Search

Background. It is widely accepted that there is a molecular weight (MW) cut-off of 500, such that single chemicals with MWs higher than 500 cannot be skin sensitizers. If true, this could serve as a useful principle for designing non-sensitizing chemicals. Objectives. To assess whether the 500 MW cut-off is a myth or a reality. Methods. A database of 699 chemicals tested for skin sensitization in guinea pigs or mice was analysed to establish the number of tested chemicals with MW > 500, and to establish whether any of these were sensitizers. Results. Only 13 (2%) of the 699 chemicals in the database have MW > 500. Of the 13 tested compounds with MW > 500 in the database, five are sensitizers and eight are non-sensitizers. Conclusions. The 500 MW cut-off for skin sensitization is a myth, probably derived from the widespread misconception that ability to efficiently penetrate the stratum corneum is a key determinant of sensitization potency. The scarcity of sensitizers with MW > 500 simply reflects the general scarcity of chemicals with MW > 500. [ABSTRACT FROM AUTHOR]

Background: Simultaneous contact allergies to the reactive diluent phenyl glycidyl ether (PGE) and epoxy resins based on diglycidyl ether of bisphenol A (DGEBA) or epoxy resins of the bisphenol F-type have been reported. The latter epoxy resins contain three isomers of diglycidyl ether of bisphenol F (DGEBF). PGE, DGEBA, and DGEBF are chemically similar with respect to the reactive glycidyl group and an aromatic ring, making cross-reactivity one of the possible explanations to simultaneous reactions. Aim: To investigate the sensitizing capacity of PGE and the cross-reactivity of PGE versus the epoxy resin monomers DGEBA and the three DGEBF monomers and vice versa. Method: The guinea-pig maximization test. Results: PGE is a strong sensitizer. Induction with DGEBA resulted in a statistically significant number of animals reacting to PGE, but when induced with PGE, the animals did not react significantly to DGEBA. Conclusions: When the results are applied to humans, it can be assumed that patients sensitized primarily to DGEBA react to PGE, but when sensitized exclusively to PGE, they do not react to DGEBA. Both reactive diluents and epoxy resins should be tested when contact allergy to epoxy resin systems are suspected. [ABSTRACT FROM AUTHOR]

There are currently available no systematic experimental data on the skin sensitizing properties of acrylates that are of relevance in occupational settings. Limited information from previous guinea-pig tests or from the local lymph node assay (LLNA) is available; however, these data are incomplete and somewhat contradictory. For those reasons, we have examined in the LLNA 4 acrylates: butyl acrylate (BA), ethyl acrylate (EA), methyl acrylate (MA), and ethylhexyl acrylate (EHA). The LLNA data indicated that all 4 compounds have some potential to cause skin sensitization. In addition, the relative potencies of these acrylates were measured by derivation from LLNA dose–response analyses of EC3 values (the effective concentration of chemical required to induce a threefold increase in proliferation of draining lymph node cells compared with control values). On the basis of 1 scheme for the categorization of skin sensitization potency, BA, EA, and MA were each classified as weak sensitizers. Using the same scheme, EHA was considered a moderate sensitizer. However, it must be emphasized that the EC3 value for this chemical of 9.7% is on the borderline between moderate (<10%) and weak (>10%) categories. Thus, the judicious view is that all 4 chemicals possess relatively weak skin sensitizing potential. [ABSTRACT FROM AUTHOR]

Predictive toxicology tests for the prospective identification of skin-sensitizing chemicals are well known and have been used for many years. However, of these, only the local lymph node assay (LLNA) has actually undergone formal independent assessment to determine the accuracy of the predictions, particularly with respect to the likelihood of false positives and false negatives. Often, efforts to increase the sensitivity of a test (reducing false negatives) tend to increase the number of false positives. In this short review, these issues are discussed in particular relation to the 3 predictive tests available in regulatory toxicology, the guinea-pig maximization test, the occluded patch test of Buehler and the LLNA. A key perspective is that no predictive test is without limitations; having a good appreciation of these limitations is necessary for making the best use of the information derived from these methods. [ABSTRACT FROM AUTHOR]

Ethoxylated surfactants are used in household and industrial cleaners, topical pharmaceuticals, cosmetics and laundry products. Polyethers, e.g. ethoxylated surfactants and polyethylene glycols, are oxidized by atmospheric oxygen (autoxidized) when stored and handled. We have previously shown that a chemically well-defined non-ionic surfactant, the ethoxylated alcohol penta-ethylene glycol mono- n-dodecyl ether (C12E5), forms a complex mixture of autoxidation products when exposed to air. Predictive testing in guinea pigs showed that the surfactant itself is a non-sensitizer, but that oxidation products formed are skin sensitizers. The aim of this study was to investigate the sensitizing capacity of a total oxidation mixture of C12E5 obtained after autoxidation. The allergenic activity of different oxidation products is discussed as well as the clinical importance of the findings. This study shows that the non-ionic surfactant C12E5 containing 20% oxidation products is a sensitizing mixture. The result accords with what is observed for other compounds that are unstable when in contact with air, e.g. limonene and linalool, major fragrance terpenes. Studies regarding the clinical relevance of our findings should be performed. However, it is already clear from this study that precautions must be taken in handling and storage of ethoxylated surfactants to avoid formation of allergenic mixtures. [ABSTRACT FROM AUTHOR]

Examines the relevance of 1-2 days occlusion exposure by repeated open applications. Induction of nickel sulfate and palladium chloride to the skin of guinea pigs; Relationship between reactivity to salts of palladium and nickel; Association of palladium allergy with nickel allergy.

Investigates the structure-activity relationships in the murine local lymph node assay for skin sensitization. Overview of the biological activity of skin-sensitizing chemicals; Use of the relative alkylation index approach in the modeling of the relationships; Analysis of sensitization test data.

A patient developed a circumscribed contact dermatitis after a single contact with squaric-acid-dietbylester (SADE). Patch tests with low concentrations of SADE were positive. Based on these observations, experimental studies on the sensitizing capacity of SADE were performed on guinea-pigs. The results disclosed that this compound is a strong sensitizer. Derivatives of SADE, such as the nearly insoluble squaric acid, squaric acid-1,2-diamide and dithio-N,N'-dicyclohexyte-1,2-diamide were not able to produce allergic skin reactions in the sensitized patient nor in guinea-pigs, The chemistry and the range of uses of squaric acid and its derivatives arc briefly mentioned. A hypothesis on the molecular mechanism of conjugation of SADE to human proteins and thereby on sensitization is discussed. A warning is given for taking precautionary measures before handling this substance. [ABSTRACT FROM AUTHOR]

An experimental study was conducted in guinea pigs for the predictive assessment of the beryllium alloy hazard in occupational exposure of the skin to beryllium compounds. Guinea pigs were sensitized to beryllium sulfate according to the maximized Magnusson and Kligman test, and challenged with beryllium alloy and metallic copper, beryllium arid aluminum samples. Results showed a delayed skin hypersensitivity reaction in 30 to 60% of pre-sensitized guinea pigs challenged with copper-beryllium alloys and aluminum-beryllium alloy. .An inflammatory follicular reaction was induced by copper in both controls and pre-sensitized guinea pigs. [ABSTRACT FROM AUTHOR]

Mometasone furoate is a new corticosteroid, synthesized to have an improved ratio of anti-in-flammatory potential to adverse effects. The guinea pig maximization test was used to determine the sensitizing capacity of mometasone furoate, and also to investigate cross-reaction patterns in animals sensitized to tixocortol pivalate and budesonide, respectively. Tixocortol pivalate was shown to be a sensitizer in the guinea pig, but cross-reactions to other tested corticosteroids were not observed. Furthermore, no sensitizing capacity could be demonstrated for budesonide or mometasone furoate. [ABSTRACT FROM AUTHOR]

While conducting a guinea pig sensitization protocol, using the maximization test, it was discovered, at challenge, that the test animals were more responsive to the vehicle (acetone) than they were to the proprietary test material. During rechallenge, conducted to clarify the specific immune status of the test animals, it was determined that they were also hyperreactive to an alternate vehicle (diethyl phthalate), to which they were naïve. This bizarre set of data is presented and it is suggested that this type of response is the prototype for the presence of false-positive responses experienced by toxicologists using this test. The test conditions imposed on the immune system by the maximization test that could result in these anomalous results are discussed. These data suggest that investigators need cautiously to interpret data that are produced by the injection of Freund's complete adjuvant (FCA). [ABSTRACT FROM AUTHOR]

The guinea pig maximization test (GPMT) of Magnusson and Kligman was published in 1969. Since then, a vast body of practical experience with the test has been accumulated. New information requires that certain aspects of the procedure be re-evaluated, especially with regard to the interpretation of challenge results. In particular, awareness of the phenomenon of hyperirritable skin (the 'angry back' phenomenon) suggests that presently used controls are not always adequate and may overstate allergenicity owing to false-positive reactions. The control group should be exposed to a chemical insult at induction which provokes an inflammatory reaction comparable to the test substance. We present strategies to distinguish irritant from allergic responses. Allergic reactions should persist on rechallenge weeks later, while nonspecific irritant reactions generally fade and are irreproducible in particular animals. Finally, when a chemical is identified as a contact sensitizer in the GPMT, that result is simply a categorical statement a1 a theoretical hazard. An assessment of risk is necessary to estimate the relevance of the test result to usage in the real world. [ABSTRACT FROM AUTHOR]

8 alkyl gallates, including the widely used antioxidants propyl, octyl, and dodecyl (=lauryl) gallate, have been subjected to experimental sensitization in guinea pigs. Using a modern sensitization procedure, the results showed that all gallates are moderate to strong contact sensitizers; dodecyl (=IauryI) gallate was found to be the strongest. A characteristic correlation between side chain length and mean response was observed, giving a maximum of sensitization at a length of 12 carbon atoms (dodecyl gallate). A literature review revealed that the frequency of reports of allergic contact dermatitis from antioxidants of the gallate type has increased in the last 4 years. In most cases, the moderate sensitizer propyl gaIIate was the source of sensitization. [ABSTRACT FROM AUTHOR]

Skin blood flow in allergic contact reactions and cross-sensitivity were evaluated using laser Doppler flowmetry (LDF) to study the dose-response relationships in phases of induction and challenge in guinea pigs. Guinea pigs were sensitized with different doses of 1-chloro-2,4-dinitrobenzene (DNCB) and challenged with different doses of DNCB and 2,4-dinitrobenzene sulfonic sodium salt (DNBS). The skin reactions were evaluated by LDF and visual reading score. The results indicated that there were dose-response relationships between the doses of DNCB and LDF measurements in both phases of induction and challenge, that there was a cross-reaction between DNCB and DNBS, and that the reactions at 24 h were greater than that at 48 h after removal of the patches. LDF may discriminate between positive patch test reactions and negative or doubtful reactions, but not between weak positive and strong positive reactions. This is because vascular dilatation and increase of flow already reaches a maximum in weak reactions. The more advanced phases are dominated by edema formation. This is simply the nature of the inflammatory reaction, rather than a methodological error. The important point is that LDF can separate positive reactions from negative/uncertain reactions. The results indicated that LDF, as a non-invasive technique, may objectively and quantitatively evaluate the dose-response relationships of contact sensitivity of sensitizers. [ABSTRACT FROM AUTHOR]

26 different compounds have been investigated experimentally for their sensitizing capacity in guinea pigs. 19 of these occur in propolis as well as in poplar bud exudates, and 14 of them are also found in balsam of Peru. 4 caffeates and benzyl isoferulate were found to be strong sensitizers. 7 compounds were moderate, and 13 compounds showed only weak sensitizing potency. Methyl cinnamate was negative. Patch tests in 11 propolis-sensitive patients once more revealed 3-methyl-2-butenyl caffeate and phenylethyl caffeate as the major sensitizers. In addition to the 8 compounds already known to occur in propolis as well as in balsam of Peru, we detected 5 further substances that both materials have in common. Among these, benzyl isoferulate is considered a noteworthy sensitizer. Coniferyl benzoate, which was shown to be a moderate sensitizer, is present in fresh samples of balsam of Peru, while in propolis it has been detected only once so far. The flavonoid aglycones occurring in poplar bud exudates, and hence also in propolis, are weak sensitizers which play only a minor role in propolis hypersensitivity. [ABSTRACT FROM AUTHOR]

Studies in guinea pig and man have shown that eugenol can quench non-specifically contact urticarial responses, whereas limonene seems largely ineffective. In a comprehensive series of studies, there was little evidence of quenching of delayed contact hypersensitivity reactions to cinnamic aldehyde or citral, including in 'pre-quenched' material supplied by a perfume/flavour company, and in a similar mixture prepared in this laboratory, in the guinea pig model. In addition, there was no evidence of the quenching by eugenol of allergic reactions to cinnamic aldehyde in a panel of human subjects with a proven history of cinnamic-aldehyde-induced allergic contact dermatitis. Overall, the results lend little credibility to earlier literature reports of quenching phenomena in delayed contact hypersensitivity responses. [ABSTRACT FROM AUTHOR]

12 young men developed allergic contact dermatitis form wearing yellow cotton sweaters. We attempted to identify ) the causative agents by an experimental screening method in animals. Guinea pigs were sensitized with an acetone extract of the sweater material, by means of the guinea pig maximization test (GPMT). Active ingredients were then separated form the extract, by step-by-step patch test screening of chromatographic fractions in the guinea pigs, and finally analyzed by gas chromatography-mass spectrometry (GC-MS). Although there were 2 allergens with important activity (1 in the fraction eluted from the silica gel column with hexane, and 1 in the methanol fraction), the present study is focused on the fat-soluble allergens in the hexane fraction, GC-MS analysis revealed that 4 kinds of phosgene(chlorophenyl) hydrozones (PCPHs) were present in the hexane fraction. PCPHs prepared in our laboratory showed strong eliciting activities, not only in the guinea pigs sensitized with the extract, but also in a male volunteer sensitized by exposure to a yellow sweater during irritancy testing. Phosgene(2,5-dichlorophenyl)hydrazone(PCPHs) which was the main component among the PCPHs found in the sweater, sensitized guinea pigs even at the 1 ppm level. From these results, we conclude that PCPHs were one of the allergens responsible for the cases. [ABSTRACT FROM AUTHOR]

The contact sensitizing activity of dithranol and butantrone (10-butyryl dithranol) was studied in 3 animal models: the guinea pig maximization test (GPMT), the closed patch test (CPT), and the ear swelling test (MEST) in 2 different mouse strains. In the GPMT, both dithranol and , to a greater extent, butantrone showed sensitizing potential. Because butantrone was less irritant, the concentrations used were 10 × higher than those of dithranol. In the CPT, only butantrone was slightly positive. In the MEST, with both CF-I and Balb.c mice, dithranol caused less swelling of the test ear after challenge than butantrone. According to the evaluation criteria of the MEST, only butantrone caused sensitization in 50% of the CF-I mice and in 40% of the Balb.c mice. Thus, the GPMT was the only test which indicated the minor contact sensitizing potential of dithranol. On the other hand, the 10-butyryl analogue of dithranol showed undoubtedly stronger contact sensitizing potential than the parent compound in all tests. Therefore, as compared to dithranol, an increased risk of sensitization should be considered. [ABSTRACT FROM AUTHOR]

3 minor resin acids and 7 commercial modified-colophony products of different origins were studied by experimental sensitization by means of a modified FCA method. All 3 resin acids were almost negative. The commercial products gave different results. While the maleic-modified product of Greek origin showed a strong sensitizing power, the fumric-modified, terpene-phenol-modified and a disproportioned rosin were only moderate. A remarkable difference was obtained with the Swedish and Finnish tall oil rosins. which, in contrast to the previously studied French product, exhibited only a weak sensitizing capacity. [ABSTRACT FROM AUTHOR]

During clinical trials, a clonidine transdermal device has been found to induce clonidine-specific allergic contact dermatitis in up to 25% of patients during a treatment period of year. Using 3 different guinea pig strains, development was attempted of an experimental guinea pig model that would allow for in-depth studies into the mechanism of sensitization, and a possible role of transdermal device components. Transient low-level clonidine allergy could be obtained only in a minority of animal, with severe sensitization procedures departing from epicutaneous applications, combined with intradermal (adjuvant) FCA injections. Sensitization was not potentiated by additional booster procedures, including cyclophosphamide pretreatment, nor any of the putative cofactors (UV-treatments. C. parvum or acetaldehyde involvement) studied. These results suggest that the persistent skin contacts in man, with transdermal devices for sustained drug delivery, generate unique conditions favouring the development of allergic contact dermatitis, which are difficult to mimic in experimental animal models. Thus, clinical allergy may develop even to extremely weak sensitizing drugs that can be safely used orally, and escape most currently available predictive contact allergy animal models. Clinical studies remain unavoidable for studying factors that may reduce sensitization rates to more acceptable levels. [ABSTRACT FROM AUTHOR]

The allergenicity of the maleic-modified rosins and their esters has been studied. The unesterified resins are mainly used in paper size and the esters in printing inks, varnishes and adhesives. The levopimaric-maleic anhydride Diels-Alder adduct (maleopimaric acid) is the main component obtained in the maleic-modified resins. This compound was synthesized and its structure was determined. Its sensitizing potential was investigated in guinea pigs according to different methods. It was shown that maleopimaric acid is a very potent sensitizer, comparable with the strongest allergen isolated from unmodified gum rosin. The allergen may also be present after esterification unless the process is carried out to completion. The animals sensitized to maleopimaric acid did not react to unmodified rosin, which shows that maleopimaric acid is structurally different from the allergens in rosin. [ABSTRACT FROM AUTHOR]

Pyridostigmine bromide (PB) delivered transdermally may be a useful pretreatment for organophosphate poisoning. PB transdermal formulations were developed since this route has the potential to provide a more constant, prolonged and therapeutically-effective drug level in the body. Guinea pig skin sensitization studies, using a variation of the split adjuvant technique, were conducted with various PB transdermal formulations as part of a safety evaluation profile. 3 gel matrix formulations were tested. The 3 Formulations contained 50% PB, 30% PB with 0.198% sodium lauryl sulfate (SLS) and 30% PB with 0.21% of a proprietary surfactant (PS), respectively. SLS and the proprietary surfactant were added to the formulations as dermal penetration enhancers. 9 groups of 10 animals were induced and challenged with 1 of the 3 PB or PB/surfactant formulations (3 groups per formulation). In addition, 2 groups of 10 animals were included in the study as positive controls that were induced and challenged with 2,4-dinitrochlorobenzene (DNCB), 44% of the animals responded positively at challenge to 50% PB. 80% of the animals responded positively at challenge to 30% PB/0.198% SLS and 82% of the animals had positive responses at challenge to 30% PB/0.21% PS. This study demonstrates that PB is a potential contact sensitizer that shows a potentiated response in the presence of surfactants. [ABSTRACT FROM AUTHOR]

A predictive study comparing the sensitizing potentials of some topical antimicrobials, using a modified Beuhler's technique, showed that over-the-counter (OTC) antimicrobials were more sensitizing than prescribed topical antibiotics. Among OTC antimicrobials, proflavine was the most potent sensitizer (4/10 guinea pigs); parachlorometaxylenol, benzalkonium chloride and propamidine isethionate moderate sensitizers (2/10 guinea pigs); iodine a weak sensitizer (1/10 guinea pigs); and chlorhexidine and cetrimide very weak sensitizers (0/10 guinea pigs). Among prescribed topical antibiotics, neomycin was a moderate sensitizer (2/10 guinea pigs); gentamycin and chloramphenicol weak sensitizers (1/10 guinea pigs); kanamycin, clioquinol, polymyxin B, bacitracin, tetracycline, sodium fusidate and fusidic acid very weak sensitizers (0/10 guinea pigs). There was good correlation between sensitizing potentials in animal studies and clinical experience of contact allergy to these topical antimicrobials. [ABSTRACT FROM AUTHOR]

9 coumarins used as chemical reagents, laser dyes, in perfumery, cosmetics or occurring naturally, were investigated experimentally in guinea pigs to determine their contact sensitizing capacity. 5,7-dihydroxycoumarin, limettin and 5,7-dihydroxy-4-methylcoumarin were found to be moderate sensitizers, while scoparone, isoscopoletin and 4-hydroxycoumarin were weak. The 3 laser dyes were completely negative. The results indicate that substitution in the 6 and 7 or 5 and 7 positions with 2 hydroxy groups supports allergenic capability, while other substituents (e.g., methoxy groups) in the same positions, or an additional (third) substituent, diminish activity. [ABSTRACT FROM AUTHOR]

The efficacy of 4 barrier preparations presented as cream or foam against percutaneous absorption of organic solvents was investigated in the guinea pig. An ordinary hand cream was also tested. Slight reduction in blood concentration of the solvents was seen when normal skin treated with barrier creams was exposed. Absorption of butanol through stripped skin treated with barrier creams was higher than absorption through skin not so treated. Barrier creams can be considered to give poor skin protection against the organic solvents investigated. [ABSTRACT FROM AUTHOR]

Experimental sensitization of guinea pigs with 6 azo and anthraquinone dyes used frequently as disperse dyes for fabrics (stockings, panty hose) revealed that the blue dyes were moderate sensitizers while the red, yellow and orange dyes were only weak ones. This was found to be in contrast with the order based on the frequency of observed allergic sensitization, which showed the yellow and orange dyes at the top of the list and the blue dyes at the bottom. [ABSTRACT FROM AUTHOR]

Cyclosporine (CSA) is an effective immunosuppressive agent and is used in tissue transplantation. The present investing was undertaken to determine the effect of topical delivers of CSA on allergic contact dermatitis in guinea pigs. Topical 15% CSA in an azone (1-dodecylazacycloheptan 2-one)-containing vehicle blocked local elicitation in previously dinitrochlorohenzene (DNCB) sensitized animals that received a single topical application just prior to elicitation. Elicitation was not blocked at a distant site, indicating a local effect of topical CSA. In contrast, topical CSA when applied twice daily for a total of 5 applications during sensitization only, did not block subsequent elicitation. These experiments suggest that cyclosporine may be beneficial in the therapy of human contact dermatitis, as swell as other T cell medicated dermatoses. [ABSTRACT FROM AUTHOR]

The potential of 3,4,5-trichloropyridazine to induce contact sensitization was assessed in the guinea pig maximization test of Magnusson and Kligman and also in the closed patch test described by Buchler. The test material was a 1% solution of 3,4,5-trichloropyridazine in a highly refined mineral oil. The test material elicited moderate to severe irritation when diluted in mineral oil to concentrations of 15-25% and minimal irritation at concentrations of 1-3%. Both tests clearly indicated that 3,4,5-trichloropyridazine was a contact sensitizer to guinea pigs, although the response was stronger in the maximization test. Sensitization was distinguished from irritation by the use of concurrent irritation control groups. [ABSTRACT FROM AUTHOR]

The methylating agents, methyl dudecane sulphonate, methyl hexudecane 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 hut 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 α-methylene-γ-butyrolactone derivatives. [ABSTRACT FROM AUTHOR]

The sensitizing capacities of 2-methylol phenol (2-MP), 4-methylol phenol (4-MP) and 2,4,6-trimethylol phenol (2,4,6-MP) were investigated with the guinea pig maximization test. These compounds are known sensitizers in phenol-formaldehyde resins, The studs was performed in order to assess and compare the degree or the sensitizing capacities of these chemically related substances. The animals were also rechallenged with the sensitizer and 5 chemically related compounds in order to study the cross-reaction patterns. 2-MP was demonstrated to be a strong sensitizer, 4-MP a moderate sensitizer and 2,4,6-MP a weak sensitizer. With 2-MP as the sensitizer, p-cresol and 2,4-dimethyl phenol were possible cross- reacting substances, p-cresol and 2,4-dimethyl phenol were possible cross-reacting compounds for 4-MP. The chemical investigation by high pressure liquid chromatography indicated that the compounds tested were pure and separable. [ABSTRACT FROM AUTHOR]

In order to investigate whether abietic acid itself is the allergenic component of colophony, 2 commercial samples were extensively purified and tested in guinea pies and in colophony-sensitive patients. In the modified FCAT method, sensitization was obtained with Portuguese colophony and when challenged with purified abietic acid, the animals showed no reaction. In the GPMT method, the animals were exposed to purified abietic acid. Challenging with 2 different samples of it gave no significant reaction. When patch tested, patients sensitive to colophony showed no reactions to abietic acid which had been purified immediately before the test. It is concluded that abietic acid itself is not a contact allergen. [ABSTRACT FROM AUTHOR]

Benzoyl peroxide (BP) is shown to be a weak allergen. Of 25 guinea pigs, only 5 were sensitized in the TINA test. Before treatment, only 2 of 172 acne patients gave a positive patch test with 1% BP, but not with 0.1% BP. The following results suggest that BP is a strong irritant. The irritant potential ID50 in rabbits was 2.52%, and the IT50 was 2.31 days with 5% BP, 4.34 days with 1% and 8.35 days with 0.1% BP. 29% of acne patients and non-exposed controls had a positive patch test with 5% BP. However, only 11 of 155 acne patients had clinical signs of intolerance, which settled despite continued use in 10 cases. The possible reasons for this dichotomy are explored. Neither the irritant nor allergenic properties of BP impaired its clinical use. [ABSTRACT FROM AUTHOR]

Chlorocresol sensitization from 5 topical preparations was determined in guinea pigs using the cumulative contact enhancement test. Chlorocresol 5% in olive oil/acetone (4/1), and 5% in aqueous suspension stabilized with carbomer 941 were more seasitizing (55% and 60% of the animals positive, respectively) than chlorocresol 5% in propylene glycol with or without carbomer 941 (20% positive). The sensitization from a saturated aqueous chlorocresol solution (about 0.38% w/v) was comparable to that of a 5% propylene glycol solution containing 13 times more chlorocresol. The fraction of the applied dose (from each preparation) that remained in the bandage material and the patch test skin site was determined by combined gas chromatography-mass spectrometry using an isotopic dilution technique. From 0.2% to 1.6% of the applied doses remained at the patch test skin sites as free chlorocresol. 75% of the chlorocresol in aqueous suspension permeated the skin in contrast to 34% and 35% of the chlorocresol in olive oil/acetone (4/1) and propylene glycol, respectively. In spite of the same amount of chlorocresol absorption from the 2 latter preparations, they showed a significant difference in sensitizing capacity. No simple relationship between the sensitization rates and the calculated bioavailability was observed with the preparations tested. [ABSTRACT FROM AUTHOR]

Most composite materials in dentistry used today. contain resins based on dimethacrylates. BIS-GMA (2,2-bis-4-(2-hydroxy-3-methacryIoxypropoxy)phenyI)propane], the addition reaction product of bisphenol A and glycidyl methacrylate or an epoxy resin and methacrylic acid, is used most extensively. More recently, dimethacrylates based on bisphenol A. with various chain lengths have appeared on the market as a substitute for or in addition to BIS-GMA. Such compounds are BIS-MA [2.2-bis-(4-(methacryloxy)phenyl)propane]. BIS-EMA [2,2-bis-(4-(2-methacryloxyethoxy)phenyl)propane] and BIS-PMA [2.2-bis44-(3-methacryloxypropoxy)phenyl)propane. Increasing interest in the radiaton cure of coatings and printing inks have focused attention on these substances and on epoxy diacrylates as radiation-curable resins. The sensitizing capacity of the different acrylates based on bisphenol A or epoxy resin have been investigated with the guinea pig maximization test. The pattern of simultaneous reactivity of the compounds was also studied. Epoxy diacrylate [2,2-bis-(4-(2-hydroxy-3-acryloxy- propoxy)phenyl)propane], BIS-EMA and BIS-MA are shown to be strong sensitizers, while the linear fraction of BIS-GMA and its isomers and BIS-PMA have none or a low sensitizing capacity. The impurities in the BIS-GMA and BIS-MA batches seem to have high allergenic potential. These results stress the importance of a pure substance when discussing allergenicity and cross reactions. [ABSTRACT FROM AUTHOR]

The guinea pig maximization test was used to evaluate the sensitizing potential of formaldehyde and 6 formaldehyde releasers (Forcide 78, Key worth: Forcide 78-formaldehyde - Germall 115 - (Irotan BK - Grotan OX - KM 200- Preventol D2 - beuxyihemiformaics - hexahydratriazine - imidazolidinyl urca - mcthylene-bismethyloxaxolidinc - allergic contact dermatitis - guinea pig allergy test - predictive tests. Germall 115, Grotan BK, Grotan OX, KM 200 and PreventolD2). The tests were carried out in 2 laboratories (Copenhagen and Stockholm), and although we intended the procedures to be the same, discrepancies were observed, possibly due to the use of different animal strains, test concentrations and vehicles. The sensitizing potential was in general found to be stronger in Stockholm compared to Copenhagen: formaldehyde sensitized 50% of the guinea pigs in Copenhagen and 95% in Stockholm. For Grotan BK, the corresponding rates were 20% and 74%. Forcide 78, KM 200 and Preventol D2 sensitized 20% to 25% of the animals in Copenhagen. while Germall 115 and Grotan OX sensitized 60% to 70% of the animals in Stockholm. [ABSTRACT FROM AUTHOR]

The capacity of tegobetain, pyrrolnitrin, tolcyclate and chlorquinaldol to induce delayed-type contact sensitization was studied in guinea pigs in 2 series of tests using the method of Magnusson & Kligman and the authors' modification of the wholly intradermal Draize technique. Histological examination of skin biopsies obtained from the test area demonstrated that tegobetain, pyrrolnitrin and tolcyclate are potential sensitizers. [ABSTRACT FROM AUTHOR]

The naturally-occurring sesquiterpene lactone, parthenin, is responsible for a high incidence of allergic contact dermatitis in India. Cross-sensitivity tests on guinea pigs sensitized to parthenin indicate a relatively high immunological specificity for this low molecular weight hapten. Coronopilin and damsin, sesquiterpene lactones most similar to parthenin, gave positive reactions but other structurally related lactones such as dihydroisoparthenin, tetrahydroparthenin, tetraneurin-A, hysterin, helenalin, and tenulin, or hymenin, a diastereoisomer of parthenin, were negative. [ABSTRACT FROM AUTHOR]

Concomitant sensitization to hydroquinone and p-methoxyphenol occurred in sensitization experiments with acrylic monomers in guinea pigs. No relation between the concentration of the inhibitor in the monomers and the incidence of these concomitant sensitizations could be detected. Concomitant sensitization did not influence the cross reaction pattern of the acrylic monomers. The sensitizing potential of acrylic monomers is not influenced by the inhibitors, but some acrylic monomers seem to interfere with the sensitizing potential of the inhibitors. [ABSTRACT FROM AUTHOR]

The sensitizing capacities of helenin (an extract from a Compositae Inula helenium L.). alantolactone and isoalantolactone (two isomeric sesquiterpene lactones), were assessed by sensitizing guinea pigs of different strains; albino Himalayan spotted. Pirbright and Hartley. Both alantolactone and isoalantolactone are found to be sensitizers if injected intradermally. Only Pirbright guinea pigs showed a high sensitization rate by the open epicutaneous technique; with this method, alantolactone was the more potent sensitizer. [ABSTRACT FROM AUTHOR]

A maximization test (after Magnusson & Kligman 1970), a single injection adjuvant test (SIAT) and a modified Draize test procedure for assessing contact sensitization potential in guinea-pigs have been compared for their ability to detect 19 known human contact sensitizers. The results show that the modified Draize procedure is a good screening test particularly for strong sensitizers. The maximization procedure is a very stringent test of sensitization potential, able to detect some marginal sensitizers. The sensitivity of the SlAT procedure is sufficiently similar to that of the maximization test to act as an alternative for routine testing, particularly in view of its practical advantages over the maximization procedure. [ABSTRACT FROM AUTHOR]

A modified guinea pig testing technique was developed for the detection of weak allergens and allergenicity of materials unsuitable for testing by intradermal injection. This Lest involved the use of Freund's complete adjuvant to stimulate the immune system of the animal, and external application instead of intradermal injection of the test compound in the induction stage. The allergenicity of Sudan Ill, Brilliant Lake Red R and Sudan I was tested by this procedure. In the dose-effect study of Sudan I, the dose dependency of a positive reaction of the induction and challenge concentrations was recognized. The test was compared with three other guinea pig sensitization tests. The results obtained with this test correlated well with those obtained with the guinea pig maximization test. [ABSTRACT FROM AUTHOR]

A 4-week open cumulative irritancy test in guinea pigs discriminated between two low grade irritant vehicles, nonionic base (anhydrous) and hydrophilic ointment. The procedure might be useful as a predictive test for low grade irritants. The angry skin syndrome was established in the guinea pigs by one Freunds complete adjuvant intradermal injection on day 0, or by daily open applications of 10 % sodium lauryl sulfate in petrolatum to the neck area of the animals. [ABSTRACT FROM AUTHOR]

The article discusses the control mechanism in the immunology of contact dermatitis. In the conventional immunizing process, a third population of specific lymphocytes as well as effector and memory cells are generated. These cells have an adverse activity and control the generation of effector cells. The mode of action of suppressor cells has been studied using guinea pigs as experimental animal and dinitrochlorobenzene as sensitizer. To study the effect of suppressor cells, the ability of cyclophosphamide to eliminate these cells has been used.

2.6-dimethoxy-1,4-benzoquinone has already been discovered in more than 25 different plants and woods. Several authors have shown its strong bacteriostatic activity against micro-organisms. In 1972 a positive skin reaction to 2.6-dimethoxybenzoquinone was obtained in a patient allergic to Sucupira wood (Bowdichia nitida Benth.). This compound could be isolated from the wood. During the chemical investigations of other commercial woods which have been described as the cause of allergic contact dermatitis, 2.6-dimethoxybenzoquinone could be isolated from an additional 21 different species. In the case of Australian blackwood Acacia melanoxylon R. BR., its structure was elucidated by x-ray analysis. Sensitization of guinea pigs revealed that 2.6-dimethoxybenzoquinone is a relatively good sensitizer. In some of the woods investigated, quinones have never been discovered before, for example in Makoré, Australian black-wood, Wengé, White wood, Afrormosia and Afzelia. In 10 of them only this quinone was detectable. Besides its allergenic properties, 2.6-dimethoxybeozoquinone may be responsible for the high termite resistance of these woods. In all cases of contact dermatitis from these wood species in which quinoid allergens other than 2.6-dimethoxybenzoquinone could be detected, this quinone should be used for patch tests. [ABSTRACT FROM AUTHOR]

This article presents a study related to sensitization as of March 1991. Thirty-eight hydrangea plants were purchased from the Hamburg flower market in late autumn. The leaves, stems and petals were separated and dipped for 5 minutes into peroxide-free diethyl ether. Ten female albino Pirbright white, guinea pigs were used. Sensitization was carried out with a modified fruit complete adjuvant technique. Open epicutaneous elicitation was performed by applying hydrangenol. All animals were found to be sensitized when challenged with hydrangenol. therefore it must be considered a strong contact sensitizer.

Flare-up reactions were induced in potassium dichromate hypersensitive guinea pigs by a single oral dose of 55 mg/kg. This dose is systemically toxic and higher than the dose required in humans. A total oral dose of potassium dichromate of 90-115 mg/kg induced immunological unresponsiveness for at least 6 weeks. With limitations, the guinea pig model may be helpful in screening the hyposensitization capacity of different haptens dosed orally. [ABSTRACT FROM AUTHOR]

Severe allergic contact dermatitis from a paint mildeweide, 2-n-octyl-4-isothiazolin-3-one. developed in a worker formulating latex paints within a paint manufacturing company, Guinea pig maximization testing demonstrated this to be a moderate sensitizer. Further casts of allergic contact dermatitis may be encountered as the use of this biocide increases in the market place. [ABSTRACT FROM AUTHOR]

A comparison was made between the guinea pig maximization test (GPMT), open epicutaneous test (OET) and chamber test (CT), and the allergens were neomycin sulphate and propylene glycol (PG). The sensitization rate for neomycin in petrolatum was 35% in GPMT, 25% in OET and 25% in CT. The corresponding figures for neomycin in PG were 30% in GPMT, 45% in OET and 32% in CT. PG caused no hypersensitivity in 118 guinea pigs. The results suggested that as a hygroscopic, irritant and penetrating vehicle, PG facilitates the induction of delayed contact allergy, especially in OET. [ABSTRACT FROM AUTHOR]

Skin sensitization testing in guinea pigs, using methods such as the Buchler, maximization and split adjuvant, requires wrapping the animals torso to secure the test patch to the skin. Potential health effects of wrapping other than temporary stress, are generally not considered. The repeated wrapping procedure typically used in epicutaneous skin sensitization testing can result in the development of hepatic necrosis, confirming observations made following a single wrapping during acute irritation screening.

The guinea pig maximization test (GPMT) has recently been used for sensitization studies with formaldehyde at two different laboratories. When using a toxic concentration of formaldehyde for intracutaneous induction, a decrease in the sensitization was recorded. Inflammatory processes in the guinea pig can both depress and enhance skin reactivity, so the purpose of this study was to investigate whether a toxic dose of formaldehyde would depress the skin reactivity to an unrelated contact sensitizer using the GPMT for sensitization.