Tixocortol pivalate contact allergy in the GPMT: frequency and cross-reactivity.

In spite of their intrinsic anti-inflammatory properties, corticosteroids can induce contact allergy. When studying the allergenic properties of corticosteroids it has to be considered that both the allergenic and anti-inflammatory effect may influence the induction phase as well as the elicitation phase and that such effects may be dose-dependent. A multiple dose guinea pig maximization test (GPMT) was therefore used to study the dose-response relationship of tixocortol pivalate. The GPMT was conducted according to OECD guideline #406, using a multiple-dose design and test results were analysed with logistic regression analysis. There was a significant tixocortol pivalate sensitization of the test animals compared to the control group (p<0.05), after both challenge and re-challenge. The challenge with 1% tixocortol pivalate gave more positive reactions than the challenge with 3%. The highest frequency of positive animals was observed when the animals were treated with low to intermediate induction concentrations and intermediate to high challenge concentrations with tixocortol pivalate in the TRUE Test. Cross-reactivity was found between tixocortol pivalate and hydrocortisone, which was expected from their close molecular resemblance, whereas no cross-reactivity was seen between tixocortol pivalate and the 3 other corticosteroids: amcinonide, budesonide, and hydrocortisone-17-butyrate.

Comparison of the sensitivities of the Buehler test and the guinea pig maximization test for predictive testing of contact allergy.

International test guidelines, such as the Organisation for Economic Cooperation and Development (OECD) guideline #406, recommend 2 guinea pig methods for testing of the contact allergenic potential of chemicals: the Guinea Pig Maximization Test (GPMT) and the Buehler test. Previous comparisons between the methods suggested that the Buehler test was less sensitive than the GPMT although modified Buehler test protocols were used. Parallel GPMT and Buehler tests were conducted according to OECD guideline #406 using a multiple-dose design and test results were analysed using a standard logistic dose-response model. To compare the sensitivity of the 2 test procedures the test conditions were kept identical and the following chemicals with a range of sensitization potentials were tested: chloraniline, chlorhexidine, eugenol, formaldehyde, mercaptobenzothiazole and neomycin sulphate. Formaldehyde and neomycin sulphate were strong sensitizers in both tests. Mercaptobenzothiazole, eugenol and chloraniline were all strong sensitizers in the GPMT, eugenol and mercaptobenzothiazole were negative in the Buehler test and equivocal results were obtained with chloraniline. Chlorhexidine was negative in the GPMT and equivocal responses were obtained with the Buehler test. Higher induction concentrations were needed to show allergenicity in the Buehler test and for some allergens the Buehler test protocol was not sensitive enough to demonstrate allergenic potential.

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

The guinea pig maximization test (GPMT) has played a primary rôle in the evaluation of potential skin contact sensitizers for 25 years. In the OECD Guideline 406 from 1993, it is specifically suggested that equivocal results from the initial challenge in the GPMT should be evaluated further with a repeated challenge. However, there exist few published rechallenge data and the guideline does not describe how rechallenge data should be interpreted. In this paper, we have used examples from published results to illustrate both the positive value and the limitations of repeated challenges, including cross challenge. Testing with modified concentrations may also help to indicate whether or not the response is allergic in nature, particularly where there has been a low level of skin reaction observed in shamtreated controls, or where a low level of skin reaction is the dominant response in the test animals. In conclusion, the data presented demonstrate that, as a tool for the investigation of skin sensitizing potential, the GPMT can benefit from an experienced scientific evaluation of rechallenge data, but that this information should not be treated in a mechanistic fashion.

The guinea pig maximization test--with a multiple dose design.

The guinea pig maximization test (GPMT) is usually performed with one moderately irritant induction dose of the allergen and gives a qualitative assessment-hazard identification-of the allergenicity of the chemical. We refined the GPMT by applying a multiple dose design and used 30 guinea pigs in a test divided into a control group and 5 test groups of 5 animals. Each group was treated with different induction concentrations of the allergens: formaldehyde, cinnamic aldehyde, propyl paraben, lidocaine, mercaptobenzothiazole or chlormethylisothiazolinone/methylisothiazolinone. The test results were analysed using a logistic multidose response model. The precision of the results depends only on the total number of animals, the dose design and the response pattern. The maximal sensitization rate for a chemical was determined, and the intracutaneous induction concentration that sensitized 50% of the animals (EC50) (or another percentage) was estimated. Further studies are needed to prove the validity of this idea. However, improvements in protocols for the GPMT are needed to reduce interlaboratory variability in results and to reduce the number of animals used for allergenicity tests.

Effect of sodium lauryl sulfate (SLS) on in vitro percutaneous penetration of water, hydrocortisone and nickel.

The dose- and time-related effect of sodium lauryl sulfate (SLS) on in vitro percutaneous penetration was studied using 3 radiolabeled tracer compounds with different physicochemical properties: tritiated water, hydrocortisone and nickel. Human cadaver abdominal skin from caucasian women was used as membrane in static in vitro penetration cells. Simultaneous application of SLS together with 1 of the tracer compounds showed, after 48 h, a significant dose-effect relationship between SLS concentration (0.25%, 2% and 10%) and penetration of tritiated water or nickel (p < 0.001, Spearman), whereas SLS had no significant effect on penetration of hydrocortisone. When 4% SLS was applied as pretreatment, a significant time-effect relationship, after 48 h, was found between pretreatment time (0.5, 2 and 8 h) and penetration of tritiated water. A similar relationship was not found for penetration of nickel or hydrocortisone. Pretreatment of the skin with SLS for 2 h using 3 concentrations (0.25%, 4% and 10%) showed, after 48 h, a significant dose-effect relationship between SLS treatment and penetration of tritiated water or nickel (p < 0.001, Spearman). Pretreatment had no effect on penetration of hydrocortisone. Pretreatment simulates a cleaning-washing situation. The present in vitro skin penetration model, using human cadaver skin, described the dose-effect and time-effect relationships for SLS on the penetration profiles of 3 different compounds. The model may be extended to other compounds with suspected irritant/damaging effect on the skin barrier. It should be kept in mind that the model uses a dead skin membrane without the barrier repair mechanisms of live skin.

[Use of thermotherapy, ultrasound and laser by practising physiotherapists. Physiotherapists' choice of treatment]. / Praktiserende fysioterapeuters anvendelse af termisk terapi, ultralyd og laser. Fysioterapeuters behandlingsvalg.

The purpose of this examination was to examine the practising physiotherapist's way of treating patients with nine selected diagnoses (fibrosites, osteoarthritis, rheumatoid arthritis, cervical slipped disc, lumbar slipped disc, generalized lumbar/back pain, generalized bursitis, generalized tendinitis, and sprains). In addition, nine different forms of therapy were examined (hot packs, infra-red light, ice packs, short waves, microwaves, diadynamic current, ultrasound, transcutaneous electric nerve stimulation and laser). All in all, 41 clinics with 2,018 treatment confrontations in the examination period, the last week of March 1990, took part in the survey. The majority of therapists were in possession of short wave, hot packs, ultrasound and laser which are also the four forms of therapy most frequently used for treatment. Compared to a Swedish examination from 1979, there is a doubling in ultrasound treatments from 24% to 48%, while the amount of short wave and microwave treatment remained unchanged. There was a remarkable variation in the physiotherapist's choice of therapy in each different diagnosed case. This can be due to the lack of specification of the diagnosis, so that different symptoms, course and stage of illness changed the treatment pattern elected.