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EC number: 275-639-3 | CAS number: 71566-54-6
The substance is considered to be too large to be taken up after ingestion or after dermal uptake. This consideration is based on the physico-chemical properties and the findings of the subacute oral toxicity studies. It is insoluble in both hydrophilic and lipophilic solvents and cannot accumulate in tissues.
COLOUR INDEX NAME CAS NUMBER
Pigment Brown 23 35869-64-8
Pigment Brown 41 68516-75-6
Pigment Red 144 5280-78-4
Pigment Red 166 3905-19-9
Pigment Red 214 40618-31-3
Pigment Red 220 68259-05-2
Pigment Red 221 71566-54-6
Pigment Red 242 52238-92-3
Pigment Red 262 79665-24-0
An overview on the structures is given in the attached document as chemical structures cannot be inserted into the freetext fields of IUCLID.
The high molecular weights ranging from 781.7 g/mol (Pigment Red 262) to 930.5 g/mol (Pigment Red 242) are just below the general threshold of 1000 g/mol for cellular uptake. Both water and octanol solubility is less than 0.1 mg/L which impedes transport in both aqueous and non-aqueous compartments. None of the groups are ionisable at physiological pH; specifically no increased solubility or degradation in stomach acid is possible.
Modelling of the molecular dimensions shows that the substances are large and bulky; all dimensions are larger than 10 Angström for Pigment Red 262, which has the lowest molecular weight (BASF 2012). As the pigments completely consist of conjugated systems, the molecule is not flexible which again hinders uptake.
All the disazocondensation red pigments included in this category contain azo and amide bonds which according to textbook knowledge on xenobiotic metabolism are susceptible to enzymatic cleavage. This would in all cases result in the formation of aromatic mono- and p-di-amines. Available toxicity data on these amines is summarized in table C below. Their hazard potential depends on the electron-donating or withdrawing character of the substituent as well as its position on the ring. For example, if Pigment Red 166 would be metabolized, p-phenylene diamine would be released and for this substance, a NOAEL of 16 mg/kg bw for subchronic oral exposure was obtained (ECHA dissiminated dossier on CAS 106-50-3).
Therefore, absence of systemic toxicity upon subacute oral exposure to Pigment Red 220 and 166 is a strong argument against systemic uptake and consequential metabolism of disazocondensation red pigments.
Also, azo-pigments which are smaller in size and soluble in stomach acid such as Pigment Red 57:1 (CAS 5281-04-9) cause signs of systemic effects upon subacute gavage exposure. For details it is referred to the dissiminated REACH dossiers.
Release of aromatic amines would also have been detected via genotoxicity in the in-vivo study for unscheduled DNA synthesis with Pigment Brown 23 and in the in-vivo micronucleus assays with Pigment Brown 23, Pigment Red 166 and Pigment Red 221. However, all of these tests were negative, as were the in-vitro tests both with and without Prival modification for azo compounds. Pigment Red 144 and 166 were tested with the Prival modification. Absence of uptake into cells and the body is consistent with the physico-chemical properties. Indeed, the red chromophore of the pigment remains intact during the passage through the gastrointestinal tract, as indicated by the red color of the feces of orally treated rats.
Dermal route of exposure
The molecular weight of each category member is well above the threshold of 500 g/mol which is given in the EU guidance document on dermal absorption (Sanco/222/2000 rev. 7, March 19, 2004). This threshold allows the assumption of 10% dermal permeation if the n-octanol/water partition coefficient is either very low (-1) or high (> 4). The threshold for log Pow is not reached for every member, but this is due to the overall very poor solubility of the pigments. Solubility is in the lowmg/L range which is hindering any transport process.
None of the available data indicates that the pigments cause skin irritation which would damage the dermal barrier. Absence of systemic uptake after ingestion postulated.
Inhalation route of exposure
Considering the size and the poor solubility, disazocondensation red pigments are considered to behave like inert nuisance dust. Significant systemic uptake via the respiratory epithelium is not expected. Overall, since the substance is not soluble in organic solvents, accumulation in fat tissues is not possible and the substance has no potential for bioaccumulation.
Table A: Overview of physico-chemical data of the disazocondensation red pigments
Decomp. above 370°C
Decomp. above 349°C
Decomp. above 300°C
0.5 – 1
(calculated from solubilities)
1.7 - 2.1
Table B: Overview of the toxicity data of the disazocondensation red pigments
Skin and eye irritation
acute oral tox (LD50 in mg/kg bw)
> 10 000
acute dermal tox (LD50 in mg/kg bw)
acute inhalation tox
(LC50 in mg/m3)
28-day gavage study (OECD 407)
NOAEL = 1000 (lymph nodes in males at 1000)
Combined reproductive and toxicity screening gavage study (OECD 422)
NOEL = 1000 mg/kg bw
Prival and non-Prival)
Clastogenici-ty in vitro
Mutagenicity in mammalian cells in vitro
not mutagenic (hprt + MLA)
Clastogenic-ity in vivo (MN)
Mutagenicity in mammalian cells in vivo (UDS)
* Single positive Ames tests due to impurity.
Table C: Overview of toxicity data on the amine components (data sources *OECD QSAR Toolbox v2.3, **ECHA Dissimination view, accessed Oct 30, 2012 or ***company data)
PBr 23 amine a
PR 144, 166, 214
PR 144, PB 23
No CAS available
Acute oral toxicity (LD50, mg/kg bw)
ca.1500 in mice, (BG-Chemie MN study, 1999)***
Ca 300 (minimum lethal dose = 75)**
Acute dermal toxicity (LD50)
NOEL = 60 mg/kg bw (haematology)*
Clastogenicity in vitro
Subchronic or chronic toxicity in rats
NOAEL < 50 mg/kg bw (spleen, liver, kidney)*
(mortality at 0.3% in the diet, range-finder study)**
NOAEL = 16 mg/kg bw (OECD 408). NOAEL < 25 mg/kg bw (chronic) (Spleen, liver and kidney) *
Toxicity to reproduction
Table C, continued:
PR 214, 221, 242
PR 220, 262
Acute oral toxicity
(LD50, mg/kg bw)
>5000 (Ciba, 1983)***
27 (Clayton, 1979)***
Acute dermal toxicity (LD50 mg/kg bw)
Genotoxicity in vivo
Repeated dose toxicity
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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