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Description of key information

3 studies were available to determine the toxicokinetic

•       In a comparable OECD guideline 417 (Toxicokinetics) of Reindl (1990), absorption, the distribution and excretion of 6-chloro-4-nitro-2-aminophenol were studied by oral route. Male and female Sprague-Dawley rats, in two studies (Study A and B) received orally, 3% solution of the radiolabeled test substance dissolved in water/DMSO 1:1.

Study A: This study was conducted to determine the distribution into the organs, mode and rate of elimination 72 hour after test substance administration.

Study B: This study was conducted to determine the blood level after oral administration of test substance.

The animals were killed 72 hours (Study A) or 24 hours (Study B) after the administration.

Interpretation of results: low bioaccumulation potential based on study results

2-Amino-6-chloro-4-nitrophenol, given orally to rats, is quickly absorbed and excreted within 72 h, with the majority eliminated within the first 24 hour after administration. Excretion takes place predominantly (70 %) via urine and to a minor extent via faeces. Radioactivity was found in several organs including femur.

•       In the ADME study of Kennedy (2004), the bioavailability of 2-Amino-6-Chloro-4-Nitrophenol was determined in-vitro: A-B (apical to basolateral) permeability of the test substance across the intestinal barrier using the TC-7 human intestinal epithelial cell line.

The mean apparent permeability coefficient (Papp) of 2-Amino-6-Chloro-4-Nitrophenol was 133.2 x 10 (-6) cm/s (high permeability). As the absorption from the gastro-intestinal tract is likely to be permeability limited, the high permeability observed in this assay indicates a good absorption of 2-Amino-6-Chloro-4-Nitrophenol after oral administration.

•       In a comparable OECD guideline 417 (Toxicokinetics) of Reindl (1990), absorption,  distribution and excretion by dermal route of 6-chloro-4-nitro-2-aminophenol were studied with male and female Sprague-Dawley rats.

Three studies (Studies A, B and C) were conducted using the radiolabeled test substance. In Studies A and B, formulations 1 and 2 were utilized, respectively. In Study C, a solution of test substance in water/DMSO was used. The details of test formulation/ solution were as follows:

o       Formulation 1: Formulation without H2O2 containing 3% radiolabeled test substance.

o       Formulation 2: Formulation with H2O2 containing 3% radiolabeled test substance.

o       solution of test substance: 9.99% solution of the radiolabeled test substance in water/DMSO (1:1).

Interpretation of results: no bioaccumulation potential based on study results

Dermal absorption of 6-chloro-4-nitro-2-aminophenol (Chlororange) after 30 min of exposure was low. When absorbed; excretion took place mainly via the urine. Radioactivity in all analysed organs was near or below the detection limit 72 hours post-application.

2 Studies were available to estimate the dermal absorption:

•       In the study of Wyss (2003), The cutaneous absorption (in-vitro) of 0.5% 2-Amino-6-chloro-4-nitrophenol in acolor fresh liquid formulation was determined following methods comparable to the OECD Guideline 428. Pig skin samples (from back and flanks) were used as the test system. The receptor fluid was sampled after 16, 24, 40, 48, 64 and 72 hours to determine the test substance concentration. At the termination of the experiment, the skin was heat-treated to separate the upper and lower skin compartments. Different matrices (rinsing solution, receptor fluid, upper dermis and epidermis) were processed and analyzed by means of HPLC (High performance Liquid Chromatography) to determine test concentrations. The following amounts of test substance were found: Rinsing solution (after 30 minutes): 100.316 ± 1.354% or 498385 ± 6725 µg/cm². Nearly half of all fractions of test substance in the receptor fluid were below the limit of quantification of approximately 1.6 ng per injection. Taking all fractions of receptor fluid together, the maximum content of test substance was found to be 0.013 ± 0.002 or 63 ± 12µg/cm² of applied dose, which was certainly an overestimation. Probably due to the overestimated quantity of test substance, there was no observable gradient of increasing quantities against the skin surface. The quantities found in the upper dermis and in the epidermis were 0.008 ± 0.006% or 41 ± 29 µg/cm² and 0.028 ± 0.012% or 140 ± 59 µg/cm² respectively + the  receptor fluid 0.013 % ± 0.002% = 0.049% ± 0.02%

The mass balance (total recovery) was 100.365 ± 1.351%(or 498628 ± 6714 µg/cm²)of the dose applied to the pig skin samples.

Under the conditions of this in vitro cutaneous absorption study of 2-Amino-6-chloro-4-nitrophenol in Color Fresh Liquid Neu 5/55 formulation, a maximum amount of 0.013% (an overestimated value) of applied test substance was found in receptor fluid after 72 hours of application. In addition, 0.008 ± 0.006% and 0.028 ± 0.012% of applied test substance was found in upper dermis and epidermis respectively.

The majority of test substance (100.31 ± 1.35%) was found in rinsing solutions after 30 sec exposure.

•       In the study of Beck (2005), the cutaneous absorption (in-vitro) of 1% 2-Amino-6-chloro-4-nitrophenol in a typical hair dye formulation was determined following methods according to the OECD Guideline 428. Pig skin samples were used. The receptor fluid was sampled after 16, 24, 40, 48, 64 and 72 hours to determine the test substance concentration. At the termination of the experiment, the skin was heat-treated to separate the upper and epidermis compartments. Different matrices (rinsing solution, receptor fluid, epidermis and upper skin) were processed and analyzed by means of HPLC to determine test concentrations.

Most of the applied test substance remained on the skin surface and was recovered in the rinsing solutions (97.43 ± 3.50% or 974.32 ± 35.0 µg/cm²) after 60 minutes of application. Small amounts of test substance were detected in the upper dermis (0.06 ± 0.07or 0.61 ± 0.68 µg/cm²), in the epidermis (0.12 ± 0.03%or 1.18 ± 0.29 µg/cm²) compartments and in the fractions of the receptor fluid collected within 72 hours (0.03 ± 0.01% or 0.29 ± 0.11 µg/cm²).

The mass balance (total recovery) was 97.64 ± 3.45% (or 976.41 ± 34.46 µg/cm²) of the dose applied to the pig skin samples.

As the worst case assumption, considering the kinetics observed, a maximal amount of 2.08 ± 0.75 µg/cm² of test substance in a typical oxidative hair dye formulation containing 1% 2-Amino-6-chloro-4-nitrophenolin the presence of hydrogen peroxide is considered as biologically available.

Receptor fluid + upper dermis + epidermis; 0.29 µg/cm² +0.61µg/cm²+1.18 µg/cm² = 2.08 µg/cm²

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - dermal (%):
0.049

Additional information