1-(2,5-ジメトキシフェニルアゾ)-2-ナフトール

Dyes -> Azo Dyes

Carcinogens

Foods -> FDA Regulatory Status of Color Additives

COLOR OR COLORING ADJUNCT -> FDA Substance added to food

Orange to yellow solid or dark red powder (NTP, 1992)

Crystals

less than 1 mg/mL at 72 °F (NTP, 1992)

Partially soluble in ethanol and vegetable oils

311 to 315 °F (NTP, 1992)

156 °C

Citrus red no. 2 appears as orange to yellow solid or dark red powder. (NTP, 1992)

Orange to yellow or dark red solid; [CAMEO] Red crystalline solid; [MSDSonline]

Warning

H351 (100%): Suspected of causing cancer [Warning Carcinogenicity]

P203, P280, P318, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 39 reports by companies from 2 notifications to the ECHA C&L Inventory.

Warning

H351: Suspected of causing cancer [Warning Carcinogenicity]

Hazard Traits - Carcinogenicity

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

CITRUS RED NO. 2 is an azo compound. Toxic gases are formed by mixing compounds containing azo groups with acids, aldehydes, amides, carbamates, cyanides, inorganic fluorides, halogenated organics, isocyanates, ketones, metals, nitrides, peroxides, phenols, epoxides, acyl halides, and strong oxidizing or reducing agents. Flammable gases are formed by mixing materials in this group with alkali metals. Explosive combination can occur with strong oxidizing agents, metal salts, peroxides, and sulfides.

Carc. 2 (100%)

Carcinogenicity - Category 2

Carcinogenicity - Category 2

Carcinogens

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for CITRUS RED 2 (6 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for CITRUS RED 2 (9 total), please visit the HSDB record page.

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves.

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2.3X10+4(SRC), determined from a structure estimation method(2), indicates that Citrus Red 2 is expected to be immobile in soil(SRC). Volatilization of Citrus Red 2 from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.2X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Citrus Red 2 is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data in soil were not available(SRC, 2011).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2.3X10+4(SRC), determined from a structure estimation method(2), indicates that Citrus Red 2 is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.2X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 10(SRC), from an estimated log Kow of 5.67(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC,2011). However, Azo dyes, such as Citrus Red 2, are hydrophobic compounds, suggesting they will partition strongly to bottom sediments where reductive cleavage of the azo linkage may occur. This transformation process could result in the release of potentially hazardous aromatic amines to the water column(8), in this case 1-amino-2,5-dimethoxybenzene and 2-hydroxy-1-napthylamine(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), Citrus Red 2, which has an estimated vapor pressure of 3.0X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase Citrus Red 2 may be removed from the air by wet or dry deposition(SRC). Citrus Red 2 contains chromophores that absorb at wavelengths >290 nm(3), and therefore may be susceptible to direct photolysis by sunlight(SRC).

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

Using a structure estimation method based on molecular connectivity indices(1), the Koc of Citrus Red 2 can be estimated to be 2.3X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that Citrus Red 2 is expected to be immobile in soil.

ANAEROBIC: Azo dyes are hydrophobic compounds, suggesting they will partition strongly to bottom sediments where reductive cleavage of the azo linkage may occur. This transformation process could result in the release of potentially hazardous aromatic amines to the water column(1), in this case 1-amino-2,5-dimethoxybenzene and 2-hydroxy-1-napthylamine(SRC).

Citrus Red No. 2

Group 2B: Possibly carcinogenic to humans

Volume 8: (1975) Some Aromatic Azo Compounds

1987

1987

An estimated BCF of 10 was calculated in fish for Citrus Red 2(SRC), using an estimated log Kow of 5.67(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for the neutral species of Citrus Red 2 is estimated as 5.2X10-13 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that Citrus Red 2 is expected to be essentially nonvolatile from water and moist soil surfaces(2). Citrus Red 2 is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-9 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Nineteen beagle dogs received 0, 50 and 200 mg of the color per kg body weight per day by capsule, six days per week for 76 or 104 weeks. Clinical studies did not show differences between control group and the group with 50 mg/kg/day. The animals of the group of 200 mg/kg/day showed in the beginning decreased activity and periods of poor appetite. The animals progressed in about 26 weeks and seemed comparable with the control animals in their appearance and behavior. A decrease in cell volume, hemoglobin and total erythrocyte count was found in this group after 26 weeks. Five of the six animals of the 200 mg/kg/day showed an increase in total counts of leucocytes. No biochemical values and urine analyses showed abnormalities. Four dogs of the 50 mg group and three control groups were sacrificed after 76 weeks. The other dogs were sacrificed after 104 weeks. No significant gross or microscopic pathological abnormalities were found in the control animals and the animals of the 50 mg/kg/day. The organs, liver, kidneys and spleen of the animals with 200 mg/kg/day were significantly increased in weight. Histologically no abnormalities were found, except an evidence of hemopoietic hyperplasia.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of 50 male and 50 female mice were fed diets containing 0.0, 0.01, 0.03, 0.1, 0.3, 1.0 or 3.0% Citrus Red No. 2 (CR2) for periods up to 80 weeks. Further groups received repeated subcutaneous injections of CR2 or control solvent over an 80-week period. All tumors and other observed lesions seen at autopsy were examined histologically in animals which died or which were killed because moribund during the test or which were killed after 80 weeks. The food intake of mice was recorded. Diets containing 0.3, 1.0 and 3.0% CR2 caused increased morbidity and mortality and the feeding test was terminated a few weeks after administration commenced. At the 0.1% level, there were increases in the mortality rate in both sexes and in the incidence of degenerative changes in the livers of female mice. No untoward effects were found in mice on the 0.03% level. Dietary levels up to 0.1% had no significant effect on the type, incidence or time of appearance of tumors. In female but not in male mice receiving CR2 by repeated subcutaneous injection, an increased incidence of malignant tumours was observed; these tumours appeared earlier than those in the control group. ...

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Seven hundred and eighty rats received dietary levels of 0, 0.05, 0.1, 0.5, 1.0, 3.0 and 5.0 percent of the color for two years. The animals of the groups with three and five percent showed a significant inhibition of the growth. These animals were killed after 31 weeks. The animals of the 0.05 and 0.1 percent exhibited normal appearance and behavior. Some rats of 0.5 percent and of higher levels developed subcutaneous edema-like swelling of the head, neck, thoracic region and forelimbs. Hydrothorax was revealed in a number of these animals. At 31 weeks clinical studies were performed and in the female animals at the five percent level the plasma-protein, hemoglobin and hematocrit values were significantly lowered. The male animals showed only the decreased plasma-protein levels. The ratio liver weight/bodyweight of the animals of the 0.5 percent and higher was increased. The histopathological examination of the organs of the animals of 0.05 and 0.1 percent did not show abnormalities. At 0.5, 1.0, 3.0 and 5.0 percent cardiac changes consisting of interstitial edema and fibroblastic cell proliferation were found.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Two groups of 50 male and 50 female rats were given once a week subcutaneously respectively 0.2 mL tricaprylin and 0.2 mL tricaprylin containing 20 mg of the color for two years. The injections were given alternated in the axillary and inguinal regions. These injections gave small subcutaneous deposits or nodules located at the injection sites. During the experiments the nodules persisted but there was no evidence of active enlargement. These nodules showed histologically the encapsulated injected material with a thin fibrous wall. No tumors were found.

For more Non-Human Toxicity Excerpts (Complete) data for CITRUS RED 2 (11 total), please visit the HSDB record page.

Citrus Red 2 is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Citrus Red 2 contains chromophores that absorb at wavelengths >290 nm(1), and therefore may be susceptible to direct photolysis by sunlight(SRC).

When citrus red number 2 was administered to rats with cannulated bile ducts, 6 red-colored, water-soluble metabolites were detected in bile, and traces of 1-amino-2-naphthol glucuronide and 1-amino-2-naphthol sulfate were present in urine.

1-Amino-2-naphthyl glucuronide is a metabolite of citrus red number 2 in humans.

The urine of normal rats dosed with the color contained 6 metabolites: 1 of the two red-colored metabolites was the O-glucuronide of citrus red number 2 (2,5-dimethoxyphenylazo-2-naphthyl glucuronide); two of the products were unidentified; two others were 1-amino-2-naphthol glucoronide and 1-amino-2-napthol sulfate. The urine of dogs given color contained 12 metabolites, one of which, 1-amino-2-naphthol sulfate, was present in high concentrations; however, 1-amino-2-napthyl glucoronide was not detected.

In vitro incubation of emulsions of the color with the intestinal contents of the rat, rabbit and dog resulted in destruction of the color by the bacterial flora.

Small amounts of 1-amino-2-naphthyl sulphate were identified in the urine of rats. This demonstrates that the color is reduced at the azo linkage in the animal body followed by conjugation to give the o-glucuronide and ethereal sulphate derivatives of 1-amino-2-naphthol.

After single oral doses of 2-20 mg in corn oil solution to rats, five to seven percent of the administered color was recovered in the feces in 48 hr. When the dose was reduced to 0.5 mg no color was found. When administered as a 0.5 percent dry mixture, 26.3 percent was found in the feces. Rabbits and dogs showed similar results.

After a single dose small amounts of the color were found in the body fat. Repeated administration resulted in gradual reduction of the concentration of the color in the fat and finally it disappeared altogether after seven to 10 days.

Used formerly as dye for orange skins that are not processed; [HSDB]

Considered unsafe for food use by FAO/WHO committee in 1973; [HSDB]

To color orange skins

Citrus Red No. 2 shall be used only for coloring the skins of oranges that are not intended or used for processing (or if so used are designated in the trade as Packinghouse elimination) and that meet minimum maturity standards established by or under the laws of the States in which the oranges are grown.

2-Naphthalenol, 1-[2-(2,5-dimethoxyphenyl)diazenyl]-: ACTIVE

In USA, color is permitted only for coloring skins of oranges that are not intended or used for processing, at level not exceeding 2 ppm on basis of wt of the whole fruit. (US Code of Federal Regulations, 1974).

Color additives were initially regulated in the United States under the U.S. Department of Agriculture's (USDA) Bureau of Chemistry. In 1906, the Food and Drugs Act was passed by Congress, which prohibited the use of poisonous or deleterious colors in confectionery and the coloring or staining of food to conceal damage or inferiority. In 1927, responsibility of the Food and Drugs Act was transferred to FDA. Increasing government oversight, the Federal Food, Drug, and Cosmetic Act (FFDCA) was passed in 1938 and established the three following categories for colors: FD&C: colors used in foods, drugs and cosmetics; D&C: colors used in drugs and cosmetics when in contact with mucous membranes or ingested; and Ext. D&C: colors used in products applied externally.

The joint FAO/WHO expert committee on food additives ... considers citrus red number 2, on basis of toxicological evidence, to be unsafe for use in food (FAO/WHO, 1973).

This color should not be used as a food additive.

The US International Trade Commission last reported US production of Citrus Red 2 (Solvent Red 80) in 1970 by two US manufacturers (Allied Chemical Corp and American Cyanamid)