Soile Jungewelter, K. Aalto-Korte
Oct 29, 2008
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Quality indicators
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Contact Dermatitis
Abstract
A 26-year-old pharmaceutical worker with no history of atopic disease was involved for the first time in the first step of the synthesis of flutamide, an anti-androgen drug used in the treatment of prostate cancer. For 1 hr, he dug about 50 kg of pulverized intermediate product out of a centrifuge. He was completely covered with special protective equipment: gloves, overall, and a compressed air breathing apparatus/hood. After 1 hr, he suffered from pruritus, and after 3 hr, he had erythema on his face, upper thorax, and neck. The erythema lasted for 3 days. Several weeks later, he carried out the same task for the second time and had the same symptoms with exactly the same timing. The starting materials in the first step of flutamide (2-methyl-N[4-nitro-3-(fluoromethyl)-phenyl]propanamide, CAS 13311-84-7) synthesis were potassium phthalimide, dimethylformide, 5-chloro-2-nitrobenzotrifluoride, tetrabutylammonium hydrogen sulfate, and isopropanole, and the intermediate product was N(3-trifluoromethyl-4-nitrophenyl) phthalimide. In the patient’s 3 years of employment in the plant, the production of flutamide had taken place three times a year. At the time of our investigation, the skin was normal. The prick tests with the standard environmental allergens showed no reactions. Patch tests with the standard series, antimicrobial, and coconut fatty acid derivative series gave no reactions. The patient’s own chemicals were also tested: the starting materials were negative, but the intermediate product, N-(3-trifluoromethyl-4-nitrophenyl)phthalimide, gave extremely strong allergic reactions in 5–0.16% pet. (þþþ), strong allergic reactions in 0.05– 0.005%pet. (þþ), a doubtful reaction in 0.0016% pet. (?þ), and 0.0005% was negative. Twenty control patients were negative to 0.016% and 0.005% N-(3-trifluoromethyl-4-nitrophenyl)phthalimide.