Journal of Toxicology-cutaneous and Ocular Toxicology最新文献

{"title":"Ocular Side Effects Associated with Systemic Isotretinoin","authors":"A. Oner, Ayten Ferahbaş, S. Karakucuk, S. Utaş, B. Karaman, C. Kutlugun, M. Somdas, Ertuǧrul Mirza","doi":"10.1081/CUS-200035368","DOIUrl":"https://doi.org/10.1081/CUS-200035368","url":null,"abstract":"Purpose. To evaluate ocular side effects associated with systemic isotretinoin. Patients and Method. Thirty‐five patients with severe recalcitrant acne were enrolled in this prospective study. Isotretinoin was administered at a dose of 0.5–1 mg/kg/day in two divided doses with food for 16 weeks. In all patients, visual acuity, anterior segment examination, intraocular pressure (IOP) measurement, Schirmer I test, tear film break‐up time (BUT), and color vision by Farnsworth‐Munsell (FM) 100 Hue color test were evaluated and microbiological investigation of conjunctival flora and anterior nares were performed. All these eye examinations were repeated before, during, and after treatment with isotretinoin by the same examiner. Results. There was no difference in visual acuity, and fundus examination in any of the cases after administration of the drug. No statistically significant difference was found between averages of IOP measurements and refraction (NS). On the other hand, the differences between FM 100 Hue test scores, Schirmer values, and BUT measurements that were evaluated before and during treatment were statistically significant (p < 0.05). Subjective symptoms such as dryness, itching, and contact lens intolerance occurred in 34% of the patients. Colonization of the conjunctiva and anterior nares by Staphylococcus increased significantly during treatment. All abnormal findings disappeared 1 month after stopping therapy. Conclusion. There are ocular side effects of isotretinoin that are treatable and they disappear after discontinuation of therapy.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"9 3-4 1","pages":"189 - 195"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75386754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corneal Organ Culture Model for Assessing Epithelial Recovery After Surfactant Exposure","authors":"Keping Xu, Jing Zhang, F. X. Yu","doi":"10.1081/CUS-120027485","DOIUrl":"https://doi.org/10.1081/CUS-120027485","url":null,"abstract":"We previously reported the use of an ex vivo model of bovine corneal organ culture for predicting ocular irritation and evaluating acute chemical toxicity. Since the ability to recover after chemical exposure is a key parameter for assessing ocular toxicity of test chemicals, we sought to determine if cultured porcine cornea is able to recover after surfactant exposure and if functional recovery might be used as an ex vivo parameter for an ocular toxicity assay. Corneal chemical injury was created by placing a 7‐mm circular filter paper soaked in different concentrations of sodium dodecyl sulfate (SDS) on the center of porcine corneas for 2 minutes. The corneas exposed to surfactant with mild irritation (1% and 3% SDS, Draize score < 16.9) were able to recover from the initial damage, but no evidence of recovery was observed after exposure to surfactant with severe irritation (15% SDS, Draize score 59.2) as assessed by reestablishment of epithelial barriers. There was a concentration‐dependent increase in fluorescein retention in SDS‐exposed corneas. Furthermore, NF‐κB DNA‐binding activity was greatly altered after exposure to SDS in a concentration‐dependent manner. Our data suggest that functional corneal recovery after surfactant exposure correlates with known toxicity testing in vivo and may serve as a key endpoint for predicting ocular irritation of test chemicals and consumer products.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"1 1","pages":"29 - 40"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76244391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in Response to Topical Irritants in Haired and Hairless Guinea Pigs","authors":"F. Andersen, K. Hedegaard, A. Fullerton","doi":"10.1081/CUS-200035361","DOIUrl":"https://doi.org/10.1081/CUS-200035361","url":null,"abstract":"The hairless guinea pig offers the possibility of performing irritant studies without the use of depilatory agents or clipping. Studies have shown a response to allergens and simple irritants comparable to that of the haired guinea pig but with differences depending on substance and concentration used. Histoanatomical studies have demonstrated differences in cutaneous structure in the two strains, differences that might influence the response to complex low‐grade irritants such as composite vehicles. The purpose of this study was to compare the usability of hairless (HLGP) and clipped haired guinea pigs (CGP) in tolerability studies of composite formulations. The tolerability of six selected skin care formulations (SCF), known to cause a differentiated irritative response in the HLGP, was studied in 15 male CGPs and 15 male HLGPs. All animals were treated on a 5 × 5 cm area on each side of the dorsal trunk twice daily for 4 consecutive days with SCF. The tolerance of the different SCF was assessed by clinical assessment, measurement of transepidermal water loss (TEWL), and colorimetry (a*‐parameter). The results obtained using clinical scoring and noninvasive measurements were consistent for the HLGP. Colorimetry was found to be unsuited for the evaluation of cutaneous irritation in the CGP over a period of days as regrowth of fur will obfuscate the underlying erythema. Both species were able to differentiate between SCFs in relation to skin tolerance, and although the response pattern was somewhat different in the two species, the ranking of the SCF was essentially the same. However, HLGP appears to be a more suitable model for tolerability testing of composite formulations due to the avoidance of clipping, being both time‐consuming and having the risk of affecting the clinical outcome.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"36 1","pages":"159 - 171"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82644903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender Differences in the Pharmacokinetics of Oral Dermatologic Medications","authors":"D. Fife, H. Maibach","doi":"10.1081/CUS-120030169","DOIUrl":"https://doi.org/10.1081/CUS-120030169","url":null,"abstract":"Physiological differences exist between men and women that lead to different efficacy and side effect profiles of medications. Although some of this may be explained by differing pharmacodynamics, pharmacokinetic differences between the genders have been found for many medications. The oral dermatologic medications which have shown the most gender‐related differences are cyclosporine, erythromycin, and methotrexate. Cyclosporine and erythromycin are cleared faster in females, which may be due to either higher cytochrome P‐450 3A (CYP3A) activity in females or higher P‐glycoprotein levels in males. Methotrexate is cleared faster in males, which appears to be due to a higher glomerular filtration rate (GFR) and creatinine clearance in males. Gender differences in each pharmacokinetic parameter (absorption, distribution, metabolism, and excretion) have been described. Metabolism, in particular, varies greatly between the genders. Women clear substrates of CYP3A enzymes more rapidly than men, but it is debated whether this is a result of increased CYP3A activity in females or increased P‐glycoprotein in males. Most of the gender‐related differences in pharmacokinetics are considered important only for those medications with a low therapeutic index. In the future, drugs, such as cyclosporine, erythromycin, and methotrexate, may require different dosage recommendations, depending on gender.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"20 1","pages":"119 - 133"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77744616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selegiline Transdermal System (STS): Preclinical Assays of Dermal Safety","authors":"M. Pauporte, Melissa L. Goodhead, A. Azzaro, G. Moonsammy, H. Maibach","doi":"10.1081/CUS-200035363","DOIUrl":"https://doi.org/10.1081/CUS-200035363","url":null,"abstract":"Two preclinical sensitization studies were conducted to determine the potential for allergic contact dermatitis with the selegiline transdermal system (STS), a novel transdermal system being developed to treat major depressive disorder. These included a qualitative structure‐activity relationship (QSAR) analysis to assess the allergic dermatitis potential of selegiline, and a guinea pig dermal sensitization study to determine the delayed contact hypersensitivity potential of the STS. In the QSAR analysis, selegiline was classified as a nonallergen. In the guinea pig study, the STS was found not to act as a dermal sensitizer. Thus, based upon the results of these two preclinical studies, treatment with the STS is unlikely to pose a risk of causing significant allergic contact dermatitis. Human data, reported elsewhere, support this hypothesis.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"106 1","pages":"173 - 178"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83343048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Combination Drug Treatment Against Ocular Sulfur Mustard Injury","authors":"Michael C. Babin, K. M. Ricketts, M. Gazaway, R. Lee, R. Sweeney, J. Brozetti","doi":"10.1081/CUS-120027483","DOIUrl":"https://doi.org/10.1081/CUS-120027483","url":null,"abstract":"The eye is considered to be one of the most sensitive organs to sulfur mustard [bis(2‐chloroethyl) sulfide (SM)], with injuries ranging from mild conjunctivitis to advanced corneal disease. Even mild ocular involvement from sulfur mustard exposure can result in both physical and psychological incapacitation. In this study we explored the use of Food and Drug Administration (FDA) approved medications (prednisolone acetate ophthalmic suspension, triamcinolone, and cefazolin) as ocular treatments for sulfur mustard injury. Female New Zealand White rabbits were divided into a SM positive control group (n = 8) and a single treatment group (n = 7). At 10, 20, 30, 60, 90, and 120 min after SM exposure, two drops of prednisolone acetate ophthalmic suspension was administered to each treatment group rabbit while the control group received saline drops. At 120 min after SM exposure, each treatment group animal received a single 1.0 mL sub‐Tenon's injection containing 20 mg triamcinolone and 50 mg cefazolin. Control group rabbits did not receive an injection. Rabbits were observed for a total of 16 weeks after SM exposure. Corneal thickness, corneal stromal injury, neovascularization (NV), eyelid notching, and chemosis were recorded weekly for 6 consecutive weeks and on week 16 after exposure. The SM treatment group at weeks 2, 3, and 4 had a significantly lower index value for corneal thickness than the SM positive control group. For corneal stromal injury, NV, eyelid notching, and chemosis, significant evidence of a protective effect due to treatment was seen at weeks 4, 5, and 6. In addition, corneal stromal injury was reduced at weeks 2 and 3 and notching at week 2. By week 3, all SM positive control animals developed NV in contrast to 1 of 7 treatment animals. By week 6 all positive control animals still exhibited NV compared to 2 of 7 treatment animals. These data suggest that prednisolone acetate suspension dosed for the first 2 h after SM exposure followed by a single sub‐Tenon's injection of a triamcinolone/cefazolin combination is effective in treating the early stages of corneal injury from SM exposure.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"74 1","pages":"65 - 75"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90268618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutagens and Sensitizers—An Unequal Relationship?","authors":"A. Wolfreys, D. Basketter","doi":"10.1081/CUS-200025577","DOIUrl":"https://doi.org/10.1081/CUS-200025577","url":null,"abstract":"For some years, those involved with the safety assessment of chemicals have in one way or another considered the degree to which data on either skin sensitization potential or on carcinogenicity may inform them on the other endpoint for a particular substance. In this work, we have taken a pragmatic perspective on the question and assessed mutagens, rather than carcinogens, and sensitizers as this better reflects the potential for biological macromolecule interaction. A dataset of 100 substances, the majority of which have come under scrutiny for one reason or another during our own toxicology investigations, was interrogated. We focused on the extent to which results from the primary screen for skin sensitization correlated with the results from the two in vitro tests used as a screen for mutagenicity, namely the bacterial mutation assay and the in vitro chromosome aberration assay. Although there was some concordance between the two endpoints, as standalone methods, neither predicted the other particularly accurately, with 32% showing disagreement. It is probable that there are several critical elements missing from this top level assessment, not least an appreciation of which substances are positive in mutagenicity tests via non‐genotoxic mechanisms which could seriously impair such a correlation between results from the two different endpoints.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"59 1","pages":"197 - 205"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90477011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of Refractive Errors in Victims of Chemical Weapons as Delayed Effects","authors":"A. Riazi, K. Jadidi, A. K. Zarchi, M. Naderi","doi":"10.1081/CUS-200025578","DOIUrl":"https://doi.org/10.1081/CUS-200025578","url":null,"abstract":"Introduction: Many victims of chemical warfare (VCW) manifest some degree of refractive errors which were not present before exposure. These refractive errors are presumably long‐term (delayed) effects of sulfur mustard exposure. However, no related research studies have been done to confirm this. Myopia, hyperopia, and astigmatism are the refractive errors of the eye and prevalence of these errors depends on several factors such as hereditary factors, age, profession, and also several geographical factors. The effect of sulfur mustard on the eye may be very complex and relates basically to the intensity of the injury. Sulfur mustard targets the cornea resulting in early effects of exposure. The delayed effects of exposure are less documented and are discussed in this study. Materials and Method: In this study, cross‐sectional study refractive errors were studied as one of the delayed effects of sulfur mustard in VCW. 2252 eyes of VCW and 2248 normal eyes were chosen as controls. The mean age of both groups were 34.3 (SD = 9.1) and 32.1 (SD = 10.1) respectively. Both groups went through an optometric and ophthalmic examination. The refractive errors were measured by autorefractometer (Topcon RM 2300). The Student t‐test and chi‐square test were used and P < 0.05 was considered significant. Results: The prevalence of refractive errors in the VCW group was 89.8% which was higher than the control group of 72.6% p < 0.001. Astigmatism was the main refractive error in the VCW group and their prevalence (76.2%) was higher than the control group (47%) p < 0.001. The types of astigmatism found were “against” and “oblique.” Prevalence of myopic astigmatism in the VCW group was also higher than in the other types of astigmatisms. Discussion: There are three main causes for refractive errors. Change in anterior‐posterior length of the eye or change in curvature of refractive surfaces and change in the index or combinations of them. All VCW have photophobia, dry eyes, and excessive blinking. They have narrow eye opening (narrow palpebral fissure). Eyelid pressure and excessive blinking, and dry eyes add gradual pressure on the cornea and in the long term lead to induce refractive errors such as astigmatism. Further studies will be needed however to confirm this.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"92 6 1","pages":"207 - 214"},"PeriodicalIF":0.0,"publicationDate":"2004-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83336763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Augmented Latex‐Specific IGE Antibody Response in BALB/c Mice Upon Concurrent Exposure to Natural Rubber Latex Proteins with Glutaraldehyde","authors":"K. Fairley, Michael D. Howell, V. Tomazic‐Jezic, T. Leakakos, W. Truscott, B. Meade","doi":"10.1081/CUS-200037220","DOIUrl":"https://doi.org/10.1081/CUS-200037220","url":null,"abstract":"Health care workers are exposed to numerous agents that are known to induce hypersensitivity‐mediated diseases. Yet, little is known regarding the role of coexposure to these agents on the development of hypersensitivity responses. The present studies were conducted to evaluate the immunomodulatory role of dermal exposure to glutaraldehyde (Glut) on the induction of IgE antibodies to natural rubber latex (NRL) proteins. Female BALB/c mice were dermally exposed to Glut (0.05–1 ppm; 0.1–1%) and nonammoniated latex (NAL; 25 µg) 5 days/week for up to 86 days. The NAL alone at concentrations up to 1% did not induce significantly elevated levels of total serum or latex specific IgE. In contrast, both total and NAL‐specific serum IgE were dose‐dependently (p < 0.01 and p < 0.05, respectively) elevated in mice concurrently exposed to 25 µg NAL and increasing concentrations of Glut up to 0.75 ppm. Further testing was performed to investigate the mechanism by which Glut augmented the latex‐specific response. Barrier integrity tests demonstrated that Glut did not induce sufficient disruption of the strateum corneum (less than 1% 3H20 penetration was observed in a guinea pig model) to allow for increased penetration of the latex proteins. However, co‐exposure to 25 µg NAL and 0.75 ppm Glut for 2 days as compared to the vehicle control was shown to induce a 15‐fold increase in MHC II positive Langerhans' cells in the epidermis. Additional experiments confirmed the upregulation of a Th2 response. Upon sacrifice following 86 days of exposure, animals exposed to 25 µg NAL and 0.75 ppm Glut demonstrated a significant increase (p < 0.01) in CD40 + (3.95 ± 0.38 × 106), B220 + (7.67 ± 1.18 × 106), and IgE + B220 + (3.28 ± 0.75 × 106) cells as compared to the vehicle control groups (2.29 ± 0.18 × 106, 3.31 ± 0.18 × 106, and 0.82 ± 0.15 × 106 cells), respectively. These studies demonstrate the potential for mixed exposures in the health care environment to modulate the development of IgE mediated responses to natural rubber latex proteins, underscoring the importance of environmental factors in the development of allergies to foreign antigens.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"191 1","pages":"303 - 320"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75030389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations of Gene Expression in Sulfur Mustard‐Exposed Skin Topically Treated with Vanilloids","authors":"C. Sabourin, J. Rogers, Mindy K. Stonerock, N. Niemuth, R. C. Kiser, Stacy L. Casbohm, Michael C. Babin, J. Schlager, R. Casillas","doi":"10.1081/CUS-200041508","DOIUrl":"https://doi.org/10.1081/CUS-200041508","url":null,"abstract":"Sulfur mustard [bis(2‐chloroethyl)sulfide, SM] is a chemical warfare agent that penetrates the skin rapidly and causes extensive blistering. Using the mouse ear vesicant model (MEVM), we evaluated the effect of topically applied anti‐inflammatory agents (octyl homovanillamide and heptyl isovanillamide) on ear edema formation and gene expression following SM exposure. Relative ear weight and real‐time reverse transcriptase polymerase chain reaction of GM‐CSF, IL‐1β, and IL‐6 were used to evaluate the effects of octyl homovanillamide and heptyl isovanillamide. Both vanilloids significantly reduced SM‐induced edema. At the single dose and number of animals/group tested, octyl homovanillamide produced a trend of reduced mRNA levels; however, the reduction was not significant for GM‐CSF, IL‐1β, or IL‐6. Heptyl isovanillamide significantly reduced (p ≤ 0.05) GM‐CSF, IL‐1β, and IL‐6 mRNA levels. These results show that octyl homovanillamide and heptyl isovanillamide reduce skin edema and heptyl isovanillamide significantly reduced cytokine mRNA expression following SM exposure. In addition to measuring edema formation, monitoring expression of biomarkers such as GM‐CSF, IL‐1β, and IL‐6 may also serve to evaluate therapeutic treatments against SM‐induced dermal injury.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"39 1","pages":"321 - 328"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90365195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}