Registration Dossier

Administrative data

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

Link to relevant study records
Reference
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
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
The study was conducted according to an internal 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
Specific details on test material used for the study:
- Purity: approx. 100%
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gassner (breeder)
- Weight at study initiation: mean weight: males: 230 g, females: 180 g
- 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 % in water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 % in 0.5 % aqueous CMC
- Amount of vehicle (if gavage): 10 ml/kg

MAXIMUM DOSE VOLUME APPLIED: males: 2.3 ml; females 1.8 ml (10 ml/kg bw).
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
- Frequency of observations: daily (except on weekends)
- Frequency of weighing: before treatment and on days 2, 7 and 13
- Necropsy of survivors performed: yes
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 exposure period.
Clinical signs:
No abnormal observations, animals were in good general health throughout the study.
Body weight:
Day 3, mean weight (g): males: 261; females 204
Day 8, mean weight (g): males: 295; females 215
Day 14, mean weight (g): males: 324; females 230.
No abnormal body weight gain.
Gross pathology:
No abnormal observations.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 400 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13.10.1982 - 27.10.1982
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
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 or test system and environmental conditions:
TEST ANIMALS
- Source: THOM; Zuchtbetrieb: Dr. K. Thomae GmbH, 7950 Biberach
- Age at study initiation: 8 weeks
- Weight at study initiation: 245 g (males) and 179 g (females)
- Housing: type DIII (Fa. Becker)
- Diet: SSNIFF R 10 mm Pellet, Ssniff-Versuchstierdiäten GmbH, 4770 Soest, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20- 24
- Humidity (%): 30 - 70
- Air changes (per hr): Fully airconditioned room
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose/head only
Vehicle:
clean air
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 dust generator.
- 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

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter): 1.9 µm
- GSD: 3.9
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric determination
Duration of exposure:
4 h
Concentrations:
5.4 mg/L
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Body weights: at the beginning of the study, after 7 days and at the end of the study
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.4 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: Erratic breathing, slight nasal excretion, ruffled fur during the first 4 days of the observation period, no abnormal findings were observed from day 5 onward.
Body weight:
Normal weight gain.
Day 7, mean weight (g): males: 267; females 201
Day 14, mean weight (g): males: 316; females 211.
Gross pathology:
No abnormal findings.

Results of analytical measurements:

Sample No Analyt. Conc. (mg/l)
1 5.31
2 5.07
3 5.40
4 5.65
Mean 5.4
standard deviation of the mean 0.33
Nominal concentration 39

Particle size analysis:

Stage EACD 50% [µm] [mg] percentage distribution [%] cummulative distribution [%]
pre-impactor 26.6 9.35 2.502 97.498
0 29.5 0.618 2.032 95.466
1 18.2 0.502 6.133 89.333
3 8.5 1.515 13.209 76.124
4 5.5 3.263 18.22 57.904
5 2.8 4.501 18.755 39
7 1.2 4.633 39.149 149
backup filter < 1.2 9.671
Sum 34.053

The MMAD 50% = 1.9 µm (geometrical standard deviation =3.9) was calculated from the results of the particle size analysis.

A respirable dust aerosol fraction that might reach the alveolar region of 89% was obtained from the results of the particle size analysis.

Interpretation of results:
GHS criteria not met
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 for cross-reference:
read-across source
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.4 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 an acute inhalation study performed with the read-across substance, the target substance was not assumed to induce mortality. Thus, the LC50 was concluded to be greater than 5.4 mg/l.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 000 mg/m³

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

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
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
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 or test system 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 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:
Under the conditions chosen, the test substance was practically non-toxic to experimental animals.
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 for cross-reference:
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 an acute dermal toxicity study conducted with the read-across, the target subtance was not assumed to induce mortality. Thus, the LD50 was concluded to be greater than 2500 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
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, rats (5/sex/dose) were treated with the test substance at a dose level of 5000 mg/kg bw by single dose (gavage) followed by a 14-day observation period (BASF AG, 1979). None of the animals died during the exposure period. All animals showed normal body weight gains and no abnormal findings were observed regarding clinical signs and at necropsy. The LD50 was therefore determined at greater than 5000 mg/kg body weight.

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. An inhalation risk test (BASF 77/826, 1979), which demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components, was performed with the test article. The nominal concentration is calculated as quotient of the amount of the test substance weight loss during exposure. Two groups of rats (3/sex/group) were exposed sequentially to the dusts for 7 h. None of the animals died during the exposure period and no abnormal clinical signs were reported. Body weights and gross pathology were normal. Average concentration of the test article in the atmosphere was given as 0.89 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 other category members 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).

The read-across test substance was tested in an acute inhalation experiment using rats exposed to dust via inhalation. The test was performed equivalent to OECD 403 and not in compliance with GLP (BASF, 1983). Ten animals per sex were exposed for 4 h to the limit dose of 5.4 mg/L. After an observation period of 14 days, no deaths were observed. Clinical signs occurred including erratic breathing, slight nasal excretion, ruffled fur during the first 4 days of the observation period. No abnormal findings were observed from day 5 onward and thus, the LC50 was concluded to be greater than 5.4 mg/L.

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 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. Based on the data, classification for acute toxicity is not warranted under Regulation (EC) No.1272/2008.