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Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) for Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No.: 911-358-0) was considered based on prediction studies and data available for the structurally and functionally similar read across chemicals. The LD50 value is >2000 mg/kg bw.Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone cannot be classified for acute oral toxicity. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
experimental data of read across substances
Justification for type of information:
Data for the target chemical is summarized based on the predicted data and structurally and functionally similar read across chemicals
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
WoE report is based on 6 acute oral toxicity studies as - WoE-2 to WoE-7.
Acute Oral toxicity test was carried out to study the effects of the test chemicals on rodents.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Specific details on test material used for the study:
- Name of test material : Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone
- Substance type : Organic
- Physical state : Solid
Species:
rat
Strain:
other: WoE-2 to WoE-5 - not specified; WoE-6 - not specified; WoE-7 - Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
WoE-2 to WoE-5 - not specified;
WoE-6 - not specified;
WoE-7 - TEST ANIMALS
- Source: National Institute of Biosciences, Pune
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 8 to 12 weeks old
- Weight at study initiation: Body weight range was 199.8 to 211.7 grams.
Body weights at the start : Mean: 204.54 g (= 100 %), Minimum : 199.8 g (- 2.32 %), Maximum : 211.7 g (+ 3.50 %)
- Fasting period before study: approximately 16 hours or more
- Housing: The rats were housed in polycarbonate cages.
- Diet (e.g. ad libitum): Rodent feed supplied ad libitum.
- Water (e.g. ad libitum):Water was provided ad libitum from individual bottles attached to the cages.
- Acclimation period: at least 5 days prior to administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 21.9 °C
- Humidity (%): 56.3% to 59.8%
- Air changes (per hr): at least 10 to 15 air changes/hour of 100% fresh air that had been passed through the HEPA filters.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room
IN-LIFE DATES: From: 08-06-2017 To:02-08-2017
Route of administration:
other: WoE-2 to WoE-5 - oral: unspecified; WoE-6 - oral: unspecified; WoE-7 - oral: gavage
Vehicle:
other: WoE-2 to WoE-5 - not specified; WoE-6 - not specified; WoE-7 - corn oil
Details on oral exposure:
WoE-2 to WoE-5 - not specified;
WoE-6 - not specified;
WoE-7 - VEHICLE
- Concentration in vehicle: 300 mg/kg and 2000 mg/kg
- Amount of vehicle (if gavage):10 ml/kg body weight
- Justification for choice of vehicle: Given test solution is soluble in corn oil.
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg
DOSAGE PREPARATION (if unusual): The test item was prepared by dilution of the test item in corn oil to obtain 30 mg/ml strength of solution. The formulation was prepared fresh on the day of dosing. The test item was administered in the dose volume of 10 ml/kg body weight.
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 300 mg/kg
Doses:
WoE-2 - 5500 mg/kg bw
WoE-3 - 4600 mg/kg bw
WoE-4 - 3500 mg/kg bw
WoE-5 - 3100 mg/kg bw
WoE-6 - 4350 mg/kg bw
WoE-7 - 300 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
WoE-2 to WoE-5 - not specified;
WoE-6 - not specified;
WoE-7 - Total - 12 (Females); Step I (300 mg/kg) - 3; Step II (300 mg/kg) - 3; Step I (2000 mg/kg) - 3; Step II (2000 mg/kg) - 3
Control animals:
not specified
Details on study design:
WoE-2 to WoE-5 - not specified;
WoE-6 - not specified;
WoE-7 - Duration of observation period following administration: 14 days
- Frequency of observations :Animals were observed for clinical signs, mortality and morbidity, until sacrifice.The clinical signs and mortality observations were conducted at immediately (0 to 5 minutes), 5, 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
- Weighing: Individual animal body weights were recorded, before fasting, prior to administration of the test item (fasting body weights), weekly thereafter and at termination on day 14. Weight changes were calculated and recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, were performed.
Statistics:
WoE-2 to WoE-5 - not specified;
WoE-6 - not specified;
WoE-7 - not specified;
Preliminary study:
WoE-2 to WoE-5 - not specified;
WoE-6 - not specified;
WoE-7 - not specified;
Sex:
not specified
Dose descriptor:
LD50
Effect level:
5 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Sex:
not specified
Dose descriptor:
LD50
Effect level:
4 600 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Sex:
not specified
Dose descriptor:
LD50
Effect level:
3 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Sex:
not specified
Dose descriptor:
LD50
Effect level:
3 100 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Sex:
not specified
Dose descriptor:
LD50
Effect level:
4 350 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
WoE-2 to WoE-5 - not specified;
WoE-6 - 50% mortality was observed
WoE-7 - No mortality was observed at 2000 mg/kg.
Clinical signs:
other: WoE-2 to WoE-5 - not specified; WoE-6 - not specified; WoE-7 - Group I Step I and II : At 300 mg/kg There was no signs of toxicity on day 2 after the dosing; coloured faces and diarrhoea with onset from 4 hours to day 1 after the dosing was observed. G
Gross pathology:
WoE-2 to WoE-5 - not specified;
WoE-6 - not specified;
WoE-7 - Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.
Other findings:
WoE-2 to WoE-5 - not specified;
WoE-6 - not specified;
WoE-7 - No data
Interpretation of results:
other: Not classified
Conclusions:
According to CLP regulation the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No.: 911-358-0) cannot be classified for acute oral toxicity, as the LD50 value is >2000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from database.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity:

In different studies, Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No.: 911-358-0) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone along with the studies available on its structurally and functionally similar read across substances. The predicted data using the Danish QSAR has also been considered. The studies are summarized as below –

Based on the QSAR prediction done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No.: 911-358-0). The LD50 values were estimated to be 5500, 4600, 3500, and 3100 mg/kg bw, with moderate prediction quality (0.5-0.75), when rats were treated via oral route.

The above prediction is supported with the data available for the structurally and functionally similar read across chemicals. The studies are summarized as below –

1. Acute oral toxicity study of test chemical was conducted in rat at the concentration of 4350 mg/kg bw. 50% mortality was observed at 5000 mg/kg bw. Therefore, LD50 was considered to be 4350 mg/kg bw, when rats were treated with test chemical via oral route.

2. In a acute oral toxicity study, 12 Sprague Dawley female rats treated with test chemical by oral gavage route at the concentration of 300 and 2000 mg/kg bw in 4 different steps. The dose of 300 mg/kg of test item was prepared by dilution of the test item in corn oil to obtain 30 mg/ml strength of solution. The formulation was prepared fresh on the day of dosing. The test item was administered in the dose volume of 10 ml/kg body weight. The dose of 2000 mg/kg of test item was administered undiluted. Female rats (taken from National Institute of Biosciences, Pune) of the age of approximately 8 to 12 weeks old were used and its weight were within ± 20% of the mean weight of any animal used for dosing. Body weight range was 199.8 to 211.7 grams. The rats were housed in polycarbonate cages.The animal room was independently provided with at least 10 to 15 air changes per hour of 100% fresh air that had been passed through the HEPA filters. Room temperature was maintained at 20.1 to 21.9° C and room humidity was maintained at 56.3% to 59.8%.An artificial light and dark cycle of 12 hours each was provided to the room. Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders. Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use. The single dose of test item was administered to fasted rats (approximately 16 hours or more) by oral intubation, using a ball-tipped intubation needle fitted onto a syringe of appropriate size. Initially, 3 female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg resulted in test item coloured faces and diarrhoea with onset from 4 hours to day 1 after the dosing and no mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, 3 female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg resulted in test item coloured faces and diarrhoea with onset from 4 hours to day 1 after the dosing and no mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional 3 female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in test item coloured faces with onset on day 1 after the dosing and no mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional 3 female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg resulted in test item coloured faces with onset on day 1 after the dosing and no mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. Therefore, LD50 value of the test compound was considered to be >2000 mg/kg bw, when Sprague Dawley female rats treated via oral gavage route.

Thus, based on the above summarised studies, Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No.: 911-358-0) and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone cannot be classified for acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and prediction, Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No.: 911-358-0) and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone cannot be classified for acute oral toxicity.