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Biomedical subjects

D Basketter

Publications and source records attributed to D Basketter.

12 recordsLinked to original sources
PubMed2003

The fragrance hand immersion study - an experimental model simulating real-life exposure for allergic contact dermatitis on the hands.

Recently, we showed that 10 x 2% of consecutively patch-tested hand eczema patients had a positive patch test to a selection of fragrances containing fragrances relevant to hand exposure. In this study, we used repeated skin exposure to a patch test-positive fragrance allergen in patients previously diagnosed with hand eczema to explore whether immersion of fingers in a solution with or without the patch-test-positive fragrance allergen would cause or exacerbate hand eczema on the exposed finger. The study was double blinded and randomized. All participants had a positive patch test to either hydroxycitronellal or Lyral (hydroxyisohexyl 3-cyclohexene carboxaldehyde). Each participant immersed a finger from each hand, once a day, in a solution containing the fragrance allergen or placebo. During the first 2 weeks, the concentration of fragrance allergen in the solution was low (approximately 10 p.p.m.), whilst during the following 2 weeks, the concentration was relatively high (approximately 250 p.p.m.), imitating real-life exposure to a household product like dishwashing liquid diluted in water and the undiluted product, respectively. Evaluation was made using a clinical scale and laser Doppler flow meter. 3 of 15 hand eczema patients developed eczema on the finger immersed in the fragrance-containing solution, 3 of 15 on the placebo finger and 3 of 15 on both fingers. Using this experimental exposure model simulating real-life exposure, we found no association between immersion of a finger in a solution containing fragrance and development of clinically visible eczema on the finger in 15 participants previously diagnosed with hand eczema and with a positive patch test to the fragrance in question.

Adult↗
PubMed2001

Skin sensitisation testing--new perspectives and recommendations.

Various methodological aspects of skin sensitisation testing have been explored, particularly in the context of animal welfare considerations and reliability and sensitivity of test methods. Recommendations are made for the conduct of current and proposed OECD skin sensitisation tests with respect to appropriate test configurations for the purposes of hazard identification and labelling, and the requirement for positive controls. Specifically, the following aspects of guinea pig sensitisation test methods have been addressed: (1) the number of test and control animals required; (2) the option of using joint positive controls between independent laboratories; (3) the choice of positive control chemicals; (4) the optimal conduct and interpretation of rechallenge; and (5) the requirement for pretreatment with sodium lauryl sulfate. In addition, the use of the murine local lymph node assay (LLNA) has been considered. A number of conclusions have been drawn and recommendations made as follows: In many instances, particularly with the conduct of the guinea pig maximisation test, it is acceptable to halve the number of test and control animals used. An optional scheme for the conduct of joint positive control studies within a co-ordinated group of laboratories is appropriate. Only one positive control chemical (alpha-hexyl cinnamic aldehyde) is necessary for the routine assessment of assay sensitivity. The proper conduct and interpretation of rechallenge can provide valuable information and confirmation of results in guinea pig sensitisation tests. Sodium lauryl sulfate should no longer be used as a pretreatment in the guinea pig maximisation test. The LLNA is a viable and complete alternative to traditional guinea pig test methods for the purposes of skin sensitisation hazard identification. These recommendations provide the opportunity for both animal welfare benefits and improved hazard identification.

Allergens↗
PubMed2001

Investigation of the threshold for allergic reactivity to chromium.

Allergy to chromium is relatively common, often in association with exposure to cement or in leather manufacture. However, in certain locations, there appears to be a relatively large cohort of chromium-sensitive individuals whose allergy cannot be explained by these common sources. In particular, this group include Israeli housewives with persistent hand eczema and concomitant patch test positivity to chromium. The causation of their allergy has been linked with relatively high levels of chromium contamination in household products. To provide further information in respect of the definition of safe levels for such products, we examined 17 chromium-allergic individuals to determine their threshold for reaction under closed patch test and repeated open application test (ROAT) conditions. The data derived indicated that, on normal skin, the patch test threshold was 10 ppm chromium; in the presence of an irritant (sodium lauryl sulfate) the threshold was closer to 1 ppm, 2/17 subjects giving 1+ reactions at this concentration. In the more realistic exposure conditions of the ROAT, 8/14 individuals failed to react to 50 ppm, whilst 3/15 reacted to 5 ppm. Interestingly, there was very poor correlation between patch test sensitivity and ROAT sensitivity. To ensure the large majority of chromium-allergic individuals do not suffer elicitation of their allergy, as well as to limit the development of new chromium-sensitive subjects, it is recommended that household products adhere to a previously published standard of a maximum limit of 5 ppm, with an ultimate target of 1 ppm contamination by chromium.

Adult↗
PubMed2000

Quenching: fact or fiction?

Fragrance chemicals are a frequently reported cause of allergic contact dermatitis (ACD), a matter which has recently come into considerable prominence, to the point that legislation in Europe is under serious consideration. Certain skin-sensitizing fragrance chemicals have been reported by the producing industry to be rendered safe (quenched), at least in terms of ACD, when they are used in the presence of a specific quenching agent. Accordingly, it seemed timely to review this apparent quenching phenomenon, considering the available data and potential mechanistic hypotheses that might be used to explain it. If it is correct, it should be a phenomenon of potentially enormous value in the elimination of the allergenic properties of at least a proportion of common skin sensitizers. Whilst there is some evidence in man for the occurrence of quenching during the induction of skin sensitization, a much more substantial body of work has failed to find supportive evidence in various animals models, at a chemical level or at elicitation in human subjects with existing allergy. On balance, it is concluded that quenching of fragrance allergens is a phenomenon still awaiting positive evidence of existence.

Chemical Industry↗
PubMed1999

Regulatory classification of substances oxidized to skin sensitizers on exposure to air.

Regulatory classification of substances in the European Union (EU) is intended to identify their hazardous toxicological properties in a formal and harmonized manner. In the regulatory work, a specific chemical with its molecular structure is classified as a skin sensitizer. This implies that the compound is stable throughout its lifetime. The purpose of the present paper is to discuss the problem of skin sensitizing oxidation/degradation products formed by air exposure of various materials or substances with very low allergenic activity. In regulatory classification work on skin sensitizers, the intrinsic suspectibility of a chemical to air oxidation (autoxidation) should be taken into consideration. We give examples of natural terpenoid materials, but the concept of allergens formed by air oxidation can apply to other materials widely used in industrial products. If a positive classification is made for a substance with a known chemical structure, a note should indicate that the primary chemical structure of the notified substance is not a skin sensitizer, but that (some of) its oxidation products are. Complex mixtures which inevitably contain sensitizing oxidation products should (on the basis of sufficient evidence) be classified as skin sensitizing.

Allergens↗
PubMed1998

Patch tests versus use tests in skin irritation risk assessment.

In the risk assessment of the ability of a substance or preparation to cause skin irritation, a patch test involving human volunteers is often seen as providing definitive information. However, the skin exposure conditions found in an occluded patch may be far removed from those in a particular use situation, not least for such reasons as the high dose per unit area, the duration of exposure and the maceration of the skin. Whilst these factors may enhance sensitivity in the identification of intrinsic hazard, they may do little to ensure accurate safety evaluation for real use. In this paper, we report data from a series of studies with an unmarketed facial skin cosmetic product. Whilst the product was unexpectedly highly irritating in a standard patch test in 30 volunteers, subsequent use tests, including a 6x daily open application to the elbow for 3 weeks and 2x daily application in a half-face test lasting 3 to 4 weeks and involving 52 volunteers failed to show any evidence of skin irritation. It is concluded that the most meaningful results for skin irritation risk assessment are likely to come from studies which involve relevant patterns of exposure.

Adult↗
PubMed1997

Visual assessment of human skin irritation: a sensitive and reproducible tool.

Human volunteer studies of skin irritation have been carried out for decades, both for research and for safety evaluation purposes. For the majority of this time, and consequently for the majority of the studies, assessment of the skin reactions has been made visually. Typical endpoints include erythema, oedema, dryness and scaling, some or all of which would be rated on a simple scale, eg 0, +/-, +, ++, + + +. Such approaches can be criticized as subjective, of poor reproducibility, lacking in sensitivity and highly variable between observers and/or institutions. In consequence, instrumental methods of assessment have been strongly promoted and do indeed offer several advantages, not least their objectivity. However, it is possible to use the human eye, which is a very sensitive tool, to make detailed, accurate and reproducible descriptions of skin irritation reactions. To achieve this, it is necessary to give prolonged and thorough training to each observer. In this paper, 3 examples of human volunteer studies, in which different pairs of trained observers independently carried out double blinded scoring of the irritation reactions, are reported. The grading patterns produced were almost identical; statistical analysis showed that properly trained observers are in fact able to reliably measure a grade of erythema to within +/- 1 on a 10 point scale; 97.6% of scores were within 2 grade points on this scale. These results provide evidence that visual scoring can be sensitive, reliable and reproducible within a testing institution.

Dermatitis, Irritant↗
PubMed1996

The impact of atopic status on a predictive human test of skin irritation potential.

There has been much interest in recent years in the replacement of the Draize rabbit skin test for the identification of chemical skin irritants. A considerable effort has gone into the development of cell culture based assays. However, where ethical and safety considerations permit, the most obvious alternative is to use man himself. Data obtained using a suitable assay based on the endpoint of concern in the species of concern should be accurate and will represent a vital data base on which to develop sound in vitro assays. Thus, it is important to ensure the data produced in human assays is representative for man generally. To this end we have chosen to examine a number of variables and in this work report the effect of atopic status on the results obtained in a recently described human 4-h patch test. 30 atopic (defined by specific IgE to common allergens and by elevated total IgE) and 28 non-atopic volunteers were tested in this human 4-h patch test using 20% sodium dodecyl sulfate (SDS), 10% hydrochloric acid (HCl) and undiluted cocotrimethyl ammonium chloride (coco TAC). The level of irritant reaction was higher for SDS in the atopic panel, but was similar for HCl and coco TAC. The rank order of irritancy was the same in both panels. The results indicate that, whilst the intensity of reactions may be higher in atopics, their pattern of responses is similar to non-atopics. There is no evidence to indicate that they should either be deliberately included or excluded from the test panels recruited on a routine basis.

Animal Testing Alternatives↗
PubMed1995

The chemistry of contact allergy: why is a molecule allergenic?

This review concentrates on some specific aspects of the chemistry of allergic contact dermatitis. The way low molecular weight chemicals react with skin proteins to form complete antigens will be discussed and the development of molecular modelling techniques to analyse molecular recognition presented. Subsequently, how knowledge of the chemical structure can be used to estimate the allergenic activity of a molecule will be considered. This aspect includes work with qualitative and quantitative structure-activity relationships (SAR) in the field of contact allergy.

Allergens↗
PubMed1988

Methyl groups as antigenic determinants in skin sensitisation.

The methylating agents, methyl dodecane sulphonate, methyl hexadecane sulphonate and methyl hexadec-3-ene sulphonate are strong skin sensitisers, cross-reactive with one another, in guinea pig adjuvant tests. Differences in potency are observed among these 3 compounds, and the possible reasons for this are discussed. Isoeugenol fails to elicit a sensitisation response when challenged onto guinea pigs sensitised to methyl dodecane sulphonate, indicating that the mechanism of isoeugenol sensitisation is not based on methyl transfer. It is proposed that, in skin sensitisation involving small haptenic groups, antigenic specificity is directed not against the haptenic groups but against portions of the carrier protein whose configuration has been modified as a result of the carrier-hapten reaction. This concept is supported by published data on cross-reactivity patterns with enantiomeric pairs of alpha-methylene-gamma-butyrolactone derivatives.

Alkanesulfonates↗