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Administrative data

Description of key information

Not acutely harmful/toxic by oral route.

Not expected to be acutely harmful/toxic by dermal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
GLP compliance:
no
Remarks:
pre GLP
Test type:
standard acute method
Species:
rat
Sex:
male
Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
- Amount: 1.5 ml per 100 g bw
Doses:
5000 mg/kg
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
study cannot be used for classification
Conclusions:
LD50 > 5000 mg/kg
Executive summary:

The oral acute toxicity potential of the test item was assayed in rats. The substance was administrated by gavage, using DMSO as vechicle. Unfortunately, only a brief sheet of results is available, thus details about test procedures, results and test conditions are lacking. Therefore, a reliability cannot be assigned. The LD50 was indicated to be greater than 5000 mg/kg.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From January 17th to February 05, 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
The read across approach is detailed into the document attached to the IUCLID section 13.
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 22 March 1996
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: drinking water
Vehicle:
water
Remarks:
distilled water
Doses:
Single oral administration of 2000 mg/kg bw
No. of animals per sex per dose:
3 females
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily; clinical signs and bodyweight development were monitored during the study.
- Necropsy of survivors performed: yes; all animals were subjected to gross necropsy.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No deaths occurred.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Other findings:
No abnormalities were noted at necropsy.
Interpretation of results:
other: not classified, according to the CLP Regulation (EC) No 1272/2008
Conclusions:
LD50 (male and female) > 2000 mg/kg
Executive summary:

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley Crl:CD@ (SD) IGS BR rat. The method followed the OECD Guidelines No. 423 and EU Commission Directive 96/54/EEC Method B1 tris Acute Oral Toxicity. A group of three fasted females was treated with the test material at a dose level of 2000 mg/kg bodyweight. The treatment was followed by a group of three fasted animals of the other sex at the same dose level. The test material was administered orally as a dispersion in distilled water. No deaths ocurred; no signs of systemic toxicity were noted during the study. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.

Conclusion

LD50 (male and female) > 2000 mg/kg

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
The read across approach is detailed into the document attached to the IUCLID section 13.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany.
- Age at study initiation: young adult animals, approx. 10 weeks.
- Weight at study initiation: mean weight of 6 animals 177.7 g
- Fasting period before study: 16 hours before administration.
- Housing: Makrolon cage, type III, single housing with Bedding.
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum.
- Water: Tap water, ad libitum.
- Acclimation period: at least 5 days before.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: approx. 10 per hour.
- Photoperiod: 12 hrs dark / 12 hrs light
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5% solution in deionized water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 g/ml
- Amount of vehicle: 10 ml/kg bw
- Justification for choice of vehicle: a good homogeneity in water could not be guaranteed, because the test item preparation was a suspension. Therefore a 0.5 % solution of CMC in deionized water was applied.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter. A check for any dead or moribund animals was made at least once each workday.
- Necropsy: necropsy and gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations. No histological examinations were performed.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality occurred.
Clinical signs:
All animals of the first test group showed a red discoloration of feces from study day 1 until day 3 and red discolored urine from day 2 until day 3. In addition, two of these animals showed impaired general state and piloerection from hour 3 until hour 4.
All animals of the second test group showed a red discoloration of feces from study day 1 until day 2. In addition, two of these animals showed impaired general state and piloerection from hour 2 or 3 until hour 5.
Body weight:
The body weight increased in one animal of the first test group within the normal range throughout the study period. The other five animals of both test groups showed a normal body weight increase during the first observation week, but a stagnation of body weight during the second week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth.
Gross pathology:
There were no macroscopic pathological findings in all animals sacrificed at the end of the observation period.
Interpretation of results:
other: not classified, according to the CLP Regulation (EC) No 1272/2008
Conclusions:
LD50 (female) > 2000 mg/kg
Executive summary:

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Wistar rats. The method followed the OECD Guidelines No. 423 and EU Commission Directive 96/54/EEC Method B1 tris Acute Oral Toxicity. A group of three females was treated with the test material at a dose level of 2000 mg/kg bodyweight. The treatment was followed by a group of three fasted animals of the at the same dose level. The test material was administered orally as a suspension in 0.5 % solution of CMC in deionized water.

No mortality occurred. All animals of the first test group showed a red discoloration of feces from study day 1 until day 3 and red discolored urine from day 2 until day 3. In addition, two of these animals showed impaired general state and piloerection from hour 3 until hour 4. All animals of the second test group showed a red discoloration of feces from study day 1 until day 2. In addition, two of these animals showed impaired general state and piloerection from hour 2 or 3 until hour 5.

The body weight increased in one animal of the first test group within the normal range throughout the study period. The other five animals of both test groups showed a normal body weight increase during the first observation week, but a stagnation of body weight during the second week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth. There were no macroscopic pathological findings in all animals sacrificed at the end of the observation period.

Conclusion

LD50 (female) > 2000 mg/kg

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

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
GLP compliance:
no
Remarks:
pre GLP
Test type:
standard acute method
Species:
rat
Sex:
male
Vehicle:
DMSO
Details on dermal exposure:
Gauze pads were soakedwith test item and fixed on the depilated dorsal skin of rats.
The treated skin areas were not washed off afterwards.
Duration of exposure:
4 hours
Doses:
5000 mg/kg
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
study cannot be used for classification
Conclusions:
LD50 > 5000 mg/kg
Executive summary:

The dermal acute toxicity potential of the test item was assayed in rats. Gauze pads were soaked with test item and fixed on the depilated dorsal skin of rats. The bendage was removed after 4 hours and the treated skin areas were not washed off. Unfortunately, only a brief sheet of results is available, thus details about test procedures, results and test conditions are lacking. Therefore, a reliability cannot be assigned. The LD50 was indicated to be greater than 5000 mg/kg.

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

Additional information

ORAL ACUTE TOXICITY

The oral acute toxicity potential of Direct Orange 118 was assayed in rats. The substance was administrated by gavage, using DMSO as vechicle. Unfortunately, only a brief sheet of results is available, thus details about test procedures, results and test conditions are lacking. Therefore, a reliability cannot be assigned. The LD50 was indicated to be greater than 5000 mg/kg.

In order to confirm the oral acute toxicity potential of Direct Oragne 118, the available data on structural analogues Similar Substance 01 ans Similar Substance 02 have also been taken into account. The read across approach can be considered as reliable and suitable for the purpose; details and explanations are detailed in the report attached to the IUCLID section 13.

Similar Substance 01 was tested for acute oral toxicity following a single oral administration of 2000 mg/kg bw in rats. The method followed the OECD Guidelines No. 423 and EU Method B1 tris. No deaths ocurred and no signs of systemic toxicity were noted during the study. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.

Consistent results were obtained in a similar test conducted with Similar Substance 02 and following the same testing guidelines. The substance was administrated as a suspension in 0.5 % solution of CMC in deionized water. No mortality occurred. All animals of the first test group showed a red discoloration of feces from study day 1 until day 3 and red discolored urine from day 2 until day 3. In addition, two of these animals showed impaired general state and piloerection from hour 3 until hour 4. All animals of the second test group showed a red discoloration of feces from study day 1 until day 2. In addition, two of these animals showed impaired general state and piloerection from hour 2 or 3 until hour 5. The body weight increased in one animal of the first test group within the normal range throughout the study period. The other five animals of both test groups showed a normal body weight increase during the first observation week, but a stagnation of body weight during the second week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth. There were no macroscopic pathological findings in all animals sacrificed at the end of the observation period.

DERMAL ACUTE TOXICITY

The inhalation and the skin contact of Direct Orange 118 are unlikely.

According to the REACH Regulation, Annex VIII, Column 1 Standard information required, testing by the dermal route does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation).

Furthermore, in the Commission Regulation (EU) 2016/863, amending Annexes VII and VIII to REACH Regulation (EC) No 1907/2006, it is explained that recent scientific analysis of available data from in vivo a cute toxicity studies have shown that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. Therefore, testing those substances via the dermal route does not provide essential information for their safety assessment. The amendment is the consequence of studies and scientific debates. In particular, the 15th Meeting of Competent Authorities for REACH and CLP (CARACAL, 2014) concluded that an adaptation of point 8.5.3 of Annex VIII to REACH is justified in order to not require information on acute dermal toxicity for substances that have shown no toxicity in acute oral toxicity test up to the limit dose of 2000 mg/kg bw.

In the oral acute toxicity tests perfromed on structural analogues no signs of systemic toxicity were recorded, either in the repeated dose toxicity test by oral route. The skin sensitisation assay perfromed on Similar Substance 02 did not revealed test item-related systemic clinical signs. No reason of concern is raised on the basis of the skin/eye irritation investigations.

In addition, an old experimetn of low reliability is available; however, due to the fact that details on testing procedures and results are lacking, a reliability cannot be assiged. The dermal acute toxicity potential of Direct Orange 118 was assayed in rats. Gauze pads were soaked with test item and fixed on the depilated dorsal skin of rats. The bendage was removed after 4 hours and the treated skin areas were not washed off. The LD50 was indicated to be greater than 5000 mg/kg.

Justification for classification or non-classification

According to the CLP Regulation (EC) No 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 2000 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).

Dermal and inhalation exposure is unlikely. Regarding acute toxicity by inhalation route, no value is available; on the contrary, the acute dermal LD50 value was indicated to be greater than 5000 mg/kg in an old experiment of non-assignable reliability. In any case, no further investigation is required.

In conclusion, the test substance is non classified for oral acute toxicity, according to the CLP Regulation (EC) No 1272/2008.