Registration Dossier

Administrative data

Description of key information

key, oral, rat: LD50 > 5000mg/kg bw; transient signs of toxicity: no clinical signs observed (non-GLP,  OECD 401; BASF SE, 1982)
key, inhalative, rat: LC50 >5.42 mg dust/L air; no mortality and no toxicity observed (non-GLP, similar to OECD 403; BASF SE, 1982)
read-across CAS 36888-99-0, key study, dermal, rat: LD50 > 2500mg/kg bw; transient signs of toxicity: no abnormality detected (non-GLP, similar to OECD 402; BASF SE, 1973)

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD)
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted 12th May 1981
Deviations:
no
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: Dr. K. Thomae GMBH, Biberach, Germany
- Age at study initiation: 12 weeks
- Mean weight at study initiation: 170 g (males), 180 g (females)
- Fasting period before study: 16 hours before administration, but water is available ad libitum.
- Housing: 5 per cage, Stainless steel wire meeh cages, type DK-III
- Diet (e.g. ad libitum): Ssniff R; FA. SSNIFF, Soest, Germany
- Water: Demineralized water each workday, tap water on holidays; ad libitum
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26
- Humidity (%): 45-75
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25 % in 0.5% aqueous carboxymethyl cellulose

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg
Doses:
5000 mg/kg
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: weighing: day of application, then days 3, 7 and 13;
cageside observations: < 15', 15', 30', 1 h, 2 h, 4 h and 5 h after administration of the test substance and then once each workday.
Check for moribund and dead animale twice each workday and once on holidays.
- Necropsy of survivors performed: yes, withdrawal of food 16 houre before sacrifice; necropsy with grose-pathological examination.
- Other examinations performed: body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality, no toxicity observed.
Mortality:
No mortality observed (0/10 animals).
Clinical signs:
No clinical signs observed.
Body weight:
Mean Body weigt (g)
males: day of application: 170, day 3: 188, day 7: 223, day 13: 267
females: day of application 180, day 3: 187, day 7: 204, day 13: 225
No abnormality in body weight gain was detected.
Gross pathology:
No abnormalities detected.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
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
Study period:
03.11.1981 - 17.11.1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to Guideline 403. non GLP, but comparable reporting details
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
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 Versuchstierzuchtanstalt, Sulzfeld, Germany, outbred strain: CAW-ICO-Wiga
- Age at study initiation: about 8 - 10 weeks
- Weight at study initiation: male animais 318 +/- 27 g, female animals 228 +/- 19 g
- Housing: five per cage, cages of Becker, type D III, without bedding.
- Diet: SSNIFF R complete diet for rats and mice, manufacturer: SSNIFF-Versuchstierdiaeten GmbH, Soest, Germany, ad libitum
- Water: tap water ad libitum during the observation period


ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature 22 +/- 2
- Humidity (%): 55 +/- 5
- Photoperiod (hrs dark / hrs light): 12 h/12 h
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose/head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Read-nose inhalation system INA 20 (glass-steel construction, BASF AG)
- Exposure chamber volume: 55 L
- Method of holding animals in test chamber: The animals are restrained in tubes and their snouts project into the inhalation chamber.
- Source and rate of air: 1500 L/h compressed air by the injector and 1500 L/h ventilator air as dilution air.
- System of generating particulates/aerosols: A mixture of dust and air was generated by means of dust metering equipment (BASF).
By means of a dust generator the substance to be tested was generated into a dust aerosol, which was passed into the inhalation system.
An automatic vibrator was used for dust generation. The concentration was adjusted by varying the apertural width and varying the amplitude of oscillations of the metering beaker.
- Method of particle size determination: Andersen Stack Sampler Mark III Millipore vacuum compressed air pump XX 60 220 50, limiting orifice 3 L/min, Millipore sampling probe, internal diameter 6.9 mm, 30 minutes after the beginning of the test at the earliest, one sample was taken for the particle size analysis. Before the sampling, the impactor was equipped with glass-fiber collecting discs and a backup particle filter.
The impactor was connected to the pump and the test apparatus, and one sample (9 L) was removed.
The impactor was taken apart, and the collecting discs and the backup particle filter were weighed. The contents of the pre-impactor were determined gravimetrically.
- Pressure in air chamber: 1500 L/h compressed air by the injector and 1500 L/h ventilator air as dilution air
- To ensure, that the mixture of the test substance and air was not diluted with fresh air, the air suction system was reduced about 10 % compared to the supply air system (excess pressure).

TEST ATMOSPHERE
- Brief description of analytical method used:
• Vacuum compressed air pump (Millipore) XX 60 220 50,
• Filtration equipment with probe (Millipore) (internal diameter: 4 mm),
• Filter: MN 85/90 Bf (d = 4.7 cm),
• Balance: Cahn 26
Gravimetric determination of the concentration: the preweighed filter was placed into a filtration equipment. By means of a vaccuum compressed air pump a volume of the dust aerosol characterized by a limiting orifice 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.
- Samples taken from breathing zone: yes,
• Sampling: Velocity: 1.25 m/s, amount: 1 L, probe diameter: 4 mmm, frequency: half-hourly, in the immediate vicinity of the animal noses


- Particle size distribution: EACD 50% (effective aerodynamic cutoff diameter 50%);
Stage: Pre-impactor / EACD 50 % (µm): 26.6
Stage: Cascade impactor: Backup filter / EACD 50 % (µm): <1.2 / Percentage distribution (%): 41.14
Stage: Cascade impactor: 7 / EACD 50 % (µm): 1.2 / Percentage distribution (%): 18.69 / Cumulative distribution (%): 41.14
Stage: Cascade impactor: 5 / EACD 50 % (µm): 2.8 / Percentage distribution (%): 22.28 / Cumulative distribution (%): 59.83
Stage: Cascade impactor: 4 / EACD 50 % (µm): 5.5 / Percentage distribution (%): 8.40 / Cumulative distribution (%): 82.11
Stage: Cascade impactor: 3 / EACD 50 % (µm): 8.5 / Percentage distribution (%): 5.22 / Cumulative distribution (%): 90.51
Stage: Cascade impactor: 1 / EACD 50 % (µm): 18.2 / Percentage distribution (%): 2.14 / Cumulative distribution (%): 95.73
Stage: Cascade impactor: 0 / EACD 50 % (µm): 29.5 / Percentage distribution (%): 2.13 / Cumulative distribution (%): 97.87

A respirable dust fraction of 90.5% was obtained from the results of the particle size analysis.

- MMAD (Mass median aerodynamic diameter) 50 % = 1.7 µm/ GSD (Geometric st. dev.): 4.0
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.42 mg/l (analytical), 19.7 mg/l (nominal)
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: daily observation, weighing; before start of application, then on day 7 and day 14,
- Necropsy of survivors performed: yes, with grosspathological examination.
- Other examinations performed: body weight
Statistics:
The statistical evaluation of the concentrations-response relationship was carried out in accordance with the binomial test (Wittig, H.: Mathematische Statistik 1974, pp.32 - 35) using tables of the BASF Computer Center.
The particle size was determined in accordance with mathematical and graphical methods of evaluating particle measurements (Silverman, L.: Particle Size Analysis in Industrial Hygiene, 1971, pp. 235-259).
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.42 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No mortality and no toxicity observed.
Mortality:
no mortality
Clinical signs:
During exposure: no abnormalities;
After exposure: fur discolored by the test substance, particularly the region of the head; otherwise no abnormalities.
Body weight:
The body weight of the animals showed no adverse effects in comparison with that of the control.
Mean body weight (male / female)
- Before the study
Treatment group: 318 / 228
Control: 307 / 230
- After 7 days
Treatment group: 345 / 242
Control: 340 / 240
- After 14 days
Treatment group: 368 / 251
Control: 367 / 249
Gross pathology:
No abnormalities detected.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
5 420 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (occlusive treatment, 24 h exposure, incomplete documentation)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
(occlusive treatment, 24 h treatment)
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, Ottobrunn, Germany
- Weight at study initiation: mean weight: males 151 g, females 129 g

ENVIRONMENTAL CONDITIONS: not reported
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal, p.c., 50 cm²
- % coverage: > 10 %

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5 g/kg animal
- Concentration (if solution): 50 % aequous solution
- For solids, paste formed: yes

Duration of exposure:
24 h
Doses:
2.5 g/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: No weighing was done. Observation was several times at the day of exposure and daily on working days.
- Necropsy of survivors performed: yes
Statistics:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality and no clinical signs were observed.
Mortality:
0/10 animals died after the exposure
Clinical signs:
no abnormalities detected
Body weight:
not recorded
Gross pathology:
9/10 no abnormalities detected
1/10 right peak pulmonary lobe with chronic Bronchopneumonia
Other findings:
- Other observations: after 24 h local orange substance residues
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 500 mg/kg bw

Additional information

There are reliable studies available to assess the acute oral and inhalative toxicity of the test substance. For acute dermal toxicity there is only a study with the analogous test substance CAS 36888-99-0 available.

Oral:

An oral acute toxicity study was performed with the test substance in Wistar rats according to OECD guideline 401 (BASF SE, 1982). A group of five animals per sex were administered a single oral dose of 5000 mg/kg bw test material preparation by gavage (dose volume: 20 ml/kg bw of an aqueous solution of the test substance in 0.5% carboxymethyl cellulose). The animals were examined for clinical signs several times on the day of administration and once on workdays. The observation period was 14 days. No clinical signs were observed during the study. When the tested animals were necropsied at the end of the study no abnormalities were observed.

Under the conditions of this study the median lethal dose of the test substance after oral application was found to be greater than 5000 mg/kg body weight for male and female rats.

 

Inhalative:

In an Industrial Hygiene Orientating Investigation study evaluating acute toxicity following inhalative administration, Sprague-Dawley rats were exposed to the test substance similar to OECD guideline 403 with deviations (BASF SE, 1982). Five male and female animals were exposed to 5.42 mg/l (analytical) test substance in a read-nose inhalation system for 4 hours. The MMAD 50% (mass median aerodynamic diameter 50%) is 1.7 µm, calculated from the results of the particle size analysis and the respirable dust fraction was calculated to be 90.5%. During the observation period of 14 days, the animals were examined for clinical signs daily and at the end of the study necropsied with gross pathological examination. All animals survived until the end of the study period. No clinical signs were observed during the study period. Only the fur was discolored by the test substance, particularly the region of the head.

Under the conditions of this study the median lethal concentration of the test substance after inhalative exposure was found to be greater than 5.42 mg dust/L air for male and female animals.

Dermal:

An Industrial Hygiene Orientating Investigation study was performed with the analogous test substance CAS36888-99-0 to assess the acute toxicity following dermal administration of the test substance in Sprague-Dawley rats similar to OECD guideline 402 with deviations (BASF SE, 1973). Five animals per sex were treated with the test substance at 2500 mg/kg bw by dermal occlusive application. The test item was diluted in vehicle (an aqueous solution of carboxymethyl cellulose) at a concentration of 50%. The application period was 24 hours. During the observation period of 14 days, the animals were examined for clinical signs several times on the day of exposure and daily afterwards on working days. All animals survived until the end of the study period. No clinical signs were observed during the study period. In nine of ten animals no abnormalities were detected at necropsy. In only one of ten animals right peak pulmonary lobe with chronic Bronchopneumonia was observed in gross pathology.

Under the conditions of this study the median lethal dose of the analogous test substance after dermal application was found to be greater than 2500 mg/kg body weight for male and female animals.

Absence of acute dermal toxicity is supported by absence of mortality in mice observed in the study with intraperitoneal injection at the dose level of 2000 mg/kg bw (BASF AG 1982). For this route of exposure, 100% systemic availability is given. Pigment Yellow 185 is considered too insoluble for skin permeability.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute oral or dermal or inhalation toxicity under Directive 67/548/EEC, as amended for the 31st time in Directive2009/2/EG.

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 oral or dermal or inhalation toxicity under Regulation (EC) No. 1272/2008, as amended for the third time in Directive EC 618/2012.