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EC number: 455-600-9 | CAS number: 790240-84-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- Type of information:
- other: expert statement
- Adequacy of study:
- key study
- Study period:
- 2010
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Expert statement comprising all available data on toxicokinetics
Data source
Reference
- Reference Type:
- other: expert statement
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
- Objective of study:
- other: Assessment of toxicokinetic behaviour
Test guideline
- Qualifier:
- no guideline required
- GLP compliance:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 455-600-9
- EC Name:
- -
- Cas Number:
- 790240-84-5
- Molecular formula:
- CAS formula: C34 H46 N12 O5 S . C3 H6 O3
- IUPAC Name:
- 2-hydroxypropanoic acid; 7-{[4,6-bis({[3-(diethylamino)propyl]amino})-1,3,5-triazin-2-yl]amino}-4-hydroxy-3-[(1E)-2-(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-5-yl)diazen-1-yl]naphthalene-2-sulfonic acid
Constituent 1
Results and discussion
Any other information on results incl. tables
1 Introduction
The substance is a dye intended to be registered under REACH Regulation (Regulation (EC) 1907/2006). Thus, an assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information is made.
2 Available studies with relevant information
A toxicokinetic study of the substanceis not available. The
following studies are available and were identified to contain relevant
information for the estimation of toxicokinetic properties:
Study type Test Laboratory Report
No. Melting point / boiling point RCC Ltd.
857550 Vapour pressure
RCC Ltd. 857552 Partition
coefficient n-octanol / water RCC
Ltd. 857555 Water
solubility RCC Ltd. 857555
Particle size distribution RCC
Ltd. 857560 Hydrolysis
at different pH RCC Ltd. 857581
Acute oral toxicity study in rats RCC
Ltd. 857561 Acute
dermal toxicity study in rats RCC
Ltd. 857562 Acute
skin irritation study in rabbits RCC
Ltd. 857563 Acute
eye irritation study in rabbits RCC
Ltd. 857564 Skin
sensitisation test (LLNA) RCC Ltd.
857565 28-day oral toxicity
study in rats RCC Ltd. 857566
3 Discussion
3.1 Physico-chemical properties
The substance is a solid with high water solubility (188.8 g/L at 20°C) and a low log POWof -3 (estimated from the respective solubility in water and in n-octanol). The substance is hydrolytically stable in water at pH 4-9 and at temperatures up to 50°C. Regarding the high water solubility it can be expected that the substance is likely to be bioavailable, at least by the oral route. However, the estimated low log POW indicates a certain polarity of the substance. Therefore, only limited enteral resorption of the test item may be assumed. The substance has a molecular weight of >700 g/mol, which may hamper enteral absorption and influence the mechanism of excretion, as substances with a molecular weight > approximately 400 g/mol are also excreted into the intestine via the bile.
3.2 Uptake
Available toxicity studies with the substance did not include plasma level measurements of the test substance. Therefore, there is no direct data to clarify the extent of systemic availability of the parent molecule.
3.2.1 Oral route
No evident systemic toxicity was observed in the acute oral study in rat. Also in a subacute 28 day oral gavage toxicity study, the substance was administered at dose levels of 50, 200 and 1000 mg/ kg body weight daily to rats. No mortality occurred during the study period. No test item related findings of toxicological relevance were noted at any dose level during week 1-3 of treatment. No changes in clinical appearance or behaviour were noted during the observation period that were considered to represent a clear sign of toxicity. The assessment of haematology and clinical biochemistry data indicated no changes of toxicological significance at termination of the treatment. Urinalysis, however, showed yellow-brown to red-brown discoloration of the urine in animals treated with 1000 mg/kg/day. This was considered to be a passive effect of the test item that was excreted via the kidneys. Therefore, it can be concluded that the substance is absorbed in the gastrointestinal tract after oral application but gives no indication of the amount absorbed.
3.2.2 Dermal route
In the acute dermal study in rats, no signs of systemic toxicity were observed. However, red discoloration of the skin, persisting until day 5-6 of the observation period was noted, indicating a low tendency for adsorption on skin. The substance has been tested for irritating effects on skin; it was considered not to be irritant, showing mean erythema and edema scores of 0 for all time points. The sensitizing potential of the substance has been investigated by a Local Lymph Node Assay (LLNA). It is not considered to be a skin sensitizer when tested up to the highest applicable concentration. Thus, bioavailability via the dermal route cannot be confirmed by the available data.
3.2.3 Inhalational route
No toxicity study after pulmonary uptake of the substance is available to date. When taking into account the determined melting range of 49-157°C and the very low vapour pressure of 5×10-24Pa at 25°C, evaporation of the substance into air is not likely to happen. Inhalation of dust may be another route of exposure via inhalation. Analysis of particle size distribution shows a range from 0.3 to 90 µm with a mass median diameter (MMD) of 3.9 µm. As half of the particles have a size smaller than 4 µm, a potential for respiration of the substance is clearly given. However, the registration substance is only manufactured and marketed as aqueous solution at a maximum of 20% (w/w). The solid form of the registration substance is generated solely for registration purposes.
3.3 Distribution in tissues Repeated dose studies on rats revealed yellow-brown to red-brown discoloration of the urine after oral application of the test item. It can therefore be concluded that the substance after uptake in the gastrointestinal tract, is transferred to the liver via the portal vein and then distributed in the body by blood circulation.
3.4 Metabolism
No specific metabolism studies have been performed with the substance. Based on the present data, it is not possible to reason about the metabolisation in the body.
3.5 Excretion
No test item or metabolite analysis was performed on urine or feces in either available study. In the subacute 28 day toxicity study, red discoloration of feces (in the 200 and 1000 mg/kg bw/day study groups) and yellow-brown to red-brown discoloration of the urine (in the 1000 mg/kg bw/day study group) were noted. Due to its stability and the absence of adverse effects of toxicological relevance regarding cage site observations and urinanalysis data it can be expected, according to the results of the present toxicity studies that, after oral exposure, the substance would not tend to accumulate in the organism, but to be excreted via urine and faeces. 4 Summary
Results from oral toxicity studies in rats up to 28 days indicated that there is systemic availability of the substance or metabolites at a high oral dosage. Direct evidence in the form of plasma data is not available. No evidence of dermal bioavailability is given, based on the available studies. The level of inhalation exposure is negligible due to the low vapour pressure, but inhalation of dust of the substance may be possible. Observation of yellow-brown to red-brown discoloration of the urine after repeated oral administration indirectly shows a certain distribution of the substance in the body. The estimated low log POWindicates a low potential for accumulation in fatty tissues. Excretion of the substance in the form of discoloration is observed in urine and feces; direct evidence in the form of analytical data is not available.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): low bioaccumulation potential based on study results
Results from oral toxicity studies in rats up to 28 days indicated that there is systemic availability of the substance or metabolites at a high oral dosage. Direct evidence in the form of plasma data is not available. No evidence of dermal bioavailability is given, based on the available studies. The level of inhalation exposure is negligible due to the low vapour pressure, but inhalation of dust of the substance may be possible.
Observation of yellow-brown to red-brown discoloration of the urine after repeated oral administration indirectly shows a certain distribution of the substance in the body. The estimated low log POW indicates a low potential for accumulation in fatty tissues.
Excretion of the substance in the form of discoloration is observed in urine and feces; direct evidence in the form of analytical data is not available. - Executive summary:
1 Introduction
The substance is a dye-intended to be registered under REACH Regulation (Regulation (EC) 1907/2006). Thus, an assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information is made.
2 Available studies with relevant information
A toxicokinetic study of the substance is not available.
The following studies are available and were identified to contain relevant information for the estimation of toxicokinetic properties:
Study type
Test Laboratory
Report No.
Melting point / boiling point
RCC Ltd.
857550
Vapour pressure
RCC Ltd.
857552
Partition coefficient n-octanol / water
RCC Ltd.
857555
Water solubility
RCC Ltd.
857555
Particle size distribution
RCC Ltd.
857560
Hydrolysis at different pH
RCC Ltd.
857581
Acute oral toxicity study in rats
RCC Ltd.
857561
Acute dermal toxicity study in rats
RCC Ltd.
857562
Acute skin irritation study in rabbits
RCC Ltd.
857563
Acute eye irritation study in rabbits
RCC Ltd.
857564
Skin sensitisation test (LLNA)
RCC Ltd.
857565
28-day oral toxicity study in rats
RCC Ltd.
857566
3 Discussion
3.1 Physico-chemical properties
The substance is a solid with high water solubility (188.8 g/L at 20°C) and a low log POW of -3 (estimated from the respective solubility in water and in n-octanol).
The substance is hydrolytically stable in water at pH 4-9 and at temperatures up to 50 °C.
Regarding the high water solubility it can be expected that the substance is likely to be bioavailable, at least by the oral route. However, the estimated low log POW indicates a certain polarity of the substance. Therefore, only limited enteral resorption of the test item may be assumed.
The substance has a molecular weight of >700 g/mol, which may hamper enteral absorption and influence the mechanism of excretion, as substances with a molecular weight > approximately 400 g/mol are also excreted into the intestine via the bile.
3.2 Uptake
Available toxicity studies with the substance did not include plasma level measurements of the test substance. Therefore, there is no direct data to clarify the extent of systemic availability of the parent molecule.
3.2.1 Oral route
No evident systemic toxicity was observed in the acute oral study in rat.
Also in a subacute 28 day oral gavage toxicity study, the substance was administered at dose levels of 50, 200 and 1000 mg/ kg body weight daily to rats. No mortality occurred during the study period. No test item related findings of toxicological relevance were noted at any dose level during week 1-3 of treatment. No changes in clinical appearance or behaviour were noted during the observation period that were considered to represent a clear sign of toxicity. The assessment of haematology and clinical biochemistry data indicated no changes of toxicological significance at termination of the treatment.
Urinalysis, however, showed yellow-brown to red-brown discoloration of the urine in animals treated with 1000 mg/kg/day. This was considered to be a passive effect of the test item that was excreted via the kidneys.
Therefore, it can be concluded that the test substance is absorbed in the gastrointestinal tract after oral application but gives no indication of the amount absorbed.
3.2.2 Dermal route
In the acute dermal study in rats, no signs of systemic toxicity were observed. However, red discoloration of the skin, persisting until day 5-6 of the observation period was noted, indicating a low tendency for adsorption on skin.
The substance has been tested for irritating effects on skin; it was considered not to be irritant, showing mean erythema and edema scores of 0 for all time points.
The sensitizing potential of the substance has been investigated by a Local Lymph Node Assay (LLNA). It is not considered to be a skin sensitizer when tested up to the highest applicable concentration.
Thus, bioavailability via the dermal route cannot be confirmed by the available data.
3.2.3 Inhalational route
No toxicity study after pulmonary uptake of the substance is available to date. When taking into account the determined melting range of 49-157°C and the very low vapour pressure of 5×10-24 Pa at 25°C, evaporation of the substance into air is not likely to happen.
Inhalation of dust may be another route of exposure via inhalation. Analysis of particle size distribution shows a range from 0.3 to 90 µm with a mass median diameter (MMD) of 3.9 µm. As half of the particles have a size smaller than 4 µm, a potential for respiration of the substance is clearly given.
3.3 Distribution in tissues
Repeated dose studies on rats revealed yellow-brown to red-brown discoloration of the urine after oral application of the test item. It can therefore be concluded that the substance after uptake in the gastrointestinal tract, is transferred to the liver via the portal vein and then distributed in the body by blood circulation.
3.4 Metabolism
No specific metabolism studies have been performed with the substance.
Based on the present data, it is not possible to reason about the metabolisation in the body.
3.5 Excretion
No test item or metabolite analysis was performed on urine or feces in either available study.
In the subacute 28-day toxicity study, red discoloration of feces (in the 200 and 1000 mg/kg bw/day study groups) and yellow-brown to red-brown discoloration of the urine (in the 1000 mg/kg bw/day study group) were noted.
Due to its stability and the absence of adverse effects of toxicological relevance regarding cage site observations and urinanalysis data it can be expected, according to the results of the present toxicity studies that, after oral exposure, the substance would not tend to accumulate in the organism, but to be excreted via urine and faeces.
4 Summary
Results from oral toxicity studies in rats up to 28 days indicated that there is systemic availability of the substance or metabolites at a high oral dosage. Direct evidence in the form of plasma data is not available. No evidence of dermal bioavailability is given, based on the available studies. The level of inhalation exposure is negligible due to the low vapour pressure, but inhalation of dust of the substance may be possible.
Observation ofyellow-brown to red-brown discoloration of the urine after repeated oral administration indirectly shows a certain distribution of the substance in the body. The estimated low log POW indicates a low potential for accumulation in fatty tissues.
Excretion of the substance in the form of discoloration is observed in urine and feces; direct evidence in the form of analytical data is not available.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.