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Diss Factsheets

Administrative data

Description of key information

Oral: Read-across, NOAEL (90d) >= 1133 mg/kg bw/d, rat, equivalent to OECD 408, no GLP

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
see attached justification
Reason / purpose for cross-reference:
read-across source
Dose descriptor:
NOAEL
Effect level:
>= 1 133 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOAEL
Effect level:
>= 982 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOAEL
Effect level:
>= 1 285 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Remarks on result:
not determinable due to absence of adverse toxic effects
Critical effects observed:
no
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
study is not fully compliant with current guidelines.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
other: albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Mean weight at study initiation: 130 g (males) and 121 g (females)
- Housing: Makrolon cages on wood shavings, 5 animals per cage
- Diet (e.g. ad libitum): ALTROMIN R, manufactured by Altromin GmbH in Lage/Lippe
- Water (e.g. ad libitum): tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 25
- Humidity (%): 35 - 60
- Air changes (per hr): partially air-conditioned animal rooms
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): pelleted feed was freshly prepared at 7-8-day intervals
- Mixing appropriate amounts with (Type of food): ALTROMIN R, manufactured by Altromin GmbH in Lage/Lippe
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
90 days
Frequency of treatment:
daily
Dose / conc.:
190 mg/kg bw/day (actual dose received)
Remarks:
females, 1 % test substance in feed, actual dose recieved calculated from the body weight (243 g) and the food consumption relative to body weight (7.8 %)
Dose / conc.:
255 mg/kg bw/day (actual dose received)
Remarks:
males, 1 % test substance in feed, actual dose recieved calculated from the body weight (370 g) and the food consumption relative to body weight (6.9 %)
Dose / conc.:
982 mg/kg bw/day (actual dose received)
Remarks:
females, 5 % test substance in feed, actual dose recieved calculated from the body weight (269 g) and the food consumption relative to body weight (7.3 %)
Dose / conc.:
1 285 mg/kg bw/day (actual dose received)
Remarks:
males, 5 % test substance in feed, actual dose recieved calculated from the body weight (378 g) and the food consumption relative to body weight (6.8 %)
No. of animals per sex per dose:
15
Control animals:
yes, plain diet
Observations and examinations performed and frequency:
Each rat was monitored daily to determine its behaviour and general state of health. The body weight of each animal was determined once a week and the food consumption at 7-day intervals.
Before the start and at the end of the trial haematological and urine investigations were carried out in 10 male and 10 female rats from each group. The haematological investigation included determination of the haemoglobin content, number of red and white blood cells as well as the evaluation of the differential blood count and the possible presence of Heinz bodies. The urine investigation covered appearance, colour, protein and sediment.
Sacrifice and pathology:
At the end of the trial all the animals were killed and autopsied and the organs were subjected to histological examination.
Macro- and microscopic examination of the organs heart, lung, liver, kidney, adrenal glands, spleen, cerebrum, cerebellum, testes and ovaries, pancreas, pituitary, thyroid gland, stomach and small intestine.
Clinical signs:
no effects observed
Description (incidence and severity):
All the animals displayed normal behaviour during the trial and no signs of a toxic effect were observed which would have been caused by the pigment. The pigment was excreted via the faeces.
Mortality:
mortality observed, non-treatment-related
Description (incidence):
There were isolated spontaneous deaths during the trial. One rat (animal no. 304) from group 1 (5%) died after 33 trial days and a further rat (animal no. 337) after 73 trial days. One rat (animal no. 362) from group III (control) died after 23 trial days. The rats died of pneumonia. No connection between the substance administered and the deaths could be detected.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
The weight gains of the male and female rats from groups I (5%) and II (1%) were normal and corresponded to those of the control animals.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
The food consumption of the experimental animals was the same as that of the control rats.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Description (incidence and severity):
The haematological investigations showed no pathological findings even at the end of the trial.
Clinical biochemistry findings:
not examined
Urinalysis findings:
no effects observed
Description (incidence and severity):
The urine investigations showed no pathological findings at the end of the trial. The male rats showed slight protein excretion at the end of the trial which is a physiological feature of adult male rats.
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
The organ weight gains of the male and female rats from groups I (5%) and II (1%) were normal and corresponded to those of the control animals.
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Macroscopic examination of the organs of rats that had received the pigment in their feed in a 90-day trial revealed no pathological organ damage. Inflammatory lung changes were detected at autopsy in experimental animals no. 304 and 337. Animal no. 322 displayed a liver change for which no reason could be found. The controls no. 360 and 362 also had inflammatory lung processes arid the liver of no. 400 was interspersed with yellowish spots the size of a pinhead. The striking feature of no. 413 was very marked liver lobule patterning.
Neuropathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
Histological examination of the organs of rats that had received the pigment in their feed in a 90-day trial revealed no pathological organ damage. The lymphocytic infiltrates frequently observed in the heart, liver, kidneys and intestine are a manifestation of quiescent infections. The perifollicular hyperplasia in the spleen should also be assessed as a non-specific defense reaction of this type. The histo-lymphocytic granulomas found in the liver may be a manifestation of a pre-existing infection, most probably salmonellosis. The lung changes found are characteristic of rat-specific pneumonia. In many of the animals there was impaired spermiogenesis in the form of varying degrees of desquamation of prespermatid cells. The striking frequency in the control group (11 cases) and in the group that received 5% test material (9 cases) and the only isolated occurrence in the group that was given 1% test item (2 cases) indicates that these changes are not attributable to the test substance. In addition, the changes in the brain in the form of meningoencephalitis occasionally observed developed in some cases with foci of glial proliferation independent of the study. These brain changes are diagnosed in rats more frequently than random findings, without causing clinical symptoms. The thyroid changes in the form of interfollicular solidification, associated with formation of follicles to varying degrees, occurred in both the control and the experimental animals.

In summary, it can be stated that no obvious study-related changes were observed. The test item therefore caused no organ-damaging effects in rats in the dosages given and over the selected period of administration.
Dose descriptor:
NOAEL
Effect level:
>= 1 133 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOAEL
Effect level:
>= 982 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOAEL
Effect level:
>= 1 285 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Remarks on result:
not determinable due to absence of adverse toxic effects
Critical effects observed:
no
Conclusions:
Based on the results of this study, a NOAEL of >= 50000 ppm (5 % of the diet) for male and female rats was observed for the test article.
Executive summary:

A subchronic toxicity study was performed with the test substance using crossbred albino rats in a 90-day feeding trial. Three groups of Sprague-Dawley rats (15/sex/dose) were administered the test article at 10000 (group II) and 50000 ppm (group I) in the diet. Control animals (group III) received plain diet. The following parameters were evaluated: clinical signs, body weight, food consumption, haematology, urinalysis, macroscopy and microscopy. The following organs were examined histologically: heart, lung, liver, kidney, adrenal glands, spleen, cerebrum, cerebellum, testes and ovaries, pancreas, pituitary, thyroid gland, stomach and small intestine. The general behaviour in groups I and II was normal throughout the entire trial period and did not differ from that of the control animals. None of the experimental animals showed signs of a toxic effect. The test article was excreted via the feces. The food consumption and the weight gains of the treated rats were normal and did not differ from that of the control rats. The haematological investigations revealed no pathological findings. Investigation of the urine showed no pathological findings which could be attributed to the test article administered. Macroscopic and microscopic examination revealed no pathological organ damage. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 133 mg/kg bw/day
Study duration:
subchronic
Species:
rat

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

Oral toxicity


Regarding reapeated oral toxicity, no data is available for the test substance. To fill this data gap, read-across to the category members CAS 4948-15-6 und EC 479-300-2 were performed.


A subchronic toxicity study was performed with the test substance using crossbred albino rats in a 90-day feeding trial (Hoechst, 1967). Three groups of Sprague-Dawley rats (15/sex/dose) were administered the test article at 10000 (group II) and 50000 ppm (group I) in the diet. Control animals (group III) received plain diet. The following parameters were evaluated: clinical signs, body weight, food consumption, haematology, urinalysis, macroscopy and microscopy. The following organs were examined histologically: heart, lung, liver, kidney, adrenal glands, spleen, cerebrum, cerebellum, testes and ovaries, pancreas, pituitary, thyroid gland, stomach and small intestine. The general behaviour in groups I and II was normal throughout the entire trial period and did not differ from that of the control animals. None of the experimental animals showed signs of a toxic effect. The test article was excreted via the feces. The food consumption and the weight gains of the treated rats were normal and did not differ from that of the control rats. The haematological investigations revealed no pathological findings. Investigation of the urine showed no pathological findings which could be attributed to the test article administered. Macroscopic and microscopic examination revealed no pathological organ damage. Based on the results of this study, a NOAEL of >= 50000 ppm (1133 mg/kg bw/d) for male and female rats was observed for the test article.


 


In a supporting repeated dose 28-day oral toxicity study conducted in accordance with OECD TG 407 and in compliance with GLP regulations, the test substance was administered daily for 28 days by oral gavage to SPF-bred Wistar rats (BASF AG, 2006). One vehicle control group and three treated groups were tested, each consisting of 5 males and 5 females. An extra 5 animals per sex in the control and high dose group were allowed 14 days of recovery. The following parameters were evaluated: clinical signs daily, functional observation tests, body weight and food consumption weekly, clinical pathology at the end of treatment, macroscopy at termination, organ weights and histopathology on a selection of tissues. In addition, a histopathological investigation of liver, kidneys and adrenal glands of the animals of test groups 2 and 3 (100 and 300 mg/kg bw/day) was performed. Accuracy, homogeneity and stability over 5 hours of formulations of test substance in Milli-U water were demonstrated by analyses. No toxicologically relevant changes were observed in any of the parameters determined in this study. No evidence for neurotoxicity or immunotoxicity was obtained in this study. The additional histopathological investigation of liver, kidneys and adrenal glands of the animals of test groups 2 and 3 (100 and 300 mg/kg bw/day) did not reveal any findings related to treatment with the test substance. All the findings noted were single observations and/or were biologically equally distributed in both test groups. They were all considered to be incidental and spontaneous in nature. From the results presented in the report a definitive No Observed Adverse Effect Level (NOAEL) for the substance of 1000 mg/kg bw/day was established.


 


Further toxicological data of category members:


The test article belongs to the "perylene based organic pigments" category (see attached document for details on category members and for read across justification). According to the category approach, missing toxicity endpoints can be addressed with data available for other category members. Regarding repeated dose toxicity, reliable data are available for other members of the "Perylene based pigments category". All of these data are taken into account for the evaluation and assessment of the repeated dose toxicity of the test article.


Additional data is available for the oral and the inhalation route of exposure. After the oral exposure in further 28-day and/or 90-day repeated dose toxicity studies no adverse effects could be observed at the highest dose tested. In additional studies for the inhalation route of exposure local effects in the lung could be observed. After 5 and/or 90-day exposure inflammation processes were induced in the lung that were not fully reversible in two of the studies. Systemic effects after inhalation exposure could not be observed, even at the highest dose tested.


 


 


Statement on the Human Health Hazard Assessment of the Members of the Perylene Pigment Category including the Justification for Classification or Non-Classification


In the following statement the human health hazard of the Perylene pigments is assessed in the broader context of inhalation toxicity of poorly soluble particles. Therefore, a joint evaluation of particle specific properties (solubility, surface activity) and toxicological data of the perylene pigments was performed. Based on expert judgment, a classification or non-classification is derived for the individual members of the Perylene pigment category.


 


Particle specific investigations:


Solubility:


The available data consistently demonstrate that Perylene pigments are poorly soluble substances.  All category members have a low water solubility (solubility < 0.1 mg/L for all substances) and low solubility in n-octanol (< 10 mg/l for all substances). While this indicates poor solubility, it is not sufficient to conclude the assessment, as biosolubility may differ significantly from the solubility in water. Therefore, the OECD ‘Guidance document on inhalation toxicity studies’ suggests assessing the solubility of a solid material by measuring solubility in a simulated biofluid (OECD, 2018). The OECD guidance document further defines poor solubility if a material has a solubility of less than 0.1 g dissolved in 100 ml dissolvent within 24 hours. A test on biosolubility (static) and on dissolution kinetics (dynamic) in phagolysosomal simulant fluids was performed with all pigments of the category, except the intermediate product Pigment Red 224 (CAS 128-69-8), to determine the persistence after uptake in cells, e.g., alveolar macrophages. All substances tested were insoluble in phagolysosomal simulant fluid at pH 4.5 in the static and dynamic dissolution assay.


Surface Reactivity:


The surface reactivity of the pigment particles was investigated in chemico as well as in vitro using the FRAS (Ferric Reduction Ability of Serum) in combination with the EPR (Electron Paramagnetic Resonance) method and the in vitro macrophage assay. The assays were performed with all pigments of the category, except the intermediate Pigment Red 224 (CAS 128-69-8). None of the substances induced pro-inflammatory effects or cytotoxicity in rat alveolar macrophages according to the classification criteria of Wiemann et al. (2016.). The ability to induce biological oxidative damage in chemico was analyzed using the Ferric Reduction Ability of Serum (FRAS) assay and Electron Paramagnetic Resonance spectroscopy (EPR). The majority of the perylene pigments tested were classified as “passive” in both assays. Pigment Red 149 (CAS 4948-15-6) and 178 (CAS 3049-71-6), however, were classified as “passive” in the FRAS assay but “active” in EPR assay. Of note, the results of the red and violet Perylenes were consistently higher than those of the black Perylenes in the EPR assay. The black pigments appear to be significantly less surface active than the red and violet ones.


 


Toxicological in vivo data:


The available experimental data show, that the pigments of this category are not acutely toxic nor toxic after repeated oral exposure, not irritating to skin or eyes, do not cause skin sensitization, and are not genotoxic. In addition, no hazard concerning reproductive and developmental toxicity is concluded for members based on the currently available data. The only adverse effects observed were local effects after short-term and sub-chronic exposure via the inhalation route, whereas systemic effects could not be observed after inhalation exposure.


Up to now, three studies on inhalation toxicity following repeated exposure are available, two 5-day short-term inhalation toxicity studies (STIS) according to OECD guideline 412 on Pigment Red 178 (CAS 3049-71-6) and 179 (CAS 5521-31-3) and a 90-day subchronic toxicity study according to OECD guideline 413 with Pigment Red 179.


Both pigments caused inflammation in the lung tissue at concentrations of 20mg/m3 and above in the STIS, with the effects being reversible within 3 weeks for Pigment Red 179. At the top dose of 60 mg/m³, Pigment Red 178 and 179 caused increased total cell count, increased absolute and relative lymphocytes, neutrophils and monocyte counts in bronchioalveolar lavage fluid. Moreover, several biochemical parameters (protein concentration, enzyme activities and cytokine concentrations) were significantly increased in lavage fluid. Consistently, minimal infiltration of neutrophils within bronchiolar epithelium was observed. Most of these findings were also observed at 20 mg/m3 with reduced severity. For both pigments a NOAEC of 5 mg/m3 for local effects and a systemic NOAEC of above 60 mg/m3 was determined. The lung and the tracheobronchial lymph nodes were identified as target organs.


Due to the irreversibility of the effects of Pigment Red 178, the 90-day repeated dose inhalation study was performed with Pigment Red 178 following a worst-case approach. In this study, inflammation was observed at 20 and 5 mg/m3 as shown by increased inflammatory factors and protein levels in the lavage fluid, migration of inflammatory cells, cell debris, which correlated with the significantly increased lung weight and several histological changes in lungs. In line with the STIS results, there was not any indication for systemic effect. The effects were not reversible within 60 days. A NOAEC of 1 mg/m3 for local effects and a systemic NOAEC of above 60 mg/m3 was determined. The lung was identified as target organ. The observed effects were regarded as adverse and are presumably relevant for humans.


Overall, the perylene-based pigments are characterized by very low systemic toxicity even after repeated exposures to high doses. The absence of systemic effects observed after exposure via the oral or inhalation route and the insolubility observed in the solubility studies, indicate that the perylenes have a very low bioavailability. Therefore, the induction of local inflammation processes in the lung reported in the short-term inhalation studies as well as in the 90-day inhalation study are most likely induced by the surface activity of the particles. The results of the activity assays are evidence for the generation of reactive oxygen species at the particle surface for some of the Perylene pigments.


 


Conclusion:


As described above, the local effects after inhalation exposure are based on particle specific abiotic surface activity. Since the subgroups of the perylene pigments were demonstrated to differ in this property, a different evaluation of the pigments based on their measured abiotic surface activity is justified in this case.


 


Justification for Classification of Pigment Red 178 (CAS 3049-71-6), Pigment Red 179 (CAS 5521-31-3), Pigment Red 149 (CAS 4948-15-6), Pigment Violet 29 (CAS 81‑33-4) and intermediate product Pigment Red 224 (CAS 128-69-8):


As mentioned above, repeated inhalation exposure to Pigment Red 178 was shown to induce local inflammation processes in the lung at concentrations of 5 mg/m3 and above, but no systemic toxicity was observed in this subchronic inhalation study or any other of the toxicological in vivo studies available. The local effects to the lung were regarded as adverse and are presumably relevant for humans. Therefore, classification for Specific target organ toxicity (STOT RE) is justified under Regulation (EC) No. 1272/2008. However, due to the nature of the toxic effect observed, the guidance values mentioned in paragraphs 3.9.2.9.6 (Cat. 1) and 3.9.2.9.7 (Cat. 2), which take into account the duration of exposure and the dose/concentration which produced the effect(s), are not suitable for subclassification into category 1 or 2 in this case. Based on the explanations in chapter 3.9.2.9.8 these guidance values “are not intended as strict demarcation values”. Rather, in chapter 2 article 9 as well as in Annex I chapter 1.1.1, it is expressively permitted to “carry out an evaluation by applying a weight of evidence determination using expert judgement […] where the criteria cannot be applied directly to available identified information” and that “Expert judgement may also be required in interpreting data for hazard classification”. As outlined in chapter 3.9.1.3, adverse health effects in experimental animals relevant for STOT RE are defined as “toxicologically significant changes which have affected the function or morphology of a tissue/organ, or have produced serious changes to the biochemistry or haematology of the organism and these changes are relevant for human health”. One important reason for the deviation from the guidance values is that the local effects observed with the perylene pigments are not comparable to the effects that should be considered to support classification for STOT RE exposure according to chapter 3.9.2.7.3 such as e.g. morbidity or death, significant changes in biochemistry, significant organ damage noted as necropsy, microscopic changes indicative of necrosis or fibrosis. None of the listed effects nor any other effects indicative of a severe impairment of organ function or morphology were observed in the subchronic inhalation study on Pigment Red 178. As already mentioned above, in contrast to substances typically classified for STOT RE 2, it has a low systemic toxicity resulting from its insolubility and associated low bioavailability and the local effects observed in the respiratory tract can be most likely attributed to the surface activity of the pigment particles. Therefore, the effects are regarded as less severe compared to a STOT RE 1 classification. In order to still consider the adverse local effects to the lung, a classification for STOT RE 2 (H373, <lung>) is justified.


There are no data available on subchronic inhalation toxicity of Pigment Red 179 (CAS 5521-31-3), Pigment Red 149 (CAS 4948-15-6) and Pigment Violet 29 (CAS 81 33-4). In order to fill this data gap, a read-across from Pigment Red 178 (CAS 3049-71-6) was performed. The read-across is supported by the comparable high values measured in the EPR assay for the red and violet pigments as well as by the results from the STIS for Pigment 179. Therefore, Pigment Red 179, Pigment Red 149 and Pigment Violet 29 are classified for STOT RE 2 (H373, <lung>) too.


 


Justification for Non-classification of Pigment Black 31 (CAS 67075-37-0), Pigment Black 32 (CAS 83524-75-8), Perylen Black I (EC 479-300-2) and Perylen Black II (EC 475-310-6):


The induction of local inflammation processes in the lung reported in the short-term inhalation studies as well as in the 90-day inhalation study are most likely induced by the surface activity of the respective particles, as indicated in the results of the EPR. However, the values of the red and violet Perylenes were significantly higher than those of the black Perylenes in this assay. This means that although all category members are enormously similar in structural and physicochemical and toxicological parameters, there are differences between the substances in this property. The black pigments appear to be significantly less surface active than the red and violet ones and therefore are expected not to be less toxic to the lung.


Since, the results of the red and violet Perylenes were visibly higher than those of the black Perylenes it is justified to treat and classify the perylenes differently based on their activity measured in the EPR assay. This approach will be supported by two future short term inhalation studies investigating Pigment Black 32 and another of the much less active black pigments of this category. It is expected that no inflammatory, local effects will occur in these studies, further supporting the arguments for non-classification.


As described above, due to the local, partly non-reversible effects of Pigment Red 178, the red and violet pyrelene pigments must be classified as STOT RE2 under Regulation (EC) No. 1272/2008. However, as these effects are triggered by the surface activity of the pigments, a classification for the black pigments (Pigment Black 31/32 and Perylene Black I/II) is not justified. Therefore, no read-across from Pigment red 178 is performed.


 


References


OECD, 2018. Guidance document on inhalation toxicity studies. Series on testing and assessment No.39 (Paris).


Wiemann, Martin, et al. "An in vitro alveolar macrophage assay for predicting the short-term inhalation toxicity of nanomaterials." Journal of Nanobiotechnology 14.1 (2016): 1-27.


Regulation. "1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directive 67/548/EEC and 1999/45/EC and amending Regulation (EC) No 1907/2006." Official J Eur Union 353 (2008): 1.

Justification for classification or non-classification

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


The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008.


No data on repeated inhalation toxicity is available for the test substance, but data are available for the category member CAS 3049-71-6 (Pigment Red 178). In this study, repeated inhalation exposure to Pigment Red 178 was shown to induce local inflammation processes in the lung at concentrations of 5 mg/m3 and above, but no systemic toxicity was observed in this subchronic inhalation study or any other of the toxicological in vivo studies available for all category members.


The induction of local inflammation in the 90-day inhalation study, however, is most likely induced by the surface activity of the respective particles, as indicated in the results of the EPR (Please also refer to the Assessment Report in Chapter 13.2. or detailed explanations). However, the values of the red and violet Perylenes were significantly higher than those of the black Perylenes in this assay. This means that although all category members are enormously similar in structural and physicochemical and toxicological parameters, there are differences between the substances in this property. The black pigments appear to be significantly less surface active than the red and violet ones and therefore are expected not to be less toxic to the lung.


Since, the results of the red and violet Perylenes were visibly higher than those of the black Perylenes it is justified to treat and classify the perylenes differently based on their activity measured in the EPR assay. This approach will be supported by two future short term inhalation studies investigating Pigment Black 32 and another of the much less active black pigments of this category. It is expected that no inflammatory, local effects will occur in these studies, further supporting the arguments for non-classification.


As described above, due to the local, partly non-reversible effects of Pigment Red 178, the red and violet pyrelene pigments must be classified as STOT RE2 under Regulation (EC) No. 1272/2008. However, as these effects are triggered by the surface activity of the pigments, a classification for the black pigments (Pigment Black 31/32 and Perylene Black I/II) is not justified. Therefore, no read-across from Pigment red 178 to the test substance is performed.


As a result, the test substance is not considered to be classified for repeated dose toxicity under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.