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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 201-143-3 | CAS number: 78-79-5
- 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
Key value for chemical safety assessment
- Bioaccumulation potential:
- low bioaccumulation potential
- Absorption rate - dermal (%):
- 0.3
- Absorption rate - inhalation (%):
- 10
Additional information
Endogenous Production
Isoprene is formed endogenously in humans; the sources proposed include mevalonic acid via the intermediate product dimethylallyl pyrophosphate (precursors of cholesterol), the peroxidation of squalene, and from the decomposition of farnesyl (3 isoprene units) or geranylgeranyl residue (4 isoprene units) of prenylated proteins. Isoprene is found in the exhaled air of humans and is the major (30-70%) hydrocarbon component. It has been reported that the amounts of isoprene exhaled within a 24-hour period were determined to be 0.36 to 9.36 mg (Conkle et al., 1975) and 2 to 4 mg (Gelmont et al., 1981). The mean endogenous blood concentration of isoprene was 37 +/- 25 nmol/L.
Concentrations of isoprene in exhaled air from untreated rats and mice were originally reported by Peters et al. (1987). Subsequently, it was found that the gas chromatography and flame ionisation detection method used employed a column packing material which was unable to differentiate between endogenously produced isoprene and acetone (Filser et al.,1996). Using a different gas chromatography and mass detection technique, very low concentrations of isoprene (some ppb values) were found in the exhaled air of rats.
Toxicokinetics
Isoprene exhibits saturation kinetics in rats and mice. The rate of metabolism was directly proportional to the exposure concentration at concentrations up to 300 ppm. However, both species exhibited saturation kinetics when exposed to isoprene at concentrations above 300 ppm. Saturation of isoprene metabolism was nearly complete at about 1000 ppm in rats and at about 2000 ppm in mice. The maximal metabolic elimination rate in mice was determined to be at least 400 µmol/hr/kg, which is about three times faster than that found in rats (130 µmol/hr/kg). The whole body half-life of isoprene was 6.8 minutes in rats and 4.4 minutes in mice.
The internal dose of isoprene was found to be greater in mice than rats after exposure to the same concentration. At concentrations above 1000 ppm, mice absorb three times more isoprene per kg body weight compared to rats, though at lower concentrations, the species difference in uptake became smaller (approx. two-fold at 700 ppm).
Metabolites of isoprene were detected in the blood, nose, lungs, liver, kidneys, and fat of male F344/N rats exposed to 1,480 ppm [14C]-labelled isoprene.
Metabolism
In liver microsomes, isoprene is metabolized by cytochrome P450 oxidation to the monoepoxide metabolites, 3,4-epoxy-3-methyl-butene and 3,4 -epoxy-2-methyl-butene. Both monoepoxides can be further metabolized to the diepoxide metabolite, 1,2:3,4-diepoxy-2-methyl-butane. The epoxides can also be hydrolysed or can be conjugated with glutathione. It is also expected that epoxide diols can be formed.
Physiologically-based Toxicokinetic Model
A physiologically-based toxicokinetic (PT)-model has been constructed and used to simulate the inhalation of isoprene, its distribution by the blood flow, its metabolism, endogenous production, and exhalation as unchanged isoprene (Filser et al., 1996; Csanady and Filser, 2001). The model compartments consist of air, lung, richly perfused tissues, fat, muscle, and liver. Mouse, rat and human partition coefficients were determined experimentally. The endogenous production of isoprene was considered to occur only in the human liver and was described by zero-order kinetics. Metabolism was assumed to follow Michaelis-Menten kinetics and was allocated to hepatic and also to extrahepatic tissues. Toxicokinetic parameters were derived from reanalysing closed-chamber data measured in rodents (Peter et al., 1987) by means of a two-compartment model. This calculation was based on the assumption that in rodents the endogenous production of isoprene can be neglected quantitatively (Filser et al., 1996). The maximum rate of metabolism (Vmax) was directly incorporated into the PT model; the value of Kmwas scaled. In order to predict toxicokinetics if isoprene in humans, the maximum rate of metabolism was extrapolated allometrically from rats based on body weight to ¾ power. Rat and humans were used to have identical Kmvalues. The rate of endogenous production in humans was estimated from the atmospheric plateau concentration of isoprene measured in a spirometer system (Filser et al., 1996).
In the low exposure concentration range, isoprene metabolism was limited by transport to the metabolizing enzymes and not by metabolic capacity. Taking into account species-specific partition coefficients and physiological processes (ventilation or blood flow), pulmonary uptake, accumulation in the blood and tissues, exhalation and rates of isoprene metabolism were comparable in rodents and humans. The PT model predicted that for exposure concentrations up to 50 ppm, the rate of isoprene metabolism are about 14 times faster in mice and about 8 times faster in rats than in humans.
At 0 ppm atmospheric isoprene, the rate of metabolism in humans is 0.31 µmol/hr/kg body weight and represents the part of endogenously produced isoprene that is metabolized. About 90% of the endogenously produced isoprene is metabolized, and only about 10% is exhaled unchanged.
Lower steady-state concentrations of isoprene are predicted in venous blood of humans compared to the mouse and the rat due to the relatively comparatively faster uptake of isoprene in rodents and because isoprene metabolism is perfusion limited. This can also be predicted from the blood:air partition coefficients which are significantly larger in rodents than in humans. Because of the rapid isoprene metabolism, Csanady and Filser (2001) concluded that isoprene cannot accumulate in humans at low exposure concentrations.
Using the PT model, the area under the blood concentration-time curve (AUC) following an 8 hour exposure to 10 ppm isoprene was calculated to be about 4 times higher than the AUC resulting from the 24 hour exposure to endogenous isoprene (Filser et al., 1996; Filser and Csanady, 2001).
Discussion on absorption rate:
The dermal absorption of isoprene was predicted using a model which considers dermal absorption as a two stage process, permeation of the stratum corneum followed by transfer from the stratum corneum to the epidermis. The model predicted a maximum flux = 0.000638 mg/cm2/min giving an absorption of approximately 0.3% (ten Berge, 2009).
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.