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EC number: 234-042-8 | CAS number: 10508-09-5
- 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)
Description of key information
There is no experimental absorption, distribution, metabolism and excretion (ADME) data on DTA.
Absorption and Distribution
Oral route
Oral absorption is favoured for molecular weights below 500 g/mol. Based on the high log Kow of 4.7, DTA can be regarded as lipophilic substance. Such lipophilic compound may be taken up by micellular solubilisation. This mechanism may be of particular importance, as the substances are only slightly soluble and would otherwise be poorly absorbed. DTA showed adverse effects at 1000 mg/kg bw/day in repeated dose toxicity studies when administered in corn oil. Therefore it can be assumed that at least some absorption across the gastrointestinal tract occurs when administered in repeated dosages. DTA is not expected to hydrolyse in water.
Using a model to predict either high or low fraction absorbed for an orally administered, passively transported substance, the rates of absorption were 100 and 90% for a dose of 1 and 1000 mg of DTA, respectively (Danish QSAR database).
As well, high absorption rates were also predicted with the pkCSM method (ca. 95%) (Pires et al., 2015) and the ADMETlab platform (70-90%) (Dongsheng Cao et al., 2018).
Inhalation exposure
Based on the relatively high vapour pressure of DTA, inhalation exposure is likely. If the substance reaches the lung, they may be absorbed by micellular solubilisation.
Dermal exposure
Based on physical-chemical properties of DTA, the substance is not likely to penetrate skin to a large extent as the high log Kow value and low water solubility do not favour dermal penetration. Between water solubility of 1-100 mg/l absorption is anticipated to be low to moderate. For substances with a log Kow between 4 and 6, the rate of penetration is limited by the rate of transfer between the stratum corneum and the epidermis. Only the uptake into the stratum corneum will be high.
The dermal absorption rates of DTA was estimated with IH SkinPerm v2.04 model (AIHA, 2018). Compared to in vitro data from OECD 428 studies, IH skinPerm allowed the estimation of the dermal absorption rate with a good confidence and a low frequency (ca. 2%) of underestimation for liquids (Arkema’s internal validation study, 2018). According to the data input, IH SkinPerm v2.04 model leads to the following results according to the input data:
Fraction absorbed (%)* |
Instantaneous deposition |
Deposition over time |
Di-tert-pentyl peroxide |
0.7 |
1.24 |
*End time observation 8 hr
The skin absorption is therefore very limited.
Distribution
When reaching the body, DTA may be distributed into cells due to their lipophilic properties and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues.
The pkCSM (Pires et al., 2015) and the ADMETlab platforms (Dongsheng Cao et al., 2018) allow to predict some parameters related to distribution.
Parameters |
Predicted Value DTA |
Interpretation |
pkCSM |
|
|
Steady state volume of distribution (VDss human) (log L/kg) |
0.087 |
VDss is considered low if below 0.71 L/kg (log VDss < -0.15) and high if above 2.81 L/kg (log VDss > 0.45 |
Fraction unboundto serum proteins (human) (Fu) |
0.536 |
the predicted fraction that would be unbound in plasma is calculated |
Blood Brain Barrier (BBB) permeability (log BB) |
0.519 |
a logBB > 0.3 is considered to readily cross the blood-brain barrier |
CNS permeability(blood-brain permeability- surface area product, log PS) |
-2.796 |
Compounds with a logPS > -2 are considered to penetrate the CNS, while those with logPS < -3 are considered as unable to penetrate the CNS |
ADMETlab |
|
|
PPB (Plasma Protein Binding) |
65.363 % |
Significant with drugs that are highly protein-bound and have a low therapeutic index. |
VD (Volume Distribution) |
0.16 L/kg |
Optimal: 0.04-20L/kg; Range: <0.07L/kg: Confined to blood, Bound to plasma protein or highly hydrophilic; |
BBB (Blood–Brain Barrier) |
+++ (0.986) |
BB ratio >=0.1: BBB+; BB ratio <0.1: BBB- These features tend to improve BBB permeation: H-bonds (total) < 8–10; MW < 400–500; No acids. |
Metabolism
There is no metabolism data on DTA, but it is thought that DTA will be enzymatically hydrolysed to tert-amyl alcohol (TAA). In this case, excretion would probably occur in urine.
In silico cytochrome P450 metabolism
Cytochrome P450s play a fundamental role in the oxidative metabolism of xenobiotics. The reactivity of DTA with cytP450 was evaluated in three models available online.
The evaluation of DTA in the pkCSM method (Pires et al., 2015) for predicting small-molecule pharmacokinetic and toxicity properties does not show any inhibitor effects in the cytochrome P450 metabolism.
Model Name |
Predicted Value DTA |
Unit |
CYP2D6 substrate |
No |
Categorical (Yes/No) |
CYP3A4 substrate |
No |
Categorical (Yes/No) |
CYP1A2 inhibitor |
No |
Categorical (Yes/No) |
CYP2C19 inhibitor |
No |
Categorical (Yes/No) |
CYP2C9 inhibitor |
No |
Categorical (Yes/No) |
CYP2D6 inhibitor |
No |
Categorical (Yes/No) |
CYP3A4 inhibitor |
No |
Categorical (Yes/No) |
As well, no interactions with cytochrome P450 metabolism were predicted with the ADMETlab platform (Dongsheng Cao et al., 2018).
Property |
Predicted values* DTA (Probability#) |
P450 CYP1A2 inhibitor |
--- (0.086) |
P450 CYP1A2 Substrate |
- (0.47) |
P450 CYP3A4 inhibitor |
--- (0.005) |
P450 CYP3A4 substrate |
--- (0.282) |
P450 CYP2C9 inhibitor |
--- (0.059) |
P450 CYP2C9 substrate |
- (0.378) |
P450 CYP2C19 inhibitor |
--- (0.097) |
P450 CYP2C19 substrate |
- (0.356) |
P450 CYP2D6 inhibitor |
--- (0.206) |
P450 CYP2D6 substrate |
- (0.421) |
*Predicted values : 0-0.1 (---) ; 0.1-0.3 (--) ; 0.3-0.5 (-); 0.5-0.7 (+) ; 0.7-0.9 (++) ; 0.9-1.0 (+++)
#Probability of the positive (+)
XenoSite Cytochrome P450 Prediction Models (Dang et al., 2016) provide predictions of regio-selectivity (which atoms on a molecule are likely to be oxidized by a given CYP enzyme), but they do not explicit model selectivity (which molecules are substrates of a given CYP enzyme). For DTA, the oxidation by cytP4502B6 appears to be the most potent.
In silico UGT-Mediated Metabolism
Sites of uridine diphosphate glucunosyltransferases (UGTs) metabolism of DTA was predicted with the XenoSite platform (Dang et al., 2016) . The peroxide group was predicted the site for UGT metabolism.
Excretion
The evaluation of DTA in the pkCSM (Pires et al., 2015) and ADMETlab (Dongsheng Cao et al., 2018) platforms allow to predict some parameters related to excretion.
pkCSM model name |
Predicted Value DTA |
Total Clearance (log ml/min/kg) |
1.605 |
Renal Organic Cation Transporter 2 (OCT2) substrate |
No |
ADMET lab property |
Predicted values DTA |
Meaning & Preference |
T1/2(Half Life Time) |
1.775 h |
Range: >8h: high; 3h< Cl < 8h: moderate; <3h: low |
CL (Clearance Rate) |
1.744 mL/min/kg |
Range: >15 mL/min/kg: high; 5mL/min/kg< Cl < 15mL/min/kg: moderate; <5 mL/min/kg: low |
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 100
- Absorption rate - dermal (%):
- 10
- Absorption rate - inhalation (%):
- 100
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.
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