2-Amino-6-chloro-4-nitrophenol

EU 1223/2009 Annex III — SCCS opinion: Opinion on 2-Amino-6-chloro-4-nitrophenol

EU 1223/2009 Annex III — SCCS opinion: Opinion on the Use of Permanent Hair Dyes and Bladder Cancer Risk

EU 1223/2009 Annex III — SCCS opinion: Assessment Strategies for Hair Dyes

EU 1223/2009 Annex III — SCCS opinion: Memorandum on Hair Dye Substances and their Skin Sensitising Properties

EU 1223/2009 Annex III — SCCS opinion: Request for a Re-evaluation of hair dyes listed in Annex III to Directive 76/768/EEC on Cosmetic Products

Please refer to the original safety assessment. REPRODUCTIVE AND DEVELOPMENTAL TOXICITY Please refer to the original safety assessment. GENOTOXICITY Genotoxicity studies are summarized in Table 1. 2-Amino-6-chloro-4-nitrophenol was not mutagenic with or with- out metabolic activation in the Ames test (≤5000 µg/plate) or mouse lymphoma assay (≤960 µg/ml), and it was not genotoxic in a micronucleus test with intraperitoneal administration in mice (≤75 mg/kg).3 2-Amino-6-chloro-4-nitrophenol did have the potential to induce micronuclei in cultured human peripheral blood lymphocytes in the presence of metabolic activation (≥1100 µg/ml). Please refer to the original safety assessment for additional in vitro and in vivo genotoxicity data. CARCINOGENICITY No published data were found. 2 CIR Panel Book Page 8  Distrubted for Comment Only -- Do Not Cite or Quote IRRITATION AND SENSITIZATION Skin Sensitization Non-Human 2-Amino-6-chloro-4-nitrophenol was a skin sensitizer in a local lymph node assay in female CBA/J mice.3 Five mice were used per group, and 25 µl of 0, 0.5, 1.5, or 10% 2-amino-6-chloro-4-nitrophenol in DMSO and in a mixture of water/acetone (1:1) with olive oil (4:1) were applied to the surface of the ear for three consecutive days. p-Phenylenedi- amine, 1% in DMSO, was used as the positive control. A dose-response was observed with the DMSO vehicle; the mean stimulation indices were 1.2, 1.2, 2.0, and 4.7 with 0.5, 1.5, 5, and 10% 2-amino-6-chloro-4-nitrophenol, respectively. An … [kırpıldı — bölüm toplam 6624 karakter]

Definition and Structure 2-Amino-6-Chloro-4-Nitrophenol (CAS No. 6358-09-4) is the substi- tuted aromatic compound that conforms to the following formula: Another name for this ingredient is Phenol, 2-Amino-6-Chloro-4-Nitro- (Wenninger and McEwen, 1993). Chemical and Physical Properties 2-Amino-6-Chloro-4-Nitrophenol is described as yellow needles or an orange-yellow, fine-grained powder. The molecular weight of the free base is 188.56, and the monohydrate is 206.60. 2-Amino-6-Chloro-4- Nitrophenol is soluble in water, at a pH greater than 7.0 (COLIPA, 1990). Ultraviolet Light Absorbance The absorption maximum for 2-Amino-6-Chloro-4-Nitrophenol is 204.8 nm; additional absorption maxima occurred at 262.3 nm, 229.1 nm, and 316.1 nm, in order of decreasing absorption (COLIPA, 1990). COSMETIC USE 2-Amino-6-Chloro-4-Nitrophenol Hydrochloride is used as a hair col- orant in hair dyes and colors requiring caution statements and patch test instructions and in hair tints (Wenninger and McEwen, 1992; Food and Drug Administration [FDA], 1995). The product formulation data submitted to the FDA in 1995 reported that 2-Amino-6-Chloro-4- Nitrophenol Hydrochloride was used in a total of 15 hair-coloring prod- ucts (Table 1; FDA, 1995). There was no listing for 2-Amino-6-Chloro-4- Nitrophenol in 1995. Concentration of use values are no longer reported to the FDA by the cosmetic industry (FDA, 1992); however, product formulation data sub- CIR Panel Book Page 16  Distrubted for Comment Only -- Do Not Cite or Quote 2-AMINO-6-CHLORO-4-NITROPHENOL 133 Table 1. Cosmetic product formulation data on 2-Amino-6-Chloro- 4-Nitrophenol Hydrochloride No. of formulations No. containing Product category in category ingredient … [kırpıldı — bölüm toplam 24712 karakter]

CIR re_review (n.d.): On the basis of the animal and clinical data included in this report, the CIR Expert Panel concludes that 2-Amino-6-Chloro4-Nitrophenol and its hydrochloride salt are safe for use in hair dye formulations at con- centrations of up to 2.0%.

EPA ToxValDB skin/eye data — endpoint: skin irritation: in vivo, classification: Studies Indicate No Significant Irritation, species: rabbit, study: skin irritation, guideline: OECD Guideline 404 (Acute Dermal Irritation / Corrosion) Deviations, reliability, and validity evaluated against current OECD 404 (Apr. 24, 2002) according to, year: 1988. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: eye irritation: in vitro / ex vivo, classification: Severe Irritation, species: chicken, study: eye irritation, guideline: other guideline: OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage) Adopted : 26 July 2013 according to, year: 2017. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: skin sensitisation: in vivo (non-LLNA), classification: Not likely to be sensitizing, species: guinea pig, study: skin sensitization, guideline: according to OECD Guideline 406 (Skin Sensitisation), year: 1988. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: skin sensitisation: in vivo (LLNA), classification: High Frequency of Sensitization, species: mouse, study: skin sensitization, guideline: according to OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay), year: 2004. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: eye irritation: in vivo, classification: Studies Indicate No Significant Irritation, species: rabbit, study: eye irritation, guideline: OECD Guideline 405 (Acute Eye Irritation / Corrosion) Low concentration used, not in accordance with REACh requirement. according to, year: 1988. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.