL METHODS
1. Methods of statistical analysis:
Table # [Heading]
| methods of statistical analysis | parameters tested |
|---|---|
2. Comments:
V. Results
A. DOSE VERIFICATION [30]
1. Were doses verified?
Table # [Heading]
| dose group | targeted concentration (ppm or mg/kg) |
concentrations found in feed (ppm or mg/kg) |
standard deviation |
N* |
|---|---|---|---|---|
| low | ||||
| mid | ||||
| high |
* Number of measurements (N)
2. Verified by:
3. Comments:
B. PARENTAL FEED/WATER CONSUMPTION CHANGES [31]
f0 parents
1. Observations during Premating and Postmating (males):
2. Observations during Premating (female):
3. Observations during Gestation (female):
4. Observations during Lactation (female):
5. Comments:
f1 parents
1. Observations during Premating and Postmating (males):
2. Observations during Premating (female):
3. Observations during Gestation (female):
4. Observations during Lactation (female):
5. Comments:
C. PARENTAL INTAKE OF TEST MATERIAL [32]
1. Observations:
Table # [Heading]
| dose group | f0 males DAILY DOSE (mg/kg body-weight/day) |
f0 females daily dose (mg/kg body-weight/day) |
f1 males daily dose (mg/kg body-weight/day) |
f1 females daily dose (mg/kg body-weight/day) |
|---|---|---|---|---|
| control | 0 | 0 | 0 | 0 |
| low | ||||
| mid | ||||
| high |
2. Comments:
D. PARENTAL FEED EFFICIENCY [33]
f0 parents
1. Was feed efficiency calculated?
2. Comments:
f1 parents
1. Was feed efficiency calculated?
2. Comments:
E. PARENTAL BODY WEIGHT CHANGES [34]
f0 parents
1. Observations during Premating and Postmating (males):
2. Observations during Premating (female):
3. Observations during Gestation (female):
4. Observations during Lactation (female):
5. Comments:
f1 parents
1. Observations during Premating and Postmating (males):
2. Observations during Premating (female):
3. Observations during Gestation (female):
4. Observations during Lactation (female):
5. Comments:
F. PARENTAL ABNORMAL CAGE-SIDE OBSERVATIONS [35]
f0 parents
1. Observations:
2. Comments:
f1 parents
1. Observations:
2. Comments:
G. PARENTAL MORTALITY[36]
f0 parents
1. Observations:
2. Comments:
f1 parents
1. Observations:
2. Comments:
H. MATING, FERTILITY, AND REPRODUCTION
1. Observations:
Table # [Heading]
| GENERATION | F0 | F1 | ||||||
|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
||||||
| Number of Females Paired | ||||||||
| Number of Females Achieving Pregnancy | ||||||||
| Female Fertility Index (%) | ||||||||
| GENERATION | F0 | F1 | ||||||
|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
||||||
| # Died | ||||||||
| # Died Pregnant | ||||||||
| # Died Nonpregnant | ||||||||
| # Aborted | ||||||||
| # Premature Delivery | ||||||||
| GENERATION | F0 | F1 | ||||||
|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
||||||
| Total # Corpora Lutea (N) | ||||||||
| Corpora Lutea/Dam (MEAN S.D.) | ||||||||
| GENERATION | F0 | F1 | ||||||
|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
||||||
| Total # Implantations (N) | ||||||||
| Implantations/Dam (MEAN S.D.) |
||||||||
| GENERATION | F0 | F1 | ||||||
|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
||||||
| Number Stillborns - Total Per Liter (MEAN S.D.) |
||||||||
| Number Live-born - Total Per Liter (MEAN S.D.) |
||||||||
| Live-born Index (%) | ||||||||
(Specify methods of statistical analysis): * p<0.05, **=""><>
2. Sperm Evaluation:
Table # [Heading]
| GENERATION | F0 | F1 | ||||||
|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
||||||
|
% Motile Sperm (N MEAN S.D.)
|
||||||||
|
% Progressively Motile Sperm (N MEAN S.D.)
|
||||||||
|
% Abnormal Sperm (N MEAN S.D.)
|
||||||||
|
# Homogenization Resistant Spermatids per Testis (N MEAN S.D.)
|
||||||||
|
# Homogenization Resistant Spermatids per mg Testis (N MEAN S.D.)
|
||||||||
|
# Sperm per Cauda (N MEAN S.D.)
|
||||||||
|
# Sperm per mg Cauda (N MEAN S.D.)
|
||||||||
(Specify methods of statistical analysis): * p<0.05, **=""><>
2. Estrous Cycling Evaluation:
3. Comments:
I. PARENTAL ORGAN WEIGHTS [37]
1. Observations:
Table # [Heading]
| SEX | f0 males | f0 females | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0CONTROL | 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[b] | ||||||||||
| 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] | % | |||||||||
| PITUITARY GLAND | ||||||||||
| Absolute Weight[a] | gram | |||||||||
| Per Body Weight[a] | % | |||||||||
| Per Brain Weight[a] | % | |||||||||
| PROSTATE[b] | ||||||||||
| Absolute Weight[a] | gram | |||||||||
| Per Body Weight[a] | % | |||||||||
| Per Brain Weight[a] | % | |||||||||
| SEMINAL VESICLES WITH COAGULATING GLAND[b] | ||||||||||
| 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[b] | ||||||||||
| 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[b] | ||||||||||
| Absolute Weight[a] | gram | |||||||||
| Per Body Weight[a] | % | |||||||||
| Per Brain Weight[a] | % | |||||||||
| UTERUS[b] | ||||||||||
| Absolute Weight[a] | gram | |||||||||
| Per Body Weight[a] | % | |||||||||
| Per Brain Weight[a] | % | |||||||||
a: Group means at the end of terminal necropsy are shown.
b: Sexual organ weights should be recorded regardless of significant findings.
(Specify methods of statistical analysis): * p<0.05, **=""><>
Table # [Heading]
| SEX | f1 males | f1 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[b]
|
||||||||||
|
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]
|
% | |||||||||
|
PITUITARY GLAND
|
||||||||||
|
Absolute Weight[a]
|
gram | |||||||||
|
Per Body Weight[a]
|
% | |||||||||
|
Per Brain Weight[a]
|
% | |||||||||
|
PROSTATE[b]
|
||||||||||
|
Absolute Weight[a]
|
gram | |||||||||
|
Per Body Weight[a]
|
% | |||||||||
|
Per Brain Weight[a]
|
% | |||||||||
|
SEMINAL VESICLES WITH COAGULATING GLAND[b]
|
||||||||||
|
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[b]
|
||||||||||
|
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[b]
|
||||||||||
|
Absolute Weight[a]
|
gram | |||||||||
|
Per Body Weight[a]
|
% | |||||||||
|
Per Brain Weight[a]
|
% | |||||||||
|
UTERUS[b]
|
||||||||||
|
Absolute Weight[a]
|
gram | |||||||||
|
Per Body Weight[a]
|
% | |||||||||
|
Per Brain Weight[a]
|
% | |||||||||
a: Group means at the end of terminal necropsy are shown.
b: Sexual organ weights should be recorded regardless of significant findings.
(Specify methods of statistical analysis): * p<0.05, **=""><>
1. Comments:
J. PARENTAL GROSS PATHOLOGY CHANGES OBSERVED [38]
f0 parents
1. Observations:
2. Comments:
f1 parents
1. Observations:
2. Comments:
K. PARENTAL HISTOPATHOLOGY CHANGES OBSERVED [39]
1. Observations:
Table # [Heading]
| SEX | F0 MALES | F0 FEMALES | ||||||
|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
||||||
| number of animals | ||||||||
|
digestive system
|
||||||||
| name of organ/tissue[#] | ||||||||
|
gross pathology
|
||||||||
|
histopathology-number of animals w/non-neoplasticlesions
|
||||||||
|
lesion
|
||||||||
|
lesion
|
||||||||
|
number of animals w/
neoplastic lesions |
||||||||
|
lesion
|
||||||||
|
lesion
|
||||||||
|
reticuloendothelial/
hematopoietic system |
||||||||
|
name of organ/tissue[#]
|
||||||||
|
gross pathology
|
||||||||
|
histopathology-number of animals w/non-neoplasticlesions
|
||||||||
|
lesion
|
||||||||
|
lesion
|
||||||||
|
number of animals w/neoplastic lesions
|
||||||||
|
lesion
|
||||||||
|
lesion
|
||||||||
|
urogenital system
|
||||||||
|
name of organ/tissue[#]
|
||||||||
|
gross pathology
|
||||||||
|
histopathology-number of animals w/non-neoplasticlesions
|
||||||||
|
lesion
|
||||||||
|
lesion
|
||||||||
|
number of animals w/neoplastic lesions
|
||||||||
|
lesion
|
||||||||
|
lesion
|
||||||||
|
neurologic system
|
||||||||
|
name of organ/tissue#
|
||||||||
|
gross pathology
|
||||||||
|
histopathology-number of animals w/non-neoplasticlesions
|
||||||||
|
lesion
|
||||||||
|
lesion
|
||||||||
|
number of animals w/neoplastic lesions
|
||||||||
|
lesion
|
||||||||
|
lesion
|
||||||||
|
glandular system
|
||||||||
|
name of organ/tissue#
|
||||||||
|
gross pathology
|
||||||||
|
histopathology-number of animals w/non-neoplasticlesions
|
||||||||
|
lesion
|
||||||||
|
lesion
|
||||||||
|
number of animals w/neoplastic lesions
|
||||||||
|
lesion
|
||||||||
|
lesion
|
||||||||
|
other
|
||||||||
|
name of organ/tissue#
|
||||||||
|
gross pathology
|
||||||||
|
histopathology-number of animals w/non-neoplasticlesions
|
||||||||
|
lesion
|
||||||||
|
lesion
|
||||||||
|
number of animals w/neoplastic lesions
|
||||||||
|
lesion
|
||||||||
|
lesion
|
||||||||
(Specify methods of statistical analysis): * p<0.05, **=""><>
# Organs/tissues listed under section IV.M.
In general, data at end of dosing period can be shown; however, if there were additional noteworthy findings at earlier time points, these should be included. Note severity of lesions as needed.
Table # [Heading]
| SEX | F1 MALES | F1 FEMALES | ||||||
|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
||||||
| number of animals | ||||||||
| digestive system | ||||||||
| name of organ/tissue[#] | ||||||||
| gross pathology | ||||||||
| histopathology-number of animals w/non-neoplasticlesions | ||||||||
| lesion | ||||||||
| lesion | ||||||||
| number of animals w/neoplastic lesions | ||||||||
| lesion | ||||||||
| lesion | ||||||||
| reticuloendothelial/hematopoietic system | ||||||||
| name of organ/tissue[#] | ||||||||
| gross pathology | ||||||||
| histopathology-number of animals w/non-neoplasticlesions | ||||||||
| lesion | ||||||||
| lesion | ||||||||
| number of animals w/neoplastic lesions | ||||||||
| lesion | ||||||||
| lesion | ||||||||
| urogenital system | ||||||||
| name of organ/tissue[#] | ||||||||
| gross pathology | ||||||||
| histopathology-number of animals w/non-neoplasticlesions | ||||||||
| lesion | ||||||||
| lesion | ||||||||
| number of animals w/neoplastic lesions | ||||||||
| lesion | ||||||||
| lesion | ||||||||
| neurologic system | ||||||||
| name of organ/tissue# | ||||||||
| gross pathology | ||||||||
| histopathology-number of animals w/non-neoplasticlesions | ||||||||
| lesion | ||||||||
| lesion | ||||||||
| number of animals w/neoplastic lesions | ||||||||
| lesion | ||||||||
| lesion | ||||||||
| glandular system | ||||||||
| name of organ/tissue# | ||||||||
| gross pathology | ||||||||
| histopathology-number of animals w/non-neoplasticlesions | ||||||||
| lesion | ||||||||
| lesion | ||||||||
| number of animals w/neoplastic lesions | ||||||||
| lesion | ||||||||
| lesion | ||||||||
| other | ||||||||
| name of organ/tissue# | ||||||||
| gross pathology | ||||||||
| histopathology-number of animals w/non-neoplasticlesions | ||||||||
| lesion | ||||||||
| lesion | ||||||||
| number of animals w/neoplastic lesions | ||||||||
| lesion | ||||||||
| lesion | ||||||||
(Specify methods of statistical analysis): * p<0.05, **=""><>
# Organs/tissues listed under section IV.M.
In general, data at end of dosing period can be shown; however, if there were additional noteworthy findings at earlier time points, these should be included. Note severity of lesions as needed.
2. Comments:
L. OTHER PARENTAL TESTS [40]
1. Observations:
2. Comments:
M. OFFSPRING BODY WEIGHT CHANGES [41]
1. Observations:
Table # [Heading]
| GENERATION | F1 MALES | F1 FEMALES | |||||||
|---|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
|||||||
| pup weight (g) | |||||||||
|
Day 0
|
mean S.D. N |
||||||||
|
Day 4
|
mean S.D. N |
||||||||
|
Day 7
|
mean S.D. N |
||||||||
|
Day 14
|
mean S.D. N |
||||||||
|
Day 21
|
mean S.D. N |
||||||||
(Specify a method of statistical analysis): * p<0.05, **=""><>
Table # [Heading]
| GENERATION | F2 MALES | F2 FEMALES | |||||||
|---|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
|||||||
| pup weight (g) | |||||||||
|
Day 0
|
mean S.D. N |
||||||||
|
Day 4
|
mean S.D. N |
||||||||
|
Day 7
|
mean S.D. N |
||||||||
|
Day 14
|
mean S.D. N |
||||||||
|
Day 21
|
mean S.D. N |
||||||||
(Specify a method of statistical analysis): * p<0.05, **=""><>
2. Comments:
N. OFFSPRING OBSERVATIONS [42]
1. Observations:
Table # [Heading]
| GENERATION | F1 LITTER | F2 LITTER | |||||||
|---|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
|||||||
| litter size | |||||||||
| Number Born - TotalPer Litter | N MEAN S.D. |
||||||||
| Day 0 - TotalPer Litter | N MEAN S.D. |
||||||||
| Day 4 - TotalPer Litter | N MEAN S.D. |
||||||||
| Day 7 - TotalPer Litter | N MEAN S.D. |
||||||||
| Day 14 - TotalPer Litter | N MEAN S.D. |
||||||||
| Day 21 - TotalPer Litter | N MEAN S.D. |
||||||||
| litter weight (g) | |||||||||
| Day 0 | N MEAN S.D. |
||||||||
| Day 4 | N MEAN S.D. |
||||||||
| Day 7 | N MEAN S.D. |
||||||||
| Day 14 | N MEAN S.D. |
||||||||
| Day 21 | N MEAN S.D. |
||||||||
| viability Indices | |||||||||
| Day 0-4 | N MEAN S.D. |
||||||||
| Day 4-7 | N MEAN S.D. |
||||||||
| Day 7-14 | N MEAN S.D. |
||||||||
| Day 14-21 | N MEAN S.D. |
||||||||
| weaning Index | N MEAN S.D. |
||||||||
| Sex Ratio | |||||||||
| Day 1 | |||||||||
| Day 21 | |||||||||
(Specify a method of statistical analysis): * p<0.05, **=""><>
2. Comments:
O. OFFSPRING MORTALITY [43]
f1 offspring
1. Observations:
2. Comments:
f2 offspring
1. Observations:
2. Comments:
P. SEXUAL MATURATION
1. Observations (in F1 offspring only):
Table # [Heading]
| GENERATION | F1 MALES | F1 FEMALES | |||||||
|---|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
|||||||
| Age of Preputial separation | mean S.D. N |
||||||||
| Age of vaginal opening | mean S.D. N |
||||||||
(Specify a method of statistical analysis): * p<0.05, **=""><>
2. Comments:
Q. ANOGENITAL DISTANCE [44]
3. Observations (in F2 offspring only):
4. Comments:
R. OFFSPRING DEVELOPMENTAL ENDPOINTS AND NEUROTOXICITY - OPTIONAL [45]
f1 offspring
1. Developmental Endpoints:
- Detachment of Pinna:
- Eye Opening:
- Tooth Eruption:
2. Gross Neurotoxicity Observations:
- Pupil Reflex:
- Startle Reflex:
- Surface and/or Mid-air Reflex:
- Vibrissae Placing:
3. Comments:
f2 offspring
1. Developmental Endpoints:
- Detachment of Pinna:
- Eye Opening:
- Tooth Eruption:
2. Gross Neurotoxicity Observations:
- Pupil Reflex:
- Startle Reflex:
- Surface and/or Mid-air Reflex:
- Vibrissae Placing:
3. Comments:
S. OFFSPRING IMMUNOTOXICITY - OPTIONAL [46]
1. Observations:
Table # [Heading]
| SEX | f1 males | f1 females | |||||||
|---|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
|||||||
| NUMBER OF ANIMALS | |||||||||
| white blood cells | |||||||||
| Basophils | |||||||||
| Eosinophils | |||||||||
| Lymphocytes | 10[9]/L | ||||||||
| Macrophage/Monocytes | |||||||||
| Neutrophils | 10[9]/L | ||||||||
| Total Leukocytes (WBC) | 10[9]/L | ||||||||
| others | |||||||||
| Acute phase proteins | |||||||||
| Total Serum Protein | |||||||||
| Albumin | |||||||||
| Albumin-to-Globulin Ratio | |||||||||
| Bone marrow cytology | |||||||||
| Globulin | |||||||||
| Immunoglobulin G | |||||||||
(Specify a method of statistical analysis): * p<0.05, **=""><>
Table # [Heading]
| SEX | f2 males | f2 females | |||||||
|---|---|---|---|---|---|---|---|---|---|
| DAILY DOSE (mg/kg body-weight/day) |
0 CONTROL |
0 CONTROL |
|||||||
| NUMBER OF ANIMALS | |||||||||
| white blood cells | |||||||||
| Basophils | |||||||||
| Eosinophils | |||||||||
| Lymphocytes | 10[9]/L | ||||||||
| Macrophage/Monocytes | |||||||||
| Neutrophils | 10[9]/L | ||||||||
| Total Leukocytes (WBC) | 10[9]/L | ||||||||
| others | |||||||||
| Acute phase proteins | |||||||||
| Total Serum Protein | |||||||||
| Albumin | |||||||||
| Albumin-to-Globulin Ratio | |||||||||
| Bone marrow cytology | |||||||||
| Globulin | |||||||||
| Immunoglobulin G | |||||||||
(Specify a method of statistical analysis): * p<0.05, **=""><>
2. Noted Organ/Tissue Weight Changes:
- Lymph Nodes:
- Peyer's Patches:
- Spleen:
- Thymus:
3. Electrophoretic Analysis of Serum Proteins:
4. Immunostaining of spleen and lymph nodes for B and T cells:
T. OFFSPRING ORGAN WEIGHTS [47]
1. Observations:
Table # [Heading]
| SEX | f1 males | f1 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] | % | ||||||||
| SPLEEN | |||||||||
| 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] | % | ||||||||
a: Group means at the end of terminal necropsy are shown.
(Specify methods of statistical analysis): * p<0.05, **=""><>
Table # [Heading]
| SEX | f2 males | f2 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] | % | ||||||||
| SPLEEN | |||||||||
| 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] | % | ||||||||
a: Group means at the end of terminal necropsy are shown.
(Specify methods of statistical analysis): * p<0.05, **=""><>
2. Comments:
U. OFFSPRING GROSS PATHOLOGY CHANGES OBSERVED [48]
f1 offspring
1. Observations:
2. Comments:
f2 offspring
1. Observations:
2. Comments:
V. OFFSPRING HISTOPATHOLOGY CHANGES OBSERVED [49]
f1 offspring
1. Observations:
2. Comments:
f2 offspring
1. Observations:
2. Comments:
W. OTHER OFFSPRING TESTS [50]
1. Observations:
2. Comments:
VI. Evaluation and Comment on Study [51]
VII. Summary and Conclusions [52]
A. BRIEF SUMMARY OF MAJOR FINDINGS FROM THE STUDY
1. Parental Toxicity:
2. Offspring Toxicity:
B. RELATIONSHIP BETWEEN DOSE AND INCIDENCE/SEVERITY OF LESIONS OR ABNORMALITIES
C. NOEL
1. Was there a parental no observed effect level?
2. Was there an offspring no observed effect level?
3. Comments:
VIII. References
End Notes
[1]Please refer to the Introduction to the Template for general instructions before you begin using this form.
[2]Make note of: study file location (Volume, pages), study title/report #, testing facility name, publication dates of study, study objective, and comments, if needed. Indicate Yes or No for the rest of this section. However, you may want to elaborate on the type of GLP compliance (USFDA, OECD, etc.) or make other notations.
[3]Date protocol was signed by study director.
[4]Date the final report was signed by the study director.
[5]FDA Good Laboratory Practice (GLP) regulations became effective June 20, 1979 and include the requirement for a Quality Assurance Statement. FDA also recognizes EPA and OECD GLP standards as being equivalent to those of FDA.
[6]Is a signed and dated Good Laboratory Practice Compliance Statement included in the study report? Answer Yes or No. If yes, provide the location of the statement in the study report and identify the GLP standard (FDA, EPA or OECD)
[7]Is a signed Quality Assurance Statement, including dates of inspections, provided in the study report? Answer Yes or No. If yes, provide the location of the statement in the study report.
[8]Description of the test substance should be given, including purity, any possible contaminants or impurities, and any properties of the test substance that might have affected its integrity. Are there factors that might have affected the actual administered dose, as opposed to the intended dose?
[9]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, you are free to use other methods of depicting the molecular structure.
[10]Indicate how the test substance was given and whether any vehicle was used to dissolve/suspend the test substance (e.g., dissolved in corn oil and mixed into the feed). Also note if there was adequate testing for concentration and homogeneity (appropriate tests with replicates) and whether there were stability tests done. Was the strength of the test material checked over the period and under the conditions that the feed mix, test article in vehicle, etc., would be stored?
[11]Note anything that might have affected the study. Use the comments to indicate extremes or other factors that might have impacted the study.
[12]Note anything that might have affected the study. Use the comments to indicate extremes or other factors that might have impacted the study.
[13]Provide adequate details so the information can be used to help prepare a toxicology evaluation report. 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.
[14]Describe how animals were mated. Indicate when and how females were examined for pregnancy. Note if sibling mating was avoided.
[15]Standardization of the number of pups per litter is optional. If performed, describe how the litters were standardized (on what day, standardized to how many, if standardized in a random manner, etc.).
[16]Indicate the measurements or observations that were made by placing an 'X' in the 'Examined' side. Those parameters not examined will not contain an 'X' in the 'Examined' side. Use the comments to indicate when observations were made and any other notable fact.
[17]Indicate the measurements or observations that were made by placing an 'X' in the 'Examined' side. Those parameters not examined will not contain an 'X' in the 'Examined' side. Use the comments to indicate when observations were made and any other notable fact.
[18]Indicate the measurements or observations that were made by placing an 'X' in the 'Examined' side. Those parameters not examined will not contain an 'X' in the 'Examined' side. Use the comments to indicate when observations were made and any other notable fact.
[19]Indicate the measurements or observations that were made by placing an 'X' in the 'Examined' side. Those parameters not examined will not contain an 'X' in the 'Examined' side. Use the comments to indicate when observations were made and any other notable fact.
[20]To split a table (between 2 pages): Place the cursor in the table. From the 'Table' menu, choose 'Select Table' to highlight. From the 'Format' menu, select 'Paragraph' then the 'Line and Page Breaks' tab. Uncheck the box 'Keep with next' to split the table.
[21]When other tests are conducted, make note of the tests and any significant treatment-related effects.
[22]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.
[23]For litter weight, pup body weight and sex, sex ratio, and viability index, please list the days examined in parentheses, especially if different from those listed in the table below.
[24]Anogenital distance should be measured at day zero for all F2 pups that show treatment-related effects in F1 sex ratio or sexual maturation.
[25]This section is optional. 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.
[26]This section is optional. 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.
[27]Indicate the measurements or observations that were made by placing an 'X' in the 'Examined' side. Those parameters not examined will not contain an 'X' in the 'Examined' side. Use the comments to indicate when observations were made and any other notable fact.
[28]For F1 and F2 weanlings, histopathology examination of treatment-related abnormalities noted at macroscopic examination should be considered, if deemed appropriate and would contribute to the overall quality of the study data.
[29]When other tests are conducted, make note of the tests and any significant treatment-related effects.
[30]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, was the level of the test substance in the feed analyzed? Was this done more than once? Are there adequate data to permit the calculation of the actual dose that was administered?
[31]Note any statistically or biologically significant feed/water consumption changes. You may also want to note feed/water consumption changes that are not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend.
[32]Knowing what the intake of feed/water was and the level of test substance in the feed/water, what was the dose actually being delivered to the animals? This section would not be relevant for a gavage study.
[33]Note in this section if feed efficiency was determined; when in the study determinations were made; if any changes were observed; if feed efficiency was calculated for all groups or only selected groups; and if calculations were made per group, per cage, or per animal.
[34]Note any statistically or biologically significant body weight changes. You may also want to note body weight changes that are not statistically significant (e.g., at low or mid dose) but could indicate a treatment-related trend. You may wish to insert graphs or tables in this section.
[35]List significant, dose-related abnormal clinical observations reported. This may include neurotoxicity endpoints.
[36]For each animal with an unscheduled death, note the group, date of death, and any observations, including lesions observed at necropsy.
[37]Note findings that are statistically or biologically treatment-related. Also note the changes that are 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.
[38]Note findings that are statistically or biologically treatment-related. The type of lesion should be noted. The comment section is available to explain data findings, if needed.
[39]Note findings that are statistically or biologically treatment-related. The type of lesion should be noted. The comment section is available to explain data findings, if needed.
[40]When other tests are conducted, make note of the tests and any significant treatment-related effects.
[41]Note findings that are statistically or biologically treatment-related. Also note the changes that are 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. If the study measures pup weight on days that are different than those listed, please correct the information so it corresponds with the study.
[42]List significant, dose-related abnormal observations reported. If the study measures litter size, litter weight, viability, or sex ratio on days that are different than those listed, please correct the information so it corresponds with the study.
[43]For each pup with an unscheduled death, note the group, date of death, and any observations, including lesions observed at necropsy.
[44]Anogenital distance should be measured at day zero for all F2 pups that show treatment-related effects in F1 sex ratio or sexual maturation.
[45]This section is optional. List significant, dose-related developmental or neurotoxicity changes observed.
[46]This section is optional. List treatment-related findings in the immune system that were noted under result sections V.T: Offspring Organ Weights, V.U: Offspring Gross Pathological Changes, and V.V: Offspring Histopathological Changes. Provide a statement about whether or not the test substance presents a potential hazard to immunology.
[47]Note findings that are statistically or biologically treatment-related. Also note the changes that are 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.
[48]Note findings that are statistically or biologically treatment-related. The type of lesion should be noted. The comment section is available to explain data findings, if needed.
[49]Note findings only if treatment-related abnormalities were noted at macroscopic examination and contributed to the overall quality of the study data. The type of lesion should be noted. The comment section is available to explain data findings, if needed.
[50]When other tests are conducted, make note of the tests and any significant treatment-related effects.
[51]Give your impressions of the study: what was done well; what the problems were; did the study accomplish what it was supposed to do?
[52]Summarize the key findings from the study. Was there a dose-effect relationship? Were target organs identified? Was a parental NOEL achieved for each significant effect/observation? What was the NOEL? Was an offspring NOEL achieved for each significant effect/observation? What was the NOEL? The whole study should be summarized in this section.