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EC number: 615-064-0 | CAS number: 700874-87-9
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics, other
- Type of information:
- other: Assessment
- Adequacy of study:
- supporting study
- Study period:
- October 2017
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The assessment is conducted according to generally accepted scientific criteria (Ref:Guidance on Information Requirements and CSA). Uncertainty of the assessment mainly due to the limited amount of information available for supporting the evaluation.
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
- Qualifier:
- according to guideline
- Guideline:
- other: ECHA Guidance on Information Requirements and Chemical Safety Assessment_Chapter R.7c: Endpoint specific guidance
- Version / remarks:
Version 3.0 – June 2017- Executive summary:
No experimental studies of toxicokynetic are available therefore the toxicokinetic behaviour of MOVE3 is estimated basing on the physical and chemical properties and on relevant information deriving from other toxicological studies.
Basing on the physical and chemical properties of MOVE 3 the main route of human exposure is by inhalation. Respiratory absorption has been observed in rat but no sufficient data are available for estimating the absorption rate. Basing on the physical and chemical properties oral absorption following ingestion cannot be excluded but no sufficient data are available for estimating the absorption rate. Significant dermal absorption is expected to be prevented by the extreme volatility of the substance.
No sufficient data are available for estimating distribution rate and tissues affinity.
No sufficient data are available for predicting the metabolic changes and potential metabolites.
If absorbed, basing on its physical and chemical properties, excretion with exhaled air may be a significant excretion route. Urinary excretion may be favorited by the limited molecular weight of MOVE 3 but no sufficient data are available for confirming this hypothesis.
Reference
No experimental studies of toxicokynetic are available. The toxicokinetic behaviour of MOVE3 is assessed basing on the available relevant information:
Molecular weight: 232.02
Molecular structure features: Absence of ionizable moieties, absence of hydrolizable moieties.
Physical status: Liquid
Vapour pressure: 97000 Pa (20°C)
Water solubility: 2.4 - 6.2 mg/l
Exitisiting relevant toxicological studies: “Acute toxicity by inhalation on rat (limit test)”; “Combined repeated dose toxicity study and reproduction/developmental toxicity screening test by Inhlalation on rat”; “in vitro skin irritation (Reconstructed Human Epidermis Model Test)”; “Skin sensitization test in mouse (LLNA)”.
Log Kow > 2.58
ABSORPTION
Oral /GI absorption
No toxicity studies by oral routes are available therefore no information on the potential of oral absorption can be extrapolated from them.
Molecular weight below 500 are favourable for oral absorption.
No exact estimation of the lipophilicity is available.
In general, log Kow values between -1 and 4 are favourable for absorption, but even when Log Kow is in this range a substance can be poorly soluble in lipids and hence not readily absorbed when its water solubility is very low. The Log Kow of MOVE 3 is > 2.58 indicating it may fall in the favourable lipophilicity range. Nevertheless the water solubility of MOVE 3 is limited (2.4 - 6.2 mg/l ) suggesting that the absorption by passive diffusion could be reduced.
Absorption by micellular solubilisation may be of particular importance for highly lipophilic compounds (log Kow >4), particularly those that are poorly soluble in water (1 mg/l or less) that would otherwise be poorly absorbed. Being no exact value of log Kow available for MOVE 3, absorption by this mechanism cannot be excluded.
MOVE 3 is not not hydrolizable therefore hydrolisis of the molecule is not expected to occurr before a potential absorption.
In conclusion absorption by oral route is not excluded. No sufficient data are available for estimating the absorption rate.
Respiratory Absorption
The substance is highly volatile, therefore it is available for inhalation as vapour.
No exact estimation of the lipophilicity is available therefore absorption accross the respiratory tract epithelium by passive diffusion or absorption by micellular solubilisation cannot be excluded, even if passive diffusion is expected to be limited by the reduced water solubility.
Low water solubility enhances penetration to the lower respiratory tract.
Basing on physical-chemical properties, a certain absorption of MOVE 3 vapours through the respiratory system can be expected.
The potential of MOVE 3 to be absorbed by inhalation is confirmed by the results of the combined repeated dose toxicity study and reproduction/developmental toxicity screening test by Inhlalation on rat, where some signs of systemic absorption (increase in bile acids) have been observed in male rats following 29 days exposure at the highest dose.
No sufficient data are available for estimating the absorption rate.
MOVE 3 is not not hydrolizable therefore hydrolisis of the molecule is not expected to occurr before absorption.
Dermal absorption
Absorption of volatile liquids across the skin may be limited by the rate at which the liquid evaporates off the skin surface.
No exact Log Kow value is available therefore the capacity of MOVE 3 of penetrating into the stratum corneum cannot be definitively estimated.
However, the rate at which gasses and vapours distribute from the air into the stratum corneum will be offset by the rate at which evaporation occur therefore although a substance may readily partition into the stratum corneum, it may be too volatile to penetrate further. This can be the case for substances with vapour pressures above 100-10,000 Pa.
As MOVE 3 has a vapour pressure of 97000 Pa at 20°C, the volatilization rate is expected to prevent any significant absoption through the stratum corneum.
Moreover, even in case a certain amount of MOVE 3 would be able to penetrate throught the stratum corneoum the distribution from the stratum corneum to the epidermids may be too limited for inducing a significat absorption.
In fact, a substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis.
For substance having water solubility lower than 1 mg/l dermal uptake is likely to be low, while for substance with water solubility between 1-100 mg/l absorption is anticipated to be low to moderate.
As the water solubility of MOVE 3 is 2.4 - 6.2 mg/l, the distribution from the stratum corneum into the epidermis is expected to be limited.
MOVE 3 was observed to be not irritant and not corrosive in an in vitro skin irritation test with Reconstructed Human Epidermis and in a skins sensitization test on mouse. The potential of MOVE3 of inducing skin damage able to enhance dermal penetration can be excluded.
In conclusion MOVE 3 is not expected to be significantly absorbed through the skin.
DISTRIBUTION
No sufficient data are available for estimating distribution rate and tissues affinity.
The lack of target organ toxicity observed in the combined repeated dose toxicity study and reproduction/developmental toxicity screening test by Inhlalation prevent the identification of the organs of distribution, if any.
METABOLISM
No sufficient data are available for predicting the metabolic changes and potential metabolites.
EXCRETION
Characteristics favourable for urinary excretion are low molecular weight (below 300 in the rat), good water solubility, and ionization of the molecule at the pH of urine.
Urinary excretion of MOVE 3 appear to be not extremely favorable but it cannot be excluded.
Volatile liquids and volatile metabolites may be excreted as vapours in exhaled air.
Description of key information
No experimental studies of toxicokynetic are available therefore the toxicokinetic behaviour of MOVE3 is estimated basing on the physical and chemical properties and on relevant information deriving from other toxicological studies.
Basing on the physical and chemical properties of MOVE 3 the main route of human exposure is by inhalation. Respiratory absorption has been observed in rat but no sufficient data are available for estimating the absorption rate. Basing on the physical and chemical properties oral absorption following ingestion cannot be excluded but no sufficient data are available for estimating the absorption rate. Significant dermal absorption is expected to be prevented by the extreme volatility of the substance.
No sufficient data are available for estimating distribution rate and tissues affinity.
No sufficient data are available for predicting the metabolic changes and potential metabolites.
If absorbed, basing on its physical and chemical properties, excretion with exhaled air may be a significant excretion route. Urinary excretion may be favorited by the limited molecular weight of MOVE 3 but no sufficient data are available for confirming this hypothesis.
Key value for chemical safety assessment
Additional information
Ref: ECHA Guidance on Information Requirements and Chemical Safety Assessment_Chapter R.7c: Endpoint specific guidance.
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