The value and limitations of rechallenge in the guinea pig maximization test

Frankild, Søren; Basketter, D.A.; Andersen, Klaus Ejner

doi:10.1111/j.1600-0536.1996.tb02330.x

Cited by 34 publications

(10 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, it is true to say that at the time no rigorous assessment of the sensitivity and specificity of the GPMT was conducted; this only occurred much later, as an alternative method went through formal validation (see below). Perhaps not surprisingly, given this effort to optimize the sensitivity of guinea pig assays as predictive animal models, difficulties with the GPMT were noted; false positive results were identified (8, 9), and problems with the interpretation of apparent weakly positive reactions were described (10, 11).…”

Section: Contact All_ergy Predictive Tests: the Factsmentioning

confidence: 99%

Predictive testing in contact all_ergy: facts and future

Basketter

Kimber

2001

Allergy

Self Cite

View full text Add to dashboard Cite

Allergic contact dermatitis results from skin sensitization. Topical exposure of susceptible subjects to a contact allergen induces a cutaneous immune response that will, if of sufficient magnitude, result in the elicitation of a cutaneous inflammatory reaction if the same individual is exposed to the inducing chemical allergen on a subsequent occasion. Thus, a key question for toxicologists is how to predict which chemicals possess this property. In fact, several questions are associated with toxicologic evaluation of contact allergy. If the protocols used in the last half of the 20th century were as good as some believe, notwithstanding special cases such as nickel or plant dermatitis, why is there currently such a clinical burden related to this condition? How can toxicologists identify potential contact allergens and estimate their potency? Why do some individuals appear to be relatively readily sensitized, while others may undergo substantial exposure to the same contact allergens without any apparent ill effect? These questions may not seem at once related, but there is in fact an important correlation. Existing predictive tests may do a good job of identifying chemicals with the intrinsic ability to behave as a contact allergen, but they are not perfect. It is our thesis that while the process of hazard identification is amenable to modest improvement, proper risk assessment and consequent risk management can be enhanced significantly by taking advantage of recent improvements in predictive methods and by understanding better the immunobiology of contact allergy.In particular, knowledge of the latter will pave the way in the future for the development of appropriate nonanimal models of contact allergy.Contact allergy predictive tests: the facts

show abstract

Section: Contact All_ergy Predictive Tests: the Factsmentioning

confidence: 99%

Predictive testing in contact all_ergy: facts and future

Basketter

Kimber

2001

Allergy

Self Cite

View full text Add to dashboard Cite

show abstract

“…In spite of the efforts to reduce the influence of irritant reactions, occasional reactions due to irritation were seen at challenge test sites in the control animals and in the vehicle controls which may have influenced the results and are a matter of concern (37)(38). The irritant reactions in the control groups slightly influenced the base level (P 0 ) in the data assessment ( Table 2, Figs.…”

Section: Discussionmentioning

confidence: 98%

Dose‐response studies of contact allergens using 3 guinea pig models

1999

View full text Add to dashboard Cite

A multi-dose-response induction protocol for the guinea pig maximization test (GPMT), including a statistical computer program, has earlier been developed to improve the power of predictive tests for identification of contact allergens. This dose-response protocol, with 2 modifications (i.e., increased number of animals in each group and increased number of challenge concentrations) was evaluated in the GPMT, the cumulative contact enhancement test (CCET) and the Freund's complete adjuvant test (FCAT), using potassium dichromate and hydroxycitronellal as model contact allergens. Application of the dose-response protocol on the CCET and the FCAT resulted in either monotone or non-monotone curves with significant dose-response. However, application of the dose-response protocol on the GPMT gave curves with no significant dose-response. The protocol makes it possible to obtain an EC50 value, thus improving the possibility of ranking contact allergens, which is of substantial use for risk assessments. The dose-response protocol could benefit from a few adjustments: a wider span in the induction doses; change to simultaneous increase in intradermal and topical induction doses to obtain a proper dose-response for the GPMT; the addition of further challenge concentrations. In addition the computer program should allow calculation of threshold concentration for sensitization and EC50 value for a non-monotone curve.

show abstract

“…This is particularly important when considering relatively weak skin sensitizers that are also irritating. Resolution of this problem can often be achieved by a rechallenge procedure (documented in Kligman and Basketter, 1995;Frankild et al, 1996;Basketter, 2008). However, this can only define whether a substance is truly a skin sensitizer and not whether it should classify.…”

Section: Discussionmentioning

confidence: 99%

Skin sensitization, false positives and false negatives: experience with guinea pig assays

Basketter

Kimber

2010

J of Applied Toxicology

View full text Add to dashboard Cite

The advent of the local lymph node assay (LLNA), and efforts to develop in vitro alternatives for the identification of skin sensitizing chemicals has focused attention on the issue of false positive and false negative results. In essence, the question becomes 'what is the gold standard?' In this context, attention has focused primarily on the LLNA as this is now the preferred assay for skin sensitization testing. However, for many years prior to introduction of the LLNA, the guinea pig maximization test and the occluded patch test of Buehler were the methods of choice. In order to encourage a more informed dialogue about the relative performance, accuracy and applicability of the LLNA and guinea pig tests, we have here considered the extent to which guinea pig methods were themselves subject to false positives and negative results. We describe and discuss here well-characterized examples of instances where both false negatives (including abietic acid and eugenol) or false positives (including vanillin and sulfanilic acid) have been recorded in guinea pig tests. These and other examples are discussed with particular reference to the fabrication of a gold standard dataset that is required for the validation of in vitro alternatives.

show abstract

The value and limitations of rechallenge in the guinea pig maximization test

Cited by 34 publications

References 37 publications

Predictive testing in contact all_ergy: facts and future

Predictive testing in contact all_ergy: facts and future

Dose‐response studies of contact allergens using 3 guinea pig models

Skin sensitization, false positives and false negatives: experience with guinea pig assays

Contact Info

Product

Resources

About