Registration Dossier

Administrative data

Description of key information

Rat oral LD50 > 5000 mg/kg bw
Rat inhalation LC50 > 1895 mg/m3
Rat dermal LD50 > 5000 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:
migrated information: 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. The test was performed on a similar substance within the category of Stilbene Fluorescent Whitening Agents, the analogous dihydroxyethyl derivative disulphonated sodium salt. 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:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
limited data
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Stain: Albino rat, strain not specified.
- Age at study initiation: young
Route of administration:
oral: gavage
Vehicle:
not specified
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
3 x sex x dose
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, histopathology
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed
Clinical signs:
Dyspnoea, exophthalmoses, ruffled fur, and curved body position were seen, being common symptoms in acute toxicity testing. The animals recovered within 11 days
Gross pathology:
At autopsy, no deviations from normal morphology were found.
Interpretation of results:
not classified
Remarks:
Migrated information according to the CLP regulation Criteria used for interpretation of results: EU
Conclusions:
LD50 > 5000 mg/kg bw.
Executive summary:

Method

The exploratory (approximate) acute oral LD50 for test substance was investigated by administering a single dose of 5000 mg/kg bw by gavage to the young adult albino rats.

Results

LD50 > 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The study is supported by studies on a similar substance and in agreement with the results for all category members (see Category Justification Report attached to the section 13).

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:
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:
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 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: 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.
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

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: The test procedure cannot be subsumed under a testing guideline, nevertheless are scientifically acceptable.
Principles of method if other than guideline:
Acute percutaneous toxicity test.
The acute dermal toxicity of the test item was investigated in male rats, in a 40 % of aqueous gum tragacanth. 12.5 ml of the substance was spreaded dermally and covered with an aluminum foil. After the exposure time of 24 hours, mortalities, signs of toxicity and dermal toxicity were observed.
GLP compliance:
no
Remarks:
Pre GLP.
Species:
rat
Strain:
other: CFY
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 229 - 249 g.
Type of coverage:
occlusive
Vehicle:
other: aqueous gum tragacanth (0.5 %)
Details on dermal exposure:
TEST CONCENTRATION
- Dose concentration: 12.5 ml/kg at 40 % of substance.

TEST SITE
- Area of exposure: dorso-lumbar region, 10 % of the total body surface.
- Hair removing method: electric clippers. No shaving or chemical depilation.
- Day of the preparation: one day prior to treatment.
- Type of wrap if used: with "Sleek" waterproof plaster, firmly round the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing with warm diluted soap solution (40-50 °C), rinsing in clean warm water and blotting dry with absorbent paper.
Duration of exposure:
24 hours.
Doses:
0 and 5000 mg/l.
No. of animals per sex per dose:
5 males per dose.
Control animals:
yes, concurrent no treatment
Details on study design:
- Duration of observation period following administration: 14 days.
- Observations: daily, for signs of of dermal irritation, according to the scoring system. All animals were sacrificed terminally and examined macroscopically in an attempt to identify any target organs.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
No mortalities were found.
Clinical signs:
No signs of toxicity were observed.
Body weight:
Slightly depressed bodyweight gains were observed during the first week of treatment, but returned to normaI during the second week , compared with controls.
Gross pathology:
Normal.
Other findings:
No dermal reactions were observed.

Results

Sex Dosage level Body weight (g) at Mortality
Male (g/kg) Dosing 1 week 2 weeks
0 249 327 382 0/5
5 243 270 318 0/5
Interpretation of results:
not classified
Remarks:
Migrated information according to the CLP regulation Criteria used for interpretation of results: EU
Conclusions:
LD50 (percutaneous) > 5000 mg/l, non toxic.
Executive summary:

Method

The acute dermal toxicity of the test item was investigated in male rats, in a 40 % of aqueous gum tragacanth. 12.5 ml of the substance was spreaded dermally and covered with an aluminum foil. After the exposure time of 24 hours, mortalities, signs of toxicity and dermal toxicity were observed.

Results

The percutaneous LD50 was > 5000 mg/l, therefore the test item could be considered non toxic.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Additional information

The acute oral toxicity of the substance under registration was investigated in male rats, undiluted and diluted in DMSO. The substance was administered orally (gavage) at dose from 1.3 ml/100g to 1.50 ml/100 g. The LD50 was > 5000 mg/l, therefore the test item could be considered non toxic. The reliability of the study has been set as 4 because only a summary is available.

In order to confirm the outcomes on the substance under registration, the results for the analogous substances dihydroxyethylamino disulphonated sodium salt and sodium/potassium salt (CAS 4193-55-9 and CAS 70942-01-7, respectively) were considered.

No mortality was observed up to the dose of 5000 mg/kg bw in rat, when the CAS 4193-55-9 was administered them (Ciba-Geigy Ltd., 1987) and a further good GLP study for acute oral toxicity on rat was reported for the analogous dihydroxyethyl derivative sodium/potassium salt (CAS 70942-01-7) (Ciba Geigy Ltd., 1979), performed at 2200 mg/Kg bw with no effect (Ciba-Geigy Ltd., 1979).

The substances CAS 27344-06-5 and CAS 4193-55-9/CAS 70942-01-7 differ in the fact that the substitution on the triazino moiety is a carbamoyl/hydroxyethyl for the substance under registration and a diyhdroxyethyl for both the two analogous. The metabolic liver simulation indicates practically no metabolism for CAS 27344-06-5, while the monohydroxyethylamino metabolite is indicated for the substances included in the subgroup 3a, as CAS 4193-55-9 and CAS 70942-01-7; furthermore, the substances have a Tanimoto similarity greater than 80 %, very similar molecular weight (1014 vs. 961/977 dalton, respectively), very similar thermal behaviour (decomposition at 370 °C and 300/237 °C, respectively), very similar estimated log Kow (-4.11 vs -3.5 for both the analogous) and very high solubilities (57.4 g/l vs. 48.2/13.45 g/l, respectively).

Within the whole category, ten over fourteen registered substances were tested and none of the existing tests arisen any concern for acute oral toxicity.

The acute dermal toxicity of the substance under registration was investigated in male rats, in a 40 % of aqueous gum tragacanth. 12.5 ml of the substance was dermally spreaded and covered with an aluminium foil. After the exposure time of 24 hours, no mortalities or signs of toxicity were observed, thus the percutaneous LD50 was greater than 5000 mg/l (Kynoch R. and Lloyd K., 19875). The result is supported by a other two studies, for which only a summaries are available (Goldman et al., 1975 and Benz et al., 1972).

Skin adsorption was 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, estimation with OECD Toolbox of the dermal metabolism was performed in order to verify if breakdown products may be formed. Results are negative for all 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, 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, on the substance under registration.

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 5000 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).