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EC number: 700-954-4 | CAS number: 1338-23-4
- 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
- Type of information:
- other: expert statement
- Adequacy of study:
- key study
- Study period:
- 2010-07-28
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- other: expert statement
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
Materials and methods
- GLP compliance:
- no
Test material
- Reference substance name:
- 2-[(2-hydroperoxybutan-2-yl)peroxy]butane-2-peroxol; butane-2,2-diperoxol
- EC Number:
- 700-954-4
- Cas Number:
- 1338-23-4
- Molecular formula:
- Mixture of C4H10O4 and C8H18O6
- IUPAC Name:
- 2-[(2-hydroperoxybutan-2-yl)peroxy]butane-2-peroxol; butane-2,2-diperoxol
- Test material form:
- liquid
Constituent 1
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Methyl-ethylketone peroxide (MEKP) is a colourless liquid at room temperature with a molecular weight of 122.12 g/mol (monomer) and 210.23 g/mol (Dimer), respectively. The substance is highly soluble in water (6.53 g/L). The logPow of MEKP monomer was estimated to be < 0.3. The assumed log Pow of the MEKP dimer is < 2.04. Based on this log Pow a log BCF of 0.5 was calculated for the monomer and log BCF of 0.66 for the dimer. MEKP has a vapour pressure of 73.6 Pa (monomer) respectively 0.184 Pa (dimer) at 25°C (estimated by QSAR).
MEKP might hydrolyse to acetic acid (CAS 64-19-7), ethyl acetate (CAS 141-78-6), methyl ethyl ketone (butanone, CAS 78-93-3) and hydrogen peroxide (CAS 7722-84-1). All four substances have very low log Pow values as MEKP itself (range: -1.5 to 0.6). Based on these very low log Pow values no bioconcentration potential is expected. The only available BCF of 30 for ethyl acetate confirms this assumption. The degradation products are highly soluble in water (range: 2.5 g/L to completely miscible). - Details on distribution in tissues:
- Oral absorption is favoured for molecular weights below 500 g/mol. Based on the high water solubility and the low logPow value MEKP is expected to be readily absorbed via the GI tract. As the substance is water soluble and the molecular weight is low (less than 200) MEKP may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. MEKP revealed NOAELs of 65 mg/kg bw/day and 50 mg/kg bw/day in repeated dose and reproduction toxicity studies, respectively. Administered in an acute study MEKP leads to a LD50 of 1017 mg/kg bw/day (potentially due to local tissue damage). Therefore, it can be assumed that the substance becomes systemically available and direct absorption across the gastrointestinal tract epithelium will occur when applied orally.
When administered orally MEKP might hydrolyse to acetic acid, ethyl acetate, methyl ethyl ketone and hydrogen peroxide. Based on their physical/chemical properties described above, all substances are expected to pass the epithelium.
Based on the vapour pressure (0.184 to 73.6 Pa) inhalation exposure is limited. Nevertheless, if the substance reaches the lung, MEKP may be absorbed. MEKP showed only toxic effects after inhalation administration, in an acute inhalation toxicity study when applied at high doses (LC50 = 17 mg/L). Together, this indicates low systemic availability after inhalation and if bioavailable, low toxicity via this route of administration.
Similarly, based on physical – chemical properties of MEKP the substance is not likely to penetrate skin to a large extent as the low logPow value does not favour dermal penetration, as the substance is too hydrophilic to pass the skin. Furthermore, application of MEKP to skin of rabbits did not cause systemic effects (mortality) in a skin irritation/corrosion study and an acute dermal toxicity study. Applied to the skin of guinea pigs, sensitising effects were not observed.
When reaching the body MEKP will be widely distributed due to low molecular weight and high water solubility. Based on its low BCF value MEKP is not considered to bioaccumulative in the human body. All degradation products have very low log Pow values and are in consequence expected to have low BCF values (Ethyl acetate BCF = 30) and are thus not bioaccumulative.
Based on the structure of the molecule, metabolism in the human body will mainly consist of phase-II metabolising steps, leading to an even better water solubility for excretion. This is in compliance with the results obtained in the genotoxic tests showing no effects with and without metabolising system. Metabolic activation leading to more toxic metabolites is thus not very likely.
- Details on excretion:
- Based on the water solubility and the logPow value, excretion via the urine is likely. As discussed above MEKP may hydrolyse under physiological conditions, and could thus be excreted in its hydrolysed form. All degradation products represent small good soluble and hydrophilic substances, which are in conclusion most likely excreted via the urine.
Metabolite characterisation studies
- Metabolites identified:
- not measured
Applicant's summary and conclusion
- Conclusions:
- Based on physical-chemical characteristics, particularly water solubility, octanol-water partition coefficient and vapour pressure, no or only limited absorption by the dermal and inhalation routes is expected, which is further supported by the dermal and inhalation acute toxicity studies results. For the oral route uptake of MEKP or its hydrolysis products is more relevant. Bioaccumulation of MEKP and the hydrolysis products is not likely to occur based on the physical-chemical properties. Excretion is expected to occur mainly via urine.
- Executive summary:
Toxicokinetic analysis of Methyl-ethylketone peroxide (MEKP)
Methyl-ethylketone peroxide (MEKP) is a colourless liquid at room temperature with a molecular weight of 122.12 g/mol (Monomer) and 210.23 g/mol (Dimer), respectively. The substance is highly soluble in water (6.53 g/L). The log Pow of MEKP monomer was estimated to be < 0.3. The assumed log Pow of the MEKP dimer is < 2.04. Based on this log Pow a log BCF of 0.5 (monomer) and 0.6598 (dimer) was calculated. MEKP has a vapour pressure of 73.6 Pa (monomer) respectively 0.184 Pa (dimer) at 25°C (estimated by QSAR).
MEKP hydrolyses upon contact with water to acetic acid (CAS 64 -19 -7), ethyl acetate (CAS 141 -78 -6), methyl ethyl ketone (butanone, CAS 78 -93 -3) and hydrogen peroxide (CAS 7722 -84 -1). All four substances have very low log Pow values as MEKP itself (range: -1.5 to 0.6). Based on these very low log Pow values no bioconcentration potential is expected. The only available BCF of 30 for ethyl acetate confirms this assumption. The degradation products are highly soluble in water (range: 2.5 g/L to completely miscible).
Oral absorption is favoured for molecular weights below 500 g/mol. Based on the high water solubility and the low log Pow value MEKP is expected to be readily absorbed via the GI tract. As the substance is water soluble and the molecular weight is low (less than 200) MEKP may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. MEKP revealed NOAELs of 150 mg/kg bw/day and 200 mg/kg bw/day in repeated dose and reproduction toxicity studies, respectively. Administered in an acute study MEKP leads to a LD50 of 1017 mg/kg bw/day (potentially due to local tissue damage). Therefore, it can be assumed that the substance becomes systemically available and direct absorption across the gastrointestinal tract epithelium will occur when applied orally. When administered orally, MEKP is expected to partially hydrolyze to acetic acid, ethyl acetate, methyl ethyl ketone and hydrogen peroxide. Based on their physical/chemical properties described above, the parent as well as its hydrolysis products are expected to pass the epithelium.
Based on the vapour pressure (0.184 to 73.6 Pa) inhalation exposure is limited. Nevertheless, if the substance reaches the lung, MEKP may be absorbed. MEKP showed only toxic effects after inhalation administration, in an acute inhalation toxicity study when applied at high doses (LC50 = 17 mg/L). Together, this indicates low systemic availability after inhalation and if bioavailable, low toxicity via this route of administration.
Similarly, based on physical – chemical properties of MEKP it is not likely to penetrate skin to a large extent as the low logPow value does not favour dermal penetration, as the substance is too hydrophilic to pass the skin. Furthermore, application of MEKP to skin of rabbits did not cause systemic effects (mortality) in a skin irritation/corrosion study and an acute dermal toxicity study. Applied to the skin of guinea pigs, sensitising effects were not observed.
When reaching the body MEKP will be widely distributed due to low molecular weight and high water solubility. Based on its low BCF value MEKP is not considered to bioaccumulative in the human body. Target organs in the 90-dy oral repeated dose toxicity study in rats were the spleens, accompanied by slightly elevated percentages of reticulocytes in the 150 and 50 mg/kg bw/dose groups. Spleen weight values remained within the historical control ranges, however along with changes in the percentages of reticulocytes a test item influence cannot be excluded.
MEKP itself as well as all degradation products have very low log Pow values and are in consequence expected to have low BCF values (Ethyl acetate BCF = 30) and are thus not bioaccumulative.
Based on the structure of the molecule, metabolism in the human body will mainly consist of phase-II metabolising steps, leading to an even better water solubility for excretion. This is in compliance with the results obtained in the genotoxic tests showing no effects with and without metabolising system. Metabolic activation leading to more toxic metabolites is thus not very likely.
Based on the water solubility and the log Pow value, excretion via the urine is likely. As discussed above MEKP may hydrolyse under physiological conditions, and could thus be excreted in its hydrolysed form. All degradation products represent small good soluble and hydrophilic substances, which are in conclusion most likely excreted via the urine.
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