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Administrative data

Description of key information

Rat oral LD50 > 2000 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:
From October 25 to November 15, 1978.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to internationally accepted testing guidelines, well documented and the results 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 toxicity in rats of both sexes was tested administrating the test item by gavage at doses of 7000, 8000 and 10000 mg/kg bw. The observation period following administration was of 14 days.
GLP compliance:
no
Remarks:
pre GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7 to 8 weeks old.
- Housing: housed in groups of 5 in Macrolon cages (type 3).
- Fasting period before study: animals fasted overnight.
- Diet: ad libitum rat food - NAFAG, Gossau SG.
- Water: ad libitum
- Acclimation period: minimum of 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 1 °C
- Humidity: 55 ± 5 %
- Photoperiod: 10 light cycle day.
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Doses:
7000, 8500 and 10000 mg/kg
No. of animals per sex per dose:
5 males and 5 females per dose
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: recorded at day 1, 7 and 14.
- Necropsy of survivors performed: yes; the animals were submitted at random to a necropsy at the end of the observation period.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 200 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality occurred.
Clinical signs:
other: The rats in all dosage groups showed sedation, dyspnoea, exophthalmos, salivation and curved position; ruffled fur was observed at doses of 8500 and 10000 mg/kg bw. All symptoms were recovered within 10 days.
Gross pathology:
No substance related gross organ changes were seen.

Rate of deaths

Dose
mg/kg		 Sex Total
Number
animals
in group		 Total
Number
animals
dead		 Death
rate
percentage
7000 M 5 0 0
8500 M 5 0 0
10000 M 5 0 0
7000 F 5 0 0
8500 F 5 0 0
10000 F 5 0 0

Signs and symptoms, dose of 7000 mg/kg

Signs and symptoms hrs Days
1 2 4 6 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

Signs and symptoms, dose of 8500 mg/kg

Signs and symptoms hrs Days
1 2 4 6 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

Signs and symptoms, dose of 10000 mg/kg

Signs and symptoms hrs Days
1 2 4 6 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
Interpretation of results:
not classified
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
LD50 > 2200 mg/kg bw
Executive summary:

Method

The acute oral toxicity in rats of both sexes was tested administrating the test item by gavage at doses of 7000, 8000 and 10000 mg/kg bw. The observation period following administration was of 14 days.

Results

LD50 > 2200 mg/kg bw based on active ingredient.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 200 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
other: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Particle size not specified. 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
Remarks:
Pre GLP.
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:
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 the 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:
other: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted according to internationally accepted testing guidelines and performed according to GLP. The tested substance is the analogous tetrasulphonated part of the Stilbene Fluorescent Whitening Agent category, group 3. It has therefore the same organic functional groups, but two more sulphonated groups, therefore a higher salification degree. Skin adsorption has been evaluated and calculated for all members of the category (see Category Justification Report, Section 13). As it can be noted, the influence of the variability in functional group is very low, more related to the variability in the polarity of the substance than on potential reactivity that can arise a concern. From a metabolic point of view an estimation with OECD Toolbox of the dermal metabolism has been performed in order to verify if breakdown products could be formed. Results are negative for all members. Oral acute toxicity is comparable for the two substances (CAS 16470-24-9 and 70942-01-7), with very high estimated LD50. The two substances are expected to have a similar behaviour regarding dermal acute toxicity, as well as all the other members of the Stilbene Fluorescent Whitening Agents category.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wblferstrasse 4, CH-4414 Fullinsdorf.
- Age at study initiation: 10 weeks (males), 12 weeks (females).
- Weight at study initiation: 225 - 247 g (males), 200 - 222 g (females).
- Housing: individually in Makrolon type-2 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet: pelleted standard 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: one week.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 40-70 %
- Air changes: 10 - 15 air changes per hr.
- Photoperiod: 12 / 12 hrs dark / hrs light.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: backs of the animals.
- Preparation: clipping 24 h before application.
- % coverage: 10% of the total body surface.

REMOVAL OF TEST SUBSTANCE
- Washing: with lukewarm tap water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 4 ml
- Concentration: 100%
- For solids, paste formed: yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: observations four times during test day 1, and daily during days 2 - 15; weighing on test days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathology.
Statistics:
The LOGIT-Model could not be applied to the observed rate of death. The toxicity was estimated without use of a statistical model.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality.
Clinical signs:
other: No systemic signs were observed in the animals during the entire observation period. Skin observations: males/females: scales (back) (10/10); general erythema (back) (3/10); males: erythema focal (back) (3/5). All animals had recovered from the local sign
Gross pathology:
No findings noted.
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

Upon an acute oral single administration (2000 mg/kg bw) and a 15 day post-treatment observation period, the dermal LD50 was determined for the test substance, according to the OECD guideline 402.

Results

LD50 > 2000 mg/kg bw

No deaths accorred and no systemic signs were observed in the animals during the entire observation period. Skin reactions are all recovered after 7 observation days.

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

Additional information

The acute oral toxicity of the substance under registration was investigated in a good GLP Klimish 1 study on rat of both sexes, performed at 2200 mg/Kg bw with no effects (Bathe, 1979). The result is supported by the studies performed on the analogous sodium salt CAS 4193-55-9 (Hartman 1987 and Tomlinson 1993).

A good GLP Klimish 2 study for acute dermal toxicity was conducted on the similar substance CAS 16470-24-9. It was performed just at 2000 mg/Kg bw with no effect (RCC, Research & Consulting Company AG., 1991). The tested substance is the analogous tetrasulphonated sodium salt, belonging to the Stilbene Fluorescent Whitening Agents category, group 3. Therefore, it has the same organic functional groups, but two more sulphonated groups, therefore a higher salification degree.

Skin adsorption was evaluated and calculated for all members of the category (see Category Justification Report attached to the Section 13 of the dossier). As it can be noted, the influence of the variability in functional group is very low, more related to the variability in the polarity of the substance than on potential reactivity that can arise a concern. From a metabolic point of view, an estimation with OECD Toolbox of the dermal metabolism was performed in order to verify if breakdown products maybe formed. Results are negative for all the category members.

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 CAS 4404-43-7, 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, therefore contains the same organic functional groups, but due to the sulphonation/salification degree is less soluble. This property makes the Read Across substance CAS 4404-43-7 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 ways.


Justification for selection of acute toxicity – oral endpoint
Study conducted according to internationally accepted testing guidelines

Justification for selection of acute toxicity – dermal endpoint
Study conducted according to internationally accepted testing guidelines, in GLP on an analogous substance of the category.

Justification for classification or non-classification

According to the 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 2200 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).