벤조페논-10

OBJECTIVE: To describe and identify the photoallergens causing photoallergic contact dermatitis in the population attending the outpatient clinic of the Centro Dermatologico Federico Lleras Acosta (CDFLLA), the National Institute of Dermatology of Colombia. MATERIALS AND METHODS: Eighty-two patients with clinical diagnosis of photoallergic contact dermatitis enter the study. These patients attended the CDFLLA between August 2001 and May 2003. Photopatch tests were performed using the standard series of sunscreens (Chemotechnique Diagnostics) and 6-methylcoumarin. Cetyl alcohol, phenoxyethanol, methylparabene, propylene glycol, triethanolamine, propylparabene, trichlorocarbanilide and dichromate were also included. The allergens were applied in duplicate on the healthy skin of the back and covered with opaque tape withdrawn 24 hr later, the panel on the right was irradiated with an ultraviolet A dose of 5 J/cm(2). The tests were read 24 h after the application of the allergens, 24 and 72 hr post-irradiation. The readings were assessed according to the visual scoring system recommended by the International Contact Dermatitis Research Group. RESULTS: Twenty-six patients (31.7%) showed positive photopatch test responses to one or several allergens. Four of them showed positive results to three components of the series and four patients to two components. Thirty-eight photoallergic and 18 allergic reactions were observed. Ultraviolet filters were the substances which more frequently produced positive photopatch test responses (30.5%). The most common ultraviolet filter photoallergen was benzophenone-3 with 22/82 positive results (26.8%), followed by octyl methoxycinnamate (8/82), benzophenone-4 and mexenone (2/82), phenylbenzimidazole sulphonic acid, methylbenziliden camphor and octyl dimethyl PABA (1/82). One patient showed a photoallergic response to 6-methylcoumarin. There was a concordance between the allergen which elicited the positive response and the use of different substances which contained that molecule among its compounds in 17 patients (65.3%). 19.5% of the patients (16/82) showed positive results to one or several allergens in the irradiated panel as well as in the unirradiated control site. These cases were diagnosed as contact allergy, probably caused by aeroallergens, presenting a natural history and a clinical picture similar to photocontact allergy. The most common allergen was dichromate with 10 positive results. CONCLUSIONS: The results of this study confirm that sunscreens are the more frequently involved substances in photoallergic contact dermatitis in our population. Identification of the photoallergen is the key element for adequate disease control and patient education.

INTRODUCTION: Between September 1994 and September 1999, we observed 19 cases of photoaggraved contact allergy or contact photoallergy to ketoprofen (non steroidal anti-inflammatory derived from arylpropionic acid). We present a clinical and photobiological retrospective study of these 19 cases with investigation of cross-reactivity between benzophenone-containing molecules. PATIENTS AND METHODS: On clinical level, we investigated the type of eruption, the delay of appearance, the initial area of eruption and areas of diffusion. Phototesting included patchtests and photopatchtests performed with the gel containing ketoprofen (17 patients), ketoprofen 2 p. 100 petrolatum (14 patients), fenofibrate 10 p. 100 petrolatum and 10 p. 100 water (15 patients), 3 benzophenones (19 patients): oxybenzone 10 p. 100 petrolatum, mexenone 2 p. 100 petrolatum, sulisobenzone 10 p. 100 petrolatum and the other arylpropionic derivatives (4 patients). Three identical series were applied: one was irradiated with 3/4 polychromatic minimal erythematosus dose, a second was irradiated with UVA 13 J/cm2 until January 1997, then 5 J/cm2, the third series was not irradiated (control series). RESULTS: Patients were 9 men and 10 women with an average age of 41.2 years. The type of eruption was an eczema. The delay of appearance of the eruption was one day to 3 months. For 10 patients, the delay was between 4 and 18 days. The eruption was localized to the application area in 1 case, to the application area then to the same contralateral area in 3 cases, to the application area then to all photoexposed areas in 13 cases, to the application area then to the photoexposed areas and then to non-sun-exposed areas in 2 cases. Evolution showed prolonged photosensitivity in 3 cases after withdrawal of the contact and the contact photoallergy to ketoprofen was severe. Gel-containing ketoprofen photopatchtests showed 9 photoaggravated contact allergy, 6 contact photoallergy and 2 contact allergy. Ketoprofen photopatchtests showed 12 contact photoallergy and 2 photoaggraved contact allergy. Tiaprofenic acid photopatchtests were positive in all performed cases (4/4), but photopatchtests with the other arylpropionic derivatives, without benzophenone structure, were negative. Fenofibrate photopatchtests were always positive (15/15). Benzophenones photopatchtests only showed 4 cases of contact photoallergy to oxybenzone (4/19). In 68 p. 100 of cases, patients presented a contact allergy or photoallergy to fragrances. CONCLUSIONS: This study shows the actual frequency of contact allergy and contact photoallergy to ketoprofen with a higher frequency of contact photoallergy. Thus, photopatchtesting is essential. In cases of contact photoallergy to ketoprofen, ketoprofen, tiaprofenic acid but not the other arylpropionic derivatives, fenofibrate and benzophenones have to be withdrawn.

LC50; Species: Dugesia japonica (Flatworm); Conditions: freshwater, static; Concentration: 1.5 mg/L for 24, 48, 72 hr (95% confidence interval: 1.4-1.6 mg/L) />99% purity/

LC50; Species: Dugesia japonica (Flatworm); Conditions: freshwater, static; Concentration: 1.4 mg/L for 96 hr (95% confidence interval: 1.2-1.6 mg/L) />99% purity/

Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.org

IDENTIFICATION AND USE: 2-Hydroxy-4-methoxy-4'-methylbenzophenone (Mexenone) belongs to the benzophenone group of sunscreens. HUMAN STUDIES: Mexenone was reported as one of the most frequent contact allergens among other sunscreen agents. The benzophenone group of sunscreens (mexenone, oxybenzone) were the most frequent sensitizers, accounting for 8 of the 27 positive patch tests observed for a sunscreen agents. It has also produced positive responses in photopatch testing. A case report described a patient with long-standing polymorphic light eruption who developed a photocontact allergy to mexenone and several contact allergies. ANIMAL STUDIES: There are no data available.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of February 4, 2019: http://actor.epa.gov/dashboard/]

/HUMAN EXPOSURE STUDIES/ The patients sensitized to sunscreen agents who attended our Contact Dermatitis Clinic between February 1985 to March 1987 have been reviewed. 15 (5%) of 280 patients tested with sunscreens had positive reactions; 3 of them were allergic to more than one agent. The most frequent contact allergens were hydroxy methoxy methyl benzophenone (Mexenone) [6], followed by isopropyl dibenzoylmethane (Eusolex 8020/8021) [5], octyl dimethyl para-aminobenzoate (Escalol 507) [2], and one reaction each to butyl methoxy dibenzoylmethane (Parsol 1789), amyl dimethyl para-aminobenzoate (Escalol 506), and ethoxy ethyl-p-methoxy cinnamate (Givtan F). Positive photopatch tests were seen with isopropyl dibenzoylmethane, butyl methoxy dibenzoylmethane, para-aminobenzoate (PABA) and ethoxy ethyl-p-methoxy cinnamate, one reaction each.

/HUMAN EXPOSURE STUDIES/ From 1989-1991, 214 patients (45 PD/AR, 54 PLE, 115 controls) were patch tested to a sunscreen series containing 9 constituents. 16/214 (7.5%) patients reacted to one or more sunscreens, with allergy being significantly more common in PD/AR /photosensitivity dermatitis/actinic reticuloid syndrome/ patients (10/45 versus 2/54 PLE /polymorphic light eruption/ and 4/115 contact dermatitis clinic controls). The benzophenone group of sunscreens (mexenone, oxybenzone) were the most frequent sensitizers, accounting for 8 of the 27 positive patch tests observed. Clinicians should consider contact allergy to sunscreens in PD/AR patients as an explanation for exposed-site dermatitis episodes.

/HUMAN EXPOSURE STUDIES/ Photopatch testing, although widely used in the diagnosis of photosensitivity disorders, is not standardized. We performed this study to determine the threshold ultraviolet light A (UV-A) dose required to elicit photopatch test responses. 4 patients with previously positive tests were reexposed to the offending allergen, using an incremental dosage regime. Isopropyl dibenzoylmethane (Eusolex 8020), mexenone (benzophenone-10) and oxybenzone (benzophenone-3) produced positive responses at 1.0, 1.0 and 0.7 J/sq cm, respectively. Responses to phenothiazines were deemed phototoxic. These results demonstrate that high doses of UV-A (e.g., 10-15 J/sq cm) are unnecessary, and that 5 J/sq cm should become the current standard.

/HUMAN EXPOSURE STUDIES/ INTRODUCTION: Between September 1994 and September 1999, we observed 19 cases of photoaggraved contact allergy or contact photoallergy to ketoprofen (non steroidal anti-inflammatory derived from arylpropionic acid). We present a clinical and photobiological retrospective study of these 19 cases with investigation of cross-reactivity between benzophenone-containing molecules. PATIENTS AND METHODS: On clinical level, we investigated the type of eruption, the delay of appearance, the initial area of eruption and areas of diffusion. Phototesting included patchtests and photopatchtests performed with the gel containing ketoprofen (17 patients), ketoprofen 2 p. 100 petrolatum (14 patients), fenofibrate 10 p. 100 petrolatum and 10 p. 100 water (15 patients), 3 benzophenones (19 patients): oxybenzone 10 p. 100 petrolatum, mexenone 2 p. 100 petrolatum, sulisobenzone 10 p. 100 petrolatum and the other arylpropionic derivatives (4 patients). Three identical series were applied: one was irradiated with 3/4 polychromatic minimal erythematosus dose, a second was irradiated with UVA 13 J/cm2 until January 1997, then 5 J/cm2, the third series was not irradiated (control series). RESULTS: Patients were 9 men and 10 women with an average age of 41.2 years. The type of eruption was an eczema. The delay of appearance of the eruption was one day to 3 months. For 10 patients, the delay was between 4 and 18 days. The eruption was localized to the application area in 1 case, to the application area then to the same contralateral area in 3 cases, to the application area then to all photoexposed areas in 13 cases, to the application area then to the photoexposed areas and then to non-sun-exposed areas in 2 cases. Evolution showed prolonged photosensitivity in 3 cases after withdrawal of the contact and the contact photoallergy to ketoprofen was severe. Gel-containing ketoprofen photopatchtests showed 9 photoaggravated contact allergy, 6 contact photoallergy and 2 contact allergy. Ketoprofen photopatchtests showed 12 contact photoallergy and 2 photoaggraved contact allergy. Tiaprofenic acid photopatchtests were positive in all performed cases (4/4), but photopatchtests with the other arylpropionic derivatives, without benzophenone structure, were negative. Fenofibrate photopatchtests were always positive (15/15). Benzophenones photopatchtests only showed 4 cases of contact photoallergy to oxybenzone (4/19). In 68 p. 100 of cases, patients presented a contact allergy or photoallergy to fragrances. CONCLUSIONS: This study shows the actual frequency of contact allergy and contact photoallergy to ketoprofen with a higher frequency of contact photoallergy. Thus, photopatchtesting is essential. In cases of contact photoallergy to ketoprofen, ketoprofen, tiaprofenic acid but not the other arylpropionic derivatives, fenofibrate and benzophenones have to be withdrawn.

Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/