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Description of key information

LD50 oral in rats >10000 mg/kg bw
LC50 inhalation in rats > 5000 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:
supporting 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 protocol which in principle is comparable to the OECD Guideline 401. Test groups consisting of 5 animals/sex/dose were 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 225 g, females 165 g
- Diet (e.g. ad libitum): HERILAN MRH-Haltung Alleinfutter, Heinrich EGGERSMANN KG Rinteln
Route of administration:
oral: gavage
Vehicle:
other: water solution with 0.5% Carboxymethylcellulose- Zubereitung G/V
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50% solution
- Amount of vehicle (if gavage): 20 and 13.62 ml/kg

MAXIMUM DOSE VOLUME APPLIED:
20 ml/kg
Doses:
6810 and 10000 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:
> 10 000 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:
At the beginning dyspnea was observed. Red colored feces observed on first day. All animals recovered within two days.
Body weight:
No effects were reported.
Gross pathology:
No abnormal observations.

In a pretest 2 female rats per dose group were treated with dose levels of 1000 and 4640 mg/kg. No deaths occurred and no clinical symptoms were recorded except for red colored feces on the first day. No deviations from normal at autopsy.

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was not acute toxic and thus, a LD50 greater than 10,000 mg/kg bw was established.
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 protocol 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:
OTHER SPECIFICS:
- The purity of the test substance was 30% and 70% water
- Form: press cake
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: average weight males: 250 g, females: 160 g
- Diet (e.g. ad libitum): Altromin R 1324, Altromin GmbH Lage
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test substance was given as 50 % aqueous solution.
Doses:
10000 mg/kg bw (3000 mg/kg bw of the active ingredient)
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:
> 3 000 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: no mortality observed
Mortality:
None of the animals died.
Clinical signs:
Systemic dark red coloring of the skin and dark red coloring of the faeces.
Body weight:
No effects were reported.
Gross pathology:
No abnormal observations.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was not acute toxic and thus, a LD50 greater than 10,000 mg/kg bw was established.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
10 000 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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
It was not verified that the saturated dust concentration is the maximum possible.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
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: Bantin and Kingman Ltd., Grimston, Aldbrough, Nr. Hull
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 190-370 g
- Housing: solid floor polypropylene cages furnished with sterilised sawdust, in groups of 5
- Diet (e.g. ad libitum): Rat and Mouse No. 1 Expanded Diet (BP Nutrition (UK) Ltd., Stepfield, Witham, Essex), ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: for a minimum of 3 days before exposure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 10
- Air changes (per hr): 8-10
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical Perspex exposure chamber
- Exposure chamber volume: 7 L
- Rate of air: 15 L/min
- System of generating particulates/aerosols: Timbrell dust generator was used to produce the atmosphere
- Method of particle size determination: CS5 cascade impactor was employed with 6 separation stages covering the particle aerodynamic mass median diameter range 0.35-4 µm. Upper class limits for the 6 stages were 0.35, 0.5, 0.75, 1.0, 2.0 and 4.0 microns.

TEST ATMOSPHERE
- Brief description of analytical method used: The absolute concentration of the atmosphere generated was measured gravimetrically before and after each exposure period using a glass fibre filter disc placed adjacent to the outside wall of the exposure chamber.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter): 0.87 µm
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric determination
Duration of exposure:
4 h
Concentrations:
0.41 mg/L (analytical concentration)
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
The rats were observed for toxic or pharmacological effects during exposure and subsequently at least twice daily through a 14 day observation period. All observations were recorded daily. Body weights were determined on the day before exposure, immediately after exposure and on days 1, 3, 7, 10 and 14 after the day of exposure. Mortalities were recorded at daily intervals. Gross necropsy was performed at the end of the study.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.41 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: no mortality observed
Mortality:
No deaths occurred during exposure or during the observation period as a result of exposure to the test material. One male treated rat suffocated as a result of turning around in the restraining tube. A planned sacrifice was made of one female treated rat, one male control and one female control rat after exposure to assess the degree of primary lung irritation.
Clinical signs:
Treated rats had chromodacryorrhoea for a few hours after exposure and their pelts remained stained red throughout the observation period.
Control rats had nasal secretion and chromodacryarrhaea on the day of exposure presumably an irritant effect of the restraining tubes. Their pelts were ruffled, a condition which persisted throughout the observation period.
Body weight:
The mean body weights of the male and female control rats rose throughout the experiment, slowly until day 2 but thereafter more rapidly. The mean body weights of the treated rats were depressed following exposure but raised steadily throughout the observation period.
Gross pathology:
All the control rats and 6 male and 7 female treated rats, sacrificed after the 14 day observation period showed a moderate degree of pulmonary congestion and edema was present in some control rats. A similar degree of congestion was also noted in the female treated rat examined immediately after exposure, but congestion was more severe in the male, which had suffocated. No congestion was noted in the two control rats sacrificed at the same time, and no other abnormalities were noted in any of the control animals. The treated rats examined after exposure had red stained pelts.
Interpretation of results:
GHS criteria not met
Conclusions:
In the study presented, acute toxicity of the test substance was investigated using rats exposed via inhalation. Only one concentration was tested which was not verified being the maximum possible saturated dust concentration.No animal died during the study period and thus, the LC50 was concluded to be greater than 0.41 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:
> 0.41 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, no mortality was suggested to occur with the target substance and thus, the LC50 was concluded to be greater than 0.41 mg/l.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
5 000 mg/m³

Acute toxicity: via dermal route

Link to relevant study records

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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 study conducted with the read-across substance, the target substance was not assumed to induce mortality and thus, a LD50 greater than 2500 mg/kg bw was concluded.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 500 mg/kg bw

Additional information

The test article belongs to the "perylene based organic pigments" category (see attached CSR 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, the test substance was administered to rats (5/sex/dose) at a single dose of 10,000 mg/kg bw by gavage followed by a 14-day observation period (BASF AG, 1978). None of the animals died during the exposure period. Clinical signs included agonal respiration at the beginning of the observation period. No abnormal findings were made at necropsy. The LD50 was > 10,000 mg/kg bw.

In another acute oral toxicity study comparable to OECD guideline 401, the test article was given to rats (5/sex/dose) at a single dose of 10,000 mg/kg bw by gavage followed by a 14-day observation period (BASF AG, 1976). None of the animals died during the exposure period. Clinical signs included dark red coloring of the skin and dark red coloring of the feces. No abnormal findings were made at necropsy. The LD50 was >10,000 mg/kg bw.

These results are confirmed by the data obtained with other category members. In various studies the potential for oral toxicity was found to be very low. None of these studies raised any concern regarding acute toxicity after oral application and therefore none of the substances require classification. The LD50 values observed for all category 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 10,000 mg/kg.

Inhalation toxicity

Regarding inhalation, only unreliable data is available for the test article. Two inhalation risk tests (BASF 77/360, 1978 and BASF XXV-454, 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 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 calculated at 0.31 mg/l. In the second inhalation risk test two groups of rats (3/sex/dose) were exposed to a dust atmosphere for 8 hours. No deaths were reported and no signs regarding body weights and gross pathology were reported. Slight irritation of the mucous membrane was observed. Average concentration of substance in the atmosphere as stated in the report was 14.74 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 other category members.

In an acute inhalation toxicity study performed with the read-across substance, ten Sprague-Dawley rats per sex per dose were exposed to the dust of the test item via inhalation. The test was conducted equivalent to OECD 403 and not in compliance with GLP (Hazleton, 1978). Animals were exposed for 4 h to 0.41 mg/l following a 14 -day observation period. No treatment-related deaths occurred. One male treated rat suffocated as a result of turning around in the restraining tube. A planned sacrifice was made of one female treated rat, one male control and one female control rat after exposure to assess the degree of primary lung irritation

Treated rats had chromodacryorrhoea for a few hours after exposure and their pelts remained stained red throughout the observation period.

Control rats had nasal secretion and chromodacryarrhaea on the day of exposure presumably an irritant effect of the restraining tubes. Their pelts were ruffled, a condition which persisted throughout the observation period. Pathological findings were similar for control and treated animals with the exception that treated animals examined red stained pelts after exposure. Thus, the LC50 was concluded to be greater than 0.41 mg/l.

Three substances were tested in OECD 403 guideline studies including the read across substance stated above, and a fourth substance was tested in a study similar to guideline 403. In all studies, groups of 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 procedures. 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).

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 performed with the read-across substance comparable to OECD guideline 402, 5 Sprague-Dawley rats of each sex were treated with the test article 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.