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Description of key information

Oral: LD50 (m/f) > 5000 mg/kg bw, rat, similar to OECD TG 401, no GLP


Inhalation: LC50 (m/f) > 5.2 mg/L air, rat, according to OECD TG 403, no GLP

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:
06.04.1982 - 20.04.1982
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 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Stamm:Hoe WISKf(SPF71); Eigenzucht
- Weight at study initiation: 201.2 g
- Fasting period before study: 16 h
- Housing: in groups in plastic cages with soft wooden granules
- Diet (e.g. ad libitum): ALTROMIN 1324 (Altromin GmbH, Lage/Lippe), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25% (25 g/100 mL)
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 females
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, body weight
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:
None of the animals died during the observation period.
Clinical signs:
other: No abnormal observations. The pigment was excreted via the faeces.
Gross pathology:
No abnormal findings.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 was determined to be greater than 5000 mg/kg bw.
Executive summary:

In this acute oral toxicity study comparable to OECD guideline 401, ten female Wistar rats were exposed to the test material (25 % in sesame oil) via gavage at a final dose of 5000 mg/kg bw. No control animals were used.  During the obervation period of 14 days no mortality or abnormal clinical signs were found. The test material was excreted via the feces. Additionally no effects on body weight gain nor abnormals findings at necropsy could be observed. Based on the results of this study, the LD50 was determined to be greater than 5000 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

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Lot/Batch No.: 19695
- Analytical purity: ca. 98%
- Physical state: solid
- Storage condition of test material: room temperature
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system 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).
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.2 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
not determinable due to absence of adverse toxic effects
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:
The LC50 was concluded to be greater than 5.2 mg/L.
Executive summary:

In an inhalation toxicity study according to OECD guideline 403, Wistar rats (5/sex) were exposed to the test article as dust for 4 hours at a measured concentration of 5.2 mg/L followed by a 14-day observation period. Cascade impactor measurements resulted in a particle size distribution with a mass median aerodynamic diameter (MMAD) of 3 µm (GSD: 3.6), which is well within the respirable range. None of the animals died during the study period. Clinical signs included 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. 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. No pathologic findings were noted during gross pathology. The LC50 determined on the basis of the study results was >5.2 mg/L.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
5 200 mg/m³ air
Physical form:
inhalation: dust / mist

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral toxicity


In an oral toxicity study comparable to OECD guideline 401, ten female Wistar rats were exposed to the test material (25 % in sesame oil) via gavage at a final dose of 5000 mg/kg bw (Hoechst, 1982). No control animals were used.  During the obervation period of 14 days no mortality or abnormal clinical signs were found. The test material was excreted via the feces. Additionally no effects on body weight gain nor abnormals findings at necropsy could be observed. Based on the results of this study, the LD50 was determined to be greater than 5000 mg/kg bw.


In a supporting study, also comparable to OECD TG 401, the tested dose was 15000 mg/kg bw via gavage (Hoechst, 1967). No mortaility or abnormal clinical signs could be observed after exposure of ten female albino rats. The pigment was excreted via the feces. The LD50 in this study was >15000 mg/kg bw. However, the observation period was only 7 days and the body weight was not observerd, as well as no necropsy was performed. This study is therefore only supporting to the above mentioned key study. 


 


Inhalation toxicity


In an inhalation toxicity study according to OECD guideline 403, Wistar rats (5/sex) were exposed to the test article as dust for 4 hours at a measured concentration of 5.2 mg/L followed by a 14-day observation period (BASF, 1989). Cascade impactor measurements resulted in a particle size distribution with a mass median aerodynamic diameter (MMAD) of 3 µm (GSD: 3.6), which is well within the respirable range. None of the animals died during the study period. Clinical signs included 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. 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. No pathologic findings were noted during gross pathology. The LC50 determined on the basis of the study results was >5.2 mg/L.


 


Dermal toxicity


No data regarding acute toxicity after dermal exposure is available for the test substance. However, a study performed with a category member (CAS 5521-31-3) is available. In the key study comparable to OECD guideline 402, five Sprague-Dawley rats of each sex were treated with the test substance at 2500 mg/kg bw (50 % solution in water) by single dose followed by a 14-day observation period (BASF, 1976). The type of coverage was not specified. 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.

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.