TetraQ provides a range of toxicology services including screening studies for early stage development in the Lead Selection and Candidate Confirmation stages. We also conduct later stage studies that are required for regulatory submissions (GLP recognition required). We have designed our early stage services to generate data that will provide valuable input into the planning of more expensive GLP regulatory toxicology studies.

We can assess novel therapeutics, complementary medicines, food additives and other chemicals for toxicity. TetraQ also offers advice and interpretation of toxicology reports provided by clients from other contract research organisations. Our toxicology services are conducted according to GLP standards.

• Cytotoxicity Assay
• Haemolysis Assay
• Genotoxicity assays
• - Bacterial mutation assay (Ames test)
• - Mammalian Erythrocyte Micronucleus Test
• Maximum Tolerated Dose
• Repeat Dose Toxicity (7-10 day)
• Acute and subchronic Studies
• Safety Pharmacology Studies
• CVS- Off-target screening and hERG binding assays

In vitro Services

In vitro Cytotoxicity Assay

TetraQ currently offers cytotoxicity screening assays performed in a 96 well plate format. The assays can be performed using a variety of cell lines. The following cell lines are currently available, however others can readily be accessed if required:

• Human:
• MCF7 (breast)
• HT-29 (colon)
• HeLa (cervical)
• 293 (kidney)
• Jurkat (T-cell)
• Lox (skin)
• HepG2 (liver)
• K562 (lymphoid)
• Calu6 (lung)
• Mouse:
• NIH3T3 (fibroblast)
• B16 (skin)
• B19 (embryonic)

TetraQ offers assays to assess the in vitro effect of drugs and chemicals on the haemolysis of red blood cells derived from either human or several animal species.

Bacterial mutation assay (Ames test)

This test is typically done early in the Drug Characterisation Stage and is a required element in many toxicology submissions for regulatory authorities. It is used in the Lead Selection or Candidate Confirmation stages to determine likely genotoxicity of a compound by noting growth due to reverse mutations. TetraQ offers the standard Ames Test using 5 strains of bacteria as specified by the ICH guidelines (under GLP conditions) and required for submission to regulatory authorities. We can also provide a non-GLP screening assay using 3 strains of bacteria designed to provide rapid feedback of essential information, rather than a package ready for regulatory submission.



Mammalian Erythrocyte Micronucleus test

The mammalian erythrocyte micronucleus test is a genotoxicity test that by regulatory agencies such as the FDA. This test is designed to identify drug candidates that cause cytogenetic damage and will also provide information about a compound’s genotoxicity.

In vivo Services

Maximum Tolerated Dose test in Rodents

The maximum tolerated dose study is designed to provide initial in vivo toxicology data on a compound and identify the maximum dose that has no observable toxic effects. Along with the Repeat Dose Study (below), it is commonly done in the Candidate Confirmation Stage to provide relatively inexpensive and rapid means of identifying toxicities that may arise during later stage toxicology packages (see below) and to guide the design of other preclinical testing (eg efficacy studies).

• Administer a range of doses of test article to rats or mice
• Observations typically include water intake, body weight measurement, behaviour recording, blood biochemistries and gross pathology of major organs
• Histopathology is available if required

Repeated Dose Toxicity in Rodents (7-10 day)

Using the dose identified in the MTD Studies, the animals are repeatedly dosed over a 7-10 day period and various measurements taken. This is designed to provide valuable information on likely toxicities in larger more expensive studies (GLP) and may influence their design or even the decision to proceed with them:

• Observations typically include water intake, body weight measurement, behaviour recording, blood biochemistries and gross pathology of major organs
• Histopathology of important tissues (eg liver) would typically be included

Safety Pharmacology (CVS, CNS, Respiratory)

This involves the assessment of major system functions (cardiovascular, central nervous system and respiratory) in response to the administration of a drug. These studies are additional to the standard toxicology assessments and would able to be included in regulatory submissions.

Preliminary Central Nervous System Safety Pharmacology

The safety pharmacology assessment of the central nervous system (CNS) will be conducted in mice and is aimed at providing an early indicator of adverse CNS effects. A negative result at this stage may influence the design of further preclinical testing or may even halt further development.

Preliminary Cardiovascular Safety Pharmacology

The preliminary safety pharmacology assessment of the cardiovascular system will be conducted in an anaesthetised rat and is aimed at providing an early indicator of adverse cardiac effects. A negative result at this stage may influence the deisgn of further preclinical testing and is often a "showstopper".

Off-target Screening and hERG Binding Assay

Off-target screening is often useful to indicate the likely interactions with molecular targets that may lead to toxicity and interactions with other drugs. hERG binding assays can indicate potential problems with cardiac safety due to affecting this important class of potassium channels.

TetraQ can arrange for these tests to be conducted via the Program Management Services we offer through our partner laboratories and can provide expert interpretation of the data generated from these studies.