Toxicity of Military Smokes and Obscurants: Volume 3 (1999)
Chapter: Appendix G: Disperse Red 11
Appendix G
Disperse Red 11
BACKGROUND
DISPERSE RED 11 is also called 1,4-diamino-2-methoxy-anthraquinone (DMA). Disperse red 11 is a component of the new red-dye mixture.
TOXICOKINETICS
No information is available on the toxicokinetics of disperse red 11 in humans. One study instilled a suspension containing disperse red 11 to determine its retention in the lungs of rats. The study determined that disperse red 11 is rapidly absorbed into the blood with only 66% of the instilled dose remaining at 5 min and 3.5% remaining at 24 hr (Henderson et al. 1988).
TOXICITY SUMMARY
Effects in Humans
One study was conducted with six females with histories of allergic contact dermatitis (Lisboa et al. 1994). The patients were patch tested with a series of 15 disperse dyes used in the textile industry. All six
patients had a reaction to two or more of the disperse dyes; however, none of the patients reacted to disperse red 11.
Effects in Animals
A minimal battery of toxicity studies have been conducted with disperse red 11. Those studies are summarized in Table G-1. Acute-toxicity studies using two dye lots of disperse red 11 exposed female rats by either the oral or dermal routes and established the lethal dose for 50% of the animals (LD50) to be greater than 5 grams per kilogram (g/kg) of body weight (Smith et al. 1986). In contrast, for male rats, the LD50 after oral exposure was determined to be between 0.7 and 1.0 g/kg of body weight. Acute lethal doses after dermal exposure in rabbits are greater than 2 g/kg of body weight. Disperse red 11 was found to be negative in an eye irritation study conducted in rabbits (Smith et al. 1986). However, depending upon the dye lot used, disperse red 11 was found to be moderately to mildly irritating in a dermal irritation study (Smith et al. 1986). Mice studies using an ear-swelling test or a local lymphoid assay determined disperse red 11 to be negative for production of contact hypersensitivity (Sailstad et al. 1994).
Mutagenicity
Mutagenicity studies with disperse red 11 are summarized in Table G-2. The mutagenic effects of disperse red 11 have been investigated in three experimental systems: mouse lymphoma cells, Salmonella typhimurium bacterial assay (Ames test), and Chinese hamster ovary cells. The results of those studies are conflicting. Increased mutants and micronuclei were noted in the mouse lymphoma-cell system (Harrington-Brock et al. 1991), and an increased frequency of sister-chromatid-exchange and hypoxanthine guanine phosphoribosyl transferase (HGPRT) mutant frequency were seen in Chinese hamster ovary cells (Brooks et al. 1989). However, studies using bacterial assays have shown mixed results. The studies of Brown and Brown (1976) showed that disperse red 11 was not mutagenic, but the studies of Moore et al. (1989) showed that disperse red 11 was positive in one test strain. Brooks et al. (1989) concluded that mutagenicity of disperse red 11 was dependent upon the dye lot
TABLE G-1 Summary of Toxicity Studies Conducted with Disperse Red 11
|
Study Type |
Species |
Exposure Conditions |
End Points and Comments |
Reference |
|
Acute toxicity |
Rat, Fischer 344, M |
Oral, acute, 5 g/kg |
Lot 1:5/5 died, 4-6 d; Lot 2:5/5 died, 4-5 d |
Smith et al. 1986 |
|
Acute toxicity |
Rat, Fischer 344, M |
Oral, acute, Lot 1:0.6, 0.7, 0.9, 1.4 g/kg; Lot 2:0.5, 0.9, 1.4 g/kg |
Lot 1:0/5, 0/5, 4/5, 5/5 died; Lot 2:0/5, 3/5, 3/5 died; LD50 1.0 g/kg |
Smith et al. 1986 |
|
Acute toxicity |
Rat, Fischer 344, F |
Oral, acute, 5 g/kg |
Lot 1:0/10 died at 14 d; LD50 > 5 g/kg Lot 2:0/10 died at 14 d; LD50 > 5 g/kg |
Smith et al. 1986 |
|
Acute toxicity |
Rabbit, New Zealand White, M, F |
Dermal, acute, 2 g/kg for 24 hr |
Lot 1:0/10 died at 14 d; LD50 > 2 g/kg; Lot 2:0/10 died at 14 d; LD50 > 2 g/kg |
Smith et al. 1986 |
|
Eye irritation |
Rabbit, New Zealand White, M or F |
0.1 g/eye |
Lot 1: negative; Lot 2: negative |
Smith et al. 1986 |
|
Dermal irritation |
Rabbit, New Zealand White, M, F |
Clipped skin, 0.5 g/kg for 24 hr |
Lot 1: primary irritation score 2.7; moderately irritating; Lot 2: primary irritation score 0.73; mildly irritating |
Smith et al. 1986 |
|
Contact hypersensitivity |
Mice, Balb/c, F |
Mouse ear-swelling test: 0.0006 g/d shaved back, 2 d; challenge on d 5 |
Negative |
Sailstead et al. 1994 |
|
Contact hypersensitivity |
Mice, Balb/c, F |
Local lymph node assay: 0.00005 g/d both ears, 3 d |
Negative |
Sailstead et al. 1994 |
|
Contact dermatitis |
Humans, 6 F with allergic contact dermatitis |
1% solution |
Negative |
Lisboa et al. 1994 |
|
Abbreviations: M, male; F, female. |
||||
TABLE G-2 Summary of Mutagenicity Studies Conducted with Disperse Red 11
|
Experimental System |
Exposure Conditions |
End Points and Comments |
Reference |
|
Mouse lymphoma cells |
0-40 µg/mL, 4 hr |
264 thymidine kinase mutants per 106 survivors; 109 micronuclei per 1,000 cells at 15% survival |
Harrington-Brock et al. 1991 |
|
Salmonella typhimurium (strains TA1535, TA1537, TA1538, TA98, TA100, TA1978) ± S9 |
Not specified |
Not mutagenic |
Brown and Brown 1976 |
|
Salmonella typhimurium (strains TA1537, TA1538, TA98, TA100, TA102, TA104) ± S9 |
0-7, 500 µg/plate |
Positive in TA102 +S9 |
Moore et al. 1989 |
|
Salmonella typhimurium (strains TA1535, TA1538, TA98, TA100) ± S9 |
0-1,000 µg/plate, |
Lot 1: not mutagenic; Lot 2: mutagenic activity in TA98 and TA1538 +S9 |
Brooks et al. 1989 |
|
Chinese hamster ovary cells |
0-40 µg/mL, 3 hr |
Lot 1 and 2: increased frequency of sister chromatid exchange; delay in cell growth; no increase in chromosomal aberrations; Lot 2: increase in HGPRT mutant frequency |
Brooks et al. 1989 |
|
Abbreviations: HGPRT, hypoxanthine guanine phosphoribosyl transferase. |
|||
type, suggesting that the observed mutagenicity might be due to a contaminant in the dye lot.
SUBCOMMITTEE EVALUATION OF DYE TOXICITY
The experimental data are insufficient to assess the toxic effects of disperse red 11.
REFERENCES
Brooks, A.L., F.A. Seiler, R.L. Hanson, and R.F. Henderson. 1989. In vitro genotoxicity of dyes present in colored smoke munitions. Environ. Mol. Mutagen. 13(4):304-313.
Brown, J.P., and R.J. Brown. 1976. Mutagenesis by 9-10-anthraquinone derivatives and related compounds in Salmonella typhimurium. Mutat. Res. 40(3):203-224.
Harrington-Brock, K., L. Parker, C. Doerr, M.C. Cimino, and M.M. Moore . 1991. Analysis of the genotoxicity of anthraquinone dyes in the mouse lymphoma assay. Mutagenesis 6(1):35-46.
Henderson, R.F., W.E. Bechtold, M.A. Medinsky, J. P. Fischer, and T.T. Lee. 1988. The effect of molecular weight/lipophilicity on clearance of organic compounds from lungs. Toxicol. Appl. Pharmacol. 95(3):515-521.
Lisboa, C., M.A. Barros, and A. Azenha. 1994. Contact dermatitis from textile dyes. Contact Dermatitis 31(1):9-10.
Moore, M.M., L. Claxton, V. Houk, G.M. Nelson, and K. Harrington-Brock. 1989. Toxicity of Red and Violet Dyes in M18 Grenades: Mutagenic Screening of Three Dyes for Marker Grenades in the Salmonella Reversion Assay and the L5178Y/TK +/- Mouse Lymphoma Assay. Final Report. AD A229021. U.S. Environmental Protection Agency, Health Effects Research Laboratory, Research Triangle Park, NC.
Sailstad, D.M., J.S. Tepper, D.L. Doerfler, M. Qasim, and M.K. Selgrade. 1994. Evaluation of an azo and two anthraquinone dyes for allergic potential. Fundam. Appl. Toxicol. 23(4):569-577.
Smith, S.H., G.L. Doyle, J.C. Kreuger, K.A. Mellon, D.A. Mayhew. 1986. Dermal, Eye, and Oral Toxicological Evaluations, Phase IV Report with Disperse Red 11, Disperse Blue 3, Solvent Red 1, and Red and Violet Mixtures. AD A172-758. Bioassay Systems Corporation, Woburn, MA.
