| Toxicity Area |
Number
of Methods |
Test Method [number] |
Regulatory Application and ICCVAM Recommendations |
|
Acute Oral Toxicity |
3 |
Up-and-Down Procedure (UDP) |
In 2001, recommended as replacement alternative for OECD TG 401,
the traditional in vivo rodent LD50 test for assessing acute oral systemic toxicity,
and adopted by OECD as TG 425; in 2003, accepted by U.S. agencies. |
|
In vitro basal cytotoxicity methods [2] |
In 2007, both in vitro test methods recommended as reduction alternatives to estimate
the starting dose in the UDP and Fixed Dose Procedure (FDP) for assessing acute oral systemic
toxicity. |
| Biologics Testing |
23 |
- In vivo alternatives
- Ex vivo alternatives
- In vitro cell-based methods
- In vitro enzymatic alternatives
|
In 2006, various reduction, refinement, and replacement alternatives to the
mouse LD50 assay for botulinum toxin detection and potency testing reviewed at a
NICEATM-ICCVAM/ECVAM-sponsored workshop; future activities recommended. |
| Developmental Toxicity |
1 |
Frog Embryo Teratogenesis Assay: Xenopus (FETAX) |
In 2000, reviewed at a NICEATM-ICCVAM sponsored workshop as a reduction or replacement
alternative to assess the developmental toxicity of chemicals and mixtures; data gaps and
inadequacies identified, future activities recommended. |
| Endocrine Disruptors |
138 |
- In vitro androgen receptor (AR) binding [11]
- In vitro AR transcriptional activation (TA) [18]
|
In 2002, evaluated screens for identifying
potential endocrine-disrupting chemicals, to be included in EPA’s
Endocrine Disruptor Screening Program; in 2003, report with guidance
for protocol standardization and validation studies released; in 2006, reference substance list revised. |
- In vitro estrogen receptor (ER) binding [14]
- In vitro ER TA [95]
|
Same as for in vitro AR assays. |
| Eye Corrosion/Irritation |
7 |
In Vitro Test Methods
for Detecting Ocular Corrosives and Severe Irritants [4] |
In 2007, the Bovine Corneal Opacity and Permeability (BCOP) and the Isolated Chicken Eye test methods recommended as screening tests for identifying corrosives and severe irritants, with certain
limitations; two other methods not recommended for regulatory hazard classification purposes until further
developed and evaluated. |
| In Vitro Test Methods for Assessment
of the Eye Irritation Potential of Antimicrobial Cleaning Products [3] |
An approach using the BCOP, the EpiOcular and the Cytosensor Microphysiometer test methods for
evaluating the eye irritation potential of certain antimicrobial cleaning products is
currently under review. |
| Pyrogenicity |
5 |
In vitro pyrogenicity |
In 2007, in vitro pyrogenicity test methods measuring cytokine release from human cells recommended as replacements
for the rabbit test, subject to product specific validation, to detect endotoxin contamination in parenteral drugs. |
| Skin Corrosion |
4 |
- Corrositex®
- EpiDerm™
- EPISKIN™
-
Rat Transcutaneous Electrical Resistance (TER) Assay
|
In 1999, Corrositex® recommended as a stand-alone assay for evaluating acids, bases, and acid derivatives for DOT;
otherwise, recommended as part of a tiered testing strategy; in 2000, accepted by U.S. agencies; in 2006, adopted by OECD
as TG 435. In 2002, TER and human skin models (EPISKIN™, EpiDerm™) recommended as part of a tiered testing strategy; in
2004, adopted by OECD as TG 430/431. |
| Skin Sensitization |
7 |
Murine Local Lymph Node Assay (LLNA) [4]
- Limit dose approach
- Use for potency determination
- Applicability domain
- Performance standards
|
In 1999, LLNA recommended and accepted by regulatory agencies
as alternative for guinea pig tests for allergic contact
dermatitis; in 2002, adopted by OECD as TG 429. Use of LLNA for potency determination, LLNA limit dose approach, the LLNA applicability domain
and three non-radiolabeled LLNA methods are currently under review,
in addition to revised LLNA performance standards. |
| LLNA non-radiolabeled methods [3] |
| Total |
188 |
