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EC number: 279-505-5 | CAS number: 80584-91-4
- 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: evaluation
- Adequacy of study:
- weight of evidence
- Reliability:
- other: not applicable
Data source
Reference
- Reference Type:
- other company data
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
- Principles of method if other than guideline:
- no toxicokinetic study available. Toxicokinetic behaviour was evaluated based on the substance properties and toxicity data.
Test material
- Reference substance name:
- 6,6',6''-(1,3,5-triazine-2,4,6-triyltriimino)trihexanoic acid
- EC Number:
- 279-505-5
- EC Name:
- 6,6',6''-(1,3,5-triazine-2,4,6-triyltriimino)trihexanoic acid
- Cas Number:
- 80584-91-4
- Molecular formula:
- C21H36N6O6
- IUPAC Name:
- 6,6',6''-(1,3,5-triazine-2,4,6-triyltriimino)trihexanoic acid
Constituent 1
Results and discussion
Any other information on results incl. tables
6,6',6''-(1,3,5-triazine-2,4,6-triyltriimino)trihexanoic acid (TC)
(1) evaluation of toxicokinetic behaviour
TC is produced as a press cake consisting of approximately 50 % water. For the purpose of registration the substance is registered without water as it can be removed from the substance without be separated without affecting the stability of the substance or changing its composition. This is in accordance with REACH article 3 (1).
Basic properties of TC:
Molecular weight: 468.5
Vapour pressure (experimental): 3.06E-08 Pa at 20°C (IPO, 2013)
logP (experimental): 0.94 at pH2 at 20°C (Lewandowska, 2013)
water solubility: 1.3 mg/L at 25°C (Röttig, 2012)
pKa1 (for Acid COOH-groups):3.9 (at 20°C,Sobera-Madej, 2013)
pKa2 (for basic NH-groups): was not experimentally determinable.
Physico-chemical properties “… give information about the uptake/absorption of chemicals.
Absorption of a chemical into the blood stream will depend on its aqueous solubility, its log Kow and its ionisability (pKa). In addition, log Kow is a very important determinant of the partitioning of a solute within a biological membrane (i.e. an increase of log Kow results in a higher membrane permeability and in a reduced aqueous solubility). …” (ECHA GD 7a, 2008)
In general, log P values between -1 and 4 are favourable for absorption. Nevertheless, a substance with such a log P value can be poorly soluble in lipids and hence not readily absorbed when its water solubility is very low (ECHA GD 7c, 2008). This is the case for TC with log P of 0.94 but having very low water solubility of ca. 1 mg/L. Therefore, TC is not expected to be readily absorbed.
On the other hand TC contains structural components similar to fatty acids. Therefore another hypothesis is that TC is slowly resorbed but readily and completely metabolized. This also explains a lack of toxicity.
Dermal Absorption:
Dermal LD50 value > 2000 mg/kg body weight (Ciba-Geigy Ltd., 1995). No signs of acute dermal toxicity were observed in this study (OECD 402, exposure at 2000 mg/kg body weight to rats for 24 hours). The mean body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals.
Based on the result of Magnusson-Kligman Maximisation Test in Guinea Pigs, the substance is not considered a skin sensitizer in guinea pigs. Following topical application (challenge procedure) no positive responses were noted in any of the test or control group animals (Donald, 2001).
There are no signs of systemic toxicity based on these study results with dermal application of TC. Absence of systemic toxicity implies low dermal absorption.
It is concluded based on the absent dermal systemic toxicity, the low water solubility together with the relatively large molecular size that dermal systemic absorption is unlikely to be significant.
Gastrointestinal absorption
“Generally the smaller the molecule the more easily it may be taken up. Molecular weights below 500 are favourable for absorption; molecular weights above 1000 do not favour absorption.”. With the molecular weight of 468.5 TC is favourable for absorption. However further relevant properties like water solubility, lipophilicity and ionization must be taken into account.
TC is considered to occur in its ionised form while passing the gastrointestinal tract. The dissociation constant (for the acidic COOH-groups) for TC is 3.9 (at 20°C,Sobera-Madej, 2013) based on experimental results, which indicates low potential for absorption from the gastrointestinal tract, because ionised compounds are thought not to cross biological membranes (ECHA GD 7a, 2008, ECHA GD 7c, 2008).
Substances with log P values between -1 and 4 are favourable for absorption. Nevertheless, a substance with such a log P value can be poorly soluble in lipids and hence not readily absorbed when its water solubility is very low (ECHA GD 7c, 2008), which is the case for TC (with water solubility of ca. 1 mg/L).
This evidence of negligible absorption in the rat gastro-intestinal tract is supported together with other indicators - the relatively high molecular size. “Other mechanisms by which substances can be absorbed in the GI tract include the passage of small water-soluble molecules (molecular weight up to around 200) through aqueous pores or be carried through the epithelial barrier by the bulk passage of water.” (ECHA GD 7c, 2008) which is not the case for TC with M = 468.5 which is > 200.
Acute toxicity tests with rats revealed an LD50 of more than 5000 mg/kg bw. No mortality and no clinical signs were observed. No abnormalities were seen at terminal autopsy (Ciba-Geigy, 1980).
In 28 day and 90 day studies with Sprague-Dawley rats with repeated oral dosing of up to 1000 mg/kg bw (Martin et al. 2001 and Martin et al. 2002), there were no findings that could be attributed to administration of the test material at any dose level. The No Observed Effect Level (NOEL) was therefore considered to be 1000 mg kg\day.
As there were no signs of systemic toxicity present in the acute and repeated dose studies, one explanation may be that absorption is unlikely to occur and and the other is that TC is readily and completely metabolized and therefore no accumulation of TC in the body is expected.
Absorption via inhalation:
No studies are available with inhalative exposure of TC. Inhalative absorption of TC is considered not relevant because of the very, very low vapour pressure (3.06E-08 Pa). Partition to air is considered to be nearly zero. Exposure to solid particles of respirable sizes can be neglected taking into consideration that the substance is marketed as press cake with typically 15 - 50 % water.
Metabolism, Distribution and Excretion.
The substance is either
- not absorbed and not systemically available based on the physico-chemical data and test results presented and discussed above or
- readily and completely metabolized.
An accumulation of TC in the body is not expected.
Further toxicity studies:
All performed genetic toxicity studies were negative. No adverse effects were observed in eye irritation, skin irritation/corrosion studies.
References:
Ciba-Geigy Ltd., 1995, Acute dermal toxicity in the rat. Unpublished data.
Ciba-Geigy, 1980: Acute Oral Median Lethal Dose (LD50) in Rats, Toxicology Department, Geigy Pharmaceuticals, Stamford Lodge, Wilmslow, Unpublished data.
Donald, 2001: Magnusson-Kligman Maximisation Test in Guinea Pigs for Delayed Skin Sensitisation Potential. Inveresk Research,Tranent,EH33 2NE,Scotland. Unpublished data
ECHA GD part 7a, 2008: Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance, European Chemicals Agency, 2008
ECHA GD part 7c, 2008: Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance, European Chemicals Agency, 2008
IPO 2013a: Vapourpressure of TC. Unpublished data.
Lewandowska, 2013: TC 65 Commercial grade of about 65% tested Determination of 1-octanol/water partition coefficient at one pH value. Unpublished data.
Martin et al. 2001: 4WeekDoseRangeFinding Study in Rats with Administration by Gavage. Unpublished data.
Martin et al. 2002: 13 Week Toxicity Study Incorporating Neurotoxicity Screen in Rats with Administration by Gavage Followed by a 4 Week Recovery Period. Unpublished data.
Röttig, 2012: Results from Lab REACh, Metall-Chemie GmbH & Co.KG, Institut für Organische Chemie.Unpublished data.
Sobera-Madej, 2013: TC 65, commercial grade of about 65 % Physicochemical properties study Determination of the dissociation constant. Unpublished data.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): other: no accumulation potential based on available physico-chemical properties and available toxicity studies
- Executive summary:
The substance TC is either
- not absorbed and not systemically available based on the physico-chemical data and test results presented and discussed above or
- readily and completely metabolized.
An accumulation of TC in the body is not expected.
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