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Description of key information

LD50 oral in rats >5000 mg/kg bw

LC50 inhalation in rats > 5400 mg/m³

LD50 dermal in rats > 2500 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

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Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401. A test group consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: average weight males: 180 g, females: 160g
- Diet (e.g. ad libitum): HERILAN MRH-Haltung Alleinfutter für die Haltung von Mäusen, Ratten und Hamstern, Heinrich Eggersmann KG, Rinteln

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5 % aequous solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50% supsension in 0.5% aqueous solution with carboxymethyl cellulose (w/v)

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality observed
Mortality:
None of the animals died during the observation period.
Clinical signs:
No abnormal findings.
Red stained feces were reported. All animals recovered.
Body weight:
Normal weight gain.
Gross pathology:
No deviations from normal.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions chosen, no animals died during the study period and thus, the LD50 was concluded to be greater than 5,000 mg/kg bw.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401. A test group consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 7 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: average weight males: 207 g, females: 194 g
Route of administration:
oral: gavage
Vehicle:
other: Traganth
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2, 16 and 20% aquaeous solution with Traganth (w/v)
- Amount of vehicle (if gavage): 32 and 10 ml/kg

MAXIMUM DOSE VOLUME APPLIED: 6400 mg/kg bw
Doses:
200, 1600 and 6400 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 6 400 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality observed
Mortality:
None of the animals died during the observation period.
Clinical signs:
Sedation, ruffled fur, dyspnea, curved body position, red colored feces.
Body weight:
No effects were reported.
Gross pathology:
No abnormal findings.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions chosen, no animals died during the study period and thus, the LD50 was concluded to be greater than 6,400 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

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Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: strain: SPF Wistar/Chbb: THOM; breeding facility: Dr. K. Thomae GmbH, D-7950 Biberach, FRG)
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 251 g (males) and 172 g (females)
- Housing: cages type D III of Becker, without bedding, 5 animals per cage
- Diet (e.g. ad libitum): KLIBA rat/mouse laboratory diet 24-343-4 10 mm pellets, Klingentalmühle AG, CH-4303 Kaiseraugst, Switzerland, ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose/head only
Vehicle:
other: Aerosil
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 20 (glass-steel construction, BASF Aktiengesellschaft)
- Exposure chamber volume: ca. 55 L
- Method of holding animals in test chamber: the animals were restrained in tubes and their snouts projected into the inhalation chamber
- Source and rate of air: 1500 L/h, supply air
- Method of conditioning air: The exposure system was placed in an air-conditioned laboratory. Temperatures in the exposure system were 19-25 °C
- System of generating particulates/aerosols: A dust aerosol air mixture was generated by means of a dosing-wheel dust generator (Gericke/BASF).
- Method of particle size determination: Stack Sampler Mark III (Andersen)

TEST ATMOSPHERE
- Brief description of analytical method used: The preweighed filter was placed into the filtration equipment. By means of a vacuum compressed air pump a volume of the dust aerosol was drawn through the filter. The dust concentration in mg/l 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 atmosphere. The concentration was corrected for the amount of the added excipient.
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): 1 wt% of Aerosil

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter): 3.0 µm (GSD: 3.6)
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric determination
Duration of exposure:
4 h
Concentrations:
5.2 mg/L
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of the animals was checked before the beginning of the test, after 7 days and at the end of the observation period. Clinical findings were recorded several times during exposure and at least once an each workday in the observation period. A check for dead animals was made daily.
- Necropsy of survivors performed: yes
Statistics:
The statistical evaluation of the concentration/effect relationship was carried out on the basis of the binomial test (Wittig, H.: Mathematische Statistik 1974, pp. 32 - 35) in accordance with tables of the BASF Computer Center.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.2 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: no mortality observed
Mortality:
None of the animals died during the observation period
Clinical signs:
other: Irregular, accelerated and/or intermittent respiration, flight behaviour and discoloured fur. From day 7 of the observation period onward, no abnormalities, except discoloured fur, were detected in the animals.
Body weight:
The body weight gain of male and female rats in the test group, compared with a historical control collective, was not affected by the substance over the total observation period.
Gross pathology:
No pathologic findings were noted.

Results of analytical measurements:

Sample No Analyt. Conc. (mg/l)
1 5.01
2 5.5
3 5
4 5.32
Mean 5.26
mean corrected for 1 % additive 5.22
mean rounded 5.2
standard deviation of the mean 0.2
Nominal concentration 16.8

Particle size analysis:

Cascade Impactor
Stage EACD 50% [µm] [mg] percentage distribution [%] cummulative distribution [%]
pre-impactor 26.6 0.97 4 96
0 29.5 0.79 3.3 92.7
1 18.2 2.67 11.1 81.6
3 8.5 2.69 11.2 70.5
4 5.5 6.58 27.2 43.3
5 2.8 4.45 18.4 24.9
7 1.2 6.01 24.9 -
backup filter < 1.2
Sum 24.15

The MMAD 50% = 3.0 µm (geometrical standard deviation =3.6) was calculated from the results of the particle size analysis.

A respirable dust aerosol fraction that might reach the alveolar region of 82% was obtained from the results of the particle size analysis.

Interpretation of results:
GHS criteria not met
Conclusions:
In the study presented, acute toxicity of the test substance has been investigated using rats exposed via inhalation. No animal died during the study period. The LC50 was concluded to be greater than 5.2 mg/l.
Endpoint:
acute toxicity: inhalation
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:
read-across source
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.2 mg/L air
Based on:
other: Read-across
Exp. duration:
4 h
Remarks on result:
other: no mortality assumed
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the study performed with the read-across substance, the target substance was not assumed to induce mortality. Thus, LC50 was concluded to be greater than 5.2 mg/l.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
5 400 mg/m³
Quality of whole database:
The available study for the test substance was disregarded for assessment, because the test system was not suitable. However, suitable and reliable data on acute inhalation toxicity of the source substance (read-across) was used to fill the data gap.

Acute toxicity: via dermal route

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Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: D.N.NOAKES und D.M.SANDERSON (A Method for Determining the Dermal Toxicity of Pesticides; Brit.Journ.Ind.Med. 26, 59, 1969
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Wiga, SPF-bred
- Weight at study initiation: males: 141 g; females: 132 g
Type of coverage:
not specified
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: back, area of 50 cm^2

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 ml/kg
- Concentration (if solution): 50% solution
Duration of exposure:
Not specified
Doses:
2500 mg/kg bw
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: daily
- Necropsy of survivors performed: yes
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed
Mortality:
None of the animals died during the observation period.
Clinical signs:
No abnormal findings. Red-brown staining at the application site observed.
Gross pathology:
No abnormal findings.
Interpretation of results:
GHS criteria not met
Conclusions:
In the study presented, acute toxicity of the test substance was investigated using rats exposed via dermal route. No animals died during the study period and thus, the LD50 was concluded to be 2500 mg/kg bw.
Endpoint:
acute toxicity: dermal
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:
read-across source
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
other: Read-across
Remarks on result:
other: no mortality assumed
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results obtained from an acute dermal toxicity study performed with the read-across substance, the target substance was not assumed to inducde mortality. Thus, LD50 was concluded to be greater than 2500 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 500 mg/kg bw

Additional information

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.

Oral toxicity

In an oral toxicity study comparable to OECD guideline 401 performed with the test article, groups of rats (5/sex/dose) were administered the test substance at single doses of 200, 1600, or 6400 mg/kg bw by gavage followed by a 14-day observation period (BASF, 1966). None of the animals died during the exposure period. Animals displayed clinical signs such as sedation, ruffled fur, dyspnea, curved body position, and red colored feces. No abnormal findings were made at necropsy. The LD50 was > 6,400 mg/kg bw.

In another acute oral toxicity study comparable to OECD guideline 401, Sprague-Dawley rats (5/sex/dose) were administered the test substance at a single dose of 5,000 mg/kg bw by gavage followed by a 7-day observation period (BASF, 1978). None of the animals died during the exposure period. Animals did not display any clinical signs, except red stained feces. No abnormal findings were made at necropsy. The LD50 was >5,000 mg/kg bw.

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 ranged from 5,000 to 15,000 mg/kg body weight (maximum doses).

Conclusion: Based on the available data for the test substance and taking the data of category members into account, no classification for acute toxicity is warranted. The LD50 after oral administration in rats was determined to be greater than 5,000 mg/kg.

Inhalation toxicity

Regarding inhalation, only unreliable data is available for the test article. Two inhalation risk tests (BASF XXII/87, 1972 and BASF XXV/564, 1976), which demonstrate the toxicity of an atmosphere saturated with vapors of the volatile components, were performed with the test article. The nominal concentration is calculated as quotient of the amount of the test substance weight loss during exposure. In the first test, two groups of rats (3/sex/group) were exposed sequentially to the dusts for 8 h. None of the animals died during the exposure period and no abnormal clinical signs were reported. Body weights and gross pathology were normal. The concentration of the test article in the atmosphere could not be determined. In the second inhalation risk test two groups of rats (3/sex/group) rats were exposed to a dust atmosphere for 8 hours. No deaths were reported and no signs regarding body weights and gross pathology were reported. Distinct irritation of the mucous membrane was observed. Average concentration of substance in the atmosphere as stated in the report was 2.43 mg/l. However, since this test design is insufficient for non-volatile substances, these tests are disregarded. Several other inhalation risk tests were performed for other category members, they were disregarded as well.

Reliable data is available for four other category members. Three substances were tested in OECD 403 guideline tests and a fourth substance was tested in a study similar to guideline 403. In all studies, rats were exposed to dust aerosols analytically verified 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 analytically determined concentration of the test articles was greater than 5.1 mg/l in all of the studies (5.1 - 5.4 mg/l).

One of these category members was chosen to cover the endpoint conducting a read-across entry, namely CAS 4948 -15 -6. The acute toxicity inhalation test was performed according to OECD 403 (limit test) not in compliance with GLP. The concentration used was 5.2 mg/l and five rats per sex were exposed to the dust of the test substance via inhalation. After an observation period of 14 -days, no animal was found dead. Clinical signs observed were irregular, accelerated and/or intermittent respiration, flight behaviour and discoloured fur. From day 7 of the observation period onward, no abnormalities, except discoloured fur, were detected in animals. No pathologic findings were noted. LC50 was concluded to be greater than 5.2 mg/l (BASF, 1989).

Conclusion: Based on the data obtained with members of the “Perylene based pigments” category, no classification for acute toxicity is required. The data obtained with the category members is used to define an LC50 value in rats for the test article after inhalation of above 5000 mg/m³.

Dermal toxicity

No data regarding acute toxicity after dermal exposure is available for the test substance. However, two studies performed with a category member are available. In the key study comparable to OECD guideline 402, 5 Sprague-Dawley rats of each sex were treated with the test substance at 2500 mg/kg bw by single dose followed by a 14-day observation period (BASF AG, 1976). None of the animals died during the exposure period. No abnormal clinical observations were observed and no abnormal findings were reported during necropsy. The LD50 was >2500 mg/kg bw.

In a supporting dermal toxicity study comparable to OECD guideline 402, Sprague-Dawley rats (5/sex) were administered a mixture containing 18.5% of the test substance at 5 ml/kg bw by single dose followed by a 14-day observation period (BASF, 1976). None of the animals died during the exposure period. No abnormal clinical observations were observed and no abnormal findings were reported at necropsy.

Conclusion: Based on the available data no classification for the test substance regarding dermal toxicity is warranted. The result obtained with the category member is used to set the dermal LD50 of the test substance at 2500 mg/kg bw.

Justification for selection of acute toxicity – dermal endpoint
Acceptable, well-documented study report

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 toxicity under Regulation (EC) No. 1272/2008.