1.1.1. Synonyms, structural and molecular data

Chem. Abstr. Serv. Reg. No.: 2871-01-4

Chem. Abstr. Name: 2-[(4-Amino-2-nitrophenyl)amino]ethanol

Synonyms: 2-(4-Amino-2-nitroanilino)ethanol; HC Red 3; HC Red Number 3; 4-(2-hy- droxyethyl)amino-3-nitroaniline; N¹-(2-hydroxyethyl)-2-nitro-para-phenylenediamine

1.1.2. Chemical and physical properties

From US National Toxicology Program (1986)

• (a) Description: Fine, dark-maroon crystals, with a greenish cast
• (b) Melting-point: 124–128 °C
• (c) Spectroscopy data: Infrared, ultraviolet and nuclear magnetic resonance spectral data have been reported.
• (d) Solubility: Soluble in water (0.28% w/w), ethanol and acetone
• (e) Octanol/water partition coefficient (P): 1.9

1.1.3. Trade names, technical products and impurities

HC Red No. 3 is available commercially at a purity ≥ 95%, with aminoquinoxaline, aminonaphthyridine (US National Toxicology Program, 1986) and 2-[(4-[4-amino-2-nitro-phenyl]amino-2-nitrophenyl)amino] ethanol (< 1%) as possible impurities.

1.1.4. Analysis

No data were available to the Working Group.

1.2.1. Production

HC Red No. 3 is produced by the reaction of 4-fluoro-3-nitrobenzenamine with mono-ethanolamine. Production and use of this dye began in the late 1950s. Approximately 2300 kg are used annually in the USA, according to industry estimates.

1.2.2. Use

HC Red No. 3 is used exclusively as a dye in semi-permanent hair colour products. These products are generally shampooed into the hair, lathered and then allowed to remain in contact with the hair and scalp for 30–45 min. The concentration of HC Red No. 3 used in these preparations ranges from 0.1 to 5% (Frenkel & Brody, 1973; US National Toxicology Program, 1986).

1.3.1. Natural occurrence

HC Red No. 3 is not known to occur as a natural product.

1.3.2. Occupational exposure

No data were available to the Working Group.

On the basis of a survey conducted in the USA between 1981 and 1983, the US National Institute for Occupational Safety and Health estimated that a total of 42 485 workers, including 32 059 women, were potentially exposed as beauticians and cosmetologists to HC Red No. 3 (US National Library of Medicine, 1992).

3.1.1. Mouse

Groups of 50 male and 50 female B6C3F₁ mice, eight weeks of age, were administered 0, 125 or 250 mg/kg bw HC Red No. 3 (97% pure) by gavage in corn oil on five days a week for 104 weeks and were sacrificed at 113 weeks of age. Body weight gain and survival were reduced in all groups of females because of a reproductive tract infection. Survival at the end of the study was: males—control, 30/50; low-dose, 41/50; and high-dose, 29/50; females-control, 12/50; low-dose, 8/50; and high-dose, 9/50. The incidence of hepatocellular adenomas in males was control, 11/50; low-dose, 6/50; high-dose, 16/50; the incidence of hepatocellular carcinomas was, control, 17/50; low-dose, 9/50; high-dose, 21/50. There was an increased incidence of hepatocellular adenomas and carcinomas combined in high-dose male mice (control, 25/50; low-dose, 15/50; high-dose, 35/50), which was significant (p = 0.017, incidental tumour test), but not after pair-wise comparison. The incidence in historical controls in the testing laboratory was 109/298 (37 ± 12%) (US National Toxicology Program, 1986). [The Working Group noted the poor survival of females and the unusually. high incidence of hepatocellular carcinomas in male controls.]

3.1.2. Rat

Groups of 50 male and 50 female Fischer 344/N rats, seven to eight weeks of age, were administered 0,250 or 500 mg/kg bw HC Red No. 3 (97% pure) by gavage in corn oil on five days a week for 105 weeks and were sacrificed at 113–114 weeks of age. The treatment had no effect on body weight gain throughout the study and did not reduce survival in males or females. Survival at the end of the experiment was: males—control, 34/50; low-dose, 34/50; high-dose, 32/50; females—control, 39/50; low-dose, 38/50; high-dose, 34/50. The incidence of mammary gland fibroadenomas was significantly (p = 0.019, incidental tumour test) increased in low-dose females (control, 14/50 versus low-dose, 24/50) but not in high-dose females (11/50) (US National Toxicology Program, 1986). [The Working Group noted the absence of a dose-response relationship.]

4.2.1. Humans

No data were available to the Working Group.

4.2.2. Experimental systems

In the studies reported above, no compound-related toxic effect was reported (US National Toxicology Program, 1986).

HC Red No. 3 was present at low concentrations (0.02%) in semi-permanent hair colouring formulations evaluated in a two-year feeding study in dogs (Wernick et al., 1975) and in a 20-month study of dermal toxicity in mice (Jacobs et al., 1984, 0.3%), described in detail on p. 97. No treatment-related adverse effect was detected. [The Working Group noted that the dose of each component of the formulations was very low and unlikely to have been toxic]

4.3.1. Humans

No data were available to the Working Group.

4.3.2. Experimental systems

No data were available to the Working Group on the reproductive and developmental effects of HC Red No. 3 alone. The compound was present at low concentrations in semi-permanent hair colouring formulations evaluated in a study of fertility and reproductive performance in rats (Wernick et al., 1975, 0.02%; see p. 99), in a study of heritable translocation in rats (Burnett et al., 1981, 0.01 %; see p. 104), and in studies of teratogenesis in rats and rabbits (Wernick et al., 1975) (see p. 100). No treatment-related adverse effect was detected. [The Working Group noted that the dose of each component of the formulations was very low and unlikely to have been toxic]

4.4.1. Humans

No data were available to the Working Group.

4.4.2. Experimental systems (see also Table 1 and Appendices 1 and 2)

Table 1

Genetic and related effects of HC Red No. 3.

HC Red No. 3 was mutagenic to Salmonella typhimurium.