Skin irritation: prevalence, variability, and regulatory classification of existing in vivo data from industrial chemicals

Hoffmann, Sebastian; Cole, Thomas; Hartung, Thomas

doi:10.1016/j.yrtph.2004.11.003

Cited by 33 publications

(29 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…• already classified: 73% (ECB) • human data: 1% • skin corrosive: 3% (Hoffmann et al, 2005) • pH <2 or >11.5: 2% • flammable in contact with air or water: 0.1% • peroxides: 0.1% • acute dermal <400mg: 5% • BfR rule base and (Q)SAR: 10% (Rorije and Hulzebos, 2005) • In vitro eye corrosive: 5% • Non-validated in vitro: 10% • Read-across: 10% this means that data are lacking for 26% of chemicals. Of these 45.2% can be gained without animal testing, i.e.…”

Section: Skin/eye Irritation and Corrosionmentioning

confidence: 99%

Re-evaluation of animal numbers and costs for in vivo tests to accomplish REACH legislation requirements for chemicals - a report by the Transatlantic Think Tank for Toxicology (t4)

Rovida

Hartung

2009

ALTEX

223

180

View full text Add to dashboard Cite

Section: Skin/eye Irritation and Corrosionmentioning

confidence: 99%

Re-evaluation of animal numbers and costs for in vivo tests to accomplish REACH legislation requirements for chemicals - a report by the Transatlantic Think Tank for Toxicology (t4)

Rovida

Hartung

2009

ALTEX

223

180

View full text Add to dashboard Cite

“…In order to at least partially compensate for this, traditionally used animal experiments have been thoroughly investigated by deriving estimates of variability. This has, for example, supported the regulatory acceptance of in vitro test methods for the human health effects skin irritation and eye irritation/corrosion (Hoffmann et al, 2005;Adriaens et al, 2014).…”

Section: Introductionmentioning

confidence: 91%

LLNA variability: An essential ingredient for a comprehensive assessment of non-animal skin sensitization test methods and strategies

Hoffmann¹

2015

ALTEX

Self Cite

View full text Add to dashboard Cite

SummaryThe development of non-animal skin sensitization test methods and strategies is quickly progressing. Either individually or in combination, the predictive capacity is usually described in comparison to local lymph node assay (LLNA) results. In this process an important lesson from other endpoints, such as skin or eye irritation, i.e., that the variability of reference test results -here the LLNA -must be accounted for, has not yet been fully acknowledged. In order to provide assessors as well as method and strategy developers with appropriate estimates, the variability of EC3 values from repeated substance testing in the LLNA was investigated using the publicly available NICEATM (NTP Interagency Center for the Evaluation of Alternative Toxicological Methods) LLNA database. Repeat experiments taking the vehicle into account (76 substances) or combining data over different vehicles (38 substances) were analyzed. In general, variability was higher when different vehicles were used. In terms of skin sensitization potential, i.e., discriminating sensitizers from non-sensitizers, the false positive rate ranged from 14-20%, while the false negative rate was 4-5%. In terms of skin sensitization potency, the rate to assign a substance to the next higher or next lower potency class was approx.10-15% each. In addition, general estimates for EC3 variability are provided that can be used for modelling purposes. This analysis stresses the importance of considering the LLNA variability in the assessment of skin sensitization test methods and strategies and provides estimates thereof.

show abstract

“…While the use of such conservative factors certainly mitigates the problem, it can not exclude the risk of false negatives altogether. Speciesspecific effects thus remain a substantial problem (Basketter et al 2004;Guzelian 1982;Hoffmann et al 2005). Test systems based on human cells can help to bridge this gap, be it by simply highlighting species-specific effects, as screening tools or as means to analyse species differences in more detail.…”

Section: Breakdown Of the Species Barriermentioning

confidence: 99%

Regulatory toxicology in the twenty-first century: challenges, perspectives and possible solutions

et al. 2015

View full text Add to dashboard Cite

The advent of new testing systems and "omics"-technologies has left regulatory toxicology facing one of the biggest challenges for decades. That is the question whether and how these methods can be used for regulatory purposes. The new methods undoubtedly enable regulators to address important open questions of toxicology such as species-specific toxicity, mixture toxicity, low-dose effects, endocrine effects or nanotoxicology, while promising faster and more efficient toxicity testing with the use of less animals. Consequently, the respective assays, methods and testing strategies are subject of several research programs worldwide. On the other hand, the practical application of such tests for regulatory purposes is a matter of ongoing debate. This document summarizes key aspects of this debate in the light of the European "regulatory status quo", while elucidating new perspectives for regulatory toxicity testing.

show abstract

Skin irritation: prevalence, variability, and regulatory classification of existing in vivo data from industrial chemicals

Cited by 33 publications

References 16 publications

Re-evaluation of animal numbers and costs for in vivo tests to accomplish REACH legislation requirements for chemicals - a report by the Transatlantic Think Tank for Toxicology (t4)

Re-evaluation of animal numbers and costs for in vivo tests to accomplish REACH legislation requirements for chemicals - a report by the Transatlantic Think Tank for Toxicology (t4)

LLNA variability: An essential ingredient for a comprehensive assessment of non-animal skin sensitization test methods and strategies

Regulatory toxicology in the twenty-first century: challenges, perspectives and possible solutions

Contact Info

Product

Resources

About