N-Hydroxyurea – inhalable fraction : documentation of proposed values of occupational exposure limits (OELs)
N-hydroxyurea is an organic chemical compound – N-hydroxydiamide of carbonic acid. At room temperature, it is a solid and white crystalline powder (needle), odorless, water-soluble. N-hydroxyurea is an antineoplastic drug registered for the treatment of patients with chronic myelogenous leukemia and...
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| Format: | Article in Journal/Newspaper |
| Language: | Polish |
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Centralny Instytut Ochrony Pracy
2017
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| Online Access: | https://doi.org/10.5604/01.3001.0010.594 https://bibliotekanauki.pl/articles/137943.pdf https://bibliotekanauki.pl/articles/137943 |
| Summary: | N-hydroxyurea is an organic chemical compound – N-hydroxydiamide of carbonic acid. At room temperature, it is a solid and white crystalline powder (needle), odorless, water-soluble. N-hydroxyurea is an antineoplastic drug registered for the treatment of patients with chronic myelogenous leukemia and sickle cell anemia, and idiopathic thrombocytopenia and polycythemia. Occupational exposure to N-hydroxyurea occurs during manufacturing, packing, using on a daily basis in hospitals and in veterinary practice. There is no data on the number of people exposed to N-hydroxyurea in Poland. N-hydroxyurea is completely absorbed from the gastrointestinal tract. After oral administration, the maximum plasma concentration is within 1 ÷ 4 h after ingestion. LD50 value after intragastric administration to rats is 5760 mg/kg and mice 7330 mg/kg. N-hydroxyurea does not meet the classification criteria established in the European Union for acute toxicity after oral administration established. IARC classifies N-hydroxycarbamide into group 3, i.e., substances that cannot be classified for human carcinogenicity. Main effects of N-hydroxyurea in humans include systemic toxicity manifested by suppression of bone marrow at therapeutic doses (the lowest therapeutic dose is 15 mg/kg). The side effect of hydroxycarbamide is bone marrow suppression resulting in neutropenia, granulocytopenia, thrombocytopenia, leukopenia and increased bone marrow mass. In laboratory animals treated with N- hydroxyurea at doses higher than clinical doses established for humans, cardiovascular disorders (e.g., heart rate changes, blood pressure and ECG changes), haemolysis and methemoglobinemia were observed. In subchronic and chronic studies in rats, a dosedependent, weak or moderate bone marrow hypoplasia and pulmonary congestion were observed. Dose of 50 mg/kg is the NOAEL value for the effect of N-hydroxyurea on blood parameters in rats treated with aqueous solution for 10 days. The hydroxyurea-induced genotoxic effects in humans have been observed in ... |
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