National Toxicology Program

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. ¹

Names (NTP)

• C.I. BASIC RED 1
• Rhodamine 6G
• 2-(6-(ETHYLAMINO)-3-(ETHYLIMINO)-2,7-DIMETHYL-3H-XANTHEN-9-YL)BENZOIC ACID ETHYL ESTER MONOHYDROCHLORIDE (9CI)
• BASIC RED 1

Human Toxicity Excerpts

• Some important causes of occupational phototoxic or photoallergic reactions /are rhodamine dyes/. /Rhodamine dyes/ [Zenz, C. Occupational Medicine-Principles and Practical Applications. 2nd ed. St. Louis, MO: Mosby-Yearbook, Inc, 1988., p. 148]**PEER REVIEWED**
  
• Two variants have been isolated from the cultured human cell line VA2-B which are resistant in vivo to the mitochondrial specific fluorescent dyes rhodamine 6G and rhodamine 123. Both mutants are cross-resistant to ethidium bromide but are sensitive to both colchicine and chloramphenicol. When either mutant is treated with low levels of rhodamine 6G, mitochondrial associated fluorescence is significantly lower than in wild type cells. Furthermore, when cell cultures are treated with high concentrations of either rhodamine 123 or 6G, and then washed free of the dye, mitochondrial associated rhodamine fluorescence rapidly diminishes in the parental cell line. In hybrid cell fusions between resistant and sensitive cell lines, rhodamine resistance is gradually expressed, reaching maximal expression approximately 11 days after fusion. Cytoplasmic transmission of rhodamine resistance has not been clearly demonstrated in cytoplast-cell fusions, and thus resistance is probably due to a mutation of a nuclear, rather than mitochondrial DNA gene(s). These observations indicate that mitochondria of both rhodamine resistant variants, unlike wild type, have a significantly decreased ability to bind and retain rhodamine, and thus their mitochondrial tramsmembrane electrical potential may be significantly reduced. [Wiseman A et al; Somat Cell Mol Genet 11 (6): 541-56 (1986)]**PEER REVIEWED**
  

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Non-Human Toxicity Excerpts

• 16 RATS ... MIXED SAITAMA STRAIN, WEIGHING ABOUT 200 G, RECEIVED REPEATED SC INJECTIONS OF 1 ML OF 0.02% AQ SOLN ... 2-3 TIMES/WK. AFTER 4 MO, INJECTIONS WERE DISCONTINUED FOR 1 MO ... RESUMED, UNTIL TOTAL OF 100 INJECTIONS ... 4/7 RATS THAT SURVIVED FOR 487 DAYS DEVELOPED FIBROSARCOMAS ... . 1 RAT ... SPINDLE CELL SARCOMA OF LIVER ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V16 237 (1978)]**PEER REVIEWED**
  
• OF 40 MICE OF BOTH SEXES OF MIXED SAITAMA STRAIN, WEIGHING ABOUT 20 G, FED RICE DIET CONTAINING 0.05, THEN 0.01, THEN 0.02% RHODAMINE 6G, 12 SURVIVED FOR 100 DAYS OR MORE & 1 FOR 223 DAYS (TOTAL DOSE, 90.6 MG). NONE OF MICE DEVELOPED TUMORS. (WORKING GROUP NOTED HIGH MORTALITY & SHORT DURATION OF EXPT.) [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V16 236 (1978)]**PEER REVIEWED**
  
• ... MODERATELY INJURIOUS TO RABBIT EYE. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 381]**PEER REVIEWED**
  
• COMMERCIAL RHODAMINE DYES 6G & B INDUCE HIS+ REVERSION MUTATIONS IN SALMONELLA TYPHIMURIUM & SINGLE-STRAND BREAKS IN CHINESE HAMSTER OVARY CELLS. AROCLOR 1254 INDUCED RAT LIVER HOMOGENATE (S9) IS NECESSARY FOR GENETIC ACTIVITY. FRAMESHIFT & BASE SUBSTITUTION MUTATIONS NOTED. [NESTMANN ET AL; CANCER RES 39 (11): 4412 (1979)]**PEER REVIEWED**
  
• IONIC CHARACTER & PARTITION COEFFICIENT OF 7 FLUORESCENT XANTHENIC TRACERS (RHODAMINES B, 6G & WT, SULFORHODAMINES B & G, URANINE & EOSINE) WERE DETERMINED. TOXICITY TOWARD DAPHNIA MAGNA & LEBISTES RETICULATUS WAS SHOWN. A WEAK CORRELATION BETWEEN TOXICITY & PARTITION COEFFICIENT WAS FOUND. [BENOIT-GUYOD JL ET AL; TOXICOL EUR RES 2 (5): 241-6 (1979)]**PEER REVIEWED**
  
• IN RAT LIVER MITOCHONDRIA, RHODAMINE 6G BLOCKED ATP-SUPPORTED CALCIUM(+2) ACCUM, BUT NOT THAT DRIVEN BY SUCCINATE OXIDN. CONCN OF GREATER THAN 20 MUMOLE UNCOUPLED RESP & INHIBITED RESP CALCIUM(+2) UPTAKE. [GEAR AR L; J BIOL CHEM 259 (11): 3628 (1974)]**PEER REVIEWED**
  
• F(0)F(1)ATPase activity and ADP translocation were measured on gestation day 12 in embryonic and adult mitochondria of mice following in vivo or in vitro exposure to Rhodamine 6G. ATP synthesis in embryonic mitochondria transplacentally exposed to Rhodamine 6G (0.5 mg/kg/day) given to dams by intraperitoneal injection from gestation day 7 to 10 were inhibited 49%. When isolated mitochondria were treated, dose dependent inhibition was seen: at 5 ug of dye/mg mitochondrial protein, ATP synthesis was inhibited 81% by Rhodamine 6G. When F(0)F(1)ATPase activity was assessed, in vitro Rhodamine 6G exposures at levels up to 8 ug/mg mitochondrial protein resulted in enzyme inhibition, but at 10 ug/mg, ATPase activity was stimulated. Uncoupler stimulated ATPase activity was also inhibited. ADP translocation was decreased by 37.7% by Rhodamine 6G at dye concentrations of 20 ug/mg. Results of in vitro exposure of maternal liver mitochondria were similar to those for embryonic mitochondria, whereas liver from dams exposed in vivo on gestation days 7 to 10 was unaffected on gestation day 12. [Ranganathan S, Hood RD; Terat Carc Mut 9 (1): 29-37 (1989)]**PEER REVIEWED**
  
• Rhodamine 6G was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 when tested with and without exogenous metabolic activation (S9). Rhodamine 6G gave a positive response in the absence of S9 in the mouse lymphoma assay for induction of trifluorothymidine resistance in L5178Y cells; in the presence of S9, rhodamine 6G was negative. Rhodamine 6G induced sister chromatid exchanges (SCEs) and chromosomal aberrations in cultured CHO cells in the presence, but not the absence, of S9. [DHHS/NTP; Toxicology and Carcinogenesis Studies of Rhodamine 6G (CI Basic Red 1) in F344/N Rats and B6C3F1 mice (Feed Studies) p.4 (1989) Technical Rpt Series No.364 NIH Pub No. 89-2819]**PEER REVIEWED**
  
• Rhodamine 6G is a specific inhibitor of aerobic growth of yeast (Saccharomyces cerevisiae), and isolated rhodamine-6G-resistant mutants have been used to demonstrate extrachromosomal inheritance in yeast. [DHHS/NTP; Toxicology and Carcinogenesis Studies of Rhodamine 6G (CI Basic Red 1) in F344/N Rats and B6C3F1 Mice (Feed Studies) p.14 (1989) Technical Rpt Series No.364 NIH Pub No.89-2819]**PEER REVIEWED**
  
• Positively charged dyes rhodamine 6G and rhodamine 123 inhibit heartbeat and kill Sprague-Dawley neonatal rat cardiac muscle cells in vitro but the neutral dyes rhodamine B and rhodamine 116 do not. Cationic rhodamine dyes, but not neutral dyes, inhibit oxidative phosphorylation in isolated mitochondria. Differences in the accumulation of rhodamine 123 and rhodamine 6G in cardiac and carcinoma cells were observed. Both dyes selectively inhibit the in vitro growth and in vivo growth. [DHHS/NTP; Toxicology and Carcinogenesis Studies of Rhodamine 6G (CI Basic Red 1) in F344/N Rats and B6C3F1 Mice (Feed Studies) p.13 (1989) Technical Rpt Series No.364 NIH Pub No.89-2819]**PEER REVIEWED**
  
• At low rhodamine concentrations, ATP dependent calcium ion uptake is blocked (Ki= 3 uM); at concentrations greater than 20 uM, respiration becomes uncoupled and respiration dependent calcium ion uptake is inhibited. Rhodamine 6G inhibited H+ ejection from mitochondria energized with ATP or with succinate and postulated that inhibition sites of rhodamine 6G are on membrane components related to H+ ejection by oxidation/reduction components. Rhodamine 6G has also been found to inhibit the import and processing of matrix catalyzed mitochondrial proteins ... in isolated hepatoma ascites cells or normal hepatocytes (eg, cytochrome b-c1 complex subunits) from male Sprague-Dawley rats at concentrations that did not uncouple mitochondrial respiration. [DHHS/NTP; Toxicology and Carcinogenesis Studies of Rhodamine 6G (CI Basic Red 1) in F344/N Rats and B6C3F1 Mice (Feed Studies) p.13 (1989) Technical Rpt Series No.364 NIH Pub No.89-2819]**PEER REVIEWED**
  
• Cationic rhodamines (Rh 123 and Rh 6G) can cause developmental toxicity in mice and inhibit embryonic mitochondrial respiration following in vivo or in vitro dye exposure. Rh B, a neutral rhodamine, fails to show such effects at comparable doses. To assess effects of rhodamines on development, F0F1ATPase activity and ADP translocation were measured on gestation day (GD) 12 in embryonic and adult mitochondria. ATP synthesis in embryonic mitochondria transplacentally exposed to Rh 123 (15 mg/kg/day) or Rh 6G (0.5 mg/kg/day) given to dams by ip injection from gestation day 7 to 10 were inhibited 39% and 49%, respectively. When isolated mitochondria were treated, dose-dependent inhibition was seen; at 5 ug of dye/mg mitochondrial protein, ATP synthesis was inhibited 65% and 81% by Rh 123 and Rh 6G, respectively. When F0F1ATPase activity was assessed, in vitro Rh 123 and Rh 6G exposures at levels up to 8 ug/mg mitochondrial protein resulted in enzyme inhibition, but at 10 ug/mg, ATPase activity was stimulated. Uncoupler-stimulate ATPase activity was also inhibited. ADP translocation was decreased by 19.1% and 37.7% by Rh 123 and Rh 6G, respectively, at dye concentrations of 20 ug/mg. Results of in vitro exposure of maternal liver mitochondria were similar to those for embryonic mitochondria, whereas liver from dams exposed in vivo on gestation day 7-10 was unaffected on gestation day 12. In vivo or in vitro treatment with Rh B did not affect any embryonic o maternal parameters. The results support the hypothesis that inhibition of mitochondrial energy metabolism is a mechanism for the developmental toxicity of cationic rhodamines. [Medoff-Cooper B, Verklan T; Teratogenesis Carcinog Mutagen 9 (1): 29-37 (1989)]**PEER REVIEWED**
  
• Experiments were carried out to determine whether the mitochondria specific dye rhodamine-6G can affect transmission of cytoplasmic determinants in mammalian cells. When one parental cell type was treated with rhodamine-6G prior to fusion with an untreated partner, the subsequent hybridization frequencies in both intra- and interspecific crosses were not adversely affected even though rhodamine-6G was extremely toxic to the parental cells. Cells lethally treated with rhodamine-6G could be rescued by fusion with cytoplasm alone from untreated cells. [Ziegler ML, Davidson RL; Somatic Cell Genet 7 (1): 73-88 (1981)]**PEER REVIEWED**
  
• The effects of cationic and neutral rhodamines on the developing mouse were compared. Sexually mature virgin female CD-1-mice were mated with males of the same strain. Pregnant females were treated ip with rhodamine-123, rhodamine-B, or rhodamine-116 at 15 mg/kg/day. The rhodamines were given alone or combined with 500 mg/kg/day 2-deoxy-D-glucose. Dosing occurred on gestation days seven through ten. Other pregnant mice received rhodamine-6G at 0.5 mg/kg/day. Significant increases were noted in prenatal mortality when given rhodamine-6G either alone or combined with 2-deoxy-D-glucose. Fetal growth was inhibited by treatment with rhodamine-123 or rhodamine-6G with or without 2-deoxy-D-glucose. Little effect was noted on prenatal survival or growth when treated with neutral rhodamines. A high incidence of gross malformation was noted on exposure to rhodamine-6G with or without 2-deoxy-D-glucose. No significant teratogenic effects were noted following treatment with rhodamine-116 or rhodamine-B with or without 2-deoxy-D-glucose or with rhodamine-123 without 2-deoxy-D-glucose. Skeletal malformations were increased in the groups receiving rhodamine-6G plus 2-deoxy-D-glucose, rhodamine-123 plus 2-deoxy-D-glucose, and rhodamine-6G alone. The authors suggest a relationship may exist between the charge on the rhodamine molecule and effects on the conceptus. These effects may have been mediated partly by interference with mitochondrial metabolism. [Hood RD et al; Teratology 40 (2): 143-50 (1989)]**PEER REVIEWED**
  

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Human Toxicity Values

• None found

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Non-Human Toxicity Values

• None found

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Absorption, Distribution and Excretion

• RHODAMINE 6G EXHIBITS HIGH PLASMA PROTEIN BINDING. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V16 237 (1978)]**PEER REVIEWED**
  
• Rhodamine 6G and rhodamine B were reported to be excreted in the pancreatic juice in situ after intravenous infusion of 1 mg dye per minute to dogs (strain, age, and sex not specified) followed by the administration of secretin or cholecystokinin-pancreozymin stimulation. The rate of excretion was not reported. [DHHS/NTP; Toxicology and Carcinogenesis Studies of Rhodamine 6G (CI Basic Red 1) in F344/N Rats and B6C3F1 Mice (Feed Studies) p.13 (1989) Technical Rpt Series No.364 NIH Pub No. 89-2819]**PEER REVIEWED**
  

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Metabolism/Metabolites

• None found

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TSCA Test Submissions

• None found

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Footnotes

¹ Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.