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Guidelines for Toxicological Summary Requirements
Introduction
The following guidelines respecting the content of a summary of a toxicological study were developed by Health
Canada and accepted by a government/industry/labour consensus committee.
Requirements
NOTE: For those studies that did follow OECD, Draize, or other acceptable protocols, less details of
methodology would be required.
Was a standard protocol followed?
Concentration, percentage purity, vehicle dose levels, controls?
Species, number of animals/sex/level
Duration of exposure
Which observations were made? e.g., body weights? Hematology? Biochemistry?
For gross or histopathology, which tissues were examined?
In addition to the above-noted information, the information presented below,
if available, would also be required.
ACUTE ORAL (i.e., LD50)
Observation period Mortality per dose level or LD50 value (method of calculation) and 95% confidence
intervals Treatment-related effects: e.g., behavioural, body weights, pathology
ACUTE DERMAL (i.e., DERMAL LD50)
Location and details of application (occlusion?)
Observation period
Mortality per dose level or LD50 value (method of calculation) and 95% confidence intervals
Treatment-related effects: e.g., irritation, behavioural, body weights, pathology
DERMAL IRRITATION
Location and details of application (abrasion, occlusion)
Observation period
Method of scoring
Scores obtained at each time period, primary irritation index
Observations: erythema, edema, necrosis
EYE IRRITATION
Volume instilled
Controls/Washed?/Unwashed?
Observation period
Method of scoring
Score attained for each time period
Observations (cornea [opacity?], iris, conjunctiva)
DERMAL SENSITIZATION
Induction/challenge dose and method
Positive and negative controls?
Observation period
Method of scoring
Observations (sensitizing potential?)
SHORT-TERM/SUBCHRONIC STUDIES
Route of administration
Dosing schedule
Details of which organs were weighed and which tissues examined
Results: NO(A) EL, LO(A) EL and basis for establishment
Observations (per dose level): What effects at what dose? Mortality, morbidity, body weight, food
consumption, clinical analysis, (histo)pathology
CHRONIC STUDY/CARCINOGENICITY
Route of administration
If non-dietary route utilized, details of dosing
Stability of test material in vehicle of administration
Details of which organs were weighed and which tissues were examined
Results: NO(A) EL, LO(A) EL and basis for establishment
Observations (per dose level) : What effects at what dose? Mortality, morbidity, body weight, food
consumption, clinical analysis, organ weights, (histo)pathology
Neoplastic/Nonneoplastic lesion incidence
TERATOLOGY
Strain
Method of pregnancy determination
Route of administration, dosing period
Observations: any treatment-related effects with respect to:
Maternal
- Body weight
- Food consumption
- Morbidity
- Pathology
- Reproductive indices
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Fetal
- Body weight
- Mortality
- Corpora lutea
- Resorptions
- Sex ratio
- Anomalies
- external
- visceral
- skeletal
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REPRODUCTIVE STUDY
Strain, nulliparous females?
Route of administration
Premating dose period for both sexes
Mating and culling procedure
Method of pregnancy determination
Observations: any treatment-related effects with respect to:
reproductive indices: fertility, gestation, viability, lactation
Maternal Observations
Gestation length/abortions
Body weight
Stillbirths/live births
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Fetal Observations
Birth weight/post birth weight
Survival
Sex ratio
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For those studies looking at male fertility: semen analysis, mating behaviour, testes weight and histopathology,
fertility, endocrine measures.
MUTAGENICITY ASSAYS
Was a standard protocol followed?
Dose levels, positive, negative, vehicle controls?
Metabolic activation? S9?
Gene mutation endpoint
Overall result (positive, weak or strong?)
Cell survival
Mutation frequency
ACUTE INHALATION LC50
N.B. Additional detail of evaluation criteria are provided here for clarification purposes.
Was a standard protocol followed? If so, which one (EPA, OECD, etc. )?
Percent purity of the test material. Was a vehicle used?
Target exposure levels for the study?
Was there a concurrent control group?
Species/number of animals per sex per exposure level
Duration of exposure
Chamber design: there should be sufficient information on the exposure chamber to allow the reviewer
to evaluate the suitability of the chamber used.
Were environmental parameters of chamber monitored during the exposure period? e.g.,
temperature, relative humidity and airflow rate.
Physical form e.g., dust, mist, fume, vapour
Particle size distribution: particle size determinations need to be made when test atmospheres are
generated as aerosols (sprays or dusts).
Actual concentrations achieved at each measurement period or mean concentration and standard
deviation. Frequency of measurement
Type of exposure (nose-only, whole body)
Length of post-exposure observation period
Mortality per exposure level or LC50 (method of calculation) and 95% confidence intervals
Treatment-related effects: behavioural, body weights, pathology (especially respiratory tract)
References: 1) OECD Guidelines, section 403, Acute Inhalation Toxicity 2) U.S. EPA Pesticide Assessment
Guidelines, Addendum 6 on Acute and Subchronic Inhalation Toxicity Testing.
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