Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 908-918-1 | CAS number: -
- 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
Short description of key information on bioaccumulation potential result:
The available data with the test substances suggest a rapid enzymatic conversion (hydrolysis) within minutes to the corresponding alcohols (and the corresponding acid metabolites to a minor extend) after incubation with fresh rat liver homogenates or after inhalation.
Short description of key information on absorption rate:
The available data suggest a moderate absorption through human epidermis when compared with the absorption rates of other skin penetrants.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
Metabolism
It was the objective of the study from Union Carbide Corporation (1993) to evaluate, if the metabolism in rat liver homogentae of the two isomeric components of the reaction mass, n-pentyl acetate and 2 -methylbutyl acetate, proceeds via hydrolysis, and, if so, to determine the Michaelis-Menten, first-order, metabolic (hydrolysis) rate constant for each isomer. For the study, the biological conditions under which these acetate esters are hydrolyzed and the characterization of the major metabolic endproducts were investigated using liver homogenate derived from adult male Fischer 344 rats. 14C-Labeled n-pentyl acetate and 14C-labeled 2-methylbutyl acetate were used and an analytical method for the analysis of 14C-n-pentyl acetate, 14C-2 -methylbutyl acetate, 14C-n-pentyl alcohol, and 14C-2-methylbutyl alcohol was developed at the testing facility, utilizing high performance liquid chromatography (HPLC) and a radioactive flow detector.
The results of preliminary testing involving the incubation of 25 mM 14C-n-pentyl acetate and 14C-2-methylbutyl acetate in 20% liver homogenates for 0-10 minutes demonstrate that essentially all of the 14C-n-pentyl acetate and 14C-2-methylbutyl acetate was converted to the corresponding alcohols. This was the confirmation that the degradation of the acetates proceeds via hydrolysis. The identities of the acetates and alcohols were confirmed by comparison with authentic 14C-radiolabeled standards, which were analyzed concurrently with the samples. Further experiments were conducted to determine that the hydrolysis of the acetates was enzymatic and to optimize experimental conditions. The hydrolysis of the acetates could be inhibited by the addition of approximately 5-10% Paraoxon (an esterase inhibitor) to the liver homogenate incubation, indicating that the hydrolysis was enzymatic.
The enzymatic nature of the hydrolysis was further demonstrated in experiments in which approximately 0.0913 mM14C-n-pentyl acetate and approximately 0.0690 mM of 14C-2-methylbutyl acetate were incubated with 0.2% liver homogenate in a 37°C water bath, and sampled for various times up to 10 minutes. The samples were then analyzed for the acetate ester and its corresponding alcohol. 14C-n-pentyl acetate, 14C-2-methylbutyl acetate, 14C-n-pentyl alcohol, and 14C-2 -methylbutyl alcohol were used to confirm the retention times of the analytes, and to measure the percent of acetate remaining and the percent of alcohol appearing in each incubation. The results indicated that there was a stochiometric relationship between the amount of acetate disappearing and the amount of the corresponding alcohol appearing in the incubation.
For determination of the metabolic rate constant for each isomer, 14C-labeled n-pentyl acetate and 14C-labeled 2-methylbutyl acetate were added to 0.2% homogenates in concentrations ranging from approximately 0.25-250 mM for approximately 1 min in a shaking, 37°C water bath. The samples were then analyzed as described above. Lineweaver-Burk plots of inverse substrate concentration (µM(-1)) versus inverse enzymatic hydrolysis velocity [(µmoles of substrate metabolized/mg protein/min)-1] were then constructed. Linear regression of these plots was used to determine the Michaelis-Menten, first-order, metabolic (hydrolysis) rate constant (Km) and the maximum velocity (Vmax) of enzymatic hydrolysis for each isomer.
The results of this study indicate that the most likely route of metabolic degradation of the two isomers in rat liver homogenates is hydrolysis, and that this breakdown is enzymatic. The calculated Km and Vmax values for n-pentyl acetate were approximately 484 µM and 0.17 µmoles/mg/min, respectively, while 2-methylbutyl acetate had calculated Km and Vmax values of approximately 70 µM and 0.09 µmoles/mg/min, respectively.
According to Dahl et al. (1987), pentyl acetate was also effectively hydrolysed in vitro by the S9 fractions obtained from nose, liver, lung, or tracheal tissue of hamsters, rats, and rabbits as determined via measurement of carboxylic acid. The liver fraction hydrolyzed pentylacetate most effectivly, followed by the ethmoturbinate. S9 fractions obtained from the trachea were almost as efficient as the ethmoturbinate from the nose in rat and hamster, and slightly less efficient in rabbits. Values for the liver were 0.25 nmol/mg S9 / min for rats and closely match the value obtained by Union Carbide, not only confirming metabolism rate, but also that hydrolysis by esterases and subsequent metabolism of the alcohol to the carboxylic acid is by far the main metabolic pathway. Dahl et al. also observed that pentyl acetate was metabolized faster then all other straight chain acetates (methylacetate through octyl acetate) and that branching lowers metabolism rates (as tested for butyl acetate). All values for pentyl acetate are presented in the following table:
Tissue |
Rat |
Rabbit |
Hamster |
Maxilloturbinates |
100 +/- 8 nmol/mg S9 / min |
76 +/- 13 nmol/mg S9 / min |
1110 +/- 101 nmol/mg S9 / min |
Ethmoturbinates |
120 +/- 5 nmol/mg S9 / min |
190 +/- 2 nmol/mg S9 / min |
1300 +/- 33 nmol/mg S9 / min |
Trachea |
110 +/- 10 nmol/mg S9 / min |
80 +/- 11 nmol/mg S9 / min |
930 +/- 143 nmol/mg S9 / min |
Lung |
75 +/- 4 nmol/mg S9 / min |
47 +/- 2 nmol/mg S9 / min |
180 +/- 4 nmol/mg S9 / min |
Liver | 250 +/- 6 nmol/mg S9 / min |
380 +/- 14 nmol/mg S9 / min |
1100 +/- 81 nmol/mg S9 / min |
Respiratory bioavailability
To determine the respiratory bioavailability of a series of alcohols and acetate esters in rats, combined evaluation of vapour uptake inhalation measurements, plethysmography and blood sampling system (for analysis of each parent chemical and its alcohol or acid metabolites) was developed (Oxo process Panel - ACC, 2004). The non-specific loss (in the absence of animals) of test substance vapours from the exposure chamber was biphasic, showing an initial more rapid loss, and generally tended to be slightly greater for the acetates than for the alcohols. The specific chamber loss rates were fairly high (up to 66% over the first hour). The additional loss of chemical from the chamber in the presence of a live rat was always substantially greater than non-specific chamber loss.
According to the results of the study the test substance present in blood after inhalative exposure (of 6 male Sprague-Dawley rats to 2000 ppm test substance vapours once for 2 hours) is rapidly converted to its alcohol metabolite (n-Pentanol and 2 - methyl butanol) as well as traces of its acid metabolites (valeric and methyl butyric acids). The alcohol metabolites exhibited the highest Cmax value, indicating a rapid conversion from the pentyl acetate parent to the alcohol, whereas the acid metabolite was near limits of detection.
Dermal absorption
The absorption of primary amyl acetate isomers from a 35:65 mix of 2-methylbutyl acetate and pentyl acetate was measured in vitro through human epidermis in a test protocol equivalent or similar to the OECD Guideline 428 (Skin Absorption: In Vitro Method; The Dow Chemical Company, 2000). The primary amyl acetate mixture was applied undiluted at a rate of 100 μl/cm2and left occluded throughout the entire exposure period (24h).
The absorption rates for both isomers of amyl acetate were essentially constant after the first 6 hours of exposure. The 2-methylbutyl acetate isomer was absorbed at a rate of 47.8 μg/cm2/h (Kp = 1.56 x 10-4cm/h), while the pentyl acetate isomer was absorbed at a rate of 123 μg/cm2/h (Kp = 2.16 x 10-4cm/h). These results indicate that the 2-methylbutyl acetate and pentyl acetate isomers are moderately well absorbed through human epidermis when compared with the absorption rates of other penetrants measured using this in vitro technique (Dugard et al, 1984; Dugard and Scott, 1984). The pentyl acetate isomer is absorbed through human epidermis at a faster rate than 2- methylbutyl acetate isomer.
These results are supported by a more recent in vitro study conducted with pig skin (Schenk 2018). The 2-methylbutyl acetate isomer was absorbed at a rate of 23.3 μg/cm2/h (Kp = 6.37 x 10-4cm/h), while the pentyl acetate isomer was absorbed at a rate of 62.6 μg/cm2/h (Kp = 1.19 x 10 -3cm/h).
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.