Current intelligence bulletin 47 - 4,4'-methylenedianiline (MDA) (revised) (with reference package).
NIOSH 1986 Jul; :1-24
An updated current intelligence bulletin discussed carcinogenic effects of 4,4'-methylenedianiline (101779) (MDA) exposure reported since 1976. About 99 percent of MDA was used in chemical manufacturing, and skin contact was considered the primary route of occupational exposure. Administration of MDA to Fischer-344/N-rats and B6C3F1-mice in drinking water over 2 years at concentrations of 150 and 300 parts per million resulted in significantly increased incidences of follicular cell carcinomas and adenomas and C-cell adenomas of the thyroid; hepatocellular carcinomas and adenomas and neoplastic liver nodules; malignant lymphomas; adrenal pheochromocytomas; and alveolar bronchiolar adenomas. Uncommon tumors of low incidence in historical controls were also reported and included bile duct adenomas, urinary bladder papillomas, and ovarian granulosa cell tumors. Tumor promoting activity of MDA was studied in male Wistar-rats treated with 2,2'-dihydroxy-N- nitrosodipropylamine followed by 1000 parts per million MDA in diet for 19 weeks. Significantly increased numbers of follicular cell carcinomas and adenomas and papillary adenomas of the thyroid were found in rats given combined treatment compared to controls or those receiving initiator or MDA alone. No tumors were seen in rats treated with MDA only. Epidemiological studies of human exposure to MDA have shown hepatotoxic, skin, and myocardial effects. Proportionate mortality ratios (PMRs) in a population of workers exposed to MDA and other chemicals showed statistically significant excesses of bladder and colon cancer and lymphoma/reticulosarcoma. Respective PMRs were 3.74, 2.26, and 3.45. Only the bladder cancer excess remained significant when analysis was by proportional cancer mortality ratio. Although there were problems with these data, they did suggest an increased risk for these three cancers with MDA exposure. NIOSH recommends that MDA be considered a potential occupational carcinogen and that exposures be controlled to the lowest feasible limit.
NIOSH-Current-Intelligence-Bulletin-No-47; Anilines; Phenyl-compounds; Laboratory-animals; In-vivo-studies; Carcinogenesis; Epidemiology; Occupational-exposure; Cancer-rates; Mortality-rates; Histopathology; Toxic-effects; Liver-disorders
Numbered Publication; Current Intelligence Bulletin
NTIS Accession No.
DHHS (NIOSH) Publication No. 86-115; CIB 47
National Institute for Occupational Safety and Health