MOBILE VIEW  | 

RHODAMINE

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Rhodamine B, also known as basic violet 10, is used as a color additive in drugs and cosmetics in the United States. Because of potential toxic and carcinogenic effects, rhodamine is no longer used as a food additive.

Specific Substances

    1) Basic Violet 10
    2) Food Red 15
    3) FD&C Red 19
    4) Tetraethyl-3',6'-diaminofluoran
    5) Ammonium, (9-(o-carboxyphenyl-)-6-(diethylamino)-
    6) 3H-xanthen-3-ylidene)diethyl-, chloride
    7) Acid Brilliant pink
    8) Tetraethylrhodamine
    9) C.I. 49
    10) C.I. 45170
    11) C.I. Basic Violet 10
    12) Cogilor red 321.10
    13) Cosmetic Brilliant Pink Blush D Conc
    14) Diethyl-m-amino-phenolphthalein hydrochloride
    15) 11411 red
    16) Red No. 213
    17) Molecular Formula: C28-H31-N2-O3.Cl
    18) CAS 81-88-9
    19) RHODAMINE 6G

Available Forms Sources

    A) FORMS
    1) The FDA banned the use of rhodamine B in all cosmetic products on July 15, 1988.
    B) USES
    1) Rhodamine B is used primarily as a fluorescent dye. It is used as a food additive (not in the United States) and as both an analytical agent and coloring agent in cosmetics. It is also used to test for fuel leaks in various military vehicles (Dire & Wilkenson, 1987; (Kelner, 1985; IARC, 1978). Rhodamine B is also used as a test molecule in intraocular dynamics because after either topical or systemic administration it mimics the actions of lipid soluble drugs (Guss et al, 1984).

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) There have been few human cases of overdose. Humans are currently exposed through some food products (not in the U.S.), cosmetics, and industrial uses. Symptoms have included mucous membrane irritation of the lungs, eyes, throat, nose, and gastrointestinal tract, as well as red urine. Hepatic damage has been seen in animals.
    0.2.4) HEENT
    A) Eye irritation, excessive tearing, rhinorrhea, and sore throat have all been reported after exposure to aerosolized rhodamine B.
    0.2.6) RESPIRATORY
    A) Coughing, difficulty in breathing, and a tightness or burning sensation of the chest have all been experienced after exposure to the aerosolized dye.
    0.2.7) NEUROLOGIC
    A) Headache was reported in one of 17 patients exposed to the aerosolized toxin.
    0.2.8) GASTROINTESTINAL
    A) Nausea was an uncommon symptom seen after exposure to the aerosolized toxin. Several hundred milligrams have been ingested with food without significant gastrointestinal symptoms.
    0.2.9) HEPATIC
    A) Hepatic enlargement and damage has been reported in animal studies, but has yet to be reported in human cases.
    0.2.10) GENITOURINARY
    A) Ingestion of the dye may cause the urine to become fluorescent red. The red color is not due to blood in the urine.
    0.2.14) DERMATOLOGIC
    A) The skin of victims exposed to the aerosolized rhodamine B became itchy and irritated.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

    A) There are no specific laboratory tests that have been shown to be of value. The urine of exposed individuals may become fluorescent red.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Up to several hundred milligrams have been ingested without serious effects. Toxicity of amounts greater than this is unknown and may require activated charcoal until more data are available.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) Minimum lethal human exposure is unknown.
    B) Up to several hundred milligrams have been ingested without serious effects.

Summary Of Exposure

    A) There have been few human cases of overdose. Humans are currently exposed through some food products (not in the U.S.), cosmetics, and industrial uses. Symptoms have included mucous membrane irritation of the lungs, eyes, throat, nose, and gastrointestinal tract, as well as red urine. Hepatic damage has been seen in animals.

Heent

    3.4.1) SUMMARY
    A) Eye irritation, excessive tearing, rhinorrhea, and sore throat have all been reported after exposure to aerosolized rhodamine B.
    3.4.3) EYES
    A) Excessive tearing and burning of the eyes was reported in 82% of the symptomatic patients seen after exposure to aerosolized rhodamine B (Dire & Wilkinson, 1987).
    B) Unlike other cationic dyes, rhodamine does not inhibit corneal turgescence (Grant & Schuman, 1993).
    3.4.5) NOSE
    A) Burning and itching of the nasal passages as well as rhinorrhea was reported in patients exposed to aerosolized rhodamine B (Dire & Wilkinson, 1987).
    3.4.6) THROAT
    A) Burning sensation of the throat was reported by patients exposed to aerosolized rhodamine B (Dire & Wilkinson, 1987).

Respiratory

    3.6.1) SUMMARY
    A) Coughing, difficulty in breathing, and a tightness or burning sensation of the chest have all been experienced after exposure to the aerosolized dye.
    3.6.2) CLINICAL EFFECTS
    A) DYSPNEA
    1) Dyspnea was reported after exposure to aerosolized rhodamine B. Other respiratory symptoms included chest tightness, cough, and a burning sensation of the chest (Dire & Wilkinson, 1987).

Neurologic

    3.7.1) SUMMARY
    A) Headache was reported in one of 17 patients exposed to the aerosolized toxin.
    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) Headache was reported in 6% of those exposed to aerosolized rhodamine B (Dire & Wilkinson, 1987).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea was an uncommon symptom seen after exposure to the aerosolized toxin. Several hundred milligrams have been ingested with food without significant gastrointestinal symptoms.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA
    1) Nausea was reported in 1 of 17 patients exposed to aerosolized rhodamine B (Dire & Wilkinson, 1987).

Hepatic

    3.9.1) SUMMARY
    A) Hepatic enlargement and damage has been reported in animal studies, but has yet to be reported in human cases.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOCELLULAR DAMAGE
    a) Administration of rhodamine B to mice and rats produced hepatic damage and enlargement (Hansen et al, 1959; Webb & Hansen, 1961).

Genitourinary

    3.10.1) SUMMARY
    A) Ingestion of the dye may cause the urine to become fluorescent red. The red color is not due to blood in the urine.
    3.10.2) CLINICAL EFFECTS
    A) ABNORMAL URINE
    1) CASE REPORTS: Two cases of red, fluorescent urine in two adults who had eaten bakery goods in Mexico which contained rhodamine B. No significant kidney damage was noted in these cases (Kelner, 1985).

Dermatologic

    3.14.1) SUMMARY
    A) The skin of victims exposed to the aerosolized rhodamine B became itchy and irritated.
    3.14.2) CLINICAL EFFECTS
    A) ITCHING OF SKIN
    1) Pruritus and irritation was seen in 4 of 17 patients exposed to aerosolized rhodamine B (Dire & Wilkinson, 1987).

Reproductive

    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    B) ANIMAL STUDIES
    1) FETOTOXICITY
    a) Mice dosed with 60 mg/kg intraperitoneally on days 7 through 10 of their pregnancies experienced significant fetotoxicity. Rhodamine B did not have reproductive effects in a multi-generation study in rats when administered in the diet (Pierce, 1974) and did not cause birth defects in rats or rabbits (Ebert, 1974).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS81-88-9 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Rhodamine B
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) Rhodamine B has caused tumors or has been a questionable tumorigenic agent in studies of subcutaneous injection in rats (RTECS , 2001). It increased thyroid and liver tumors in mice (Opresko, 1982) and produced lymphomas and intestinal tumors when given to mice in the drinking water (HSDB , 1997). However, rhodamine B was not carcinogenic when given at up to 4% in the diet to rats for two years (Opresko, 1982). IARC has determined that rhodamine B has limited evidence of being an experimental animal carcinogen (Group 3) (RTECS , 2001).

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) There are no specific laboratory tests that have been shown to be of value. The urine of exposed individuals may become fluorescent red.
    4.1.2) SERUM/BLOOD
    A) OTHER
    1) There are no specific laboratory tests that are required post exposure.
    4.1.3) URINE
    A) URINALYSIS
    1) The urine may become fluorescent red after an exposure.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) If pulmonary exposure is severe, a chest x-ray, and other pulmonary function tests may be of some diagnostic value.

Methods

    A) CHROMATOGRAPHY
    1) Thin layer chromatography may be used to determine rhodamine and some of its metabolites (Bell, 1974; Kelner, 1985).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) There are no specific laboratory tests that have been shown to be of value. The urine of exposed individuals may become fluorescent red.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Decontamination is not likely to be necessary for amounts under several hundred milligrams. Since the toxic dose is unknown, ingestions of more than this may require gastric decontamination.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) There is no specific treatment except decontamination. Chest x-ray and pulmonary function may be of use in those cases where pulmonary irritation is significant.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Case Reports

    A) INHALATION EXPOSURE
    1) Dire & Wilkenson (1987) reported 17 patients who were exposed to aerosolized rhodamine B (caused by 10 pounds that had been spilled and was being swept from the floor) for an average of 26 minutes (range 2 to 65 minutes). Symptoms seen, in order of frequency, were eye irritation and burning, tearing, nasal burning and itching, tightness in the chest, rhinorrhea, cough and difficulty in breathing, throat irritation, skin irritation, burning sensation in the chest, headache, and nausea. All of the above symptoms resolved in 24 hours or less and no serious sequelae were noticed. The duration of exposure did not correlate with the severity of symptoms (Dire & Wilkinson, 1987).
    B) INGESTION EXPOSURE
    1) Two young adults were inadvertently exposed to Rhodamine B following the ingestion of baked goods from Mexico. The teenager developed flank pan and red urine (+fluorescent red) while a pregnant woman developed a seizure episode. In neither case, there was no direct evidence to suggest that these symptoms were associated with Rhodamine B ingestion and no evidence of permanent renal damage (Kelner, 1985).

Summary

    A) Minimum lethal human exposure is unknown.
    B) Up to several hundred milligrams have been ingested without serious effects.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) Has not been established.

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) A 17-year-old man ate several hundred milligrams of rhodamine in cookies without obvious toxic effect except for red urine (Kelner, 1985).
    B) ANIMAL DATA
    1) RATS - Given one percent rhodamine in their diet for 30 days exhibited inhibited growth when compared with controls (Dire & Wilkenson, 1987).

Workplace Standards

    A) ACGIH TLV Values for CAS81-88-9 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS81-88-9 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS81-88-9 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Rhodamine B
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS81-88-9 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (ORAL)MOUSE:
    a) 887 mg/kg (RTECS, 2001)
    2) LD50- (INTRAPERITONEAL)RAT:
    a) 112 mg/kg (RTECS, 2001)

Toxicologic Mechanism

    A) Rhodamine appears to be an irritant and possible carcinogen. It is carcinogenic in animals (RTECS , 1991).
    B) When heated to decomposition, rhodamine emits toxic chlorine, ammonia, and nitrogen oxide fumes (Sax & Lewis, 1987).

Physical Characteristics

    A) This compound may be a reddish violet powder or green crystals. Solutions are bluish red in color and fluorescent (Budavari, 1996).

Molecular Weight

    A) 479.06 (RTECS , 2001)

Other

    A) OTHER
    1) CASE REPORTS
    a) A free-ranging polar bear was examined forensically and determined to have died from ingesting a solution of ethylene glycol and rhodamine B used to mark runways covered with ice. Death was probably due to ethylene glycol intoxication; the necessary fatal dose of rhodamine was calculated (based on mouse LD50) to be 18 grams for this 200 kg bear. However, toxic effects due to rhodamine could not be ruled out (Amstrup et al, 1989).

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