Registration Dossier

Administrative data

Description of key information

Skin Irritation :

According to the result of the key study (GLP compliant, Klimisch 1, OECD 431), the registered substance was defined to be not corrosive for skin. However, this study cannot classified the test substance category 2 or Not Classified according to GHS and EU-CLP. Based on the available information on irritation corrosion on eye of the substance, the 2 -Amino-6-Chloro-4 -Nitrophenol was classified as Category 2 for a worst case scenario. Indeed, a irritant effect cannot be discarded, the classification as Category 2 was made. In vitro irritation study is in progress, if the result differ from the worst case assumption an additional update of the classification and dossier will be performed.

Eye irritation :

According to the results of the key studies, the test item induced mild irritation in eye. Hence, the registered substance 2 -amino-6-chloro-4 -Nitrophenol was classified as Category 1B "Mild Irritant/causes eye irritation" according GHS criteria and Category 2 "Irritating to eyes" according CLP criteria.

Key value for chemical safety assessment

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

EYE IRRITATION :

Prinsen, 2016, GLP, Klimisch 1, OECD 438 Guideline :

This GLP-compliant study was performed to assess the potential irritation/corrosion property of the registered substance 2-Amino-6-Chloro-4-Nitrophenol in a Isolated Chicken Eye test (ICE test) according to OECD guideline 438 method.2-Amino-6-Chloro-4-Nitrophenol (B099; GTS119166) was evaluated neat for eye irritation potential in the Isolated Chicken Eye (ICE) test. In addition, the test included a negative control (saline) and a positive control (NaOH). Chicken eyes were obtained from slaughter animals used for human consumption. The isolated chicken eyes were exposed to a single application of 30 mg for 10 seconds followed by a 20 mL saline rinse. Three main parameters were measured to disclose possible adverse eye effects: corneal thickness (expressed as corneal swelling), corneal opacity and fluorescein retention of damaged epithelial cells. In addition, histopathology of the corneas was performed.

Under experimental conditions of the study, the registered substance 2-Amino-6-Chloro-4-Nitrophenol (B099; GTS119166) caused corneal effects consisting of very slight or slight corneal swelling (mean swelling 4%), slight corneal opacity (mean score 1.0) and moderate fluorescein retention (mean score 2.0). Microscopic examination of the corneas did revealed very slight (2/3 corneas) erosion and very slight (1/3 corneas, top region) vacuolation of the epithelium. According to the CLP regulation and OECD, the ICE test cannot be used for classify Eye irritation Category 2 due to false negative rate of the test (including alcohol). However, microscopic observation was performed on histopathologic slide of the chicken eye. Hence, by caution, the substance was considered as irritant for thee eyes  due to erosion, vacuolation of the epithelium in this test, and classified as Category 2.

Duschl, 2017, GLP, Klimisch 1, OECD 492 method

This GLP compliant in vitro study was performed to assess the eye irritation potential of 2-Amino-6-Chloro-4-Nitrophenol (B099) by means of the Human Cornea Model Test. Additional tests with viable or freeze-killed tissues had to be performed, since the test item dyed water and isopropanol in the colour interference pre-test, and proved to be a MTT reducer. About 50 mg of the test item and each 50 µL of the controls, respectively, were applied to each of duplicate EpiOcular™ tissue for 6 hours.Treatment with the positive control induced a decrease in the mean relative absorbance compared with the negative control to 17.8%, thus the validity of the test system is ensured. The acceptance criteria were met.

Relevant irritating effects were observed following 6 hours incubation with 2-Amino-6-Chloro-4-Nitrophenol (B099). The mean relative absorption value of the tissues corresponding to the cornea viability decreased to 5.0% compared with the value of the negative control (threshold for irritancy: ≤ 60%).

In conclusion, it can be stated that in this study and under the experimental conditions reported, 2-Amino-6-Chloro-4-Nitrophenol (B099) possesses an eye irritating potential.

SKIN IRRITATION

Warren, GLP, 2017, Klimisch 1, OECD 431 method

The purpose of this GLP compliant study is to evaluate the corrosivity potential of the test item using the EpiDerm™ Human Skin Model after treatment periods of 3 and 60 minutes according the OECD 431 guideline method. Duplicate tissues were treated with the test item for exposure periods of 3 and 60 minutes. At the end of the exposure period the test item was rinsed from each tissue before each tissue was taken for MTT loading in order to evaluate the cellular viability.The relative viability after the 3 and 60 minutes exposure periods were respectively 105.8% and 97.9%. Under the experimental condition of this study, the registered substance 4-amino-6-chloro-4-nitrophenol did not led to corrosion when applied on EpiDermTM Reconstructed Human Epithelium. Hence, the B099 was not classified as corrosive substance according CLP criteria.

According to the result of the key study (GLP compliant, Klimisch 1, OECD 431), the registered substance was defined to be not corrosive for skin. However, this study cannot classified the test substance category 2 or Not Classified according to GHS and EU-CLP. Based on the available information on irritation corrosion on eye of the substance, the 2 -Amino-6-Chloro-4 -Nitrophenol was classified as Category 2 for a worst case scenario. Indeed, a irritant effect cannot be discarded, the classification as Category 2 was made. In vitro irritation study is in progress, if the result differ from the worst case assumption an additional update of the classification and dossier will be performed.

Justification for classification or non-classification

According to the CLP regulation and OECD method, the ICE test of the key study cannot be used for classify Eye irritation Category 2 due to false negative rate of the test (including alcohol). However, microscopic observation was performed on histopathologic slide of the chicken eye. Hence, by caution, the substance was considered as irritant for the eyes  due to erosion, vacuolation of the epithelium in this test, and classified as Category 2. Additionnaly, on the EIT test performed according to the OECD 492 method, the substance showed eye irritation potential. Based on this informations and according to the CLP criteria, the substance was classified as Category 2 H319 .

According to the result of the key study (GLP compliant, Klimisch 1, OECD 431), the registered substance was defined to be not corrosive for skin. However, this study cannot classified the test substance category 2 or Not Classified according to GHS and EU-CLP. Based on the available information on irritation corrosion on eye of the substance, the 2 -Amino-6-Chloro-4 -Nitrophenol was classified as Category 2 for a worst case scenario. Indeed, a irritant effect cannot be discarded, the classification as Category 2 was made. In vitro irritation study is in progress, if the result differ from the worst case assumption an additional update of the classification and dossier will be performed.