Registration Dossier

Administrative data

Description of key information

Pigment Red 221 was tested for acute oral toxicity in male and female rats in four studies:

No mortality at 5000 mg/kg bw (similar to OECD 401, no GLP, 1983)

No mortality at 4640 mg/kg bw (similar to OECD 401, no GLP, 1974)

No mortality at 5000 mg/kg bw (similar to OECD 401, no GLP, 1984)

(No mortality at 10000 mg/kg bw, IBT-study of 1975, therefore disregarded)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Reliable and valid.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Regarding acute inhalation toxicity, a study with whole-body exposure to Pigment Red 220 was performed at the CRO which was later sued for having falsified study reports (IBT 1972).  This report itself appears to be plausible, since the findings regarding the focal red discoloration and the particle sizes make sense.The test concentration in testing atmosphere was 2.2 mg/l. Details on analytical verification of test atmosphere concentration are not provided.The method of particle size determination is described as follows: A sample of airborne dust was collected from the test atmosphere for the purpose of conducting a microscopic determination of particle size distribution. Particles were counted with respect to three size ranges, viz. 5 µm or smaller (considered to be respirable), 6-25 µm and >25 µm. The smallest particle which could be detected by the light-field technique employed was approximately one µm. The largest particle observed was also recorded. 55% of the particles were in the range of less than 5 µm and 35% were in the range of 6-25 µm. No deaths were noted during the four-hour exposure period or 14-day observation period which followed. Necropsy, performed on all animals at the end of the two-week observation period, revealed slight to moderate diffuse focal red discoloration of the lungs in six rats. There were no other gross pathologic alterations in any of the other tissues and organs examined.

The reported procedure and findings are plausible and would be expected for red inert pigments that are too large for passive permeation through biological membranes.

The pigments are not have irritating or sensitizing properties and are expected to cause effects via excessive deposition at high doses. Based on experience with inert organic pigments, these do not result in mortality in acute inhalation exposure studies. Exposure to inhalable dust must be controlled, and at acceptable levels (3 mg/m3) no substance-specific acute inhalation hazard is expected. Further testing of acute inhalation testing was therefore not performed.  

Pigment Red 221 (CAS 71566-54-6, 926 g/mol)

Pigment Red 221 was studied for acute oral toxicity in three studies of which two are reliable and adequate (Ciba-Geigy 1974, Centre de Recherches Biologiques 1983).

The study performed in 1974 has the deficiencies of an observation period of only 7 days. Tested doses were 2150, 3170 and 4640 mg/kg bw/day. Within 2 hours after treatment the rats in all dosage groups showed dyspnoea, exophthalmus, curved position, and ruffled fur. All animals had recovered within 4 to 7 days. No mortality occurred.

The study performed in 1983 had the deficiency that no necropsy was performed at the end of the study. All animals survived the single dose of 5000 mg/kg bw.Immediately following application, piloerection and apathy were observed; these symptoms however disappeared rapidly during the course of the observation period.

 

Justification for classification or non-classification

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. As a result the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.