N,N'-(2,5-dichloro-1,4-phenylene)bis[4-[(2,5-dichlorophenyl)azo]-3-hydroxynaphthalene-2-carboxamide]

Endpoint summary

Description of key information

The substance does not cause treatment-related adverse effects up to the limit dose upon subacute oral exposure. This assessment is based on a GLP and OECD 407 compliant study with Pigment Red 166 (CAS 3905-19-9) (Vuos 2009b) and a GLP and OECD 422 compliant study with Pigment Red 220 (CAS 68259-05-2) (BASF 2012b).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

subacute

Species:

rat

Quality of whole database:

Valid without restriction

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The table below gives an overview on the relevant parameters regarding systemic availability and subacute toxicity on the pigments and the amine building blocks. It supports the general argument that there is no systemic availability upon ingestion for disazo condensation red pigments. This was descussed in detail in the section on toxicokinetic properties.

	PR 262	PR 166	PR 144	PBr 41	PBr 23	PR 214	PR 220	PR 221	PR 242
	79665-24-0	3905-19-9	5280-78-4	68516-75-6	35869-64-8	40618-31-3	68259-05-2	71566-54-6	52238-92-3
Mol. weight	781.7	794.5	828.9	844.5	850.0	863.4	925.8	925.8	930.5
Water solubility (μg /L)	16.4	<6.5	11.2	0.5 – 1	<20	6.1	14.2	91	18.9
n-octanol solubility (μg /L)	55.4	<6.5	21.9	56	<20	17.8	<10	24	41
Log Pow  (calculated from solubilities)	0.53	n.a.	0.29	1.7 - 2.1	n.a.	0.47	<-0.15	-0.57	0.33
acute oral tox (LD50 in mg/kg bw, rat)	> 5000 K1	> 5000 K2	> 10 000 K2		> 10 000 K2	> 5000 K1	> 5000 K1	> 5000 K1	> 2000 K1
Repeated-dose toxicity		NOAEL = 1000 (OECD 407)					NOAEL = 1000 (OECD 422)
CAS of amine A	95-79-4	95-82-9	95-82-9	608-27-5	89-63-4	95-82-9	none	none	121-50-6
acute oral tox (LD50 in mg/kg bw, rat) amine A	700*	1600*	1600*	940*, 2500*		1600*
CAS amine B	6393-01-7	106-50-3	615-66-7	2243-62-1	615-66-7	20103-09-7	6393-01-7	20103-09-7	20103-09-7
acute oral tox (LD50 in mg/kg bw, rat) amine B	27***	ca 300*	ca 1500 (mice)***	>2000*	ca 1500 (mice)***	>5000***	27***	>5000***	>5000***
Other repeated dose oral toxicity data		NOAEL = 16 mg/kg bw (OECD 408, CAS 106-50-3)*		Mortality at 0.3% in the diet, 90-day range-finder study*	NOEL = 60 mg/kg bw (OECD 422, CAS 89-63-4)**

The first key study is a valid investigation of the toxicological effects resulting from repeated oral-gavage administration of the test item Pigment Red 220 according to OECD guideline 422 and GLP to rats (BASF 2012b). It is chosen because it is of slightly longer duration than the subacute oral toxicity study with Pigment Red 166. The substance was administered as a suspension in Milli-Q-water as vehicle at dosages of 100, 300, and 1000 mg/kg body weight/day, and controls received the vehicle only. It was administered to male rats for 29 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. Treatment with the test item up and including 1000 mg/kg bw/day did not reveal any clinical signs or histological findings and did not affect reproduction and development. All dose-treated males and females had dose-related reddish discolored feces during the treatment period. This finding is considered to be a typical effect resulting from oral administration of a red dyestuff and not adverse. Based on these results a general NOAEL (No Observed Adverse Effect Level) was considered to be 1000 mg/kg body weight/day. Considering reporting details, adherence to guideline and GLP status, the study is valid without restrictions.

The second key study is a valid subacute oral toxicity study with a 14 -day recovery period that was performed according to GLP and OECD testing guideline 407 (Vuos 2009b).

The study is considered to be valid with restrictions because it lacks certain reporting details. Individual data for animals are not provided, no grading scheme for histopathology was applied and historical control data is not provided. It could be retrieved upon request from the CRO.

Wistar rats of SPF quality were used for testing. The test substance was administered as suspension in olive oil using a stomach tube; oral application of rats was made daily. The study includes four main groups and two satellite groups of animals. Each main group consisted of 5 males and 5 females; each satellite group consisted of 5 males and 5 females. Main groups contained 3 treated groups (doses 160, 400, 1000 mg/kg of body weight /day) and one control group (vehic1e only). The satellite groups contained one control group (vehicle only) and one treated group (l000 mg/kg/day). The administration period lasted 28 days. After that animals of main groups were sacrificed and satellite animals were observed for the next 14 days without treatment. During the 28-day study clinical observation and health status control were performed daily. The body weight, food consumption were measured weekly and the detailed clinical observation was carried out in the same time interval. Water consumption was measured twice a week. Before the end of study the functional observation was accomplished. The study was finished by urinalysis, haematological and biochemical analysis, and gross necropsy of animals. The selected organs for weighing and histopathology examination were removed.

No treatment-related effects adverse were observed. Two animals of the high dose group showed reactive hyperplasia in paraaortic lymph nodes. This is a finding that was communicated by the laboratory to generally occur 0 - 2 times per study.

Overall, no hazard is identified for repeated dose oral exposure to disazocondensation red pigments.

Considering the high molecular weights (>> 500 g/mol) and the poor solubility in water and octanol, there is also no concern for systemic uptake after skin contact.

An inhalation hazard arises from dust exposure at concentrations exceeding general exposure limits for inhalable dust. The pigments are considered to behave like nuisance dust and would cause primarly local effects due to lung clearance overload situations.

 

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. No serious irreversible effects were observed at dose levels of less than 150 mg/kg bw upon subacute exposure. As a result the substance is not considered to be classified for repeated dose toxicity under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EG.

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. There were no significant toxic effects at doses of less than 300 mg/kg bw upon subacute oral exposure in rats. As a result the substance is not classified for repeated dose toxicity under Regulation (EC) No. 1272/2008, as amended for the third time in Directive EC 618/2012.