7,17,28,38-tetraazatridecacyclo[24.16.2.2²,⁵.1⁸,¹².1²⁹,³³.0³,²².0⁴,¹⁹.0⁶,¹⁷.0²³,⁴³.0²⁷,³⁸.0⁴⁰,⁴⁴.0¹⁶,⁴⁶.0³⁷,⁴⁵]octatetraconta-1(42),2(48),3,5(47),6,8,10,12(46),13,15,19,21,23,25,27,29(45),30,32,34,36,40,43-docosaene-18,39-dione; 7,17,28,38-tetraazatridecacyclo[24.16.2.2²,⁵.1⁸,¹².1²⁹,³³.0³,²².0⁴,¹⁹.0⁶,¹⁷.0²³,⁴³.0²⁸,³⁹.0⁴⁰,⁴⁴.0¹⁶,⁴⁶.0³⁷,⁴⁵]octatetraconta-1(42),2(48),3,5(47),6,8,10,12(46),13,15,19,21,23,25,29,31,33,35,37(45),38,40,43-docosaene-18,27-dione

Endpoint summary

Description of key information

Oral: LD50 (m/f) > 5000 mg/kg bw, rat, according to OECD TG 423, GLP compliant

Inhalation: LC50 (m/f) > 5.1 mg/L air, rat, according to OECD TG 403, GLP compliant

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 11, 2005 - Sep. 13, 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted December 17, 2001

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Remarks:

BASF AG, Experimental Toxicology and Ecology, Ludwigshafen, Germany

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Physical state: Powder / black
- Storage condition of test material: Room temperature
- Stability: The test substance was stable over the study period (demonstrated by reanalysis). Additionally, the stability of the test substance in the vehicle for the maximum application period was confirmed indirectly by analysis of the correctness of the concentration.
- Homogeneity: The test substance was homogeneous by visual inspection. Additionally, the homogeneity of the test substance preparation in the vehicle used for the first administration was confirmed indirectly by the concentration control analysis.

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services, Fuellinsdorf, Switzerland
- Age at study initiation: Young adult animals (female animals approx. 8 - 12 weeks)
- Weight at study initiation: mean (6 female animals): 179 g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing
- Diet (e.g. ad libitum): Kliba-Labordiaet (Maus / Ratte Haltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water: Tap water ad libitum
- Acclimation period: Acclimatization for at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Air changes (per hr): The animals were housed in fully air-conditioned rooms.
- Photoperiod (hrs dark / hrs light): 12 h /12 h

Route of administration:

oral: gavage

Vehicle:

other: 0.5% CMC-solution (cleaned sodium carboxymethylcellulose, Hoechst AG) in doubly distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25 g/100 ml
- Justification for choice of vehicle: Aqueous formulation corresponds to the physiological medium.

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg

DOSAGE PREPARATION: The test substance preparation was produced for each administration group shortly before administration by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on the physical and chemical characteristics of the test substance and its composition, no pronounced acute oral toxicity was expected. Therefore, a starting dose of 5000 mg/kg body weight (limit test) has been chosen.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

6 female animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study. Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals. A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Necropsy of survivors performed: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality occurred.

Clinical signs:

other: Clinical observation revealed impaired general state, dyspnoea, staggering and piloerection were observed from hour 3 until including hour 4 after administration.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (6 females) examined at termination of the study.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of the test article after oral administration was found to be greater than 5000 mg/kg body weight in rats.

Executive summary:

In a GLP compliant OECD 423 guideline study, single doses of 5,000 mg/kg body weight of test material preparations in 0.5% CMC-solution in doubly distilled water were given to two administration groups of three fasted female Wistar rats by gavage in a sequential manner. The animals were observed for a period of 14 days following administration and mortality, viability and clinical signs were recorded daily. Body weights were recorded shortly before administration (day 0), weekly thereafter and at the end of the study. All animals were necropsied and examined macroscopically. All animals survived until the end of the study period. Clinical observation revealed impaired general state, dyspnoea, staggering and piloerection. Findings were observed from hour 3 until including hour 4 after administration. The mean body weights of the administration groups increased throughout the study period. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the observation period. In conclusion, the LD50 (female rat) was determined to exceed 5000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 Sep 2005 - 02 Nov 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Qualifier:

according to guideline

Guideline:

other: Annex to the commission directive 92/69/EEC for 17. Amendment of the Council directive 67/548/EEC, Part B, B.2. Acute Toxicity, Inhalation.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Physical state: Powder / black
- Storage condition of test material: Room temperature
- CAS No. cis 41635-87-4, trans 6859-32-1
- Analytical purity: 99.9%
- Expiration date of the lot/batch: unlimited at room temperature

Species:

other: rat, HanRcc:Wist (SPF)

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services, Fuellinsdorf, Switzerland
- Age at study initiation: approx. 9 weeks for males and approx. 10 weeks for females
- Weight at study initiation: mean (males): 265.1 +/-20.5 g; mean (females): 199.1 +/- 8.1 g
- Housing: single housing in cages type DK III (Becker, Germany) without bedding
- Diet: KLIBA mouse / rat Iaboratory diet 10 mm pellets "GLP", Kliba SA, Kaiseraugst, Basel Switzerland, ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Air changes (per hr): The animals were kept in fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

other: inhalation: dust aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: 1 % of Aerosil 200 to improve dust aerosol formation

Mass median aerodynamic diameter (MMAD):

>= 1.8 - <= 2.1 µm

Geometric standard deviation (GSD):

>= 3 - <= 3.1

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 20 (glass-steel construction, BASF)
- Exposure chamber volume: 55 l
- Method of holding animals in test chamber: The animals were restrained in glass tubes and their snouts projected into the inhalation system.
- Source and rate of air: A supply air flow (compressed air) of 1.5 m3/h was used for the exposure. An air change of about 27 times per hour can be calculated by dividing the supply air flow by the volume of the inhalation system.
- System of generating particulates/aerosols: dosing-wheel dust generator (Gericke/BASF); the exposure system was located inside an exhaust cabin in an air-conditioned laboratory.
- Method of particle size determination: Cascade impactor measurements (Stack Sampler Mark III (Andersen))
- Treatment of exhaust air: The lower amount of exhaust air, which was adjusted by means of a separate exhaust air system, achieved a positive pressure inside the exposure system. This ensured that the mixture of test substance and air was not diluted with Iaboratory air in the breathing zones of
the animals.
- Temperature, humidity: 22-3 +/- 0.2°C, 56.2 +/- 0.4%,

TEST ATMOSPHERE
Test substance preparation:
The test substance was stirred in its container before a sample for dust generation was taken. The test substance was desagglomerated in a mixer under addition of 1 % (w/w) of Aerosil 200 before introduction into the dust generator, in order to improve dust aerosol formation.

- Brief description of analytical method used: Gravimetric determination. Sampling equipment: vacuum pump (Millipore). Preweighed filters were placed into the filtration equipment. By means of the vacuum pump metered volumes of the dust were drawn through the filter. For each sample the dust aerosol concentration in mg/I was calculated from the difference between the preweight of the filter and the weight of the filter after sampling, with reference to the sample volume of the inhalation atmospheres.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Sample 1: 1.8 µm; Sample 2: 2.1 µm / Sample 1: 3.1; Sample 2: 3.0

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Remarks on duration:

plus equilibration time of the inhalation systems (about 10 min)

Concentrations:

5.1 mg/l (nominal concentration: 24.7 mg/l)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of the animals was determined just prior to exposure (day 0), weekly thereafter and at the end ot the observation period. A check for overt clinical signs of toxicity or mortality as well as a check for the presence of feed and drinking water was made twice a day on workdays and once daily on weekends and public holidays. Detailed clinical observations were recorded for each animal separately several times during exposure and at least once on each workday ot the observation period.
- Necropsy of survivors performed: yes

Statistics:

The binomial test was used for statistical evaluation.
The calculation ot the particle size distribution was carried out in the inhalation laboratory on the basis ot mathematical methods for evaluating particle measurements.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.1 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable

Mortality:

One of five female but no male animals died.

Clinical signs:

other: Clinical signs of toxicity comprised visually accelerated respiration, pulmonary respiration sounds, squatting posture, piloerection, smeared and contaminated fur, black colored faeces. Findings were observed from hour 0 of exposure until including study

Body weight:

The mean body weights of all surviving male and female animals increased throughout the study period.

Gross pathology:

Gross pathological abnormalities of the organs were noted neither in the female animal that died during exposure nor in those necropsied at termination of the post exposure observation period. Contaminated fur was observed in all animals. In the female animal that died during exposure, smeared fur around the snouts was observed additionally.

Under the conditions of this study the LC50 for male and female rats after dust inhalation was > 5.1 mg/l. Although 1 female animal died during exposure, the tested high concentration is judged to be sufficient to demonstrate the low order acute toxicity of the test substance and no further concentration was tested.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the LC50 for male and female rats after dust inhalation was > 5.1 mg/l.

Executive summary:

For determination of the acute inhalation toxicity (single 4-hour-exposure) of the test substance as dust, a GLP-compliant study in male and female Wistar rats was performed according to OECD-Guideline method 403, as well as EEC and EPA guidelines. A measured concentration of 5.1 mg/l was tested (Limit test). Cascade impactor measurements resulted in particle size distributions with mass median aerodynamic diameters (MMADs) of 1.8 and 2.1 um, which were well within the respirable range. At the tested concentration, one of five female but no male animals died during exposure. Clinical signs of toxicity comprised visually accelerated respiration, pulmonary respiration sounds, squatting posture, piloerection, smeared and contaminated fur, black colored faeces. Findings were observed from hour 0 of exposure until including study day 14. Moreover, attempts to escape were observed in all animals at the very beginning of the exposure (hour 0). The mean body weights of all surviving male and female animals increased throughout the study period. Gross pathological abnormalities of the organs were noted neither in the female animal that died during exposure nor in those necropsied at termination of the post exposure observation period. Contaminated fur was observed in all animals. In the female animal that died during exposure, smeared fur around the snouts was observed additionally. Under the conditions of this study the LC50 for male and female rats after dust inhalation was > 5.1 mg/l. Although 1 female animal died during exposure, the tested high concentration is judged to be sufficient to demonstrate the low order acute toxicity of the test substance and no further concentration was tested.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 100 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral toxicity

Acute oral toxicity was evaluated in a GLP-compliant study following OECD guideline 423 which was reliable without restrictions. Six fasted female Wistar rats received a dose of 5000 mg/kg bw in 0.5% CMC by gavage (limit test, BASF, 2005). No mortality occurred. Clinical observation revealed impaired general state, dyspnoea, staggering and piloerection. The findings were observed from hour 3 until including hour 4 after administration. The mean body weights of the administration groups increased throughout the study period. No macroscopic pathologic abnormalities were noted in all animals examined at termination of the study. Due to these results a LD50 of > 5000 mg/kg bw was estimated.

 

Inhalation toxicity

Acute inhalative toxicity was evaluated in a GLP-compliant study following OECD guideline 403 (reliable without restrictions), where a dust aerosol of the test substance was generated and groups of 5 Wistar rats were exposed to 5.1 mg/l of the dust aerosol for 4 h (BASF, 2005). The observation period lasted 14 days. One of five female but no male animals died. Clinical signs of toxicity comprised visually accelerated respiration, pulmonary respiration sounds, squatting posture, piloerection, smeared and contaminated fur, black colored faeces. Findings were observed from hour 0 of exposure until including study day 14. Moreover, attempts to escape were observed in all animals at the very beginning of the exposure (hour 0). Gross pathological abnormalities of the organs were noted neither in the female animal that died during exposure nor in those necropsied at termination of the post exposure observation period. Therefore, a LC50 > 5.1 mg/l 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 acute toxicity, reliable data are available for the test article and for other members of the "Perylene based pigments category". All of these data are taken into account for the evaluation and assessment of the acute toxicity of the test article.

Additional information is available for the oral and the inhalation route:

In several studies performed with other substances from the Perylene category the potential for oral toxicity was found to be very low. None of these studies raised any concerns regarding acute toxicity after oral application and therefore none of the substances requires classification. The LD50 values observed for these compounds were greater than 5000 mg/kg bw in alle studies performed.

To assess the acute inhalation toxicity, other category members were tested in studies according or similar to OECD 403 guideline. In all studies, rats were exposed to analytically verified dust aerosols for a duration of 4 hours. Except for one study with a single case of mortality all animals survived the procedure. The observed clinical signs included accelerated respiration, pulmonary respiration sounds, squatting posture, piloerection, flight behavior and smeared fur. No pathological abnormalities of the organs were observed at termination in all animals in any of the studies. The LC50 was always greater than tested limit dose respectively.

There are also studies concerning the acute dermal toxicity. In the studies similar to OECD testing guideline 402 no signs for s local or systemic toxicity could be found.

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. No mortality occurred at the limit dose of 2000 mg/kg bw. As a result, the substance is not considered to be classified for acute oral or inhalation toxicity under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.