© 1994 Oxford University Press
research-article |
Toxicity of an Anthraquinone Violet Dye Mixture Following Inhalation Exposure, Intratracheal Instillation, or Gavage
*Man Tech Environmental Technologies, Inc., Research Triangle Park North Carolina 27709
U.S. Environmental Protection Agency, Health Effects Research Laboratory, Research Triangle Park North Carolina 27711
Received March 10, 1993; accepted September 16, 1993
Anthraquinone dyes are utilized by the military in colored smoke grenades. During production, workers in munitions plants may be exposed to fugitive emissions of these dyes or mixtures thereof. The effects of a prototype violet dye mixture (VDM) consisting of Disperse Red 11 (DR1 1), 11 ,4-diamino-2- methoxy-anthraquinone] and Disperse Blue 3 (DB3) [l-methy larnino-4-hydroxyethylarnino-anthraquinone on F344 male and female rats have been investigated. Acute 1-day inhalation exposures (6 hr) to VDM were conducted at 1000, 300, 100, 70, 40, and 10 mg/rn with an additional exposure to 40 mg/m 6 hr/day for 5 days; 4.22 ± 2.1 m (MMAD ± 
g). Lung burdens of dye, general histopathology, and/or liver function were evalu ated at 0, 3, and 7 days postexposure. Unexpected lethality due to severe liver damage was observed with acute exposures of 300 mg/rn and in the 5-day 40 mg/rn exposures. Centrilobular degeneration and necrosis of liver cells was concentration- dependent with inhalation of VDM?40 mg/m3 In addition, nasal olfactory epithelium exhibited degeneration and necrosis with acute exposures?10 mg/rn Lung instillations at 250, 500, and 1000 zg of the VDM revealed no lung or liver toxicity. Because per os exposure due to preening was suspected as a major exposure route, a gavage study with the VDM and its two component dyes DR1 1 and DB3 (800 mg/kg) was undertaken. One day following gavage with DR1 1 or DB3, serum enzymes indicative of liver toxicity (LDH, SGPT, SDH, and ICDH) were slightly elevated (1–6x control). However, rats gavaged with VDM had serum enzyme levels 10–100X control by Day 1 after gavage, indicating acute liver toxicity. Activities of liver en zymes involved in xenobiotic and glutathione metabolism were also acutely affected. All of the dyes caused various degrees of induction of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and nonprotein sulfhydryls. The enzymes involved in xenobiotic metabolism (glutathione S-transferase, NADPH cytochrome-c reductase, and P450) were also elevated by the two component dyes, in contrast to their significant depression with VDM treatment. The similarity between the liver and olfactory epithelium effects of these compounds and the lack of pulmonary tissue effects is not fully understood, but the interaction of the individual dyes as VDM emphasizes the need to assess chemicals such as the anthraqui nones as their likely-to-be-encountered mixtures.