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EC number: 271-603-6 | CAS number: 68586-02-7
- 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
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Justification for type of information:
- According to hydrolysis test results, the hydrolysis rate is estimated to be within 30 minutes. The hydrolysis products have been identified to be ethanol, 2-propanol, acetylacetone and titanium dioxide.
The properties of the target substance would lie in the hydrolysis products. - Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other:
- Principles of method if other than guideline:
- Intravenous study: The substance was given to four adult male Fischer 344 rats per dose by single intra-venous injection. Target radioactivity was 2 – 5 mCi. Blood was collected at appropriate intervals from a lateral tail vein until 30 hr post dosing. At 48 hr a cardiac puncture was performed for a final blood sam-ple with all groups. Urine and feces were. For airborne collections, room air was drawn through the me-tabolism cages at approximately 500 ml/min. Expired 14CO2 was trapped.
Inhalation study: A total of fifty animals were exposed 6 hours nose-only to a target concentration and serial groups of 3 animals were removed at the blood sampling intervals during the absorption phase. Included was a group of 4 rats which were monitored by plethysmography during exposure to ensure that there was no excessive peripheral sensory irritation with consequent changes in minute volume. Respira-tory rate was measured. After exposure the animals were transferred to metabolism cages. - GLP compliance:
- yes
- Radiolabelling:
- yes
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
- Route of administration:
- other: inhalation: dust; intravenous
- Vehicle:
- other: physiol. saline for intravenous, unchanged for inhalation
- Duration and frequency of treatment / exposure:
- IV: single exposure
Inhalation: single 6h exposure - Dose / conc.:
- 400 ppm
- Remarks:
- Inhalation
- Dose / conc.:
- 4.3 mg/kg bw/day (nominal)
- Remarks:
- I.V
- Dose / conc.:
- 43 mg/kg bw/day (nominal)
- Remarks:
- I.V.
- Dose / conc.:
- 430 mg/kg bw/day (nominal)
- Remarks:
- I.V
- Dose / conc.:
- 148.5 mg/kg bw/day (nominal)
- Remarks:
- I.V.
- No. of animals per sex per dose / concentration:
- I.V.: 4
Inhalation: 50 - Conclusions:
- Low bioaccumulation potential based on study results.
2,4-PD is readily absorbed during a 6 hr exposure to 400 ppm, and biexponentially eliminated from plasma postexposure. However, even at 48 hr postexposure, radioactivity derived from 14C-2,4-PD is still present. The majority of the dose is eliminated as CO2 and in urine, with at least 7 metabolites being detected in urine. Although there is no preferential tissue accumulation of 14C-2,4-PD-derived radioactivity, the plasma elimination profiles and the detection of some radioactivity in many tissues at 48 hr postexposure, indicates a potential for cumulative effects. The only definitive repeated exposure known toxicity, and with a latency to expression, is central neurotoxicity and 14C could still be detected in the brain 48 hr after a single exposure. The urinary elimination profiles suggest that biological monitoring might best be undertaken using a metabolite as marker. (from Frantz 1998). - Executive summary:
As the target substance hydrolyses rapidly (half-life < 30 minutes) the intrinsic properties are related to hydrolysis products of the target substance. This information is used as a supporting evidence on the toxicity of the target substance in CSA.
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Justification for type of information:
- 2-propanol and triethanolamine are two main hydrolysis prodcuts of the target substances.
- Objective of study:
- excretion
- metabolism
- toxicokinetics
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Deviations:
- no
- GLP compliance:
- not specified
- Radiolabelling:
- yes
- Remarks:
- 14C
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Route of administration:
- inhalation: vapour
- Vehicle:
- unchanged (no vehicle)
- Duration and frequency of treatment / exposure:
- single exposure for 6 hr
- Dose / conc.:
- 500 ppm
- Remarks:
- low dose group
- Dose / conc.:
- 5 000 ppm
- Remarks:
- high dose group
- No. of animals per sex per dose / concentration:
- 4
- Control animals:
- no
- Positive control reference chemical:
- none
- Type:
- absorption
- Results:
- rapid absorption
- Type:
- distribution
- Results:
- widely distributed without any accumulation
- Type:
- metabolism
- Results:
- major metabolites were acetone and carbon dioxide
- Type:
- excretion
- Results:
- predominant elimination pathway is exhaled breath
- Details on absorption:
- The concentration of radiolabel in the blood increased rapidly following the initiation of inhalation exposure at either concentration. The concentration of radiolabel appeared to still be rising at the end of the exposure to 500 ppm but appeared to have plateaued by the end of the exposure to 5000 ppm IPA.
- Details on distribution in tissues:
- Widely distributed among the tissues following nose only inhalation exposure to nominal concentrations of 500 and 5000 ppm. No evidence was observed to indicate that IPA or its radiolabeled metabolites accumulated in any tissue with the possible exception of kidney and liver, which had slightly elevated concentrations of radiolabel relative to the blood.
- Details on excretion:
- Following nose only inhalation of IPA the breath is, by far, the predominant route of excretion of radiolabel by both sexes. The excretion of the absorbed dose was rapid, with greater than 90% of the absorbed radiolabel being excreted from the breath, urine, and feces within 72 h of the beginning of the inhalation exposure. Exhalation in the breath accounted for a total of about 83% of the absorbed dose at the low exposure level while it accounted for just under 88% following the high exposure level. Even though total excretion of radiolabel in the breath was practically the same following either inhalation exposure, the distribution of radiolabel that appeared in the breath was dramatically different. Following exposure to 500 ppm males and females exhaled an average of 49% of the absorbed radiolabel as carbon dioxide in the breath. Following exposure to 5000 ppm, only 22% of the radiolabel present in the exhaled breath was found to be 14CO2. While the exhaled breath was the major route of excretion following both exposure levels, urine was a minor route of elimination of radiolabel and excretion in the feces was negligible.
- Metabolites identified:
- yes
- Details on metabolites:
- Acetone was found to be the primary radiolabeled metabolite of IPA. In the exhaled breath acetone accounted for 75-100% of the radiolabeled organic volatile compounds being exhaled. The balance of the exhaled radioactivity was accounted for by CO2 and IPA itself. A third radiolabeled metabolite (accounting for less than 5% of the total dose) was found when the urine was analyzed by HPLC; this urinary metabolite was identified as isopropyl glucuronic acid.
- Bioaccessibility (or Bioavailability) testing results:
- not reported.
- Conclusions:
- No bioaccumulation potential of 2-propanol based on the test results.
Pharmacokinetics of propan-2-ol (IPA) was studied in rats. Animals were exposed by inhalation for 6 hours to IPA vapor. Total exhalation of radiolabel (as CO2, acetone, propan-2-ol) was 83%-87% of the administered dose. Urine and feces accounted for excretion approximately 7% and 1%, respectively. No single tissue contained greater than 1.6% of recovered dose.
Referenceopen allclose all
Description of key information
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
No studies were conducted on the target substance. As the target substance hydrolyses rapidly (half-life < 30 minutes) the intrinsic properties are related to hydrolysis products of the target substance. The hydrolysis products include ethanol, 2-propanol, acetylacetone and non-hazardous titanium dioxide. This information is used as a supporting evidence on the toxicity of the target substance in CSA.
Toxicokinetics of pentane-2,4-dione (2,4-PD)
No studies are available concerning the mode of action of the substance. It is known, however, that 1,3-diketones unfold metal chelating properties in vivo which may lead to inhibition of enzymatic activity of metal containing enzymes such as peroxidases or cytochrome P450 without concomitantly lowering protein contents. In an inhalation study conducted in male Fischer 344 rats it could be shown that 14C-labeled-2,4-PD was readily absorbed by the inhalation route. Nose-only exposure to 400 ppm 14Clabeled-2,4-PD resulted in a rapid increase in plasma radioactivity during the first 3 hours of exposure, with a tendency to plateau toward the end of the 6 hour exposure period. Plasma unmetabolized 14C-labeled-2,4-PD was present throughout the whole of the exposure phase, but was significantly less than total 14C. Immediately postexposure, radioacivity was present in all tissues examined, but on a concentration basis (µg equivalents/g) there was no preferential accumulation of 14C in any tissue or organ. On a total organ basis, highest contents were in liver and kidneys. Post-exposure, plasma unmetabolized 14C-labeled-2,4-PD declined rapidly to undetectable concentrations by 12 hours. Elimination of 14C from plasma followed a biphasic pattern with a terminal half-life (beta t½) of 30.72 hours. Excretion over 48 hours of 14C was approximately equivalent between urine (37.6 %, mainly not identified metabolites) and expired 14 CO2 (36.3 %), which the most part of the radioactivity was eliminated in the first 12 hours. Expired volatiles, feces, tissues and carcass accounted for 2.29, 2.78, 1.66 and 17.15 % of the total administered radioactivity dose 48 hours postdosing, respectively (Frantz et al. 1998). (Cited from OECD SIDS, pentane-2,4-dione)
Toxicokinetics of Titanium dioxide
Titanium dioxide is insoluble in water and most ingested titanium is eliminated unabsorbed. In rats, about 95% ingested dose of titanium dioxide is recovered from faeces indicating that the most ingested titanium is not absorbed from gastrointestinal tract by blood (Patty, F. 1965). However, in humans detectable amounts of titanium can be found in the blood, brain and parenchymatous organs (Friberg, L. et al.1986). Based on average titanium concentrations found in human urine of about 10 µg/liter, it can be calculated that the absorption is about 3% (WHO, 1982).
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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