Report in vivo toxicity studies

 

This reporting checklist was developed to help researchers design, perform and report in vivo toxicity studies in a transparent way that fulfill the reliability criteria for regulatory risk assessment. Not all criteria apply to all studies.

 

Item to be described

Purpose and aim

Purpose and/or aim.

Endpoints

Endpoints included in investigation.

Test substance

Name and/or CAS-number.

Source, i.e. manufacturer and batch/lot number.

Purity, including information on contaminants, isomers, etc.

Other relevant information, e.g. radiolabelled.

Relevant and available information on toxicokinetics and toxicodynamics.

Stability and homogeneity of the preparation in the vehicle or carrier and in e.g. urine, blood and milk (as relevant) under the conditions of use and storage.

Vehicle

Type/characteristics.

Justification for choice of vehicle if other than water.

Ethical statement

Ethical review permissions, licenses and national or institutional guidelines for animal care and use, as relevant.

Animals

Species.

Strain, using complete genetic nomenclature.

Source.

Number.

Sex.

Age and life stage.

Body weight at the start of the study.

Time allowed for acclimatization to lab conditions.

Method for individual identification of animals.

Housing conditions

Temperature (oC).

Relative humidity.

Light-dark cycle, hours light vs. dark as well as if the light-dark cycle has been reversed.

Number of animals/sex/cage.

Reported for F0, pregnant dams and litters as relevant.

Cage material.

Bedding material.

NOTE: The level of phytoestrogens contained in the selected bedding material should be minimal.

Water bottle material.

Description of any cage enrichment, including materials.

Feed

Type and source.

Contaminant content, e.g. pesticide residues, persistent organic pollutants, heavy metals and mycotoxins.

Phytoestrogen content.

Frequency and method of feeding.

Drinking water

Source.

Contaminant content.

Administration of test substance

Number of animals/sex/dose groups.

Method for deciding on optimal group size, e.g. power calculations.

Dose levels and number of dose groups.

Rationale for selection of dose levels.

Enough information to calculate/convert to mg/kg body weight/day if doses are not stated in this format.

Method of assignment of animals to different dose groups, e.g. randomization, exclusion, inclusion, etc.

Information about controls, are they concurrent, historical, matched, etc.

Administration route.

Rationale for choice of administration route, e.g. most relevant to human exposure scenario.

Administration method, e.g. if oral: via feed, gavage, drink from pipette, etc.; if s.c: injection, pump, etc.

If administered in feed/water:

  • Content, homogeneity and stability of the test substance in the feed/water.
  • Feed/water consumption should be recorded and presented.

Age and life stage of animals at start of administration.

Duration of administration, e.g. days, weeks or age when administration was ended.

Frequency of administration, e.g. single, repeated or continuous.

Methods

Methods should be described in enough detail to allow replication either in the Methods section or in another publication to which a clear reference is made.

Description of randomization procedures for assigning animals to different tests/analyses.

NOTE: it should be clear if the same animals are subjected to several tests/measurements.

Number of animals/sex/dose subjected to test/tissue collection/analyses.

Age and life stage of animals at testing/analyses.

Description of method and how it is relevant to the endpoint being investigated.

Data supporting the reliability and sensitivity of the method, i.e. positive control or historical/previously published data or participation in inter-laboratory calibration programs.

Description of any apparatus used.

Description of parameters measured.

Method for termination of animals.

Age and life stage at termination of animals.

Statistics

Details of statistical methods applied.

Description that shows that the assumptions of the statistical methods used are fulfilled.

Observations

Body weight data.

Food and water consumption.

Time and cause of death for animals that died during the study.

Clinical observations.

Details of all adverse events in each experimental group.

Data

Response data by sex and treatment group.

All data relevant to the endpoints investigated, including statistically significant changes and the appropriate measures of precision/variance should be presented in a transparent manner for all treatment groups, including negative (and positive) controls.

Historical control data if available.

Number of animals/sex/dose included in each analysis in absolute numbers.

Discussion

Description of the dose-response relationships for the measured parameters.

Possible mechanism of action for the observed effects.

How do the results relate to other research within the relevant field, e.g. are the results supported by other research.

Relevance to humans.

Other

List of study personnel, including professional training.

Contact information for raw data access.

Disclosure of any financial conflicts of interest.

For reproductive and developmental toxicity studies the following additional information should be reported:

Vaginal smear data for parental females before treatment (if collected).

Designation of day of parturition, e.g. PND 0.

Description of randomization procedures to select pups for culling.

Day of culling.

Number of animals/sex/litter after culling.

Method for individual identification of offspring.

Litter of origin for all offspring.

For endpoints measured in offspring it should be clear if littermates are subjected to the same tests/analyses.

Statistical unit, i.e. if it is the litter or the individual pup.

 

 

 

 

 

Contact: anna.beronius@ki.se

 

Download the reporting checklist for in vivo toxicity studies here (excel).