3,3'-[(2-chloro-5-methyl-p-phenylene)bis[imino(1-acetyl-2-oxoethylene)azo]]bis[4-chloro-N-[2-(4-chlorophenoxy)-5-(trifluoromethyl)phenyl]benzamide]

Endpoint summary

Description of key information

Based on the physico-chemical properties and the absence of systemic toxicity in acute and repeated-dose studies, absorption of the study is unlikely. Pigment Yellow 128 was found to be insoluble both in the static and in the dynamic dissolution study (BASF 2022).

This is supported by absence of toxicity in all available toxicity studies. For organic pigments, which are all powders and some fullfil the criteria of a nanomaterial, there is no indication that nano- and non-nano forms behave differently. The publication “Indicators for lack of systemic availability of organic pigments”by Stratmann et al published in Regulatory Toxicology and Pharmacology in 2020 is attached.  

The nanoparticles of Pigment Yellow 128 generated no reactivity signal in the EPR assay with DMPO spin trap indicating some capacity for oxidative damage in an in-chemico setting. No such activity was observed in the complementary FRAS assay. (BASF 2022, attached).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There were no studies available in which the toxicokinetic properties of the ‘yellow disazo condensation pigments’ were investigated. 

The ‘yellow disazo condensation pigments’ (molecular weight betweenabout 716 g/mol and 1229 g/mol) are yellow powders at room temperature with an extremely low water solubility (highest measured water solubility of the pigments: < 50 µg/L at 20 °C (CAS 5280-80-8, see chapter "water solubility")). The substances are not prone to hydrolysis and contain the same type of linkages. The data matrices for physico-chemical and toxicological endpoints are provided below:

Tale 1: Overview of physico-chemical data

	PY 93	PY 94	PY 95	PY 128	PY 155
	5580-57-4	5580-58-5	5280-80-8	79953-85-8	68516-73-4
Molecular weight	937.053 g/mol	957.47 g/mol	916.63 g/mol	1229.18 g/mol	716.65 g/mol
Sate of the substance at 20°C and 101.3 kPa	yellow powder	yellow powder	yellow powder	yellow powder	yellow powder
Melting point	> 300 °C	>300 °C	>300 °C	>300 °C	> 300 °C
Boiling point	Not applicable (melts above 300 °C)	Not applicable (melts above 300 °C)	Not applicable (melts above 300 °C)	Not applicable (melts above 300 °C)	Not applicable (melts above 300 °C)
Relative density	1.46 g/cm³	Read-across PY 93	1.41 g/cm³	1.49 g/cm³	1.45 g/cm³
Vapour pressure	Not relevant	Not relevant	Not relevant	Not relevant	Not relevant
Water solubility (μg/L)	<10 µg/L at 20 °C	Read-across PY 93	50 µg/L at 20 °C (Limit of quantification)	<25 µg/L at 23 °C	n.d. (extremely low solubility)
n-octanol solubility	1 µg/L	Read-across PY 93	50 µg/L	<25 µg/L	not soluble
Log Pow (calculated from solubility)	0	0	0	0	not soluble
Surface tension	Not surface active: The water solubility is < 1 mg/L	Not surface active: The water solubility is < 1 mg/L	Not surface active: The water solubility is < 1 mg/L	Not surface active: The water solubility is < 1 mg/L	Not surface active: The water solubility is < 1 mg/L
Flash point	Not relevant	Not relevant	Not relevant	Not relevant	Not relevant
Auto flammability/self-ignition temperature	350 °C at 1013 hPa	Read-across PY 93	350 °C at 1013 hPa	322 °C at 1013 hPa	290 °C at 1013 hPa
Flammability	Non flammable	Non flammable	Non flammable	Non flammable	Non flammable
Explosive properties	Non explosive	Non explosive	Non explosive	Non explosive	Non explosive
Oxidizing properties	No oxidizing properties	No oxidizing properties	No oxidizing properties	No oxidizing properties	No oxidizing properties
Dissociation constant	The substance does not contain any ionic structure	The substance does not contain any ionic structure	The substance does not contain any ionic structure	Not applicable	The substance does not contain any ionic structure

Table 2: Overview of toxicity data

	PY 93	PY 94	PY 95	PY 128	PY 155
	5580-57-4	5580-58-5	5280-80-8	79953-85-8	68516-73-4
Skin and eye irritation	Not irritating K2 Purity: NA		Not irritating K1/2 Purity: NA	Not irritating K2 Purity: NA	Not irritating K2 Purity: NA
Skin sensitization	Not sensitizing K1 Purity: 98%				Not sensitizing K1 Purity: NA
Acute oral tox	LD50 >2000 mg/kg bw K2 Purity: NA		LD50 >2000mg/kg bw K1 Purity: 99.4%	LD50 >2000mg/kg bw K2 Purity: NA	LD50 >2000mg/kg bw K1 Purity: NA, (treated as 100%)
Acute dermal tox	LD50 >2000mg/kg bw K4 Purity: NA		LD50 >2000mg/kg bw K4 Purity: NA
Acute inhalation tox	LC50 >1.7 mg/L K2 Purity: NA
Subacute toxicity	NOAEL = 1000mg/kg bw (OECD 407) K1 Purity: 98%			NOAEL = 1000mg/kg bw (OECD 422) K1 Purity: 99.4%	NOAEL = 1000mg/kg bw (OECD 422) K1 Purity: 99.1%
Bacterial mutagenicity	Non mutagenic K1 Purity: > 97%	Non mutagenic K1 Purity: > 99%	Non mutagenic K2 Purity: NA	Non mutagenic K1 Purity: 97%	Non mutagenic, four strains K2 Purity: NA, (treated as 100%) Ames, Prival ongoing
Clastogenicity in vitro (micronucleus test)	Non clastogenic (nano modification)	Non clastogenic (read-across)	Non clastogenic K1 Purity: 99.4%	Non clastogenic   (nano modification)	Non clastogenic   (nano modification) Purity: 95.7%
Mutagenicity in mammalian cells in vitro	Non mutagenic (read-across)	Non mutagenic (read-across)	Non mutagenic K1 Purity: 99.4%	Non mutagenic (read-across)	Non mutagenic K1 Purity: NA, (treated as 100%)
Genetic toxicity in vivo	No data available	No data available	No data available	No data available	No data available
Toxicity to reproduction	NOAEL = 1000 mg/kg bw  K1 Purity: 99.3%	No data available	No data available	NOAEL = 1000 mg/kg bw  K1 Purity: 99.4%	NOAEL = 1000 mg/kg bw (OECD 422) K1 Purity: 99.1% OECD 414 NOAEL = 1000 mg/jg bw Purity: 95.7%
Carcinogenicity	No data available	No data available	No data available	No data available	No data available

Overview of toxicity data on amine building blocks (data sources: *OECD QSAR Toolbox v2.3/literature, **ECHA Dissimination view, accessed Oct 30, 2012 or ***unpublished company data)

	PY 93 Amine (end)	PY 93, PY 128 Amine (core)	PY 93,94,95, 128 Amine (Mid)	PY 155 Amine (core)	PY 94, 95er Amine (end)
CAS	87-60-5	5307-03-9	2840-28-0	106-50 -3	95-79-4
Acute oral toxicity (LD50, mg/kg bw)	681  ***	1700*** (male/female)	>8000***	Ca 300 (minimum lethal dose = 75)**	630*
Other	Methaemoglobin formation postulated				Methaemoglobin formation*
Bacterial mutagenicity	Negative***	Positive***	Negative*	Equivocal*	Negative*
Clastogenicity in vitro					Negative*
Mutagenicity in mammalian cells in vitro					Negative *
Clastogenicity in vivo (MN)	Negative*			Negative** (OECD 474)
Subchronic or chronic toxicity in rats				NOAEL = 16 mg/kg bw (OECD 408)**	LOEL = 125 mg/kg bw (feed, chronic), rat*
Toxicity to reproduction				NOEL(maternal) = 5 mg/kg NOAEL(developmental) = 10 mg/kg (OECD 414)**
carcinogenicity				Not carcinogenic*	IARC Cat 3 (not classifyable)   Carc Cat 2

CAS	PY 94 Amine core	PY 94, PY 95 Amine end	PY 95 Amine core	PY 128er Amine (end)	PY155er Amine (mid)
	20103-09-7	95-79-4	6393-01-7	349-20-2	none
Acute oral toxicity (LD50, mg/kg bw)	>5000***	700**	27***
Acute dermal toxicity (LD50 mg/kg bw)
Bacterial mutagenicity		Negative*, ambiguous**	positive*
Clastogenicity in vitro		Negative**
Mutagenicity in mammalian cells in vitro		Negative**
Genotoxicity in vivo
Repeated dose toxicity
Toxicity to reproduction
Carcinogenicity		IARC Cat 3 (not classifyable)   Carc Cat 2

ABSORPTION

In acute oral toxicity studies done with the‘yellow disazo condensation pigments’common clinical signs as dyspnea, exophthalmos, ruffled fur, curved body position, diarrhea and sedation were seen when the substances were applied in high concentrations. These systemic toxic effects were all transient. No indication of a substance specific systemic toxicity can be found in acute toxicity study in rats with dermal or inhalative administration (see chapter „acute toxicity“) as well as in a subacute toxicity study and a reproductive toxicity screening study in rats with oral application (see chapter „repeated dose toxicity“ and "reproductive toxcity"). Therefore absorption and bioavailability of the test substance after oral administration is not expected (see chapter "acute oral toxicity" and chapter "repeated dose toxicity").

Furthermore, calculation of the dermal absorption potential based on the criteria of the Danish EPA resulted in a very low absorption potential of 10%. Therefore, systemic absorption through the skin is expected to be low.

The test substance is a non-volatile powder at room temperature (the melting point is above 300 °C, see chapter "vapour pressure"). Furthermore, the substances decompose before boiling so that inhalation of test substances vapour is not relevant. In conclusion, based on the physical-chemical properties and the absence of systemic toxicity in acute inhalation studies, absorption of the test substances through the lung are unlikely.

 

DISTRIBUTION

There is no experimental evidence of distribution.

 

METABOLISM

There is no experimental evidence of metabolism. In theory the chemical structure indicates that the most likely route of biotransformation is by reductive cleavage of the azo bond either by bacterial enzymes in the gut or by microsomal azo reductase in the liver. Furthermore, uptake and metabolism of these substances should result in the release of aromatic amines. Such compounds have a characteristic toxicity profile. As this was not observed, the substances are not considered to have been taken up by the body. So metabolism is not expected due to lack of absorption after oral administration of the test substance. Studies on genetic toxicity (bacterial reverse mutation assay (Ames-Test), in vitro mammalian cell gene mutation and chromosome aberration test, see chapter "genetic toxicity") were negative and gave no indications of a reactivity of the test substances or its metabolites under the test conditions (i.e. no increased mutagenicity in treatments with and without metabolic activation).

 

EXCRETION

The observation of yellowish faeces in the repeated oral study is assessed as indication of intestinal passage of the pigment. The extremely low water solubility of the test substance makes absorption from the gastro-intestinal tract unlikely and the substance is expected to be eliminated unchanged (ECHA guidance document R.7c, 2017).