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Administrative data

Description of key information

Rat oral LD50 > 10000 mg/kg bw

Rat inhalation LC50 > 1895 mg/m3

Rat dermal LD50 > 2000 mg/kg bw

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:
Started on April 2, 1979.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Old study, but well documented and scientifically acceptable.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
The acute oral LD50 of the test item in rats of both sexes was assessed administering three doses at 5000, 6500, 8000 and 10000 mg/kg bw. Animals were observed over a period of 14 days.
GLP compliance:
no
Remarks:
Pre GLP
Test type:
standard acute method
Species:
rat
Strain:
other: Tif RAIf (SPF) strain
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: animals were raised on the premises were used for these experiments.
- Age at study initiation: 7 to 8 weeks old.
- Weight at study initiation: males in the range of 168-199 g; females in the range of 159-177 g.
- Housing: during the treatment and observation period the animals were housed in groups of 5 in Macrolon cages (type 3).
- Diet: ad libitum rat food - NAFAG, Gossau SG.
- Water: ad libitum.
- Acclimation period: for a minimum of 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Photoperiod: 10 hours light cycle day.
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
2 %
Details on oral exposure:
- Volume: 20 ml/kg
Doses:
5000, 6500, 8000 and 10000 mg/kg bw
No. of animals per sex per dose:
5 x sex x group.
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes; animals were at random to a necropsy at the end of the observation period.
- Examinations performed: bodyweights were recorded immediately prior to dosing (control weights) and at 7 and 14 days.
Statistics:
LD50 including 95 % confidence limits were calculated by the logit model.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Mortality:
No dead occurred at all the doses tested.
Clinical signs:
other: The rats in all dosage groups showed sedation, dyspnoea, exophthalmus, curved position and ruffled fur. The animals recovered within 6 to 7 days.
Gross pathology:
No substance related gross organ changes were seen.

Rate of deaths

Dose mg/kg Sex No. of animals No. of animals dead Death rate %
5000 M 5 0 0
6500 M 5 0 0
8000 M 5 0 0
10000 M 5 0 0
5000 F 5 0 0
6500 F 5 0 0
8000 F 5 0 0
10000 F 5 0 0

Signs and symptoms

5000 mg/kg bw

Signs and symptoms Hours Days
1 2 3 5 24 2 3 4 5 6 7 8 9 10 11 12 13 14
Sedation + + + + +
Dyspnoea + + + + + + + + +
Dacryorrhoea
Chromodacryorrhoea
Rinorrhoea
Epistaxis
Exophthalmos ++ ++ + + + +
Salivation
Ruffled fur + + + + + +
Pallor
Cyanosis
Diarrhoea
Body position (ventral)
Body position (lateral)
Body position (curved) + + + + + + + + +
Ataxia
Trismus
Tremor
Tonic clonic muscle spasms
Convulsions

 + = slight, ++ = moderate, +++ = severe

6500 mg/kg bw

Signs and symptoms Hours Days
1 2 3 5 24 2 3 4 5 6 7 8 9 10 11 12 13 14
Sedation + + + + +
Dyspnoea + + + + + + + + +  +
Dacryorrhoea
Chromodacryorrhoea
Rinorrhoea
Epistaxis
Exophthalmos ++ ++ ++ ++ + +  +  +
Salivation
Ruffled fur + + + + + +  +
Pallor
Cyanosis
Diarrhoea
Body position (ventral)
Body position (lateral)
Body position (curved) + + + + + + + + +
Ataxia
Trismus
Tremor
Tonic clonic muscle spasms
Convulsions

 + = slight, ++ = moderate, +++ = severe

8000 mg/kg bw

Signs and symptoms Hours Days
1 2 3 5 24 2 3 4 5 6 7 8 9 10 11 12 13 14
Sedation + + + + +
Dyspnoea + + + + + + + + +  +
Dacryorrhoea
Chromodacryorrhoea
Rinorrhoea
Epistaxis
Exophthalmos ++ ++ ++ ++ + +  +  
Salivation
Ruffled fur + + + + + +  +  +
Pallor
Cyanosis
Diarrhoea
Body position (ventral)
Body position (lateral)
Body position (curved) + + + + + + + + +
Ataxia
Trismus
Tremor
Tonic clonic muscle spasms
Convulsions

 + = slight, ++ = moderate, +++ = severe

10000 mg/kg bw

Signs and symptoms Hours Days
1 2 3 5 24 2 3 4 5 6 7 8 9 10 11 12 13 14
Sedation + + + + +  +  +
Dyspnoea + + + + + + + + +  +
Dacryorrhoea
Chromodacryorrhoea
Rinorrhoea
Epistaxis
Exophthalmos ++ ++ ++ ++ + +  +  
Salivation
Ruffled fur + + + + + +  +  +
Pallor
Cyanosis
Diarrhoea
Body position (ventral)
Body position (lateral)
Body position (curved) + + + + + + + +
Ataxia
Trismus
Tremor
Tonic clonic muscle spasms
Convulsions

 + = slight, ++ = moderate, +++ = severe

Bodyweight changes

Dose 5000 6500 8000 10000
Day 1 M Mean BW/SD (g) 168/4.8 184/12.9 199/12.1 190/7.4
Day 1 F 177/3.7 159/7.1 177/3.4 172/5.9
Day 7 M 268/5.9 240/10.7 244/22.4 247/11.4
Day 7 F 209/9.5 185/5.5 203/6.0 198/7.9
Day 14 M 272/15.3 282/17.4 292/11.5 280/17.4
Day 14 F 266/9.2 198/6.4 221/10.4 210/11.3
Interpretation of results:
not classified
Remarks:
Migrated information According to the CLP Regulation. Criteria used for interpretation of results: EU
Conclusions:
LD50 > 10000 mg/kg bw
Executive summary:

Method

The acute oral LD50 of the test item in rats of both sexes was assessed administering three doses at 5000, 6500, 8000 and 10000 mg/kg bw. Animals were observed over a period of 14 days.

Results

No dead occurred at all the doses tested. The rats in all dosage groups showed sedation, dyspnoea, exophthalmus, curved position, diarrhoea and ruffled fur; the animals recovered within 7 to 10 days.

LD50 > 10000 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 000 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 based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Particle size not specified. The analogous substance, part of the Stilbene Fluorescent Withening Agents, group 3, is the acid form of the disulphonated derivative dihydroxyethyl derivative. Justification for Read Across is reported in the endpoint summary and in the Category Justification Report attached to the Section 13 of this dossier.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system 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 - 4 h
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 .
- 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:
No mortality occuerred.
Clinical signs:
other: other:
Gross pathology:
No abnormalities detected.
Interpretation of results:
other: not applicable.
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
LC50 (4 h): > 1.895 mg/l air
Executive summary:

Method

Acute inhalation toxicity was assessed following the method described into the OECD guideline 403.

Results

LC50 (4 h): > 1.895 mg/l air

LC50 (1 h): 1.820 mg/l air

Conclusion

According to CLP Regulation (EC 1272/2008), 3.1 Acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

The inhalation LD50 value classification limit for dust is 5.0 mg/l (category 4: 1.0 < ATE ≤ 5.0 mg/l). In the current test an LD50 was non identified; considering the fact that no mortality occurred, a classification category can not be assigned. Thus, a classification according to the CLP Regulation (EC 1272/2008) is not applicable.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 895 mg/m³ air

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:
other: Only a summary is available but with enough details available to describe the endpoint.
Principles of method if other than guideline:
The acute dermal LD50 of the test item was tested in rabbits administered by dermal occlusive dressing (Draize method) at a single concentration of 2000 mg/kg bw.
GLP compliance:
no
Remarks:
Pre GLP
Test type:
standard acute method
Species:
rabbit
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: mean 2205 g.
- Housing: one animal per cage.
- Food: Nafag Würfel Nr. 84.

ENVIRONMENTAL CONDITIONS
- Temperature: 23°C ± 2°C
- Humidity: 55 ± 5%
- Photoperiod: 14 hrs light/day.
Type of coverage:
occlusive
Vehicle:
other: fresh suspension with gum arabic 1% / tap water
Details on dermal exposure:
APPLICATION
One application to intact skin. Occlusive dressing (Draize method) for 24 hours.

TEST SITE
- Area of exposure: dehairing of the dorsal skin by shearing.
- % coverage: SURFACE OF 200-300 cm2

REMOVAL OF TEST SUBSTANCE
- Washing: washing the application area with lukewarm water and a sponge.

TEST MATERIAL
- Concentration: 80%
Duration of exposure:
24 hours
No. of animals per sex per dose:
3 males and 3 females.
Details on study design:
- Duration of observation period following administration: 8 days.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
other: No systemic symptoms were recorded.

Skin reactions recorded

Dose mg/kg Time point N. of animals with reactions Reaction
2000 24 hrs 6/6 Erythema
2 days 1/6 Erythema, oedema
3 days 1/6
1/6		 Erythema
Oedema
4 days 1/6
1/6		 Erythema
Scaling, oedema
5 + 6 days 1/6 Scaling, oedema
7 + 8 days 2/6
1/6		 Scaling
Scaling, oedema
Interpretation of results:
not classified
Remarks:
Migrated information According to the CLP regulation. Criteria used for interpretation of results: EU
Conclusions:
LD50 > 2000 mg/kg bw
Executive summary:

Method

The acute dermal LD50 of the test item was tested in rabbits administered by dermal occlusive dressing (Draize method) at a single concentration of 2000 mg/kg bw.

Results

No deaths occurred.

LD50 > 2000 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Many summaries of tests performed according to the official guidelines are available; they are all consistent and indicate that no acute toxicity is expressed by the substance up to very high doses (> 10000 mg/Kg bw).

The Klimish 2 study for acute dermal toxicity here reported, was performed at 2000 mg/Kg bw with no effect (Ciba-Geigy Ltd., 1970).

Because of the physical state and the trade forms, inhalation is not an appropriate route of exposure. Acute toxicity results for the other two exposure routes indicate no concern therefore no testing was performed. One test is available on an analogous substance, performed at the maximum allowed concentration of 1890 mg/m3: no effects were observed.

The analogous substance, part of the Stilbene Fluorescent Withening Agents, group 3, is the acid form of the disulphonated derivative dihydroxyethyl derivative; due to the sulphonation/salification degree is less soluble. This property makes the Read Across substance OB 3a-A(free acid) a conservative representative because of the potential higher bioavailability.

As a conclusion it can be stated that the substance is not acutely toxic for all the three exposure patterns.

Justification for classification or non-classification

According to CLP Regulation (EC 1272/2008), 3.1 Acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

The oral LD50 value was established to be greater than 10000 mg/kg body weight, therefore the test substance is out of any classification limit for acute oral toxicity (oral acute toxicity category 4: 300 < ATE ≤ 2000 mg/kg bw).

The dermal LD50 value was established to exceed 2000 mg/kg body weight, which exceeded the highest CLP classification limit (dermal acute toxicity category 4: 1000 < ATE ≤ 2000 mg/kg bw).

The inhalation LC50 value was established to be greater than 1895 mg/m3. For powder the limit for classification is ATE > 5 mg/l i. e. 5000 mg/m3.

Since no effect was observed at the tested concentration and this was the maximum reachable concentration in the test condition, it is assumed that the substance is not classified for inhalation acute toxicity.

In conclusion, the available experimental data are adequate for classification and labelling and the test substance is non classified for oral and dermal acute toxicity, according to the CLP Regulation (EC 1272/2008).