Introduction to the 2-Generation Reproduction Toxicity Study Template

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Table of Contents

1. Identification of Study
2. Good Laboratory Practice
3. Executive Summary
4. Materials and Methods
   1. TEST SUBSTANCE
   2. TEST SUBSTANCE AS ADMINISTERED
   3. ANIMAL DIET
   4. TEST ANIMALS
   5. EXPERIMENTAL DESIGN
   6. MATING PROCEDURES
   7. CULLING PROCEDURES
   8. PARENTAL BODY WEIGHT AND FEED/WATER INTAKE
   9. PARENTAL CAGE-SIDE OBSERVATIONS
   10. PARENTAL REPRODUCTIVE PARAMETERS
   11. PARENTAL ORGAN WEIGHTS
   12. PARENTAL GROSS PATHOLOGY OBSERVATIONS
   13. PARENTAL HISTOPATHOLOGY OBSERVATIONS
   14. OTHER PARENTAL TESTS
   15. OFFSPRING OBSERVATIONS/BODY WEIGHT
   16. OFFSPRING DEVELOPMENTAL ENDPOINTS AND NEUROTOXICITY SCREENING - OPTIONAL
   17. OFFSPRING IMMUNOTOXICITY - OPTIONAL
   18. OFFSPRING ORGAN WEIGHTS
   19. OFFSPRING GROSS PATHOLOGY OBSERVATIONS
   20. OFFSPRING HISTOPATHOLOGY OBSERVATIONS
   21. OTHER OFFSPRING TESTS
   22. STATISTICAL METHODS
5. Results
   1. DOSE VERIFICATION
   2. PARENTAL FEED/WATER CONSUMPTION CHANGES
   3. PARENTAL INTAKE OF TEST MATERIAL
   4. PARENTAL FEED EFFICIENCY
   5. PARENTAL BODY WEIGHT CHANGES
   6. PARENTAL ABNORMAL CAGE-SIDE OBSERVATIONS
   7. PARENTAL MORTALITY
   8. MATING, FERTILITY, AND REPRODUCTION
   9. PARENTAL ORGAN WEIGHTS
   10. PARENTAL GROSS PATHOLOGY CHANGES OBSERVED
   11. PARENTAL HISTOPATHOLOGY CHANGES OBSERVED
   12. OTHER PARENTAL TESTS
   13. OFFSPRING BODY WEIGHT CHANGES
   14. OFFSPRING OBSERVATIONS
   15. OFFSRPING MORTALITY
   16. SEXUAL MATURATION
   17. ANOGENITAL DISTANCE
   18. OFFSPRING DEVELOPMENTAL ENDPOINTS AND NEUROTOXICITY - OPTIONAL
   19. OFFSPRING IMMUNOTOXICITY - OPTIONAL
   20. OFFSPRING ORGAN WEIGHTS
   21. OFFSPRING GROSS PATHOLOGY CHANGES OBSERVED
   22. OFFSPRING HISTOPATHOLOGY CHANGES OBSERVED
   23. OTHER OFFSPRING TESTS
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. NOEL
8. 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 Study² 

A.     Study File Location :
B.     Study Title/Report Number:
C.     Study Author:
D.     Name and Address of Testing Facility:
E.     Study Initiation Date³ :
F.     Study Completion Date⁴ :
G.     Study Objective:
H.     Comments:

II. Good Laboratory Practice⁵ 

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 SUBSTANCE⁸ 

1.     CAS name:
2.     Other name(s):
3.     CAS number:
4.     Molecular structure: ^{http://www.chemfinder.com/9} 

 

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

B.   TEST SUBSTANCE AS ADMINISTERED¹⁰ 

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 DIET¹¹ 

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 ANIMALS¹² 

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 DESIGN¹³ 

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

*Premating dose

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

*Premating dose

 

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 PROCEDURES¹⁴ 

1.     Description:
2.     Comments:

G.   CULLING PROCEDURES¹⁵ 

1.     Description:
2.     Comments:

H.  PARENTAL BODY WEIGHT AND FEED/WATER INTAKE¹⁶ 

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

*These parameters are recommended in Toxicological Principles for the Safety of Food Ingredients: Redbook 2000 for 2-generation reproduction toxicity studies.

 

2.     Comments: (e.g., list frequency)

 

 

I.      PARENTAL CAGE-SIDE OBSERVATIONS¹⁷ 

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 PARAMETERS¹⁸ 

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 WEIGHTS¹⁹ 

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 OBSERVATIONS²⁰ 

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 TESTS²¹ 

1.     Observations:
2.     Comments:

O.   OFFSPRING OBSERVATIONS/BODY WEIGHT²² 

 

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 - OPTIONAL²⁵ 

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 - OPTIONAL²⁶ 

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 WEIGHTS²⁷ 

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 OBSERVATIONS²⁸ 

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 TESTS²⁹ 

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 VERIFICATION³⁰ 

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 CHANGES³¹ 

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 MATERIAL³² 

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 EFFICIENCY³³ 

f₀ parents

1.     Was feed efficiency calculated?
2.     Comments:

 

f₁ parents

1.       Was feed efficiency calculated?
2.       Comments:

E.   PARENTAL BODY WEIGHT CHANGES³⁴ 

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 OBSERVATIONS³⁵ 

f₀ parents

1.     Observations:
2.     Comments:

 

f₁ parents

1.     Observations:
2.     Comments:

G.   PARENTAL MORTALITY³⁶ 

f₀ parents

1.       Observations:
2.       Comments:

 

f₁ parents

1.     Observations:
2.     Comments:

H.  MATING, FERTILITY, AND REPRODUCTION

1.       Observations:

 

Table # [Heading]

 

pregnancy

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 (%)

Maternal Wastage

GENERATION	F0				F1
DAILY DOSE (mg/kg body-weight/day)	0 CONTROL				0 CONTROL
# Died
# Died Pregnant
# Died Nonpregnant
# Aborted
# Premature Delivery

corpora lutea

GENERATION	F0				F1
DAILY DOSE (mg/kg body-weight/day)	0 CONTROL				0 CONTROL
Total # Corpora Lutea (N)
Corpora Lutea/Dam (MEAN S.D.)

implantations

GENERATION	F0				F1
DAILY DOSE (mg/kg body-weight/day)	0 CONTROL				0 CONTROL
Total # Implantations (N)
Implantations/Dam (MEAN S.D.)

births - day 0

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, ** p<0.01

 

 

 

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, ** p<0.01

 

2.       Estrous Cycling Evaluation:
3.       Comments:

I.      PARENTAL ORGAN WEIGHTS³⁷ 

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 Weighta	gram
Per Body Weighta	%
ADRENALS
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
EPIDIDYMIDESb
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
KIDNEYS
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
LIVER
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
PITUITARY GLAND
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
PROSTATEb
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
SEMINAL VESICLES WITH COAGULATING GLANDb
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
SPLEEN
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
TESTESb
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
THYMUS
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
OVARIESb
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
UTERUSb
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%

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, ** p<0.01

 

 

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 Weighta	gram
Per Body Weighta	%
ADRENALS
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
EPIDIDYMIDESb
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
KIDNEYS
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
LIVER
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
PITUITARY GLAND
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
PROSTATEb
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
SEMINAL VESICLES WITH COAGULATING GLANDb
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
SPLEEN
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
TESTESb
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
THYMUS
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
OVARIESb
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%
UTERUSb
Absolute Weighta	gram
Per Body Weighta	%
Per Brain Weighta	%

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, ** p<0.01

 

1.     Comments:

J.    PARENTAL GROSS PATHOLOGY CHANGES OBSERVED³⁸ 

f₀ parents

1.     Observations:
2.     Comments:

 

f₁ parents

1.     Observations:
2.     Comments:

K.   PARENTAL HISTOPATHOLOGY CHANGES OBSERVED³⁹ 

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