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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:

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

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.