Since 1990 7 sunscreen allergens have been included in the standard photopatch protocol at 2 Swedish dermatology clinics. 355 consecutive patients with suspected photosensitivity were tested, and in 28 of these (7.9%), a total of 42 allergic reactions were found. 80% of the reactions were of photocontact origin. The most common allergen was benzophenone-3 (Eusolex 4360), with 15 photocontact and 1 contact allergic reactions, followed by isopropyl dibenzoylmethane (Eusolex 8020) (8 photocontact, 4 contact) and butyl methoxydibenzoylmethane (Parsol 1789), with 6 photocontact reactions. There were 2 cases of photocontact allergy to phenylbenzimidazole sulfonic acid (Eusolex 232), which has not been reported previously. 1 case of contact urticaria from benzophenone-3 was accidentally found. In addition, 21 + reactions of doubtful relevance were noted in 14 patients: 16 on irradiated and 5 on non-irradiated test sites. Among these, irritant and phototoxic reactions may be included. These results indicate that the inclusion of UV filters in the standard photopatch protocol is important. Immediate-type testing for urticaria could also be of value.
The activity of carbohydrate metabolism certain enzymes [hexokinase (EC 188.8.131.52.), glucokinase (EC 184.108.40.206), phosphofructokinase (EC 220.127.116.11.1), glucoso-6-phosphate-dehydrogenase (EC 18.104.22.168.)] was studied in the sheep skin when adding vitamin A, sodium sulphate and insulin to the basic ration. The activity of the studied enzymes in the skin was established to be rather high and depend to a considerable extent on feeding, seasonal and hormonal factors. In summer the activity of such enzymes as glucoso-6-phosphate-dehydrogenase and glucokinase decreases, and that of hexokinase, vice versa, increases. Vitamin A alone against a background of the basic ration almost has no effect on the activity of the enzymes, with the exception of phosphofructokinase in certain periods of the experiment. More noticeable shifts in the activity of the enzymes were observed in the case when vitamin A and sodium sulphate were added to the ration of sheep, and also with the injection of insulin. In such cases in the sheep skin there occurs first of all an increase in the activity of glucokinase and glucoso-6-phosphate-dehydrogenase.
In the two years since the last workshop report, the environment surrounding the prediction of skin sensitisation hazards has experienced major change. Validated non-animal tests are now OECD Test Guidelines. Accordingly, the recent cross sector workshop focused on how to use in vitro data for regulatory decision-making. After a review of general approaches and six case studies, there was broad consensus that a simple, transparent stepwise process involving non-animal methods was an opportunity waiting to be seized. There was also strong feeling the approach should not be so rigidly defined that assay variations/additional tests are locked out. Neither should it preclude more complex integrated approaches being used for other purposes, e.g. potency estimation. All agreed the ultimate goal is a high level of protection of human health. Thus, experience in the population will be the final arbiter of whether toxicological predictions are fit for purpose. Central to this is the reflection that none of the existing animal assays is perfect; the non-animal methods should not be expected to be so either, but by integrated use of methods and all other relevant information, including clinical feedback, we have the opportunity to continue to improve toxicology whilst avoiding animal use.
The biochemical mechanisms of anti-inflammatory effect of endocannabinoid congener N-stearoylethanolamine (NSE) was studied on the model of experimental burn in rats. The animals after the thermal burn of the skin received per os during 7 days the water suspension of NSE in a doze 10 mg/kg of body weight. In the other groups of rats the suspension was applied to the wound (the concentration of NSE was 10 mg/ml). It was shown for the first time that NSE accelerated the process of burn wound healing by the inhibition of proinflammatory cytokines (TNFalpha, IL-6) production. NSE caused the normalization of the iNOS and cNOS activity and of nitrite content in plasma, erythrocytes, liver and spleen of rats. NSE also modified the antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) activity and diminished the level of lipid peroxidation. The discovered anti-inflammatory NSE properties suggest the possibility of its usage for burn treatment.
Eight wound preparative agents (one triclosan compound, one hexachlorophene compound, and six iodophors) were evaluated under actual operating-room conditions for efficacy in de-germing the operative site prior to the performance of 310 total hip arthroplasties. All of the preparations tested achieved a significant reduction (p less than or equal to 0.001) of indigenous skin microflora compared with the pre-scrub level in both the post-scrub and the postoperative cultures. Two iodophors, when applied as sprays, demonstrated excellent bactericidal action, were less time-consuming and easier to use than the compounds that were applied as scrubs, and did not alter the low (0.42 per cent) infection rate that we have recorded over a period of four years.
Occupational exposure to cobalt is well established in hard metal manufacture. Cobalt is known to cause contact allergy, asthma, hard metal lung disease, and lung cancer. The relationship between skin exposure and uptake determined in blood has not been extensively investigated.
To examine whether skin and inhalable air exposure to cobalt contributes to uptake, determined as cobalt in blood, in a hard metal manufacturing factory.
The amount of cobalt on the skin found with an acid wash technique, the air concentrations of inhalable cobalt and cobalt blood concentrations were determined and correlated in exposed workers.
We found a significant rank correlation for cobalt concentrations on the skin, in inhalable air, and in blood (0.376-0.498). Multiple linear regression showed significant regression coefficients for cobalt skin exposure and blood (B?=?0.01, p?
Cites: Ann Occup Hyg. 2000 Oct;44(7):519-22 PMID 11042253
Bisphenol A (BPA) has one of the highest production volumes of all chemicals worldwide. It has been widely studied because of its endocrine modulating activity. In addition to dietary intake, absorption of BPA via the skin from handling thermal papers is believed to be a relevant route of exposure. We studied BPA exposure via thermal paper receipts in simulation experiments performed by three volunteers, and examined urinary excretion of BPA. We also evaluated background BPA excretion among the Finnish working-age population. The geometric mean BPA excretion among non-occupationally exposed working-age Finns (n=121) was 2.6 µg/l, the range being 0.8-18.9 µg/l. The 95th percentile of the non-occupationally exposed people was 8 µg/l, and this was set as the reference limit for the non-occupationally exposed population. In the first simulation experiment, which was conducted under conditions representing the most likely exposure, i.e., the work of a cashier in a supermarket, BPA excretion remained below the reference limit in all participants. In the second simulation experiment, with more intensive, short-time handling of thermal paper (three times 5 min), urinary excretion also remained at or below background levels (highest value being 10.3 µg/l). The calculated maximum BPA excretion per day after handling thermal paper was less than 0.2 µg/kg of body weight, suggesting a total daily intake over 25 times lower than the European Food Safety Authority's (EFSA's) proposal for a temporary tolerable daily intake (temporary TDI) (5 µg/kg/day).
Idiosyncratic drug reactions are difficult to study in humans due to their unpredictability. Unfortunately, this characteristic also hinders the development of animal models needed for mechanistic studies. Nevirapine, used to treat human immunodeficiency virus (HIV) infections, results in a severe idiosyncratic skin rash in some patients. We found that nevirapine can also cause a significant rash in some strains of rats. At a dose of 150 mg/kg/day, the incidence in female Sprague-Dawley rats was 6/28 (21%), in female Brown Norway rats 32/32 (100%), and in female Lewis rats 0/6 (0%) while no male Sprague-Dawley or Brown Norway rats developed a rash. Female SJL mice 0/7 also did not develop nevirapine-induced skin lesions. The first sign of a reaction in Brown Norway rats was red ears at days 7-10 followed by a rash with scabbing mainly on the back; this was a shorter time to onset than in Sprague-Dawley rats. Light microscopy of the skin revealed a primarily mononuclear inflammatory infiltrate and lesions typical of self-trauma. Immunohistochemistry results suggest that the infiltrate was composed of CD4 and CD8 T cells as well as macrophages. A lower dose of either 40 or 75 mg/kg/day did not lead to a rash and, in fact, 2 weeks of the lower doses induced tolerance to the 150 mg/kg/day dose in female Brown Norway rats. A dose of 100 mg/kg/day resulted in rash in 2/4 (50%) of female Brown Norway rats. Rechallenge of Brown Norway rats that had been allowed to recuperate after a nevirapine-induced rash led to red ears in less than 24 h followed by hair loss and occasional skin lesions. Although the skin rash was less evident on rechallenge, microscopically, the cellular infiltrate was more prominent, especially surrounding the hair follicles. Moreover, there were lesions of interface dermatitis with apoptosis and satellitosis, indicative of a cell-mediated immune attack on the epidermis. While systemic signs of illness did not accompany the rash on primary exposure, on rechallenge, the animals appeared generally unwell and this forced sacrifice after 2 weeks or less of treatment. Importantly, splenocytes isolated from rechallenged animals were able to transfer susceptibility to nevirapine-induced skin rash to naïve female Brown Norway recipients, which was illustrated by a faster time to onset of rash in the recipients. The characteristics of this adverse reaction are similar to that seen in humans; that is, it is idiosyncratic in that it only occurs in some strains of animals, is delayed in onset, is more common in females, is dose-dependent, and appears to be immune-mediated. Therefore, it may represent a good animal model for the study of idiosyncratic drug reactions.