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EC number: 500-099-5 | CAS number: 37625-56-2
- 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:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Non-standard investigation; performed at a reputable laboratory and reported in detail
- Objective of study:
- absorption
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- The study investigated the absorption of CAPA 3050 in vitro in a rat gut sac model
- GLP compliance:
- no
- Radiolabelling:
- no
- Species:
- other: not relevant
- Route of administration:
- other: In vitro
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Gut (small intestine) sacs were prepated from male Han Wistar rats. The everted gut sacs were placed in a flask of 10 mL FeSSIF (Fed State Simulated Intestinal Fluid) medium containing 10 mM of CAPA 3050 at 37°C. The sacs from one rat were incubated in triplicate at 37°C for 1 hour. After 1 hour the individual sacs were removed, washed with running water and blotted dry.
- Duration and frequency of treatment / exposure:
- One hour incubation
- Remarks:
- Doses / Concentrations:10 mM
- No. of animals per sex per dose / concentration:
- The sacs from one rat were incubated in triplicate at 37°C for 1 hour.
- Control animals:
- no
- Positive control reference chemical:
- Not required
- Details on study design:
- The everted intestinal sacs were prepared by gently everting a freshly excised (male Han Wistar) rat proximal small intestine over a glass stirring rod, rinsing with TC-199 media and filling the everted intestine withoxygenated FeSSIF medium at 37°C and dividing it into sacs approximately 2.5 cm in length using braided suture silk. Each sac was placed in a flask of 10mL FeSSIF medium containing 10mM of CAPA 3050 at 37°C. The sacs from one rat were incubated in triplicate at 37°C for 1 hour. After 1 hour the individual sacs were removed, washed with running water and blotted dry. The sacs were cut open and the serosal fluid drained into small tubes. Each tube was weighed before and after collection of the serosal fluid to accurately calculate the volume of medium collected from inside the sac.
- Details on dosing and sampling:
- The contents of each sac and a sample of the external medium after incubation (400µL) were blown down to complete dryness under nitrogen at 90°C. 200µL of N,N-bis-trimethylsilyl-trifluoroacetamide (BSTFA) was added to each sample followed by 800 µL of pyridine and capped. The samples were then sonicated in a sonicating water bath for approximately 10 seconds to ensure mixing and reconstitution. The samples were then heated at 105°C for 30 minutes. A 150µL aliquot of the reconstituted sample was removed and placed in a crimp-top vial for analysis by Gas Chromatography Flame Ionisation Detection (GC-FID) to determine the concentration of the CAPA 3050 in each sample and compared against analytical standards.
- Statistics:
- Not required
- Preliminary studies:
- The results of the study showed a different peak distribution in the serosal and external media compared to the standard. For Component 1 (TMP), the peaks in the serosal and external fluid were higher than the standard. For Component 2, the serosal fluid peak was slightly higher than the standard and the external fluid peak was comparable to the standard. For Component 3, the serosal peak was markedly lower than the external medium concentration. Components 4-8 were not detected in the serosal medium. Concentrations in the external medium were lower than the standard.
- Metabolites identified:
- yes
- Details on metabolites:
- Although the study was not designed to assess metabolism, the change in peak profile is consistent with some hydrolysis of the CAPA 3050 oligomers to produce TMP [Component 1]
- Conclusions:
- Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
- Executive summary:
The aim of this study was to determine the rat small intestinal absorption potential of CAPA 3050 using an in vitro everted gut sac model. From the results it can be concluded that the lower molecular weight components of CAPA 3050 (TMP > TMP+1ECL > TMP+2ECL > TMP+3ECL) were absorbed into the serosal fluid. This would imply a negative correlation between the molecular weight of the components of CAPA 3050 and the rat small intestinal absorption potential. It was also noted that the concentrations of components 4 to 6 were greatly reduced in the external medium after the 60 minute incubation at 37°C when compared to the 10 mM standard. The reasons for this drop in concentration are unclear, but it has been suggested that a possible reason could be hydrolysis of the higher molecular weight components of CAPA 3050 and conversion to TMP. Another possible reason could be the low water solubility of the higher molecular weight components.
Reference
Summary of results
Component |
Mean peak area |
|||
Standard |
External medium |
Serosal medium |
||
#1 |
TMP |
6742 |
10304 |
10601 |
#2 |
TMP + 1eCL |
13256 |
13289 |
14725 |
#3 |
TMP + 2eCL |
17515 |
15116 |
2749 |
#4 |
TMP + 3eCL |
20634 |
6595 |
37 |
#5 |
TMP + 4eCL |
8968 |
2486 |
- |
#6 |
TMP + 5eCL |
2952 |
307 |
- |
#7 |
TMP + 6eCL |
- |
- |
- |
#8 |
TMP + 7eCL |
- |
- |
- |
Description of key information
A study of absorption in vitro is available, and indicates varying levels of gastrointestinal absorption for the various oligomeirc components of CAPA 3050. Theoretical assessment of the toxicokinetic properties of CAPA 3050 does not indicate any potential for bioaccmulation.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 50
- Absorption rate - dermal (%):
- 50
- Absorption rate - inhalation (%):
- 100
Additional information
Absorption
A study of absorption in vitro (in everted rat intestinal sacs) is available for CAPA 3050 (Powrie, 2014). This study shows significant absorption of the TMP component, with absorption of the lowest molecular weight oligomer (TMP + 1ECL), some absorption of the next lowest molecular weight oligomer (TMP + 2ECL), and limited (TMP + 3ECL) or minimal (TMP + 4ECL) absorption of the higher molecular weight oligomers (TMP = propylidynetrimethanol, ECL = hexan-6-olide). There is no evidence for the absorption of the highest molecular weight oligomers. A study of hydrolysis (Raab, 2010) indicates that CAPA 3050 is hydrolytically stable at pH 4 and at pH 7; however hydrolysis is seen at pH 9 and a half-life of 16 hours is calculated. The in vitro absorption study also indicates some hydrolysis under the conditions of the study. Both of the ultimate products of hydrolysis (trimethylolpropane and 6-hydroxyhexanoic acid satisfy Lipinski's rule of 5 (OECD QSAR Toolbox) and are therefore likely to be bioavailable. Dermal absorption of the oligomer is not predicted due to its molecular size; significant hydrolysis of the oligomer on the skin surface is not predicted. The extent of oral absorption cannot be quantified, but is clearly indicated to be less than 100% as the extent of absorption of the oligomers decreases with increasing molecular weight. Dermal absorption cannot be quantified, but is likely to be low. Inhalation absorption is potentially significant; however inhalation exposure is not predicted. In the absence of quantitative data, default assumptions are made for the extent of absorption by each route.
Distribution
Any intact oligomeric components that are absorbed from the gastrointestinal tract will be distributed to the liver via the hepatic portal vein; rapid metabolism of the absorbed oligomers is predicted, making systemic (post-hepatic) distribution of the oligomers unlikely. The hydrolysis products TMP and 6 -hydroxyhexanoic acid are highly water soluble and are therefore likely to be rapidly and extensively distributed in the blood.
Metabolism
The oligomeric substance will be metabolised by esterase enzymes to form trimethylolpropane and 6-hydroxyhexanoic acid. The hydrolysis product 6-hydroxyhexanoic acid is structurally similar to endogenous fatty acids and therefore may be incorporated into lipid metabolism pathways. The hydrolysis product TMP can be predicted to be metabolised by sequential oxidation of the alcohol groups, in common with related substances; OECD QSAR Toolbox predicts a total of 10 hepatic metabolites for TMP.
Excretion
Rapid urinary excretion of the highly water-soluble hydrolysis products and metabolites is likely; no bioaccumulation is therefore predicted.
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