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Administrative data

Description of key information

Oral:

LD50 (Pigment Orange 34, nano form) >15000 mg/kg

LD50 (strucrue analogue Pigment Orange 13, nano form) >2100 mg/kg

Inhalation:

Waiving

 

Dermal:

LD50 (strucrue analogue Pigment Orange 38, nano form) >2000 mg/kg

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:
key study
Study period:
From 16 Mar 1977 to 30 Mar 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic data given, comparable to guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was conducted
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 97-107 g
- Fasting period before study: 16 h before and 2 h after dosing
- Diet (ad libitum): Altromin 1324 (Altromin, Lage/Lippe, Germany)
- Water (ad libitum): tap water


Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Doses:
15000 mg/kg bw as 25% suspension in sesame oil
No. of animals per sex per dose:
10 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations performed, but not stated in detail; weighing was performed weekly
- Necropsy of survivors performed: yes (macroscopic examination)
Statistics:
not performed
Sex:
female
Dose descriptor:
LD50
Effect level:
> 15 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no animal died after gavage of the highest applicable dose
Mortality:
no deaths
Clinical signs:
After dosing the animals showed ruffled fur and crouched posture
Body weight:
no treatment-related effects
Gross pathology:
no treatment-related effects
Other findings:
The coloured test item was excreted in faeces
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the LD50 was > 15000 mg/kg bw in female rats.
Executive summary:

Female Wistar-rats were subjected to test acute oral toxicity. The test substance was administered by gavage in doses of 15000 mg/kg bw. After dosing the animals showed ruffled fur and crouched posture. No animal died during the 14 day observation period, resulting in a LD50 > 15000 mg/kg bw. Necroscopy revealed no macroscopic organ alterations.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 30 Oct 1980 to 13 Nov 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic data given, comparable to guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
no (GLP was not compulsory at the time the study was conducted)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200-210 g
- Fasting period before study: 16 h before and 2 h after dosing
- Housing: in groups
- Diet (ad libitum): Altromin 1324 (Altromin, Lage/Lippe, Germany)
- Water (ad libitum): tap water
Route of administration:
oral: gavage
Vehicle:
water
Doses:
5000 mg/kg as 25% aqueous suspension
No. of animals per sex per dose:
10 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations performed, but not stated in detail; weighing was performed weekly
- Necropsy of survivors performed: yes (macroscopic examination)
Statistics:
not performed
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 100 mg/kg bw
Based on:
other: submission substance
Remarks on result:
other: The test item contained 42% of the submission substance, i.e. 5000 mg test item/kg bw applied correspond to 2100 mg submission substance/kg bw. resulting in a LD50 of >2100 mg/kg bw.
Mortality:
no deaths
Clinical signs:
no treatment-related effects
Body weight:
no treatment-related effects
Gross pathology:
no treatment-related effects
Other findings:
no treatment-related effects

No signs of intoxication were observed, macroscopic examination revealed no effects

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the LD50 was > 5000 mg test item/kg bw (>2100 mg submission substance/kg bw).
Executive summary:

Female Wistar-rats were subjected to test acute oral toxicity. The test substance was administered by gavage in doses of 5000 mg/kg bw.. No animal died during the 14 day observation period, resulting in a LD50 >5000 mg test item/kg bw, corresponding to a LD50 >2100 mg/kg bw submission substance. No further toxic effects were observed.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please refer to attached read across justification document (Chapter 13).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to attached read across document (Chapter 13).

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to attached read across justification document (Chapter 13).

4. DATA MATRIX
Please refer to attached read across justification document (Chapter 13).
Reason / purpose for cross-reference:
read-across source
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 100 mg/kg bw
Based on:
other: submission substance
Remarks on result:
other: The test item contained 42% of the submission substance, i.e. 5000 mg test item/kg bw applied correspond to 2100 mg submission substance/kg bw. resulting in a LD50 of >2100 mg/kg bw.
Mortality:
no deaths
Clinical signs:
no treatment-related effects
Body weight:
no treatment-related effects
Gross pathology:
no treatment-related effects
Other findings:
no treatment-related effects

No signs of intoxication were observed, macroscopic examination revealed no effects

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the LD50 was > 5000 mg test item/kg bw (>2100 mg submission substance/kg bw).
Executive summary:

Female Wistar-rats were subjected to test acute oral toxicity. The test substance was administered by gavage in doses of 5000 mg/kg bw.. No animal died during the 14 day observation period, resulting in a LD50 >5000 mg test item/kg bw, corresponding to a LD50 >2100 mg/kg bw submission substance. No further toxic effects were observed.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 29 MAR 2012 to 18 APR 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 402), GLP compliant study
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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
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: Charles River, Sulzfeld, Germany
- Age at study initiation: males: 10-12 weeks; females: 8-10 weeks
- Weight at study initiation: males: 220-238 g; females: 213-224 g
- Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1114)
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control,
microbiological controls at regular intervals)
- The animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 110811)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period (at least five days) under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Full barrier in an air-conditioned room
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour

Type of coverage:
semiocclusive
Vehicle:
other: Aqua ad injectionem
Details on dermal exposure:
Preparation of the Animals:
The animals were marked for individual identification by tail painting.
Approximately 24 hours before the test, the fur was removed from the dorsal area of the trunk using an electric clipper.
Care was taken to avoid abrading the skin, and only animals with healthy intact skin were used.
No less than 10% of the body surface was cleared for the application.
Prior to the application a detailed clinical observation was made of all animals.
Application:
In order to ensure good skin contact, the test item was moistened with the vehicle.
The test item was applied at a single dose, uniformly over an area which was approximately 10% of the total body surface.
The test item was held in contact with the skin by a dressing throughout a 24-hour period. The dressing consisted of
a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner.
At the end of the exposure period the residual test item was removed using aqua ad injectionem.
Duration of exposure:
24 h
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
Observation period:
All animals were observed for 14 days after dosing

Weight Assessment:
The animals were weighed on day 1 (prior to the application) and on days 8 and 15.

Clinical Examination:
careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes
and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded.
Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory,
autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Attention was
directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Pathology:
At the end of the observation period the surviving animals were sacrificed with an overdosage of pentobarbital injected
intraperitoneally (Narcoren®, Merial) at the dosage of approximately 8 mL/kg bw. All animals were subjected to gross necropsy.
All gross pathological changes were recorded and in case of findings the tissues were preserved for a possible histopathological evaluation.
The preserved tissues of which no histopathological evaluation was made will be discarded 3 months after the release
of the final report unless otherwise agreed upon with the sponsor.

Evaluation of Results:
Individual reactions of each animal were recorded at each time of observation.
Toxic response data were recorded by sex and dose level.
Nature, severity and duration of clinical observations were described.
The body weight changes were summarised in a tabular form.
Necropsy findings were described.

Statistics:
According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results,
a statistical evaluation of the results is not regarded as necessary.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed during the observation period
Mortality:
No mortality was observed
Clinical signs:
No treatment-related effects were observed.
Body weight:
A slight weight loss was recorded for 3 out of 5 female animals during the first week, but 4 out of 5 female animals
showed weight gain during the second week. 1 out of 5 females animals showed weight loss during the second week.
The effects on weight development might be secondary to the dressing, and toxicological relevance of this finding cannot clearly be concluded.
The male animals showed weight gain during the first and the second week of the observation.
Gross pathology:
No treatment-related effects were observed.
Other findings:
No erythema or oedema was observed.
Eschar was observed in one male on day 12. Since this temporary effect was limited to a single animal and
a very short time period and since examination was complicated by test item residues this phenomenon was
not assumed to be a sign of irritation.

Absolute Body Weights in g and Body Weight Gain in %

Dose: 2000 mg/kg body weight

Animal No. / Sex

g
Day 1

g
Day 8

g
Day 15

%
Day 1-15

21 / male

220

232

256

16

22 / male

231

253

285

23

23 / male

238

256

284

19

24 / male

230

239

259

13

25 / male

231

258

291

26

26 / female

216

224

220

2

27 / female

213

212

219

3

28 / female

233

230

238

2

29 / female

224

224

236

5

30 / female

219

218

220

0

LD50

Dose (Unit)

 

Number of Animals Investigated

Number of Intercurrent Deaths

LD50

2000 mg/kg bw

5 males

0

> 2000 mg/kg bw

2000mg/kg bw

5 females

0

> 2000 mg/kg bw

bw = body weight

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the present study, single dermal application of the test item to rats up to 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity or irritation. The dermal LD50 was determined to be > 2000 mg / kg body weight.
Executive summary:

An acute dermal toxicity test according to OECD guideline 402 has been performed with male and female Wistar rats (5 per sex per dose group). Animals were exposed for 24 hours to 2000 mg/kg bw to the test item under semi-occlusive conditions.

Results per Step

Sex

Dose
(mg/kg bw)

Number
of Animals

Number
of Intercurrent Deaths

male

2000

5

0

female

2000

5

0

Signs of toxicity related to dose level used, time of onset and duration:

No treatment-related effects were observed.

Effect on organs (related to dose level):

No treatment-related effects were observed.

Signs of irritation:

No erythema or oedema was observed.

Eschar was observed in one male on day 12. Since this temporary effect was limited to a single animal and a very short time period

and since examination was complicated by test item residues this phenomenon was not assumed to be a sign of irritation.

Conclusion

Under the conditions of the present study, single dermal application of the test item to rats up

to 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity or irritation.

The dermal LD50 was determined to be > 2000 mg / kg body weight.
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please refer to attached read across justification document (Chapter 13).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to attached read across document (Chapter 13).

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to attached read across justification document (Chapter 13).

4. DATA MATRIX
Please refer to attached read across justification document (Chapter 13).
Reason / purpose for cross-reference:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed during the observation period
Mortality:
No mortality was observed
Clinical signs:
No treatment-related effects were observed.
Body weight:
A slight weight loss was recorded for 3 out of 5 female animals during the first week, but 4 out of 5 female animals
showed weight gain during the second week. 1 out of 5 females animals showed weight loss during the second week.
The effects on weight development might be secondary to the dressing, and toxicological relevance of this finding cannot clearly be concluded.
The male animals showed weight gain during the first and the second week of the observation.
Gross pathology:
No treatment-related effects were observed.
Other findings:
No erythema or oedema was observed.
Eschar was observed in one male on day 12. Since this temporary effect was limited to a single animal and
a very short time period and since examination was complicated by test item residues this phenomenon was
not assumed to be a sign of irritation.

Absolute Body Weights in g and Body Weight Gain in %

Dose: 2000 mg/kg body weight

Animal No. / Sex

g
Day 1

g
Day 8

g
Day 15

%
Day 1-15

21 / male

220

232

256

16

22 / male

231

253

285

23

23 / male

238

256

284

19

24 / male

230

239

259

13

25 / male

231

258

291

26

26 / female

216

224

220

2

27 / female

213

212

219

3

28 / female

233

230

238

2

29 / female

224

224

236

5

30 / female

219

218

220

0

LD50

Dose (Unit)

 

Number of Animals Investigated

Number of Intercurrent Deaths

LD50

2000 mg/kg bw

5 males

0

> 2000 mg/kg bw

2000mg/kg bw

5 females

0

> 2000 mg/kg bw

bw = body weight

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the present study, single dermal application of the test item to rats up to 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity or irritation. The dermal LD50 was determined to be > 2000 mg / kg body weight.
Executive summary:

An acute dermal toxicity test according to OECD guideline 402 has been performed with male and female Wistar rats (5 per sex per dose group). Animals were exposed for 24 hours to 2000 mg/kg bw to the test item under semi-occlusive conditions.

Results per Step

Sex

Dose
(mg/kg bw)

Number
of Animals

Number
of Intercurrent Deaths

male

2000

5

0

female

2000

5

0

Signs of toxicity related to dose level used, time of onset and duration:

No treatment-related effects were observed.

Effect on organs (related to dose level):

No treatment-related effects were observed.

Signs of irritation:

No erythema or oedema was observed.

Eschar was observed in one male on day 12. Since this temporary effect was limited to a single animal and a very short time period

and since examination was complicated by test item residues this phenomenon was not assumed to be a sign of irritation.

Conclusion

Under the conditions of the present study, single dermal application of the test item to rats up

to 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity or irritation.

The dermal LD50 was determined to be > 2000 mg / kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification

No classification

Neither in studies witn oral nor dermal exposure any adverse effects were observed at / above limit doses