Toxicity of Military Smokes and Obscurants: Volume 3 (1999)

Chapter: Appendix E: Solvent Red 1

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Suggested Citation: "Appendix E: Solvent Red 1." National Research Council. 1999. Toxicity of Military Smokes and Obscurants: Volume 3. Washington, DC: The National Academies Press. doi: 10.17226/9645.

Appendix E
Solvent Red 1

BACKGROUND

ALTERNATIVE NAMES for solvent red 1 include color index sudan red G, oil soluble red G, and α­methoxybenzenazo-ß-naphthol (MBN). Solvent red 1 is a component of the new red-dye mixture.

TOXICOKINETICS

No studies have been conducted on the toxicokinetics of solvent red 1.

TOXICITY SUMMARY

Effects in Humans

There have been no reports of humans exposed either accidentally or in controlled laboratory environments to solvent red 1.

Effects in Animals

A minimal number of toxicity studies have been conducted with solvent red 1. Those studies are summarized in Table E-1. Acute-toxicity studies of oral exposure in rats or dermal exposure in rabbits determined the

Suggested Citation: "Appendix E: Solvent Red 1." National Research Council. 1999. Toxicity of Military Smokes and Obscurants: Volume 3. Washington, DC: The National Academies Press. doi: 10.17226/9645.

TABLE E-1 Summary of Toxicity Studies Conducted with Solvent Red 1

Study Type

Species

Exposure Conditions

End Points and Comments

Reference

Acute toxicity

Rat, Sprague-Dawley, M, F

Oral, acute, 5 g/kg

0/10 died at 14d, LD50 >5 g/kg

Manthei et al. 1983

Acute toxicity

Rat, Fischer 344, M, F

Oral, acute, 5 g/kg

0/10 died at 14d, LD50 >5 g/kg

Smith et al. 1986

Acute toxicity

Rabbit, New Zealand White, M, F

Dermal, acute, 2 g/kg for 24 hr

0/10 died at 14d, LD50 >2 g/kg

Manthei et al. 1983

Acute toxicity

Rabbit, New Zealand White, M, F

Dermal, acute, 2 g/kg for 24 hr

0/10 died at 14d, LD50 >2 g/kg

Smith et al. 1986

Eye irritation

Rabbit, New Zealand White, M, F

0.1 g/eye

0/6 responded at 24 hr, 48 hr, 72 hr, 7 d; negative

Manthei et al. 1983

Eye irritation

Rabbit, New Zealand White, M, F

0.1 g/eye

3/3 positive; redness, chemosis, discharge, iritis; no irritation by d 7

Smith et al. 1986

Dermal irritation

Rabbit, New Zealand White, M, F

Clipped skin, 0.5 g/kg for 24 hr

24, 72 hr; 6/6 erythema; primary irritation score 2.08; moderate irritant

Manthei et al. 1983

Dermal irritation

Rabbit, New Zealand White, M, F

Clipped skin, 0.05 g/kg for 24 hr

Nonirritant

Smith et al. 1986

Sensitization

Guinea pig, Hartley, M

Injection 0.0001g/d for 22 d

Negative

Manthei et al. 1983

Contact hypersensitivity

Mice, Balb/c, F

Mouse ear-swelling test: 0.00005 g/d shaved back, 2 d); challenge on d 5

Contact sensitizer

Sailstead et al. 1994

Contact hypersensitivity

Mice, Balb/c, F

Local lymph node assay: 0.0005 g/d both ears, 3 d)

Weak contact sensitizer

Sailstead et al. 1994

Abbreviations: M, male; F, female.

Suggested Citation: "Appendix E: Solvent Red 1." National Research Council. 1999. Toxicity of Military Smokes and Obscurants: Volume 3. Washington, DC: The National Academies Press. doi: 10.17226/9645.

lethal dose for 50% of the test animals (LD50) to be greater than 5 grams per kilogram (g/kg) of body weight after oral administration and greater than 2 g/kg of body weight after dermal administration. Those doses (5 g/kg and 2 g/kg) were the highest doses used (Manthei et al. 1983; Smith et al. 1986).

Results regarding the eye-irritation potential of solvent red 1 are conflicting. Manthei et al. (1983) reported that this chemical did not cause ocular irritation in rabbits; however, Smith et al. (1986) reported positive results in the same species. Conflicting results were also obtained for the dermal-irritation potential of solvent red 1. Manthei et al. (1983) suggested that it was moderately irritating, and Smith et al. (1986) suggested that it was nonirritating. The dose used in the Smith et al. (1986) study was 10 times higher than that in the Manthei et al. (1983) study. Studies using either an eye-swelling test or a local lymphoid assay to evaluate contact hypersensitivity in mice exposed to solvent red 1 showed that this chemical was a contact sensitizer (Sailstad et al. 1994).

Mutagenicity

Mutagenicity tests conducted with solvent red 1 are summarized in Table E-2. Mammalian studies have yielded conflicting results. For example, in vivo mutagenicity studies using Swiss albino mice showed no increase in micronucleated femoral polychromatic erythrocytes after intraperitoneal (i.p.) injections of solvent red 1 at up to 0.1 g/kg of body weight (Manthei et al. 1983). In contrast, in vitro studies using a mouse lymphoma cell line showed increases in thymidine kinase mutants and increases in micronuclei (Harrington-Brock et al. 1991). Experiments conducted in Chinese hamster ovary cells showed that solvent red 1 was cytotoxic and induced an increase in sister-chromatid-exchange frequency but was not mutagenic or clastogenic (Brooks et al. 1989). Studies on the mutagenicity of solvent red 1 in the bacterial system Salmonella typhimurium (Ames test) have also yielded conflicting results. Some investigators determined that solvent red 1 was not mutagenic in this system (Manthei et al. 1983; Brooks et al. 1989). Another investigator determined that it was positive in one strain (TA100) when a mammalian bioactivating system was used (Moore et al. 1989). Taken together, these mutagenicity studies suggest that solvent red 1 is a weak mutagen. The possibility that a contaminant in the dye is responsible for the mutagenic effect cannot be dismissed.

Suggested Citation: "Appendix E: Solvent Red 1." National Research Council. 1999. Toxicity of Military Smokes and Obscurants: Volume 3. Washington, DC: The National Academies Press. doi: 10.17226/9645.

TABLE E-2 Summary of Mutagenicity Studies Conducted with Solvent Red 1

Experimental system

Exposure Conditions

End Points and Comments

Reference

Swiss albino male mice

i.p. injections, 0.001, 0.01, 0.1 g/kg, at 30 hr and 6 hr before euthanasia

No increase in micronucleated-femoral polychromatic erythrocytes

Manthei et al. 1983

Mouse lymphoma cells

0-9 g/L, 4 hr

+S9, 100 thymidine kinase mutants per 106 survivors; 16 micronuclei per 1,000 cells at 22% survival

Harrington-Brock et al. 1991

Salmonella typhimurium (strains TA1535, TA1537, TA 1538, TA98, TA100) ± S9

0.0001-1 g/plate

Not mutagenic

Manthei et al. 1983

Salmonella typhimurium (strains TA1537, TA1538, TA98, TA100, TA102, TA104) ± S9

0-0.3 g/plate

Positive in TA100 +S9 with mammalian bioactivating system

Moore et al. 1990

Salmonella typhimurium (strains TA1535, TA1538, TA98, TA100) ± S9

0-0.8 g/plate,

Not mutagenic

Brooks, et al. 1989

Chinese hamster ovary cells

0-40 g/L, 3 hr

Cytotoxic, increased sister-chromatid-exchange frequency, not mutagenic or clastogenic

Brooks et al. 1989

Abbreviation: i.p., intraperitoneal.

Suggested Citation: "Appendix E: Solvent Red 1." National Research Council. 1999. Toxicity of Military Smokes and Obscurants: Volume 3. Washington, DC: The National Academies Press. doi: 10.17226/9645.

SUBCOMMITTEE EVALUATION OF DYE TOXICITY

Experimental data are insufficient to assess the toxic effects of solvent red 1. The studies on contact hypersensitivity suggest that additional studies in the area might be advisable given the demonstrated dermal-sensitization potential of other dyes.

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


Eastin, W.C., M.R. Elwell, S. Grumbein, and J.H. Yuan. 1996. Effects of D&C yellow no. 11 ingestion on F344/N rats and B6C3F1 mice. J. Toxicol. Environ. Health 48(2):197-213.


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.


Krebs, J.S. 1980. Toxicity of D&C yellow 11: A literature review. SRI Project LSU-6465, Contract No. DAAK 11-17-C-0029. Chemical Systems Laboratory, Aberdeen Proving Ground, Edgewood, MD.


Manthei, J.H., F.K. Lee, D.H. Heitkamp, and W.C. Heyl. 1983. Preliminary and Acute Toxicological Evaluation of Five Candidate Smoke Compounds. Tech. Rep. ARCSL-TR-82066. U.S. Army Armament Research and Development Command, Aberdeen Proving Ground, Edgewood, MD.

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 ADA229021. 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. ADA172758. Bioassay Systems Corp., Woburn, MA.

Sun, J.D., R.F. Henderson, T.C. Marshall, Y.S. Cheng, J.S. Dutcher. J.A. Pickrell, J.L. Mauderly, F.F. Hahn, D.A. Banas, F.A. Seiler, and C.H. Hobbs. 1987. The inhalation toxicity of two commercial dyes: Solvent yellow 33 and solvent green 3. Fundam. Appl. Toxicol. 8(3):358-371.

Suggested Citation: "Appendix E: Solvent Red 1." National Research Council. 1999. Toxicity of Military Smokes and Obscurants: Volume 3. Washington, DC: The National Academies Press. doi: 10.17226/9645.
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Suggested Citation: "Appendix E: Solvent Red 1." National Research Council. 1999. Toxicity of Military Smokes and Obscurants: Volume 3. Washington, DC: The National Academies Press. doi: 10.17226/9645.
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Suggested Citation: "Appendix E: Solvent Red 1." National Research Council. 1999. Toxicity of Military Smokes and Obscurants: Volume 3. Washington, DC: The National Academies Press. doi: 10.17226/9645.
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Suggested Citation: "Appendix E: Solvent Red 1." National Research Council. 1999. Toxicity of Military Smokes and Obscurants: Volume 3. Washington, DC: The National Academies Press. doi: 10.17226/9645.
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Suggested Citation: "Appendix E: Solvent Red 1." National Research Council. 1999. Toxicity of Military Smokes and Obscurants: Volume 3. Washington, DC: The National Academies Press. doi: 10.17226/9645.
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Next Chapter: Appendix F: Disperse Red 9
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