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Diss Factsheets
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EC number: - | CAS number: -
- 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:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study. Expert statement based on all available data on toxicokinetics for the substance registered.
Data source
Reference
- Reference Type:
- other: expert statement
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guideline
- Qualifier:
- no guideline required
- Principles of method if other than guideline:
- The Toxicokinetic Assessment is meant to fulfil the requirement as defined in the REGULATION (EC) No 1907/2006 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 18 December 2006 requests in Annex VIII, point 8.8.1:
"Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information." - GLP compliance:
- no
Test material
- Reference substance name:
- bis[2-hydroxy-N,N-bis(2-hydroxyethyl)ethanaminium] 7-{[4-(4-{[2-(cyanoamino)-4-hydroxy-6-oxo-1,6-dihydropyrimidin-5-yl]diazenyl}benzamido)-3-methoxyphenyl]diazenyl}naphthalene-1,3-disulfonate
- Cas Number:
- 115811-45-5
- Molecular formula:
- C29H19N9O10S2.2C6H16NO3
- IUPAC Name:
- bis[2-hydroxy-N,N-bis(2-hydroxyethyl)ethanaminium] 7-{[4-(4-{[2-(cyanoamino)-4-hydroxy-6-oxo-1,6-dihydropyrimidin-5-yl]diazenyl}benzamido)-3-methoxyphenyl]diazenyl}naphthalene-1,3-disulfonate
- Test material form:
- solid
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 shall be 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 | RCC Ltd. | 632013 |
Vapour pressure | RCC Ltd. | 632035 |
Partition coefficient n-octanol / water | RCC Ltd. | 632068 |
Water solubility | RCC Ltd. | 632057 |
Particle size distribution | RCC Ltd. | 632125 |
Hydrolysis at different pH | RCC Ltd. | 632103 |
Acute oral toxicity study in rats | RCC Ltd. | 632136 |
Acute dermal toxicity study in rats | RCC Ltd. | 632147 |
Acute skin irritation study in rabbits | RCC Ltd. | 632158 |
Acute eye irritation study in rabbits | RCC Ltd. | 632160 |
Skin sensitisation test (GPMT) | RCC Ltd. | 632171 |
28-day oral toxicity study in rats | RCC Ltd. | 632182 |
3 Discussion
3.1 Physico-chemical properties
The substance is a solid with high water solubility (>176 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. The estimated low log POW indicates a low potential for accumulation in fatty tissues but also a certain polarity of the substance. Therefore, only limited enteral resorption of the test item may be assumed.
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.
However, deep yellow discoloration of the urine, slight changes in several hematological and biochemical parameters as well as higher kidney weights and coloration of the gastrointestinal tract were noted in the 28 day subacute toxicity study. All these findings were observed at dose levels of 200 and/or 1000 mg/kg.
These findings give rise to the assumption that the test item 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, yellow discoloration of the skin at the application site was evident in all animals after the removal of the dressing on test day 2 and persisted until study termination (day 15). This clearly shows that the substance at least adsorbed in the upper part of the skin but gives no indication on dermal absorption.
The substance has also 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, neither caused it systemic effects in the treated animals.
The sensitizing potential of the substance has been investigated by a guinea pig maximisation test. The test item was not considered to be a skin sensitizer when tested up to the highest applicable concentration.
Using the available data, no clear statement on dermal bioavailability can be made.
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 point of >220°C and the very low vapour pressure of 2×10-22Pa 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 0.5 to >100 µm with a mass median diameter (MMD) of 11.5 µm. As approximately 25% of the particles have a size smaller than 4 µm, dust of the substance may be bioavailable via inhalation. However, the registration substance is of low toxicity after acute and repeated oral application.
3.3 Distribution in tissues
The subacute repeated dose study on rats revealed yellow of the urine after oral application of the test item. It is therefore highly likely 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.
No direct plasma measurements have been performed in either toxicity study.
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 of the substance 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, orange discoloration of feces and deep yellow discoloration of urine were noted in the 200 and 1000 mg/kg bw/day study groups.
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.
No other signs of substance resorption or excretion were seen in any available toxicity study.
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, although adsorption of the dyestuff was noted in the acute dermal toxicity study. 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 dark yellow 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.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): low bioaccumulation potential based on study results
Based on the available data, there is no indication of critical bioaccumulation potential of the registration substance. - Executive summary:
1 Introduction
The substance is a dyeintended 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 shall be 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
RCC Ltd.
632013
Vapour pressure
RCC Ltd.
632035
Partition coefficient n-octanol / water
RCC Ltd.
632068
Water solubility
RCC Ltd.
632057
Particle size distribution
RCC Ltd.
632125
Hydrolysis at different pH
RCC Ltd.
632103
Acute oral toxicity study in rats
RCC Ltd.
632136
Acute dermal toxicity study in rats
RCC Ltd.
632147
Acute skin irritation study in rabbits
RCC Ltd.
632158
Acute eye irritation study in rabbits
RCC Ltd.
632160
Skin sensitisation test (GPMT)
RCC Ltd.
632171
28-day oral toxicity study in rats
RCC Ltd.
632182
3 Discussion
3.1 Physico-chemical properties
The substance is a solid with high water solubility (>176 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. The estimated low log POWindicates a low potential for accumulation in fatty tissues but also a certain polarity of the substance. Therefore, only limited enteral resorption of the test item may be assumed.
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.
However, deep yellow discoloration of the urine, slight changes in several hematological and biochemical parameters as well as higher kidney weights and coloration of the gastrointestinal tract were noted in the 28 day subacute toxicity study. All these findings were observed at dose levels of 200 and/or 1000 mg/kg.
These findings give rise to the assumption that the test item 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, yellow discoloration of the skin at the application site was evident in all animals after the removal of the dressing on test day 2 and persisted until study termination (day 15). This clearly shows that the substance at least adsorbed in the upper part of the skin but gives no indication on dermal absorption.
The substance has also 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, neither caused it systemic effects in the treated animals.
The sensitizing potential of the substance has been investigated by a guinea pig maximisation test. The test item was not considered to be a skin sensitizer when tested up to the highest applicable concentration.
Using the available data, no clear statement on dermal bioavailability can be made.
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 point of >220°C and the very low vapour pressure of 2×10-22Pa 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 0.5 to >100 µm with a mass median diameter (MMD) of 11.5 µm. As approximately 25% of the particles have a size smaller than 4 µm, dust of the substance may be bioavailable via inhalation. However, the registration substance is of low toxicity after acute and repeated oral application.
3.3 Distribution in tissues
The subacute repeated dose study on rats revealed yellow of the urine after oral application of the test item. It is therefore highly likely 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.
No direct plasma measurements have been performed in either toxicity study.
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 of the substance 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, orange discoloration of feces and deep yellow discoloration of urine were noted in the 200 and 1000 mg/kg bw/day study groups.
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.
No other signs of substance resorption or excretion were seen in any available toxicity study.
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, although adsorption of the dyestuff was noted in the acute dermal toxicity study. 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 dark yellow 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.
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.