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Description of key information

Acute toxicity of the test item has been investigated in female SPF-Wistar rats (10 animals per dose group). The animals received 4000, 6300, 10000 or 15000 mg test item / kg bw by gavage (12.5% suspension in sesame oil). The post observation period was 7 days. The mortality was 0/10, 1/10, 9/10 and 10/10 in the 4000, 6300, 10000 or 15000 mg / kg bw dose group. The LD50 was calculated to be 8252 mg/kg bw. Animals which died showed imbalance, accelerated respiration, prone position and paralysis of the limbs. No pathologic findings were observed at necropsy.

The study used as source investigated C.I. Pigment Yellow 1. The study results of the source compound were considered applicable to the target compound and were used for classification and labelling acc. to REGULATION (EC) No 1272/2008. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13 or find a link in cross reference “assessment report”.

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:
1971
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)
Deviations:
no
GLP compliance:
no
Remarks:
study was performed previous to GLP implementation
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: in house breeding, SPF rats
- Weight at study initiation: mean: 104 g (84-118g)
- Fasting period before study: yes, 16 hours
- Diet: Standard ALTROMIN R (Altromin GmbH, Lage/Lippe, Germany)
- Water: tap water
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 12.5%

- the highest concentration (15000 mg/kg bw) was applied in two portions à 7500 mg/kg bw within one hour

Doses:
4000, 6300, 10000, 15000 mg/kg bw
No. of animals per sex per dose:
10 females
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data, but necropsy of animals which died
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
8 285 mg/kg bw
Based on:
test mat.
Mortality:
4000 mg/kg bw: 0/10
6300 mg/kg bw: 1/10
10000 mg/kg bw: 9/10
15000 mg/kg bw: 10/10

the animals died within 1.5 and 24 hours after application
Clinical signs:
clinical signs of animals which died:
- imbalance, accelerated respiration, prone position, paralysis of the limbs
- the pigment was excreted via faeces
Gross pathology:
- no macroscopic anomalies in the animals
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Single application of the test item to Wistar rats by gavage resulted in an LD50 of 8252 mg/kg bw. The test item has not to be classified for acute oral toxicity.
Executive summary:

Acute toxicity of the test item has been investigated in female SPF-Wistar rats (10 animals per dose group). The animals received 4000, 6300, 10000 or 15000 mg test item / kg bw by gavage (12.5% suspension in sesame oil). The post observation period was 7 days. The mortality was 0/10, 1/10, 9/10 and 10/10 in the 4000, 6300, 10000 or 15000 mg / kg bw dose group. The LD50 was calculated to be 8252 mg/kg bw. Animals which died showed imbalance, accelerated respiration, prone position and paralysis of the limbs. No pathologic findings were observed at necropsy.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

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 07 DEC 2011 to 21 DEC 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 402) and according to GLP.
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:
Five male and five female Wistar (RccHan:WIST) strain rats.
On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals weighed at least 200g, and were eight to twelve weeks of age. The weight variation did not exceed ±20% of the mean weight for each sex.

The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24 Hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
The appropriate amount of test item, mixed with arachis oil BP, was applied as evenly as possible to an area of shaved skin (approximately 10% of the total body surface area).
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 Male
5 Female
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Frequency of observations: first day: 4 times, thereafter once daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, dermal reactions
Statistics:
No statistical analysis was performed.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no animal died within the observation period
Mortality:
There were no deaths.

Clinical signs:
There were no signs of systemic toxicity.
Body weight:
Animals showed expected gains in body weight over the study period except for one female which showed expected gain in body weight during the first week but slight body weight loss during the second week.

Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Dermal Reactions

Yellow coloured staining was noted at the test sites of all animals during the study. The staining prevented accurate evaluation of erythema in all animals one day after dosing.
Very slight erythema was noted at the test site of one female five to eight days after dosing. Crust formation and small superficial scattered scabs were also noted at this site. There were no signs of dermal irritation noted in the remaining animals.
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Executive summary:

Introduction.  The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat. The method was designed to be compatible with the following:


OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)


Method B3 Acute Toxicity (Dermal) of CommissionRegulation (EC) No. 440/2008


Method.


A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.


 


Mortality. 


There were no deaths.


 


Clinical Observations. 


There were no signs of systemic toxicity.


 


Dermal Irritation. 


Very slight erythema was noted at the test site of one female. Crust formation and small superficial scattered scabs were also noted at this site. No other signs of dermal irritation were noted. 


 


Body weight. 


Animals showed expected gains in body weight over the study period except for one female which showed expected gain in body weight during the first week but slight body weight loss during the second week.


 


Necropsy. 


No abnormalities were noted at necropsy.


 


Conclusion.


The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 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:
For details on endpoint specific justification please see read-across report in section 13 or find a link in cross-reference “assessment report”.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
assessment report
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no animal died within the observation period
Remarks:
The reported value refers to the source substance and was not converted to the target substance since (a) no adverse effects were observed and (b) the difference of the molecular weights of the target and the source substance is small (less than 20%).
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Executive summary:

The study used as source investigated C.I. Pigment Yellow 1. The study results of the source compound were considered applicable to the target compound and were used for classification and labelling acc. to REGULATION (EC) No 1272/2008. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13 or find a link in cross reference “assessment report”.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification

No classification

The test item and a close structural analogues did not cause adverse effects after oral and dermal exposures.