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Description of key information

Short description of key information on bioaccumulation potential result: 
The pharmacokinetics of iso-propyl alcohol (IPA) following inhalation, oral, and intravenous administration was investigated in rats in a GLP-compliant study.
The following absorption data have been taken into account for DNEL derivation: Oral absorption is nearly 100% as evidenced by the nearly complete lack of radiolabel in feces for up to 168 hours following gavage administration of radiolabeled IPA (see toxicokinetic statement). IPA has a molecular weight of <500 g/mol and a log Kow between 0 and 4; therefore, it is assumed to be well absorbed equivalently by the oral and inhalation route; therefore, inhalation absorption assumed to be 100%. Dermal absorption of IPA is rapid but limited. Following a 4-hour occlusive application 84 to 86% of the applied dose was recovered from the skin and 8 to 9% was lost (presumably to volatilization); thus, approximately 5 to 8% of the applied dose wasabsorbed systemically (see toxicokinetic statement) and absorption was conservatively assumed to be 8%.
Short description of key information on absorption rate:
FROM ethanol:
Dermal absorption from in vitro studies: 21% maximum absorption (worse case) Real life absorption typically ~1-2%. Evaporation half life around 12 seconds from skin.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

There are no data available for the reaction mass. However, basic toxicokinetics will be the same as for the two constituents.


The low molecular weight (60 g/mol) and log Pow value (0.05) of IPA favour its absorption via various routes of exposure. Studies in rats that have profiled the toxicokinetics of IPA following inhalation, oral, intravenous, and dermal exposure indicate that the likely routes of significant systemic exposure are inhalation and oral. In all cases IPA is absorbed rapidly and detected in the blood along with its primary metabolite, acetone. Inhalation exposure for 6 hours results in blood concentrations that increase over the course of the exposure and that decrease rapidly upon cessation. Oral absorption is nearly 100% as evidenced by the nearly complete lack of radiolabel in feces for up to 168 hours following gavage administration of radiolabeled IPA. Dermal absorption of IPA is rapid but limited. Following a 4-hour occlusive application 84 to 86% of the applied dose was recovered from the skin and 8 to 9% was lost (presumably to volatilization); thus, approximately 5 to 8% of the applied dose was absorbed systemically. By all routes of exposure the blood half life of IPA is short (on the order of 1 or 2 hours) and tissue accumulation is minimal. Tissue distribution is broad, but clearance from the tissue compartment appears to be uniform and nearly complete. In general, greater than 60% of an administered dose of IPA is excreted within 24 hours and greater than 90% is excreted within 72 hours. The major route of excretion for all routes of administration is the exhaled air, primarily in the form carbon dioxide and volatile organic compounds (including IPA and acetone). Urine and feces account for excretion of less than 10% of an administered dose, with the vast majority of this amount contributed by urine. Based on the available data and taking into consideration its low molecular weight, log Pow value, and considerable water solubility, IPA is not expected to bioaccumulate.



[1] O’Neil MJ (2006) The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals (14th Edition), Merck & Co., Inc.;,,.
(2000) CRC Handbook of Chemistry and Physics (81st Ed), CRC Press; Taylor & Francis Group,,,.

[3] Slauter RW (1991) Disposition and pharmacokinetics of isopropyl alcohol in F-344 rats after intravenous or oral administration or nose only inhalation. Report number: RTI/4444-01F.

[4] Boatman RJ et al. (1995) Dermal absorption and pharmacokinetics of isopropanol in the male and female F-344 rat. Report number: 066094.

[5] Gill MW (1991) Isopropanol Single Exposure Vapor Inhalation Neurotoxicity Study in Rats. Report number: HSE-91-0010.

[6] Burleigh-Flayer et al. (1991) Isopropanol fourteen-week vapor inhalation study in rats and mice with neurotoxicity evaluation in rats. Report number: 53-589.

[7] Burleigh-Flayer HD and Benson CL (1994) Isopropanol vapor inhalation oncogenicity study in Fischer 344 rats. Report number: 91N0133.

[8] Burleigh-Flayer HD and Wagner CL (1993) Isopropanol vapor inhalation oncogenicity study in CD-1 mice. Report number: 91N0132.

[9] Tyl RW et al. (1990) Developmental toxicity evaluation of isopropanol administered by gavage to CD (Sprague-Dawley) rats. Report number: 311C-4557.

[10] Tyl RW et al. (1990) Developmental toxicity evaluation of isopropanol administered by gavage to NewWhite rabbits. Report number: 311C-4557.

Discussion on bioaccumulation potential result:

There are no data available for the reaction mass. However, basic toxicokinetics will be the same as for the two constituents.



Ethanol has a low molecular weight (46.07) and is highly soluble in both water and lipid, allowing absorption across the surface of the gastrointestinal (GI) tract, the lungs and skin. Following ingestion, absorption of ethanol begins immediately with greater than 90% of the consumed dose being absorbed by the GI tract.  The consumption of two alcoholic beverages (approximately 20g ethanol) results in a maximum BEC of approximately 300 mg ethanol/L within one hour; the concentration of ethanol in blood then rapidly declines, reaching endogenous levels after several hours.

Ethanol can also be absorbed by inhalation.  A study investigated the respiratory uptake of methanol (a similar alcohol to ethanol) in male volunteers using a single exposure concentration of 100ppm and established that over a 10 minute period of exposure, uptake is around 61% of the inhaled concentration (Kumagai, 1999).  The authors concluded that the results of this study (which examined a number of solvents) when correlated with partition co-efficients supports the hypothesis that solvent absorbed in the mucous layer of the respiratory tract is removed by the bronchial blood circulation  An approximate figure of 60% absorption of inhaled ethanol is supported by their human studies with relatively high levels of exposure, ranging from 5000 to 10,000 ppm ethanol (Lester, 1951).  A recent study using lower levels of ethanol exposure (25 – 1000 ppm) reported a value of between 70 to 80 % absorption (Tardif, 2004), which may be more representative of occupational exposure levels. Once absorbed by this route, the degree of ethanol retention is generally low due to the ‘wash-in-wash out effect’ observed with water soluble chemicals.  Seeber et al., (1994) exposed 24 volunteers  to ethanol at 80, 400 and 800 ppm for 4 hours with resulting blood ethanol levels of 0.25, 0.85 and 2.1 mg/l.   It is possible to make a calculation from this data to derive a function BEC (blood ethanol concentration)=exposure (ppm) × 0.0029 (with a 7% error for 95% confidence).  This would give a BEC of 2.9mg/l and an AUC over 8hrs of (lower but not dissimilar).  This can be compared to a similar estimation from the oral data.  Assuming  instantaneous distribution and linear kinetics for elimination, a dose of 11.4g would give a BEC of 302mg/l (assuming a volume of distribution of 0.54l/kg and a 70kg person).  If this is eliminated at a rate of 127mg/kg/hr (8.9g/hr), total elimination would occur in 11.4/8.9=1.29hrs.  The area under the triangle is then  Calculating the at the other extreme (lighter person – 60kg, slower elimination – 83mg/kg/hr or 4.99g/hr) would lead to a peak BEC of 352mg/l, an elimination time of 2.28hrs and an AUC of  This demonstrates that a simple calculation of quantitative uptake based on inhalation concentration, duration and percentage uptake significantly overestimates the exposure by a factor of approximately 5-15x compared to when a more relevant measure is used.

A male human volunteer was exposed to ethanol vapour at 1900 mg/m3 in an exposure chamber for 3 hours. Exposures were carried out at different ventilation rates. Ethanol in blood samples remained consistently below the limit of detection of 2 mg/L. It was concluded that exposure to ethanol vapour at 1900 mg/m3 will not produce a significant blood alcohol concentration. Another study using five male exposed for six hours to air containing ethanol at concentrations of up to 1000 ppm produced a similar result. Ethanol was not detected in the blood of volunteers exposed to 250 and 500 ppm, whereas blood concentrations measured at 3 and 6 hr during exposure to 1000 ppm (about 1884 mg/m3) were 0.229 mg/100 ml and 0.443 mg/100 ml, respectively. Ethanol concentrations in expired alveolar air "reached a steady-state 3 h after the start of exposure" and ranged from 241 to 249 ppm in the volunteers exposed to air containing ethanol at 1000 ppm (suggesting that absorption of ethanol from the lungs is approximately 75%).


Irrespective of the route of exposure, following absorption into the bloodstream, ethanol is distributed throughout the body with the final volume of distribution close to that of total body water, estimated as 50 – 60 % of lean body weight in adults. Ethanol perfuses organs with the greatest blood supply most quickly (brain, lungs and liver) and equilibrium between tissues and blood is generally achieved within 1 – 1.5 hr after ingestion (Bevan, 2009 , J Tox Env Hlth B Crit Rev, 12(3), 188-205).


Prior to absorption, ingested ethanol undergoes limited metabolism (first pass metabolism) in the stomach by gastric alcohol dehydrogenase.  The role of first-pass metabolism is, however, not relevant for exposure to ethanol via inhalation and dermal routes. Once absorbed, ethanol is metabolised, principally by the liver, which accounts for 92-95% of capacity with minor amounts metabolised in other tissues such as the kidney and lung. A number of metabolic paths are available but only one is relevant to the low blood ethanol concentrations likely to result from either inhalation or dermal exposure and only this mechanism is described here.  In such cases, Ethanol metabolism in the liver is carried out in three steps, namely, (i) oxidation of ethanol to acetaldehyde (AcH), (ii) conversion of AcH to acetate and (iii) oxidation of acetate to carbon dioxide and water. In the first step, ethanol is converted to AcH by alcohol dehydrogenase (ADH) which occurs in the soluble fraction of liver cells (cytosol).  The conversion of ethanol to AcH by ADH is the rate-limiting step in ethanol metabolism as ADH has a low Michaelis-Menten constant (Km).  ADH has been shown to exhibit polymorphisms that affect functional activity, accounting for ethnic variations in the pharmacokinetics of ethanol.   In a study to examine the metabolism of ethanol and in particular the difference between humans with normal and humans with deficient ALDH, 60 volunteers were given a single oral dose of ethanol and the elimination kinetics determined by following subsequent blood ethanol levels with time. The data showed that there is a slight but not a significant difference in the ethanol elimination rates between those with normal ALDH and those with deficient ALDH.  In a study to examine the metabolism of ethanol and in particular the difference between humans with normal and humans with deficient ALDH and the contribution of first pass metabolism, male volunteers were given a oral doses of ethanol and the elimination kinetics determined by following subsequent blood ethanol levels with time. This was compared to similar doses given intravenously. The effect of fasting versus eating prior to dosing was also examined. The data showed that resultant blood ethanol concentrations were always lower by the oral route and that oral dosing on a full stomach greatly reduced oral uptake. The study also showed that deficient ALDH resulted in greatly increased blood acetaldehyde concentrations but not significantly increased ethanol levels Skin has many of the enzymes that occur in the liver but its metabolising potential is considered too small to be considered for most chemicals at an estimated 2% of that of the liver. However, there is some evidence from a more recent ex vivo animal study that repeated dermal exposure may result in increased metabolic activity in the skin . In the second step of ethanol metabolism, AcH is rapidly converted to acetate by the enzyme acetaldehyde dehydrogenase (ALDH).  Acetate formed in the liver following oxidation of ethanol has a high ratio of NADH/NAD+ and as a consequence cannot be incorporated into the citric acid cycle. In the final step of ethanol metabolism, acetate produced from the oxidation of AcH is therefore released into the blood and oxidised extra-hepatically to carbon dioxide and water by peripheral tissue.

In a human volunteer study using 24 men and women, it was established that exposures of up to 2000ppm of ethanol for periods of up to 4 hours do not saturate metabolism and that elimination kinetics are first order. A linear relationship was established between exposure concentration and resultant blood ethanol concentrations, leading to the prediction that the a maximum blood ethanol concentration of 2.9mg/l results from an (indefinite) exposure to 1000ppm of ethanol.


The majority of absorbed ethanol is eliminated from the body by metabolism (95 –-98 %); the process has limited capacity but this is extremely unlikely to be overwhelmed at the blood ethanol concentrations estimated to result from occupational exposure to ethanol.. The maximum amount of ethanol that can be metabolised per hour has been estimated to be between 83 – 127 mg/kg/hr, or 8 – 9 g ethanol/hr.  Elimination rates can be influenced by both environmental and genetic factors leading to intraspecies variation in rates. A small concentration of ethanol (2 – 5 %) is also eliminated unmetabolised in breath, urine and sweat.  This conclusion is supported by a study which both contained original data and the results of other published studies, human volunteers were given varying oral doses of ethanol and the elimination rate followed by measuring decaying blood ethanol concentration. Ethanol was found to be rapidly eliminated with a typical elimination rate constant of 11 -15mg/dl/hr over the range of doses examined (0.5 -0.8g/kg). It was noted that the elimination rate increase slightly but significantly with dose and that the range of rate constants varied by a factor of 3 from 8 -13mg/dl/hr in the relatively large number of subjects studied. Another study examined the concentration-time profiles of ethanol in capillary blood for 21 fasted men after ingesting 0.68g/kg of ethanol. The concentration-time profiles varied significantly between subjects, particularly in peak levels, however peak ethanol concentrations were close the the maximum predicted assuming 100% absorption and instant distribution in body fluids. The rate of elimination was found to be 85mg/kg/hr +/-6.4 with complete disappearance from the blood 494mins +/-38 (8.2hrs) after ingestion. In conclusion, elimination is constant and ethanol taken in at rates below the limiting rate of elimination are not likely to lead to any accumulation of ethanol in the blood.

Blood ethanol concentrations were estimated from breath analysis of a healthy male volunteer over time after consumption of 5 g ethanol diluted in orange juice. The elimination of exogenous ethanol took just over 2 hr, with a half-life of about 16 minutes. Expired alveolar air, from two men and one woman who had consumed between 0.26 and 0.6 g ethanol/kg bw in five separate experiments, was analysed for ethanol concentrations, in an attempt to determine the rate of ethanol disappearance from the human body. The rate of disappearance of ethanol was linear down to levels of ethanol in the serum of 100 mg/L, or in some subjects as low as 50 mg/L. Below this level, it was determined that the rate of disappearance, in mg/L serum/hr, may be calculated as the product of the concentration of ethanol in serum (mg/L) by the constanct 1.64.


Slauter (1991) investigated the absorption, distribution, metabolism, and excretion of IPA in male and female Fischer 344 rats following inhalation, oral, and intravenous exposure. It should be noted that inhalation is the expected route of exposure for IPA. In the inhalation study, male and female rats were exposed for 6 hours to radiolabeled IPA vapour by nose-only inhalation at nominal concentrations of 500 (low dose) and 5000 ppm (high dose). The concentration of radiolabel and of IPA in the blood increased rapidly following the initiation of inhalation exposure at either concentration. The half-life of IPA was reported to be approximately 0.8 hours in males and 0.9 hours in females at the low dose, and 2.1 hour in males and 1.8 hours in females at the high dose. The mean maximum plasma concentration (Cmax) at 6 hours was reported to be 116 μg-eq/g in males and 125 μg-eq/g in females of the low-dose group, and 1258 μg-eq/g in males and 1449 μg/g in females of the high dose group.

IPA and its radiolabeled metabolites were widely distributed among body tissues, with higher levels occuring in theadipose tissue, kidney, liver, and ovarian tissue relative to blood levels. Clearance from the tissue compartment was uniform and nearly complete and no evidence was observed to indicate that IPA or its radiolabeled metabolites accumulated in any tissue; no single tissue contained greater than 1.6% of the recovered dose in either sex, and carcasses contained an average of 5% of the dose.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. Thebreath was the predominant route of excretion of radiolabel by both sexes, with greater than 80%of the absorbed dose excreted via this route. Urine and feces accounted for excretion of approximately 7% and 2% of the absorbed dose, respectively.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 carbon dioxide.Following exposure to 500 ppm IPA, nearly all of the radiolabel present as volatile organic compounds in the exhaled breath was accounted for by acetone. Following exposure to 5000 ppm IPA, an average of approximately 80% of the radiolabeled volatile organic compounds in the breath was identified as acetone with the balance being accounted for by IPA. A third radiolabeled metabolite (accounting for less than 5% of the total dose) was detected in the urine; however, the identity of this metabolite was not determined. Based on the results of this study, no bioaccumulation potential for IPA was reported following inhalation exposure. 

In the oral study, male and female Fischer 344 rats received a single gavage dose of 300 or 3000 mg/kg body weight of IPA or were exposed to 300 mg/kg body weight/day of IPA by gavage for 8 consecutive days (Slauter, 1991). In the intravenous study, male and female Fischer 344 rats received a single intravenous injection of 300 mg/kg body weight of IPA (Slauter, 1991). Similar results as in the inhalation study were reported following both oral and intravenous routes of exposure. The radiolabel and IPA were absorbed and appeared in the blood rapidly following oral administration. Following both oral and intravenous administration, IPA and its radiolabeled metabolites were widely distributed among the tissues. The major route of elimination for both sexes was the exhaled breath, accounting for at least 70% of the dose administered following oral (single dose) and intravenous administration. Volatile organic compounds were the major metabolites identified in the exhaled breath and accounted for 55% of the administered radiolabel following both oral (single dose) and intravenous administration. Acetone was identified as the major radiolabeled volatile oraganic compound excreted in exhaled breath; IPA also was identified following high oral dose exposure and intravenous administration. Carbon dioxide was also excreted in the exhaled breath and acounted for at least 15% of the administered radiolabel. Small amounts of the radiolabel (<10% of the dose) was excreted in urine, with 3 metabolites identified as acetone, IPA, and an unknown metabolite. Less than 2% of the administered radiolabel was excreted in feces. No tissue was observed to retain more than 2.4% of the dose, and the carcass contained approximately 4% of the dose.Based on the results of these studies, no bioaccumulation potential for IPA was reported following oral or intravenous routes of exposure. 

Boatman et al. (1995) investigated the dermal absorption of IPA in male and female Fischer 344 rats exposed to a single dose of IPA (70% in water, under occlusion) for 4 hours. Maximum blood concentrations of IPA of approximately 0.2 μmoles/g of blood for both males and females were attained at 4 hours. Acetone blood levels rose steadily during the 4-hour exposure and continued to rise following removal of the test material at 4 hours, reaching peak blood levels of 0.79 and 1.17 μmoles/g in male and female rats, respectively. First-order elimination half-lives for IPA and acetone were similar for male and female rats, with mean values of approximately 0.8 hours for IPA and 2.6 hours for acetone. 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 IPA 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 and8 to 9% was lost (presumably to volatilization).Thus, approximately 5 to 8% of the applied dose was absorbed systemically over the course of the 4-hour exposure. Expired CO2and volatiles accounted for 4.1 and 2.1%, respectively, of the recovered dose in male rats and 3.7 and 2.1%, respectively, in female rats. Urine, cage wash, and feces contained approximately 0.5% of the remaining radioactivity with the majority of this present in the urine. Under the conditions of this study, the authors concluded that IPA was rapidly absorbed in vivo through rat skin. Cumulatively, these data indicate that IPA does not have bioaccumulation potential following dermal exposure.

Discussion on absorption rate:


In a study to assess the skin penetration potential of ethanol, an in vitro study was carried out using excised pig skin and radiolabelled ethanol. Ethanol penetration was greater under occlusive conditions than non-occlusive conditions, as might be expected. Absorption rates were around 21% and 1% of applied doses respectively. In a study to help understand the skin penetration potential of ethanol, an in vitro study was carried out to assess the evaporation rate of radiolabelled ethanol from excised pig skin. The evaporation half life was found to be 11.7seconds, suggesting that systemic doses of ethanol resulting from skin absorption following single exposures to ethanol will, under practical conditions, be very low due to rapid evaporation. In a study to assess the potential for skin uptake of ethanol from the use of personal care products, human volunteers applied ethanol over their whole bodies delivered from an aerosol can. The mean dose of ethanol applied was just under 10g per subject. Ethanol could not be unequivocally detected in the blood of any of the 16 volunteers in the hour immediately after application.

An in vitro system was used to assess the penetration of radiolabelled ethanol through excised, full thickness, guinea-pig skin. Less than 1% of the applied dose of ethanol penetrated the "uncovered" skin over a period of 19 hours, and there did not appear to be an increase in penetration with increasing dose volume. When the test system was "occluded" using Parafilm, a polyester Gel Bond film, or plastic Hill Top chambers, the penetration was significantly enhanced.

The absorption of ethanol was measured in the blood of twelve volunteers following repeated application of three different ethanol based hand disinfectants containing different concentrations of ethanol (95, 85, and 55%, respectively). Two exposure regimes were evaluated, mimicking worst case hygienic and surgical hand disinfection. Blood was sampled prior to, and 2.5, 5, 10, 20, 30, 60, and 90 minutes after the last hygienic disinfection. After the last application the median absorbed ethanol in the blood increased gradually and peaked after 30 minutes. The amount of absorbed ethanol was calculated at 2.3, 1.1, and 0.9% with hand rubs A, B, and C, respectively in the hygienic disinfectant simulation and 0.7, 1.1, and 0.5% with hand rubs A, B, and C, respectively in the surgical hand disinfectant simulation.