5-Amino-4-Chloro-o-Cresol HCl

Definition and Structure According to the Dictionary, 5-Amino-4-Chloro-o-Cresol (CAS No. 110102-86-8) is the organic compound that conforms to formula in Figure 1.1 5-Amino-4-Chloro-o-Cresol HCl (CAS No. 110102-85-7) is the hair colorant that is the hydrochloride salt of 5-Amino-4-Chloro-o-Cresol. However, the use of regiochemical terms such as “ortho-” (i.e., the “-o-” in 5-Amino-4-Chloro-o-Cresol) is vague and inappropriate when an aromatic system such as a benzene ring has more than 2 substituents. Figure 1. 5-Amino-4-Chloro-o-Cresol 5-Amino-4-Chloro-o-Cresol HCl is a precursor in oxidative hair dye systems.4 It reacts with primary intermediates to form the final hair-reactive dye. The reaction can be accelerated by addition of an oxidizing agent (e.g., hydrogen peroxide), but can also be achieved by air oxidation. Chemical Properties Chemical properties for 5-Amino-4-Chloro-o-Cresol and 5-Amino-4-Chloro-o-Cresol HCl are summarized in Table 1. 5-Amino-4-Chloro-o-Cresol is reported to be soluble in water, propylene glycol, and triethanolamine.2 5-Amino-4-Chloro-o- Cresol has a symmetrical absorption peak below 300 nm, which falls off sharply above 300 nm. Method of Manufacture Method of manufacturing data for 5-Amino-4-Chloro-o-Cresol and 5-Amino-4-Chloro-o-Cresol HCl were not included in the original report and were not found in the updated literature search, and unpublished data were not submitted. Composition and Impurities The specification of 97% purity for 5-Amino-4-Chloro-o-Cresol is supported by high-performance liquid chromatography (HPLC) analysis; impurities include an early peak identified as 2-methyl-5-aminophenol (2%), and two unidentified peaks (1% combined), one of which was close to the peak of the ingredient and one that eluted later.2 5-Amino-4-Chloro-o-Cresol HCl … [kırpıldı — bölüm toplam 6695 karakter]

Dermal Absorption In Vitro The dermal absorption/percutaneous penetration potential of [14C] labelled 5-Amino-4-Chloro-o-Cresol HCl (98% pure) through excised pig skin (750 µm thick) was determined from a cream formulation mixed with a developer containing hydrogen peroxide.4 The study was performed in accordance with Organisation for Economic Co-operation and Development (OECD) test guideline (TG) 428. The concentration of 5-Amino-4-Chloro-o-Cresol HCl in the final application formulation was 1.6%. Using Franz diffusion cells, 20 mg formulation per cm2 pig skin (dose of test substance was approximately 0.32 mg/cm2 skin; skin discs were 1.0 cm2) was applied for 30 min. Application of the test material was terminated by gently rinsing with 0.01% Tween 80 solution and water. The formulation was analyzed in 2 experiments with 4 replicates per experiment for adsorbed, absorbed, and penetrated amount of the test material. The receptor fluid (Dulbecco’ phosphate buffered saline; pH 7.35) was analyzed at defined intervals for up to 48 h post application. Both the amounts absorbed and penetrated were taken as systemically available. The amount of 5-Amino-4-Chloro-o- Cresol HCl systemically available from a standard cream formulation mixed with a developer was found to be 12.47 + 1.82 µg/cm2 (range 10.60 to 16.47 µg/cm2) or 3.90 + 0.69% (range 3.12 to 5.29%) of the applied dose. The SCCP noted the  Distributed for Comment Only -- Do Not Cite or Quote number of chambers used was too few and the absorbance maximum (Amax) of 16.47 µg/cm2 in an oxidizing formulation is used for the calculation of the margin of safety.4 Animal Skin absorption of [14C] labelled 5-Amino-4-Chloro-o-Cresol HCl was studied in female rats.2 A formulation containing the radiolabeled ingredient (with p-toluenediamine sulfate, basic fatty acid emulsion, propylene glycol, water, and … [kırpıldı — bölüm toplam 3226 karakter]

Acute Toxicity Studies Oral In an acute oral toxicity study, male and female rats received 5-Amino-4-Chloro-o-Cresol HCl by gavage at doses of 1184, 1539, and 2000 mg/kg.2 For males, the LD50 was between 1539 and 2000 mg/kg and for females, the LD50 was >2000 mg/kg. Acute toxicity studies of 5-Amino-4-Chloro-o-Cresol and 5-Amino-4-Chloro-o-Cresol HCl were not found in the updated literature search, and unpublished data were not submitted. Subchronic Toxicity Studies Oral In a 90-d oral study, male and female rats received 5-Amino-4-Chloro-o-Cresol HCl by gavage at doses of 0, 20, 60, and 180 mg/kg/d.2 No clinical observations or pathological findings indicative of systemic toxicity were observed. Only minor deviations in a few biochemical and hematological parameters were noted. The no-observable-adverse-effect-level (NOAEL) was 180 mg/kg/d. Repeated-dose toxicity studies of 5-Amino-4-Chloro-o-Cresol and 5-Amino-4-Chloro-o-Cresol HCl were not found in the updated literature search, and unpublished data were not submitted.

Oral The only maternal effects observed in pregnant rats dosed with aqueous 5-Amino-4-Chloro-o-Cresol HCl (up to 500 mg/kg/d) by gavage on days 6 to 15 of gestation was a brown discoloration of the urine.2 In fetuses, no developmental toxicity was associated with treatment with 5-Amino-4-Chloro-o-Cresol HCl. Development and reproductive toxicity studies for 5-Amino-4-Chloro-o-Cresol and 5-Amino-4-Chloro-o-Cresol HCl were not found in the updated literature search, and unpublished data were not submitted.

5-Amino-4-Chloro-o-Cresol (free base) was mutagenic with metabolic activation in an Ames test evaluating concentrations of up to 2500 μg/plate of 5-Amino-4-Chloro-o-Cresol HCl dissolved in water and up to 1200 μg/plate of 5- Amino-4-Chloro-o-Cresol (the free base) dissolved in dimethyl sulfoxide. 2 No increases in the number of mutations were observed in a cell gene mutation test at the HGPRT locus in V79 Chinese hamster lung cells exposed to 5-Amino-4-Chloro-o- Cresol HCl dissolved in ethanol at up to 60 μg/ml without metabolic activation and up to 550 μg/ml with metabolic activation. In an in vivo micronucleus test in mice, 5-Amino-4-Chloro-o-Cresol HCl did not induce micronuclei after a single oral dose of up to 500 mg/kg bw. In vitro and in vivo genotoxicity studies on 5-Amino-4-Chloro-o-Cresol HCl summarized here are detailed in Table 3. 5-Amino-4-Chloro-o-Cresol HCl (98% pure) was mutagenic in strain TA98 with metabolic activation in an Ames test at up to 5000 µg/plate, with and without S9 metabolic activation.4 The test material did not include an increase in the number of revertant colonies in strains TA100, TA102, TA1535, or TA1537, at any concentration tested with or without metabolic  Distributed for Comment Only -- Do Not Cite or Quote activation. 5-Amino-4-Chloro-o-Cresol HCl (98% pure) was not genotoxic in a L5178 mouse lymphoma cell assay at the tk locus at up to 500 µg/ml without metabolic activation or with up to 375 µg/ml with metabolic activation. A clear dose- dependent increase in cells with micronuclei was observed following exposure of 5-Amino-4-Chloro-o-Cresol HCl (98% pure) at up to 1000 µg/ml without metabolic activation and up to 500 µg/ml with metabolic activation in V79 Chinese hamster lung cells. In vivo testing found that 5-Amino-4-Chloro-o-Cresol HCl (purity not reported) did not induce micronuclei in mice that received a single intraperitoneal dose of 500 mg/kg bw.

EPA ToxValDB genotoxicity: positive — positive reports: 4, negative: 3, Ames: positive, micronucleus: positive. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.