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Administrative data

Description of key information

Rat oral LD50 > 5000 mg/kg bw (OECD 401, analogue approach)
Rat inhalation LC50 > 1895 mg/m³ (OECD 403, analogue approach)
Rat dermal LD50 > 2000 mg/kg bw (OECD 402, analogue approach)

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:
21 Sep - 05 Oct 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif:RAif (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7 to 8 weeks
- Body weights at study initiation: males - 175 g; females - 176 g
- Fasting period before study: overnight
- Housing: in groups of 5 in Macrolon cages (type 3)
- Diet: rat food NAFAG No. 890 NAFAG Gossau SG, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Photoperiod: 12 hours light per day
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
400
Details on oral exposure:
VEHICLE
- Amount of vehicle: 20 mL/kg body weight
Doses:
5000 mg/kg body weight
No. of animals per sex per dose:
5 animals/sex
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: physical condition and rate of deaths were monitored throughout the whole observation period; body-weights were recorded immediately prior to dosing (control weights) and at 7 and 14 days
- Necropsy of survivors performed: yes; all animals were submitted to a necropsy, whenever they died, survivors at the end of the observation period
- Other examinations performed: gross examination
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occured.
Clinical signs:
Dyspnoea, exophthalmos, ruffled fur reported, diarrhoea and curved body position were observed. Nevertheless all symptoms are recovered within 9 days.
Body weight:
No significant differences reported.
Gross pathology:
No compound related gross organs changes were reported.

Signs and symptoms hrs 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
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Executive summary:

Method

The acute oral toxicity of the test compound in rats of both sexes was tested at the single concentration of 5000 mg/kg bw and observed over a period of 14 days.

Results

The LD50 is greater than 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
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:
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, therefore contains the same organic functional groups, but due to the sulphonation/salification degree it is less soluble. This property makes of Read Across substance 4404-43-7 a conservative representative because of the potential higher bioavailability. Justification for Read Across is reported in the endpoint summary and in the Category Justification Report attached in Section 13.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
particle size not specified
GLP compliance:
no
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 occurred during the study period.
Clinical signs:
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:
not classified
Remarks:
Migrated information . 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 valueclassification 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

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: see 'Remark'
Remarks:
GLP guideline study, tested with the source substance CAS 16470-24-9. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (Dec 2012)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
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 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:
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 signs after 7 observation days.
Body weight:
Mean body weight (g): Days 1, 8, 15
- males: 236.2, 265.2, 294.8
- females: 207.3, 214.0, 217.8
Gross pathology:
No findings noted.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
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
2 000 mg/kg bw

Additional information

There are no data available for the acute toxicity of CAS 12004488-68-5. In order to fulfil the standard information requirements, a read-across from structurally related substances was conducted.

The acute oral toxicity of the structural analogue substance CAS#16470-24-9 was assessed in study performed equivalently to OECD Guideline 401. Single oral gavage dosing of 5000 mg test substance per kg bodyweight in polyethylene glycol to five fasted male and female SPF rats caused no mortality. Dyspnoea, exophthalmos, ruffled fur reported, diarrhoea and curved body position were observed. Nevertheless all symptoms are recovered within 9 days. Thus, the acute oral LD50 in rats was found to be greater than 5000 mg/kg bw. 

 

An acute dermal toxicity (limit test) was performed with CAS#16470-24-9 according to OECD Guideline 402. 5 male and female Wistar rats were exposed to 2000 mg test substance /kg bodyweight for 24 hours on back skin under semiocclusive conditions. The observation period was 15 days. No deaths or changes in bodyweight gain or abnormalities in gross pathology were observed. Skin reactions are all recovered after 7 observation days. Based on the study results the acute dermal LD50 in rats was found to be greater than 2000 mg/kg bodyweight. 

 

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 has been performed. The result of a test performed on an analogous substance at the maximum allowed concentration of 1890 mg/m³ has been reported, where no effect is indicated. The analogous substance, part of the Stilbene Fluorescent Whitening 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 of Read Across substance 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 – inhalation 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.

Justification for classification or non-classification

Based on read-across from structurally similar substances, the available data on oral, inhalation and dermal toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.