Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

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.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

The toxicokinetic assessment is mainly based on the absence of adverse findings upon acute and subacute oral toxicity testing and on physic-chemical properties. It concludes that the pigments are inert and are not taken up by the body. Therefore, there is no potential for bioaccumulation. The assessment covers the following substances, for which a data matrix (Tables A and B) is given below:

 

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

 

PBr 23

PBr 41

PR 144

PR 166

PR 214

PR 220

PR 221

PR 242

PR 262

35869-64-8

68516-75-6

5280-78-4

3905-19-9

40618-31-3

68259-05-2

71566-54-6

52238-92-3

79665-24-0

Mol.

weight

850.0

844.5

828.9

794.5

863.4

925.8

925.8

930.5

(max)

781.7(min)

Melting point

Decomp. above 370°C

nd

> 350°C

Decomp. above 349°C

Decomp. above 300°C

> 350°C

Decomp. above 300°C

nd

nd

Relative densitiy

1.57

1.58

1.51

1.49

1.54

1.4

1.39

1.61

1.4

Water solubility

(μg /L)

<20

0.5 – 1

11.2

<6.5

6.1

14.2

91

18.9

16.4

n-octanol solubility

(μg /L)

<20

56

21.9

<6.5

17.8

<10

24

41

55.4

Log Pow

 (calculated from solubilities)

n.a.

1.7 - 2.1

0.29

n.a.

0.47

<-0.15

-0.57

0.33

0.53

 

Table B: Overview of the toxicity data of the disazocondensation red pigments

 

PBr 23

PBr 41

PR 144

PR 166

PR 214

PR 220

PR 221

PR 242

PR 262

35869-64-8

68516-75-6

5280-78-4

3905-19-9

40618-31-3

68259-05-2

71566-54-6

52238-92-3

79665-24-0

Skin and eye irritation

not irritating

K2

 

not irritating

K2

not irritating

K2

not irritating

K1

not irritating

K4

not irritating

K2

not irritating

K1

not irritating

K1

skin sensitzation

 

 

not sensitizing

K1

 

not sensitizing

K1

not sensitizingK2

not sensitizingK2

not sensitizing

K1

 

acute oral tox (LD50 in mg/kg bw)

> 10 000

K2

 

> 10 000

K2

> 5000

K2

> 5000

K1

> 5000

K1

> 5000

K1

> 2000

K1

> 5000

K1

acute dermal tox (LD50 in mg/kg bw)

 

 

> 5000

 K2

 

 

 

 

 

 

acute inhalation tox

(LC50 in mg/m3)

 

 

 

 

 

>2200

K4

 

 

 

28-day gavage study (OECD 407)

 

 

 

NOAEL = 1000 (lymph nodes in males at 1000)

K1

 

 

 

 

 

Combined reproductive and toxicity screening gavage study (OECD 422)

 

 

 

 

 

 

NOEL = 1000 mg/kg bw

K1

 

 

 

Bacterial mutagenicity

not mutagenic*

K1

non-Prival

not mutagenic

K1

Non Prival

not mutagenic

K1

Prival and

Non Prival

not mutagenic*

(K1,

Prival and non-Prival)

not mutagenic

K1

Non Prival

not mutagenic

K2,

non Prival

not mutagenic

K1,

non Prival

not mutagenic

K1

Non Prival

not mutagenic

K1

Non Prival

Clastogenici-ty in vitro

 

 

 

 

 

 

 

Not clastogenic

K1

 

Mutagenicity in mammalian cells in vitro

 

 

 

not mutagenic (hprt + MLA)

K1

 

 

 

 

 

Clastogenic-ity in vivo (MN)

Non clastogenic

K1

 

 

Non clastogenic

K2

 

 

Non clastogenic

K1

 

 

Mutagenicity in mammalian cells in vivo (UDS)

not mutagenic

K1

 

 

 

 

 

 

 

 

* 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

PBr 41

Amine a

PB 41

Amine b

PR 144, 166, 214

Amine a

PR 144, PB 23

Amine b

PR 166

Amine b

 

PR 220

amine a

PR 221

amine a

PR 242

Amine a

CAS

89-63-4

 

608-27-5

 

2243-62-1

 

95-82-9

 

61702-44-1,

615-66-7,

6219-71-2

 

106-50-3

 

No CAS available

 

No CAS available

 

121-50-6

 

Acute oral toxicity (LD50, mg/kg bw)

 

940**, 

2500**

634**

1600**

ca.1500 in mice, (BG-Chemie MN study, 1999)***

Ca 300 (minimum lethal dose = 75)**

 

 

 

Acute dermal toxicity (LD50)

 

 

>2000**

 

 

 

 

 

 

Combined reproductive and toxicity screening gavage study (OECD 422)

 

NOEL = 60 mg/kg bw (haematology)*

 

 

 

 

 

 

 

 

Bacterial mutagenicity

Mutagenic*

Not mutagenic**

Mutagenic*

Not mutagenic*

Mutagenic*

Equivocal*

 

 

Not mutagenic*

Clastogenicity in vitro

 

 

 

 

 

 

 

 

 

Mutagenicity in mammalian cells in vitro

 

Negative**

(UDS)

 

 

 

 

 

 

 

Clastogenic-ity in vivo (MN)

 

Negative**

 

 

 

 

 

 

 

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

 

 

 

 

 

 

 

 

 

carcinogenicity

 

 

Carcinogenic**

 

 

Not carcinogenic*

 

 

 

 


Table C, continued:

 

PR 214, 221, 242

Amine b

PR 262

Amine a

PR 220, 262

Amine b

20103-09-7

95-79-4

6393-01-7

Acute oral toxicity

(LD50, mg/kg bw)

>5000 (Ciba, 1983)***

700**

27 (Clayton, 1979)***

Acute dermal toxicity (LD50 mg/kg bw)

 

 

 

Bacterial mutagenicity

 

Negative*, ambiguous**

Negative**

Clastogenicity in vitro

 

Negative**

 

Mutagenicity in mammalian cells in vitro

 

Negative**

 

Genotoxicity in vivo

 

 

 

Repeated dose toxicity

 

 

 

Toxicity to reproduction

 

 

 

Carcinogenicity

 

Carcinogenic*