In fact, Draize testing is the only test formally accepted and validated to assess the full range of irritation severity. Both irreversible and reversible ocular effects can be identified using this test ( Barile, 2010). Eye irritation was traditionally summarized as a “maximum average score” (MAS) which is an average value primarily focused on corneal injury, for individual KU-60019 concentration animals at the time of scoring

( Huhtala et al., 2008). However, many countries had their own scoring systems, which although similar in their approach, led to multiple classifications, labels, and data sheets for the same chemical, dependent upon which country the chemical was been marketed in. In response to this, and as a means of replacing the numerous different classification systems, with a single controlled and unified classification system, the United Nations (UN) developed the current internationally agreed, standard scoring system, known as the Globally Harmonized System (GHS), also known as the “purple book” ( UN, 2013). The GHS utilizes pictograms, signal words, hazard and precautionary statements, and safety data sheets according to standardized levels of physical, health and environmental Androgen Receptor Antagonist research buy hazards. The GHS is based upon averaged single tissue observations which can account for the reversibility of the observed chemical

effects ( Eskes et al., 2005). With regards to eye irritation, there are two primary C-X-C chemokine receptor type 7 (CXCR-7) categories. Substances which cause serious irreversible (up to 21 days) damage/destruction to the cornea, iris and/or conjunctiva are Category 1; substances which cause reversible (within 21 days) irritation including corneal opacity, iritis, redness or chemosis are Category 2. Category 2 chemicals can be split into two subcategories:

2A, irritating to eyes, chemicals which cause reversible irritation to eyes within 21 days; and 2B, mildly irritating to eyes, chemicals which cause reversible irritation to eyes within 7 days. Non irritating chemicals are assigned a GHS No Category classification. The categories are assigned based on calculations of a mean score following observational grading at 24, 48 and 72 h post application of the test chemical. The GHS was adopted in 2002 and published in 2003 ( Silk, 2003). Despite the adoption of the GHS, Draize testing is often criticized due to its subjective and time consuming nature, lack of repeatability, variable estimates, insufficient relevance of test chemical application (Davila et al., 1998), high dosages (Curren and Harbell, 2002) and over-prediction of human responses (Jester et al., 2001), primarily due to interspecies differences. In addition, for most routine and acute toxicity tests, for example skin toxicity tests, there are standardized exposure times and/or delivery methods in place.