Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 810-753-4 | CAS number: 1374639-78-7
- 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 in vitro / ex vivo
- Type of information:
- other: theoretical assessment
- Adequacy of study:
- key study
- Study period:
- not applicable
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Justification for type of information:
- This theoretical assessment was prepared, taking all currently available relevant information into account, based on the REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance.
- Objective of study:
- absorption
- distribution
- metabolism
- Qualifier:
- according to guideline
- Guideline:
- other: REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance
- Principles of method if other than guideline:
- REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance
- GLP compliance:
- yes
- Radiolabelling:
- no
- Details on study design:
- A toxicokinetic assessment was performed based on the available data of the substance.
- Preliminary studies:
- A toxicokinetic assessment was performed based on the available data of the substance.
- Details on absorption:
- The major routes by which a substance can enter the body are the gastrointestinal tract, the
lungs, and the skin. Since different parameters are relevant for absorption via the different
routes of exposure, the uptake via these three routes will be addressed individually.
After oral administration, in general, a compound needs to be dissolved before it can be taken
up from the gastrointestinal tract1. Since the water solubility of LEE011-A3 is very low
(0.246 mg/L at 20°C), the substance is expected to dissolve only to a limited extent into the
gastrointestinal fluids. Based on its molecular weight (534.7), uptake via passive diffusion
(passage of small water-soluble molecules through aqueous pores or carriage across
membranes with the bulk passage of water) is expected to be limited. LEE011-A3 has a
moderate partition coefficient (log Pow = 3.8 at pH 7). Considering also the poor water
solubility of the substance, passive diffusion (which allows crossing of epithelia) is unlikely
to occur, but uptake via micellular solubilisation may take place. Since no data are available
on the dissociation constant of LEE011-A3, it is unclear in which state (ionised or not
ionised) the substance will be present under physiological circumstances in the
gastrointestinal tract. Since it is generally thought that ionised substances do not readily
diffuse across biological membranes, the state of the substance might hamper its uptake.
For risk assessment purposes oral absorption of LEE011-A3 is set at 10%, based on its very
low water solubility, its high molecular weight and its moderate partition coefficient. The oral
toxicity data do not provide reasons to deviate from the proposed oral absorption factor.2
LEE011-A3 has a medium vapour pressure of 0.84 μPa at 20°C, which indicates that the
substance is not volatile and exposure via vapour will be limited. On the other hand, LEE011-
A3 is a powder. In humans, particles with aerodynamic diameters below 100 μm have the
potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the
thoracic region, and below 15 μm can reach the alveolar region. The median particle size of
LEE011-A3 is 7 μm, which is indicative that the compound have the potential to be inhaled
and could reach the alveolar region. Once inhaled, it will get in contact with nasopharyngeal
region and trigger sneezing and cough, which will enhance its elimination. Moreover, due to
its low water solubility, LEE011-A3 will not easily dissolve in the mucus lining the
respiratory tract and further absorption via this route is unlikely. However, since this
substance is a powder, it can accumulate in the respiratory tract and be cleared by the
mucocilliary mechanism and swallowed, reaching gastrointestinal tract. A small amount of
powder may be taken up by phagocytosis and transported to the blood or lymphatic system or
being engulfed by macrophages in the alveolar area. Furthermore, LEE011-A3 has a log Pow
3.8 at pH 7 and therefore may cross biological membranes. Taking these considerations
together it is concluded that for risk assessment purposes as a worst case the inhalation
absorption of LEE011-A3 should be set at 100%.2
LEE011-A3 is a powder with very low water solubility, it will only dissolve to a very small
extent into the surface moisture of the skin to allow uptake. Since the partition coefficient (log
Pow 3.8 at pH 7) and the molecular weight is 534.7, therefore the substance specific data do
not meet the criteria for 10% dermal absorption as given in Endpoint Specific Guidance
(MW>500 and log P outside the range -1 and 4). LEE011-A3 is neither skin irritating nor
corrosive. However, it is mildly skin sensitizer, indicating that there is absorption in some
extent. Considering also that it is generally accepted that dermal absorption is not higher than
oral absorption, a 10% skin absorption is considered for LEE011-A3 for risk assessment
purposes.2 - Details on distribution in tissues:
- Once absorbed, distribution of the substance throughout the body is expected to be moderate
based on its very low water solubility, moderate log Pow and high molecular weight.
Absorbed LEE011-A3 may be metabolized in the gastrointestinal tract or the liver. Excretion
can take place through bile and urine.3 Based on its moderate partition coefficient (log Pow =
3.8 at pH 7), LEE011-A3 might accumulate in adipose tissue (intracellular concentration may
be higher than the extracellular concentration) to some extent. However, based on its very low
water solubility and high molecular weight, the overall bioaccumulation potential of LEE011-
A3 is expected to be low. - Metabolites identified:
- not specified
- Conclusions:
- Based on the physical/chemical and toxicological properties of the substance, absorption
factors for this substance are derived to be 10% (oral), 100% (inhalation) and 10% (dermal)
for risk assessment purposes. The bioaccumulation potential is expected to be low.
Reference
Description of key information
Based on the physical/chemical and toxicological properties of the substance, absorption
factors for this substance are derived to be 10% (oral), 100% (inhalation) and 10% (dermal)
for risk assessment purposes. The bioaccumulation potential is expected to be low.
Key value for chemical safety assessment
Additional information
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.