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EC number: 701-241-0
CAS number: -
Short description of key information on bioaccumulation potential
In accordance with Regulation (EC) 1907/2006, the toxicokinetic
behaviour of the substance has been assessed to the extent that can be
derived from the relevant available information.
Short description of key information on absorption rate:
Dermal absorption of the substance has been assessed to the extent that
can be derived from the relevant available information.
The substance Reaction Products of C3 alcohols and C3
alkenes obtained as by-products from the manufacture of propan-2-ol by
hydration of propylene is a UVCB substance. The main constituent
(approximately 50%) is isopropyl ether. Minor constituents are propylene
dimers (~20%, C6 hydrocarbons, mainly C6 alkenes), propylene trimers
(~10%, C9 hydrocarbons), hexanols (~10%) and C3 alcohols (~10%
consisting of both isopropanol and n-propanol).
The toxicokinetic behaviour of the UVCB substance can be predicted
based on the toxicokinetic behaviour of its main constituents.
Isopropyl ether (IPE, also known as diisopropylether, DIPE) is
expected to be efficiently absorbed orally and via inhalation, based on
its water solubility and molecular weight. Some dermal absorption is
expected, although to a limited extent. The metabolism of IPE was
investigated by Stagliola and Schatz (2007) to determine if the two
major metabolites were as predicted, isopropyl alcohol (IPA) and acetone
(dimethyl ketone or DMK). Using rat nasal mucosa microsomes in vitro,
they found that the metabolites, IPA and DMK, were produced in a
concentration-dependent manner. P450 isoforms, CYP2A3 and 2E1, were
identified as the key enzymes involved in IPE metabolism. In vivo studies
showed a rapid systemic clearance of DIPE, secondary butyl alcohol (SBA)
and DMK from the blood of rats within 24 hours following a 6-hour
inhalation exposure to 5000 ppm IPE. Therefore, IPE nor its
biotransformation products are expected to bioaccumulate.
Data on propylene dimers can be derived by reading across from
data on C6 hydrocarbons (represented by 2-methyl pentane) and C6
alkenes. 2-Methyl pentane is poorly absorbed dermally with a measured
percutaneous absorption rate in rat skin and in vitro of
approximately 0.1 µg/cm2/hr or <1% of the total fluid
applied (Tsuruta, 1982). When dermally absorbed, 2-methyl pentane is
rapidly eliminated. Data from human biomonitoring in urine show that the
main metabolite identified in urine upon exposure to 2-methyl pentane is
2-methyl-2-pentanol. 2-Methyl derivatives of 1-, 3-, and 4-propanol, and
2-methylpentane-2,4-diol were minor metabolites (Kawai et al., 1995).
2-Methyl pentane nor its biotransformation products are expected to
The uptake, distribution, and elimination of C2-C10 1-alkenes
after inhalation exposure has been investigated in the rat (Zahlsen,
1993 and Eide et al., 1995). Male Sprague-Dawley rats were exposed via
whole body inhalation to 100 or 300 ppm vapour of the individual test
substances for 12 hours/day for 3 consecutive days. Concentrations of
the hydrocarbons were measured in blood, brain, liver, kidney and
perirenal fat immediately following each 12 hour exposure and 12 hours
following the last exposure. The results show that concentrations of
1-alkenes in blood and organs reached a steady-state level after the
first 12 h exposure, and the concentrations 12 h after the last exposure
were generally low, except in fat tissue. Higher concentrations of
linear alpha olefins were measured in each of the respective organs
compared with measured concentrations of the corresponding isoalkanes.
Concentrations of 1-alkenes in blood and the different tissues increased
with increasing number of carbon atoms.
Data on propylene trimers can be derived by reading across from
data on C9 alkanes and C9 alkenes.
Based on available data on C9 alkanes and structurally related
compounds, these hydrocarbons are expected to be readily absorbed and
distributed through the body (Zahlsen et al., 1992). n-Alkanes are
readily metabolized and excreted in urine and expired as CO2.
Iso-alkanes are less readily metabolized to a range of metabolites that
are excreted in the urine. The C9 alkenes are expected to be eliminated
at a lower rate than C9 alkanes, with the C9 alkenes being distributed
mainly to the fat tissue.
Hexanol is expected to be absorbed by the most common routes of
exposure, with dermal absorption expected to be significant (Scheuplein
and Blank, 1973). After absorption hexanol is widely distributed within
the body and efficiently eliminated. The initial step in the mammalian
metabolism of primary alcohols is the oxidation to the corresponding
carboxylic acid, with the corresponding aldehyde being a transient
intermediate. These carboxylic acids are susceptible to further
degradation via acyl-CoA intermediates by the mitochondrial ß-oxidation
process, in which C2 units are stepwise eliminated. Hexanol nor its
biotransformation products are expected to bioaccumulate (WHO, 1998).
Based on their physico-chemical properties, both isopropanol and
n-propanol are expected to be readily absorbed and distributed
throughout the body following ingestion (European Chemicals Bureau,
2008; OECD 1997). Dermal absorption is expected to be slow. n-Propanol
is metabolized by alcohol dehydrogenase to propionic acid via its
corresponding aldehyde and may enter the tricarboxylic acid cycle.
Isopropanol is quickly metabolized to acetone and subsequently excreted
as CO2. Both n-propanol and isopropanol are rapidly and
Overall, the data on the main constituents of Reaction Products of
C3 alcohols and C3 alkenes obtained as by-products from the
manufacture of propan-2-ol by hydration of propylene show that
this UVCB substance is expected to be readily absorbed via the oral and
inhalation routes of exposure and to a limited extent via the dermal
route. The substance is expected to be efficiently metabolized resulting
in a rapid systemic clearance, with the C6 and C9 alkenes being
eliminated at a lower rate than the other constituents. The substance is
not expected to bioaccumulate.
Eide I., Hagemann R., Zahlsen K., Tareke E., Tornqvist M., Kumar
R., Vodicka P., and Hemminki K. (1995) Uptake, distribution, and
formation of hemoglobin and DNA adducts after inhalation of C2-C8
1-alkenes (olefins) in the rat. Carcinogenesis 16(7):1603-1609.
European Chemicals Bureau (2008) European Union Risk Assessment
Report of propan-1-ol. Volume 82. Ispra, Italy.
Kawai T., Mizunuma K., Yasugi T., Horiguchi S., Iguchi H., Mutti
A., Ghittori S., and Ikeda M. (1995) Monitoring of exposure to
methylpentanes by diffusive sampling and urine analysis for alcoholic
metabolites. Occup. Environ. Med. 52(11):757-63.
OECD (1997) SIDS dossier on the HPV chemical Isopropanol. UNEP.
Scheuplein R.J. and Blank I.H. (1973) Mechanism of Percutaneous
Absorption. IV. Penetration of Nonelectrolytes (Alcohols) from Aqueous
Solutions and from Pure Liquids. J. Investigat. Dermatol. 60(5):286-296.
Stagliola E. and Schatz R. (2007) In vivo and in vitro metabolism
of diisopropyl ether (DIPE). The Toxicologist, Abstract 971.
Tsuruta, H. (1982) Percutaneous absorption of organic solvents
III. On the penetration rates of hydrophobic solvents through the
excised rat skin. Industrial Health 20(4):335-345.
World Health Organization – WHO (1998) Technical Report Series 884
Evaluation of certain food additives and contaminants. 49thReport
of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), Geneva.
Zahlsen K., Eide I., Nilsen A.M., and Nilsen O.G.
(1993).Inhalation kinetics of C8 to C10 1-alkenes and iso-alkanes in the
rat after repeated doses. Pharmacology and Toxicology 73:163-168.
Testing laboratory: Department of Pharmacology and Toxicology Faculty of
Medicine, University Medical Center, N-7005 Trondheim, & Statoil
Research Center, N-7004 Trondheim, Norway.
Discussion on absorption rate:
The substance Reaction Products of C3 alcohols and C3 alkenes obtained
as by-products from the manufacture of propan-2-ol by hydration of
propylene is a UVCB substance. The main constituent (approximately
50%) is isopropyl ether. Minor constituents are propylene dimers (~20%,
C6 hydrocarbons, mainly C6 alkenes), propylene trimers (~10%, C9
hydrocarbons), hexanols (~10%) and C3 alcohols (~10% consisting of both
isopropanol and n-propanol).
The dermal absorption of the UVCB substance can be predicted based
on the dermal absorption of its main constituents.
Quantitative dermal absorption information is available for the
constituents 2-methyl pentane, isopropanol and hexanol.
The dermal absorption of 2-methyl pentane was determined in rat
skin and in vitro (Tsuruta, 1982). The percutaneous absorption
was determined to be 0.1 µg/cm2/hr or <1% of the total
The dermal absorption of hexanol was determined in vitro using
human epidermis (Scheuplein and Blank, 1973). Sheets of dermis and
epidermis were obtained at autopsy, and were supported as diaphragms on
standard diffusion cells. Primary alcohols with 1 to 10 carbon atoms, in
pure form or in saturated aqueous solution, were placed in the donor
side of the diffusion cell. The receptor side was filled with distilled
water. Contents of both sides were analyzed at regular intervals, and
permeation rates were calculated. For saturated aqueous solutions,
permeation rates through dermis declined with increasing carbon number
and ranged from 5.3 micromoles per 0.01 cm per 0.1 hours for aqueous
methanol to 0.09 for aqueous octanol. Permeation rates through epidermis
rose from 0.05 for aqueous methanol to 0.71 for aqueous hexanol, then
declined to 0.02 for aqueous decanol. Permeation rates of propanol
through octanol ranged from 2.12 to 0.063 through epidermis and 24
through 0.13 through dermis.
For IPE no experimental data on dermal absorption are present.
Considering the physicochemical properties of IPE, some dermal
absorption is expected.
Boatman et al. (1995) investigated the dermal absorption of
isopropanol in male and female Fischer 344 rats exposed to a single dose
of isopropanol for 4 hours. Dermal absorption rates were calculated to
be 0.78 and 0.85 mg/cm2/hour for males and 0.77 and 0.78 mg/cm2/hour
for females, using two independent methods. Calculated permeability
coefficients of 1.37 to 1.50 x 10-3cm/hour for males and 1.35
to 1.38 x 10-3cm/hour for females indicate that isopropanol
is rapidly absorbed dermally. Of the applied radioactivity dose, 84 to
86% was recovered from the skin at the end of the 4-hour exposure and 8
to 9% was lost (presumably to volatilization). Thus, approximately 5 to
8% of the applied dose was absorbed systemically over the course of the
Based on the dermal absorption information from 2-methyl pentane,
hexanol and IPE it can be concluded that some dermal absorption of
Reaction Products of C3 alcohols and C3 alkenes obtained as
by-products from the manufacture of propan-2-ol by hydration of
propylene may be expected.
Boatman R.J., Perry L.G., and Fiorica L.A. (1995) Dermal
absorption and pharmacokinetics of isopropanol in the male and female
Report no.: 066094. American Chemistry Council, Inc. Study number:
Tsuruta H. (1982) Percutaneous absorption of organic solvents III.
On the penetration rates of hydrophobic solvents through the excised rat
skin. Industrial Health 20(4):335-345.
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.
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