Registration Dossier

Administrative data

Description of key information

 read across to various stilbene florescent brighteners:
oral: LD50 (rat) > 5000 mg/kg bw/day, OECD 401
dermal: LD50 (rat) > 2000 mg/kg bw/day, OECD 402
inhalation: LC50 (4h, rat) > 1895 mg/m³ air

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented report, which meets basic scientific principles.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif:RAIf(SPF), F3-crosses of RII 1/Tif X RII 2/Tif
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 176-223 g
- Fasting period before study: overnight
- Housing: The animals were kept under conventional laboratory conditions. They were caged in groups of 5 in Macrolon cages type 3 with standardized soft wood bedding.
- Diet: Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland) ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3 °C
- Humidity (%): 55±15 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


Route of administration:
oral: gavage
Vehicle:
other: Distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: on days 1, 7, 14 and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
no mortality occured
Clinical signs:
Sedation, dyspnea, exophthalmus, ruffled fur, and curved body position were observed up to 5 hours, 8 days, 9 days, 7 days and 6 days after exposure, respectively. All clinical signs resolved by day 10 after exposure.
Body weight:
animals gained weight, see details in remarks on results
Gross pathology:
No compound related gross organ changes were observed

Weight:

Dose: 5000 mg/kg bw  day1  day 7  day 14      
 males  212  274  307      
 females  181  209  224      
             
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is not acute toxic via oral application.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Particle size not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Wistar II
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: 180 - 200 g
Route of administration:
inhalation: dust
Type of inhalation exposure:
not specified
Vehicle:
air
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric with membrane filter
Duration of exposure:
1 h
Remarks on duration:
and 4 hours
Concentrations:
163.3, 375, 1225 and 1895 mg/m³ air at 4 hour exposure
1820 mg/m³ air at 1 hour exposure
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 895 mg/m³ air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1 820 mg/m³ air (nominal)
Based on:
test mat.
Exp. duration:
1 h
Mortality:
none
Clinical signs:
other: At concentrations of 1225 and 1895 mg/m³ air at the 4 hour exposure the animals showed a decreased general condition for about 4 - 6 hours.
Gross pathology:
no abnormalities detected
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 895 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: Guideline study (OECD 402), some minor deviations from guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Remarks:
RCC, Research & Consulting Company AG
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: BRL, Biological Research Laboratories Ltd. Wolferstrasse 4, CH-4414 Fullinsdorf
- Age at study initiation: males: 10 weeks; females: 12 weeks
- Weight at study initiation: males: 228 - 234 g; females: 198 - 206 g
- Housing: Individually in Makrolon type-2 cages with standard softwood bedding
- Diet: Kliba 343, Batches 77/90 and 78/90 rat maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst) ad libitum.
- Water: Community tap water from Itingen, ad libitum
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3 °C
- Humidity (%): 40-70 %
- Photoperiod (hrs dark / hrs light): 12/12


Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Type of wrap if used: elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: with lukewarm tap water, dried with disposable paper towels
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Four ml/kg body weight was applied to the test site, for a dose of 2000 mg/kg
- Concentration (if solution): 0.5 g/ml
- Constant volume or concentration used: yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: four times during day 1, and daily during days 2-13
- Frequency of weighing: Test days 1 (pre-administration), 8 and 15,
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortality occured
Clinical signs:
No systemic signs were observed in the animals during the entire observation period.
Local symptoms: all animals had a discoulored skin (yellow), and 1 male showes scales at the back. All animals had recovered from the local signs after 8 observation days.
Body weight:
One female lost slightly weight between day 1 and 8 of the test period. The body weight gain of the further animals was not affected throughout the
study by test article treatment.
Gross pathology:
No macroscopical organ findings were observed in the animals.

Well defined erythema (grade 2) was observed in all animals after 24 hours, as well as in 4/6 animals at 48 and 72 hours. After 24, 48 and 72 hours, the erythema scores were 2.0, 1.7 and 1.7, respectively (intact skin). Except for one slight edema (grade 2) in one male after 48 hours, only very slight edema (grade 1) was observed in some animals after 24, 48 and 72 hours. After 24, 48 and 72 hours, the edema scores were 1.0, 0.7 and 0.5, respectively (intact skin). The total of all scores, i.e. for intact AND abraded skin, was 9.3. The primary irritation index (for abraded AND intact skin) was 2.33, which was listed as being in the moderate range (2.1-4.0). All effects were fully reversible within 7 days (all scores: 0.0). There was no staining of the treated skin.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is not acute toxic via dermal application.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Oral:

Reliable data on acute toxicity after oral application is available for a close structural analogue (CAS 16090-02-1). These data reveal a very low acute oral toxicity of the substance: LD50 value is above 2000 mg/kg bw, the upper limit for classification.

No classification for acute oral toxicity is necessary for the substance and then also for the substance with CAS 133 -66 -4.

Inhalation:

In acute inhalation toxicity study (similar to OECD 403, Bayer AG 1976), groups of Wistar II rats (10/sex) were exposed to dust of a close structural analogue (CAS 4404 -43 -7) for one and 4 hours and observed for 14 days. No details are reported regarding the particle size distribution of the dust, therefore the study cannot be assigned for validity. No mortality occurred during 14 day observation. At concentrations of 1225 and 1895 mg/m³ air at the 4 hour exposure the animals showed a decreased general condition for about 4 - 6 hours. At autopsy, no deviations from normal morphology were found in all animals. 1895 mg/m³ air was the highest possible concentration. That leads to an LC50 greater than 1895 mg/m³ air at 4 hour exposure. As no lethal effects occurred at the maximum technically feasible concentration it is concluded that the substance amd then also the substance with CAS 133 -66 -4 has not to be classified for acute toxicity after inhalation exposure.

Dermal:

In an acute dermal toxicity study (OECD 402, CIBA-Geigy AG, Switzerland 1990), groups of 10 - 12 week old rats (3/sex) were dermally exposed to undiluted test substance (CAS 16090 -02 -1) for 24 hours to 10% of body surface area at 2000 mg/kg bw. Animals then were observed for 14 days. No mortality occurred. No systemic signs were observed in the animals during the entire observation period. Local symptoms: all animals had a discolored skin (yellow), and 1 male shows scales at the back. All animals had recovered from the local signs after 8 observation days. One female lost slightly weight between day 1 and 8 of the test period. The body weight gain of the further animals was not affected throughout the study by test article treatment. No macroscopical organ findings were observed in the animals.

Therefore, no classification for acute dermal toxicity is necessary for the substance and then also for the substance with CAS 133-66-4.

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, dermal or inhalatory toxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

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, dermal or inhalatory toxicity under Regulation (EC) No. 1272/2008.