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EC number: 277-923-2 | CAS number: 74563-64-7
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics, other
- Remarks:
- assessment of toxicokinetic behavior
- Type of information:
- other: In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behavior has been conducted to the extent that can be derived from the relevant available information.
- Adequacy of study:
- key study
- Study period:
- The assessment was conducted in February 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Relevant studies were reviewed by a qualified toxicologist with a view to fulfilling the requirements of Annex VIII (8.8).
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Qualifier:
- no guideline required
- Principles of method if other than guideline:
- In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behaviour has been conducted to the extent that can be derived from the relevant available information.
- GLP compliance:
- no
- Remarks:
- Not relevant for assessment
Test material
- Reference substance name:
- 3,7,11,15-tetramethylhexadecane-1,2,3-triol
- EC Number:
- 277-923-2
- EC Name:
- 3,7,11,15-tetramethylhexadecane-1,2,3-triol
- Cas Number:
- 74563-64-7
- Molecular formula:
- C20H42O3
- IUPAC Name:
- 3,7,11,15-tetramethylhexadecane-1,2,3-triol
- Test material form:
- liquid: viscous
- Details on test material:
- - Physical appearance: colourless viscous liquid
- Storage conditions: at room temperature
Constituent 1
- Specific details on test material used for the study:
- Phytantriol is a colorless to light yellow, viscous liquid.
Results and discussion
Any other information on results incl. tables
Oral Bioavailability:
No oral bioavailability study with Phytantriol has been conducted. In a combined sub-acute toxicity and reproductive/developmental toxicity screening study in the rat (OECD 422) and its preceding dose-range finding study, systemic toxicity was observed at high doses.This indicates that Phytantriol is absorbed in the gastrointestinal tract.
Phytantriol was analyzed in plasma samples of rats from the dose range finding study. Phytantriol was administered by oral gavage to three male and female rats at doses of 500 and 1000 mg/kg bw/d. Phytantriol was detected in samples of males and females only at 6 h after a single administration but not after 1 and 3 h; this may be due to the high detection limit of the analytical method. After 15 days of daily administration, Phytantriol could be detected in 3 h blood samples in a dose-dependent way. These data indicate that Phytantriol has a tmax of > 3h and may accumulate over repeated administration.
Phytantriol was analyzed in plasma samples of rats from the repeated dose toxicity study with developmental / reproductive screen. Phytantriol was administered by oral gavage to male and female rats at doses of 50, 150, and 500 mg/kg bw/d. Plasma was taken and analyzed on day14 at 6 h after administration. Phytantriol was detected in samples of all dose groups in dose-dependent concentrations. Average plasma levels (n = 5) are given in the table below:
F0-animals: At 6 hours post-dose on Day 14. Values are in ng/mL:
Group |
Males |
Females |
1 (vehicle control) |
<LLOQ1 |
<LLOQ |
2 (50 mg/kg/day) |
1958 ± 271 |
1699 ± 536 |
3 (150 mg/kg/day) |
4371 ± 1926 |
3544 ± 1291 |
4 (500 mg/kg/day) |
6700 ± 1675 |
5966 ± 2151 |
1: LLOQ was 200 ng/ml
Phytantriol was also detected in pups after birth. It has not been elucidated if the pups received the Phytantriol via the placenta during gestation or via milk during weaning.
Phytantriol is bioavailable after oral exposure. It has a tmax > 3h, accumulates in the body and can be found in plasma in a dose-dependent concentration.
Dermal Penetration:
Csato et al.(1997) has determined the dermal penetration of Phytantriol in three different formulations using pig skin. Ethanol, polyethylene glycol (PEG 400), and paraffin oil containing 0.5% Phytantriol were used. Phytantriol was labeled with 3H. The penetration of each formulation into the skin was evaluated at 1, 6, and 18h. Ro 04-3724/000 penetrated into the horny layer and living layers of the skin from each tested formulation. The highest penetration values in the stratum corneum and in the living skin tissue were detected when Phytantriol was dissolved in ethanol. Paraffin oil and PEG 400 provided for lower skin penetration of the test compound. Virtually no penetration of the test article through the skin layers into chamber fluid was detected from all the 3 tested formulations in this experiment. Detailed data are given in Table 1.
In conclusion, the experimental data of this study show that Phytantriol penetrates into the intact pig skin, the horny layer in particular and also into epidermis/dermis. The 0.5% ethanolic solution of the test compound provides for higher skin penetration as opposed to the same strength formulations prepared in paraffin oil or polyethylene glycol. The penetration of the test article through the pig skin from the 3 tested formulations maximum 5.5%.
Table 1: Dermal penetration of Phytantriol through pig skin (Csato 1997)
(in EtOH) |
1h |
6h |
18h |
Remaining on surface |
55% |
59% |
44% |
Stratum corneum |
21% |
20% |
34% |
Epidermis and Dermis |
3.6% |
3.3% |
5.4% |
Chamber fluid |
0.0% |
0.0% |
0.1% |
(in PEG) |
1h |
6h |
18h |
Remaining on surface |
94% |
77% |
77% |
Stratum corneum |
4.8% |
12% |
14% |
Epidermis and Dermis |
0.5% |
2.0% |
2.3% |
Chamber fluid |
0.0% |
0.0% |
0.0% |
(in Paraffin oil) |
1h |
6h |
18h |
Remaining on surface |
84% |
81% |
59% |
Stratum corneum |
7.4% |
8.9% |
8.1% |
Epidermis and Dermis |
1.5% |
1.1% |
1.0% |
Chamber fluid |
0.0% |
0.0% |
0.0% |
Metabolism:
Metabolism of Phytantriol in humans was assessed using Lhasa Meteor Nexus software (Meteor version 3.0.0).
Most probable metabolism would be the oxidation of the primary or secondary alcohol to the respective carboxylic acid or ketone. Also, double oxidation of both, the primary and secondary alcohol, resulting in the formation of the α-keto β-hydroxy acid is predicted. The carboxylic acid and also the α-keto acid can then be conjugated with glucuronic acid or sulfate.
Another plausible metabolism pathway starts with the hydroxylation of a terminal primary methyl group of the phytol chain followed by its oxidation to the carboxylic acid and conjugation with glucuronic acid or sulfate.
Also a combination of both metabolism steps, hydroxylation of terminal methyl and oxidation of primary and secondary alcohols could possibly occur.
At the bottom line, metabolism of Phytantriol will lead to substances that are of higher water solubility than Phytantriol itself, which facilitates its excretion.
Applicant's summary and conclusion
- Conclusions:
- Phytantriol is bioavailable after oral exposure. It has a tmax > 3h, accumulates in the body and can be found in plasma in a dose-dependent concentration.
Experimental data of this study show that Phytantriol penetrates into the intact pig skin. The penetration of the test article through the pig skin from the 3 tested formulations maximum 5.5%.
Metabolism of Phytantriol will lead to substances that are of higher water solubility than Phytantriol itself, which facilitates its excretion.
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