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EC number: 265-016-4 | CAS number: 64683-40-5
- 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
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics, other
- Type of information:
- other: expert statement
- Adequacy of study:
- key study
- Study period:
- 2017
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Objective of study:
- toxicokinetics
- Qualifier:
- according to guideline
- Guideline:
- other: according to ECHA Guidance R.7c, June 2017, v.3
- Type:
- absorption
- Results:
- estimated for risk assessement purposes: oral 30%; dermal 10%; inhalation 50%
- Conclusions:
- No bioaccumulation potential based on available data and a qualitative assessment accordind to ECHA Guidance R.7c, June 2017, v.3
Reference
Description of key information
1. Short description of key information
The toxicokinetics of the substance CAS 64683-40-5 / EC 265-016-4 has been assessed based on the physicochemical properties and available toxicological data and following the ECHA Guidance R.7c from June 2017 (version 3.0).
Although Direct Red 254 is an azo dye, its toxicity is low via the oral and dermal routes due to the high molecular weight, water solubility and electronegativity of Direct Red 254 in comparison to some other azo-dyes.
As a result of the assessment, it has been found thatthe substance is expected to be absorbed from the gastro-intestinal tract in some extent. The respiratory deposition is assessed to be low and the dermal absorption could occur on certain extent too.
Distribution in the body is expected to take place, mainlybased upon the water solubility.
Limited data were available for estimation on how this substance is metabolized in the human body.Based on the chemical structure it is known that the existing double bonds or –N=N- might react with strong acids (pH << 4) to give new structures.Reductive cleavage of the azo bond is considered to be a necessary metabolic reaction for these substances to exert their toxicity, as it releases some aromatic amines that are further converted to reactive electrophilic intermediates through metabolic activation. There are references that these dyes are reduced following oral administration and the released aromatic amines are absorbed into systemic circulation. Bioabsorption of the relatively smaller aromatic amine metabolites is expected to dominate over absorption of the intact parent dye.
From the biodegradability test results it was concluded that the substance isnot readily biodegradable. However, bioaccumulation is not expected, based on the log Kowand the calculated BCF values.
Based on the physicochemical properties of the substance one route of excretion (urine) was assessed as possible. Based on observations from a study conducted on an analogue substance, faeces are assessed too as route of excretion.
Key value for chemical safety assessment (proposal)
- Bioaccumulation potential: no
- Absorption rate oral (%): 30%
- Absorption rate dermal (%): 10%
- Absorption rate inhalation (%): 50%
2. Discussion
The assessment below is based on theECHA Guidance on information requirements and chemical safety assessment (Chapter R.7c: Endpoint specificguidance, June 2017, v. 3), for which physicochemical data may be used for a qualitative Toxicokinetic behaviour assessment. All data needed are part of the REACH registration dossier of the substance.
2.1 Absorption:
Absorption of CAS64683-40-5/ EC 265-016-4 was assessed based on physicochemical and available toxicological data. The substance is a solid with a molecular weight of ca. 826 and a water solubility of 191,000 mg/L. The octanol-water partition coefficient (log Kow) is -2.70.
These values of log Kowand molecular mass of the substance don’t suggest an absorption into the body.
(a) Oral/Gastro Intestinal (GI) absorption:
The compound is ionisable and highly soluble in water. According to its molecular weight and because of the log Kowvalue of -2.70 (not in the range -1 to 4), the compound should not be easily involved in a lipophilic micellular solubilisation and this fact doesn’t favour the oral absorption. No signs of toxicity appeared in acute oral toxicity. In a repeated dose toxicity study conducted with rats on an analogue substance, all findings in both sexes were considered to be of no toxicological significance, but suggest absorption of the substance. The compound is absorbed from the gastro-intestinal tract in a certain level. The considered value for Chemical Safety Assessment of oral absorption 30% is an estimated value calculated for this substance using Advanced Chemistry Development, Inc. (ACD/Labs).
(b) Respiratory absorption - Inhalation:
N-octanol/water partition coefficient and molecular weight of the substance don’t favour absorption. The substance is a solid and not volatile and it is not expected a high exposure by inhalation route. However, if some of the substance is inhaled, it can be expected to be absorbed, based on the high solubility. In practice, absorption is assumed to be low based on the physicochemical properties and the physical status (solid) with a particle size >100 μm. The considered value for Chemical Safety Assessment of inhalation absorption 50% is considered to better reflect the substance behaviour than the value of the ECHA Guidance proposed to be 100%.
(c) Dermal absorption:
This route of exposure is the most probable one.Based upon the fact that the substance is a solid with a molecular weight of 826 g/mole, log Kowof -2.70 and not showing skin irritation, sensitization and/or acute dermal toxicity, it might be expected that the substance is not absorbed by the skin. The dermal absorption degree is increased when the substance is dissolved in water. Having all this factors into account the dermal absorption is considered to be low. As the molecular mass is above 500 g/mole and the log Kowis outside the range (-1, 4), the value of 10% skin adsorption is chosen for Chemical Safety Assessment as default, like it is given in ECHA GuidanceChapter R.7c.
For the assessment of distribution, metabolism and excretion, physicochemical and available toxicological properties are also taken into account according to ECHA guidanceChapter R.7c.
2.2 Distribution:
Based upon the molecular weight ca. 826 g/mole, high water solubility of 191,000 mg/L and logKow-2.70, the distribution in the body is expected to take place slowly but in certain extent. This is further confirmed by findings (considered of no toxicological relevance) and observations from the toxicity study conducted on a structural analogue substance.
2.3 Metabolism and accumulation potential:
Metabolism
cannot be deduced from the data available. In the repeated dose toxicity
study conducted on an analogue substance no signs of toxicity were
observed.
Based on the chemical structure it is known that the existing double bonds -N=N- might react with strong acids (pH << 4) to give new structures. Reductive cleavage of the azo bond is considered to be a necessary metabolic reaction for these substances to exert their toxicity, as it releases some aromatic amines that are further converted to reactive electrophilic intermediates through metabolic activation.
There are references that these dyes are reduced following oral administration and the released aromatic amines are absorbed into systemic. Bio-absorption of the relatively smaller aromatic amine metabolites is expected to dominate over absorption of the intact parent dye.
Regarding bioaccumulation potential, the available data from biodegradation indicate that the substance is “not readily biodegradable”. However, the calculated Log BCF from regression-based method = 1.850 (BCF = 70.79 L/kg wet-wt), is well below the threshold value of 2000 L/kg for a PBT substance as indicated by the REACH Guidance on PBT assessment. Therefore, the substance is not expected to bio-accumulate in the body.
The relatively smaller aromatic amine metabolites are neither expected to bio-accumulate.
2.4 Excretion:
Based
on the high molecular weight, the urinary excretion of the parent
compound would not be expected. But, on the other side the high water
solubility,could favour this route of elimination. Excretion via the
saliva and sweat is considered less possible based on the log Kow value
( -2.70). Also
exfoliation should not be applicable. Excretion in the breast milk is
not considered to be the main route. Observations from the repeated dose
study conducted on a structural analogue substance show that the dye is
eliminated in the faeces of rats. This route of excretion is available
to reduce the substance in the body.
There are references that sulphonated azo dyes are poorly absorbed from the intestine after oral intake, but the substance will be degraded at the gastrointestinaI pH 1-4 and won’t be eliminated as such, but in the form of relatively smaller aromatic amine metabolites. The metabolites are absorbed, modified by the liver and excreted in the bile and urine.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 30
- Absorption rate - dermal (%):
- 10
- Absorption rate - inhalation (%):
- 50
Additional information
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