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Administrative data

Description of key information

LD50 oral in rats > 5000 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

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 22nd, 1983 - July 6th, 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: EEC Directive 79-83 1, Annex V, Part B: Methods For The Determination Of Toxicity 4.1. 1 Acute Toxicity Orally
GLP compliance:
no
Remarks:
but QAU statement included
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: HOECHST AG, Kastengrund, SPF-Zucht
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: 177 g (males) and 194 g (females)
- Fasting period before study: 16 hours prior and 2 hours after application
- Housing: Makroloncages (Type 4) on softwood granules, in groups of 5
- Diet (e.g. ad libitum): Altromin 1324 (Altromin-GmbH, Lage/Lippe), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): fully airconditioned rooms
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25% (w/v)
- Amount of vehicle (if gavage): 20 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 and weighing: weekly weighing
- 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 observation period.
Clinical signs:
The feaces were colored dark brown from 2 hours after application until day 1 post-application.
Body weight:
Normal weight gain.
Gross pathology:
No abnormal findings.
Interpretation of results:
GHS criteria not met
Conclusions:
In conclusion, under the conditions chosen the test substance was practically non-toxic to experimental animals.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
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:
supporting 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:
Under the conditions chosen, the test substance was practically non-toxic.
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
Reference
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 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 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 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 according to OECD guideline 401, Wistar rats (5/sex) were treated with the teat substance at 5000 mg/kg bw by single dose (gavage) followed by a 14-day observation period (Hoechst, 1983). None of the animals died during the exposure period. No abnormal clinical observations were observed; the test substance was excreted via the feces (stained feces observed). A normal weight gain was recorded and no abnormal findings were made at necropsy. The LD50 was therefore determined to be greater than 5000 mg/kg body weight.

In a second study following a protocol comparable to OECD guideline 401, Sprague-Dawley rats (5/sex) were treated with the test substance at 5000 mg/kg bw by single dose (gavage) followed by a 14-day observation period (BASF, 1980). None of the animals died during the exposure period. No abnormal clinical observations were observed; the test substance was excreted via the feces. A normal weight gain was observed and no abnormal findings were made at necropsy. The LD50 was therefore set at greater than 5000 mg/kg body weight.

In another OECD guideline 401 comparable study, female Sprague-Dawley rats (5/sex) were administered the test article at 2000 mg/kg bw by single dose (gavage) followed by a 14-day observation period (Hazleton Laboratories Europe Ltd., 1978). None of the animals died during the exposure period. No abnormal clinical observations were observed. A normal weight gain was observed and no abnormal findings were made at necropsy. The LD50 observed in this study was greater than 2000 mg/kg body weight.

Two more studies comparable to OECD guideline 401 are available which investigate the acute oral toxicity of the test article or of a mixture containing the test article (both BASF, 1976). Rats (n = 5) were treated with the test material at 10000 mg/kg bw by single dose (gavage) followed by a 7-day observation period. None of the animals died during the exposure period. Clinical signs in each study included apathy and dyspnea, respectively. No abnormal findings were made at necropsy. The LD50 in both studies was greater than 10,000 mg/kg bw for the material tested.

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 10,000 mg/kg.

Inhalation toxicity

In an inhalation toxicity study comparable to OECD guideline 403, single maximum concentration of the test material was administered to 20 Sprague-Dawley rats (10 male, 10 female) as dust by inhalation (nose only) over a period of 4 hours. A further 10 rats (5 male, 5 female) were exposed under similar conditions to an atmosphere of filtered air. The concentration of test material, as measured by gravimetric analysis was 0.41 mg/l. (Hazleton, 1978). It is however not verified that the saturated dust concentration is the maximum possible. The mass median aerodynamic diameter (MMAD) was 0.87 µm. 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. 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 chromodacryorrhoea 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. 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. 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 LC50 was > 0.41 mg/L.

Additionally, two unreliable inhalation risk tests are available for the test article. These tests demonstrate the toxicity of an atmosphere saturated with vapors of the volatile components. The nominal concentration is calculated as quotient of the amount of the test substance weight loss during exposure (BASF, XXIV/269, 1974 and BASF, XXIV/334, 1974). In both tests, 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 in either study. In both studies, body weights and gross pathology were normal. Average concentration of the test article in the atmosphere was given as 5.78 mg/l and 11.56 mg/l, respectively. 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 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).

Conclusion: Based on the data obtained with members of the Perylene 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

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 greater than 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 result of two dermal toxicity studies, a LD50 of greater than 2500 mg/kg body weight is derived.

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.