Prop-2-yn-1-ol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: acceptable publication

Data source

Reference

Reference Type:

publication

Title:

Disposition of propargyl alcohol in rat and mouse after intravenous, oral, dermal and inhalation exposure

Author:

Dix KJ, Coleman DP, Fossett JE, Gaudette JR NF, Stanley AP, Thomas BF & Jeffcoat AR

Year:

2001

Bibliographic source:

Xenobiotica, 31: 357- 375

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Deviations:

yes

Remarks:

, see "Principles of method if other than guideline"

Principles of method if other than guideline:

In the case of single dose administration, at least two dose levels should be used according to OECD Guideline 417.
However, for the dermal and oral route each only one dose level was used, with single target doses of 5 and 50 mg/kg bw, respectively.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Prop-2-yn-1-ol

EC Number:

203-471-2

EC Name:

Prop-2-yn-1-ol

Cas Number:

107-19-7

Molecular formula:

C3H4O

IUPAC Name:

prop-2-yn-1-ol

Details on test material:

For producing the test preparation, the radiolabelled test substance was mixed with non-labelled test substance in order to reach the required specific activity and concentration.

Radiolabelled test substance:
- Name of radiolabelled test material: [14C] Propargyl alcohol
- Radiochemical purity: 90-95 %, determined prior to each use
- Specific activity: 2.33 mCi/mmol
- Locations of the label: C2, C3
- Impurities: At least two minor radiolabelled impurities eluted prior to and one following [14C] Propargyl alcohol.
- Stability under test conditions: The stability, homogeneity and radiochemical purity were checked via HPLC.
- Other: Obtained from New England Nuclear (Boston, MA, USA)

Non-labelled test substance:
- Name of test material: Propargyl alcohol
- Analytical purity: 99 %
- Stability under test conditions: The stability, homogeneity and concentration of the test item preparations were checked via HPLC.
- Other: Obtained from Aldrich Chemical Company, Inc. (Milwaukee, WI, USA)

Radiolabelling:

yes

Remarks:

both radiolabelled and unlabelled test substances were used

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS.
Animals used for bile collection were anaesthetized and kept on heating pads to maintain body temperature throughout the experiment. In mass balance studies, animals were housed individually in all-glass metabolism cages that provided for the separate collection of urine, faeces, carbon dioxide and expired volatile organics. Animals were acclimated to the metabolism cages 1 day prior to dosing. For inhalation studies, animals were acclimated to Battelle restrainers (Geneva) for 2 hours/day on the 2 days prior to exposure and restrained during the 6-hour exposure.

- Source: Charles River Laboratories, Raleigh, NC, USA
- Age at study initiation: 10-16 weeks old
- Weight at study initiation: 201-264 g
- Individual metabolism cages: yes
- Diet: Certified Purina Rodent Chow 5002, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 64-79 °F corresponding to 17.8-26.1 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 hours / 12 hours

Administration / exposure

Route of administration:

other: i.v., oral, dermal, inhalation

Vehicle:

other: for i.v. administration: 9.1 (v/v) preparation of 0.9 % aqueous sodium chloride and ethanol; for oral administration: water; for dermal administration: ethanol; for inhalation: water (low dose only)

Details on exposure:

1. Dermal exposure

TEST SITE
- Area of exposure: 12 cm²
- Type of wrap if used: cover of charcoal-impregnated material

REMOVAL OF TEST SUBSTANCE
- Washing: yes, after the 6-hour exposure

TEST MATERIAL
- Amount applied: approximately 200 µL
- concentration (if solution): 6.25 mg/mL


2. Oral exposure

PREPARATION OF DOSING SOLUTIONS:
Oral dose formulations contained [14C] Propargyl alcohol and non-radiolabelled Propargyl alcohol in water. The target oral dose was 50 mg/kg bw in a dose volume of 5 mL/kg bw.


3. Inhalation exposure

TYPE OF INHALATION EXPOSURE: nose only

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: apparatus constructed at the Research Triangle Institute (Sauter et al., 1994)
- Method of holding animals in test chamber: Battelle restrainers (Geneva)

Duration and frequency of treatment / exposure:

i.v. exposure: single bolus
dermal exposure: single application, for a total of 6 hours
oral exposure: single treatment, by oral gavage
inhalation exposure: continuous exposure for 6 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
i.v. exposure: target dose of 1.0 mg/kg bw (1 mL/kg bw)
dermal exposure: target dose of 5 mg/kg bw (6.25 mg/mL, approx 200 µL/rat)
oral exposure: target dose of 50 mg/kg bw (5 mL/kg)
inhalation exposure: target doses of 1, 10 and 100 ppm

Please refer also to the table in "Any other information on materials and methods incl. tables"

No. of animals per sex per dose / concentration:

4-5 animals;
exception: 4 animals per timepoint for tissue distribution assessment resulting in a total of 28 animals

Please refer also to the table in "Any other information on materials and methods incl. tables"

Control animals:

no

Details on study design:

ANAESTHESIA AND EUTHANASIA
Rats were anaesthetized with ketamine/xylazine (7:1, 50-80 mg/kg bw or to effect) prior to preparation of the dermal dose site and at the time the dermal appliance was removed. Rats used in the biliary excretion study were anaesthetized with sodium pentobarbital orally (35 mg/kg) and intraperitoneally (45 mg/kg) prior to surgery and intraperitoneally (5 mg/kg) as needed to maintain a state of anaesthesia during the bile collection period. At the end of the studies, conscious rats were anaesthetized with ketamine/xylazine followed by cardiac puncture. Anaesthetized and exsanguinated rats were euthanized by section of the diaphragm.

PREPARATION OF ANIMALS FOR BILIARY EXCRETION STUDY
Rats used in the biliary excretion study were surgically prepared in-house. Animals were anaesthetized for the duration of the study. A midline incision was made from the xiphoid process to the inguinal region. The bile duct was ligated at its entrance to the duodenum, and a small cut was made in the duct anterior to the ligature. The bevelled end of a small length of PE-50 tubing was inserted into the duct and secured with silk sutures. The cannula was exteriorized and the abdominal incision closed with sutures.

PREPARATION OF ANIMALS FOR DERMAL STUDIES
About 24 hours prior to dosing, rats used in dermal dose studies were anaesthetized as described above. The back and shoulders of each animal were then clipped to remove the fur. The clipped area was washed with a soap solution, rinsed with water and inspected for cuts or nicks. If an animal had damaged skin in the area intended for dosing, it was removed from the study and replaced with another. The area to which the dose was applied ( ca. 3.0 x 4.0 cm or 12 cm² ) was outlined with a waterproof marker, and the animal was allowed to recover overnight.

Details on dosing and sampling:

DOSE PREPARATION AND ADMINISTRATION
Actual administered Propargyl alcohol doses are summarized in "Any other information on materials and methods incl. tables".

Intravenous dose formulations contained [14C] Propargyl alcohol in a 9:1 (v/v) preparation of 0.9 % aqueous sodium chloride and ethanol. They were administered into a lateral tail vein from a 1-mL glass disposable syringe (GlasPak, Becton-Dickenson Co.) equipped with a 27-gauge x 1/2 inch needle for rat. The target i.v. dose was 1.0 mg/kg bw in a dose volume of 1 mL/kg.
Oral dose formulations contained [14C] Propargyl alcohol and non-radiolabelled Propargyl alcohol in water. The target oral dose was 50 mg/kg bw in a dose volume of 5 mL/kg.
Dermal dose formulations contained [14C]PAL in ethanol at a target concentration of 6.25 mg/mL. The target dose was 5 mg/kg bw, which is about one-tenth the dermal LD50 determined for rabbit (Vernot et al., 1977). Before dosing, a non-occlusive protective appliance was attached to the animal just outside of the dose site with medical adhesive (Hollister, Inc., Libertyville, IL, USA). This protective appliance consisted of a 1-cm high frame of polyurethane foam with an outer covering of charcoal-impregnated material cut from a dust/mist respirator (Cat. 9913; 3M, St Paul, MN, USA). Immediately after dosing, a cover fashioned of the same charcoal-impregnated material was placed over the dose site and secured to the top of the frame to trap [14C] Propargyl alcohol that volatilized from the dose site. The dermal dose was administered in a volume of approximately 200 µL over a surface area of 12 cm², which corresponded to a total dose of ca. 1.25 mg/rat. The dose formulation was applied to the dose site with a 1-mL glass disposable syringe equipped with a 16-gauge, 3-mm ball-tipped needle and was spread as evenly as possible over the entire dose site.

GENERATION AND DELIVERY OF PROPARGYL ALCOHOL VAPOUR
Nose-only inhalation experiments were conducted using an apparatus constructed at the Research Triangle Institute as described (Slauter et al., 1994). All surfaces contacting Propargyl alcohol vapours prior to inspiration by study animals were stainless steel, glass or Teflon. Inlet air flow entered a glass vapour-generation column (60 cm x 11 mm i.d.) filled with 3-mm glass beads and maintained at ca. 86°C. A feedstock solution that contained water (low dose only), radiolabelled and non-radiolabelled Propargyl alcohol was metered into the bead bed through small-bore Teflon tubing using an infusion pump. The proper infusion rate was determined experimentally during preliminary trials. Target atmosphere concentrations for inhalation exposures were 1, 10 and 100 ppm.

ANALYSIS OF EXPOSURE ATMOSPHERE
Propargyl alcohol vapour concentrations in inhalation exposure atmospheres were measured by capillary GC on an EC-WAX Econo-Cap column (0.53 mm i.d. x 30 m; Alltech Associates, Inc., Deerfield, IL, USA). Standard curves were constructed using solvent standards containing the mass of Propargyl alcohol expected in 1 mL vapour at concentrations ranging from 0.5-1.5 ppm (r² = 0.999, CV < 4.5 % at all concentrations) for the 1 ppm exposure, from 5-15 ppm (r² = 0.998, CV < 2.9 % at all concentrations) for the 10 ppm exposure, and from 70-118 ppm (r² = 1.000, CV < 2.2 % at all concentrations) for the 100 ppm exposure.

TISSUE DISTRIBUTION TIME COURSE STUDIES
Animals (n = 28) received a single i.v. dose via a lateral tail vein. The average dose was 1.00 ± 0.04 mg/kg bw. Groups of four animals were sacrificed at 0.25, 0.5, 1, 2, 4, 8 and 24 hours post-dosing, and blood and the following tissues/organs were harvested: skin, muscle, adipose, kidney, liver, spleen, lung, testis, bladder, heart, brain, stomach (with contents), small intestine (with contents), caecum (with contents) and large intestine (with contents).

BILIARY EXCRETION STUDY
Anaesthetized and bile duct cannulated rats (n = 4) received a single i.v. dose (1.01 ± 0.03 mg/kg bw) via a lateral tail vein. Following dose administration, bile was collected at 30-min intervals for up to 4 hours into tared vials.

MASS BALANCE STUDIES
Mass balance studies were conducted after i.v., dermal, oral and inhalation exposure to [14C] Propargyl alcohol. Animals were housed individually in all-glass metabolism cages throughout the studies except during dose administration and removal of the protective appliance and unabsorbed Propargyl alcohol in dermal administration studies. Urine and faeces were collected over dry ice in timed fractions. Radiolabelled volatile organics and carbon dioxide were collected in cryogenic ethanol and sodium hydroxide traps, respectively. Urine, faeces, volatile organics and carbon dioxide were collected in timed fractions ending at 6 (except faeces), 12 and 24 hours post-dosing in all mass balance studies.
Additional collections were made at 48 and 72 hours post-dosing for the i.v. and oral dose studies. At necropsy, urine was removed from the urinary bladder and added to the final urine collection. Metabolism cages were rinsed at the end of the experiment with water and ethanol. Animals were killed at 24 (inhalation and dermal exposures) or 72 hours (i.v. and oral exposures) post-dosing. Blood (by cardiac puncture) and the following tissues/organs were harvested except in the dermal and inhalation exposure studies: skin (ears), muscle (hind leg and abdominal), adipose tissue (epididymal and perirenal), kidney, liver, spleen, lung, testis, bladder, heart, brain, stomach (with contents), small intestine (with contents), caecum (with contents) and large intestine (with contents). In i.v. administration studies, animals (n=5) received an average dose of 0.94 ± 0.06 mg/kg bw. In oral administration studies, animals (n=5) received an average dose of 49.9 ± 0.2 mg/kg bw. In addition to evaluating mass balance, a second objective of the oral dose study was to obtain sufficient masses of excreted metabolites for identification. Hence, the oral dose was high relative to the i.v. dose. In dermal administration studies, rats (n=4) received an average dose of 6.41 ± 1.35 mg/kg bw. After application of the dose, animals were placed in individual metabolism cages for the duration of the 6 hour exposure. At the end of the exposure period, the animals were anaesthetized, appliances removed, dose sites washed to remove any unabsorbed Propargyl alcohol, then the animals were returned to their metabolism cages for the remainder of the study. Propargyl alcohol trapped by the charcoal-impregnated filters was extracted with ethanol. At the end of the study, the animals were again anaesthetized and the dose sites gently scrubbed with gauze soaked in water. The animals were then euthanized, and the dose sites were excized and repeatedly rinsed with water. The unabsorbed dose was determined by summing the radioactivity recovered from the protective appliance, ethanol extracts of charcoal-impregnated traps, and the dose site wash. The absorbed dose was determined by summing the radioactivity recovered from excreta, expired breath traps, cage rinse, blood, carcass, and dose site.
In inhalation studies, animals (n=4 rats per exposure concentration) were exposed to Propargyl alcohol vapours at concentrations of 0.910 ± 0.190, 10.0 ± 1.54 or 101 ± 8.74 ppm. Individual animal doses were calculated based on the total mass of Propargyl alcohol absorbed by each animal during exposure. Absorbed Propargyl alcohol (mg) was calculated by dividing the total radiolabel recovered in the carcass, exhaled breath and excreta for each animal (mCi) by the specific activity of [14C] Propargyl alcohol in the feedstock solution used for vapour generation (µCi/mg). Absorbed doses were 0.0816 ± 0.0053, 0.901 ± 0.089 and 4.93 ± 0.39 mg for rat in the 1, 10 and 100 ppm exposure groups, respectively.
The percentage of inhaled Propargyl alcohol absorbed over the exposure duration was calculated to determine the effect of exposure concentration on absorption. Absorbed doses (mg) were divided by the total Propargyl alcohol mass inhaled over the exposure duration to determine the percentage of inhaled Propargyl alcohol absorbed (per cent absorption). Rat respiratory minute volume (RMV) was multiplied by the time-weighted average exposure concentration and exposure duration to calculate the total Propargyl alcohol mass inhaled during exposure. The RMV used for these calculations was 174 mL/min for rat (Chang et al., 1983; Brown, 1997).

LIQUID SCINTILLATION SPECTROMETRY (LSS)
Samples were assayed for total radioactivity by LSS either directly (urine, bile, ethanol trapping solution, sodium hydroxide trapping solution, dermal appliance, charcoal-impregnated filter extracts, skin-wash gauze) or following solubilization in Soluene-350 (faeces, tissues) or ethanolic sodium hydroxide (stomach, caecum, small and large intestines, dermal dose site, residual carcass). Control samples of urine, faeces, ethanol trapping solution, sodium hydroxide trapping solution and bile were collected prior to dose administration and analysed for radiochemical content to determine background counts.

HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC)
Radiochemical purity in the dose preparations, radiolabelled components in urine and bile, and the various radiolabelled metabolites were assessed/analysed by HPLC.

METABOLITE IDENTIFICATION
One purified metabolite was analysed by liquid chromatography/mass spectrometry (LC/MS) using a Finnigan LCQ quadrupole ion trap mass spectrometer and an electrospray atmospheric pressure interface (Finnigan, San Jose, CA, USA).

Statistics:

Summary statistics (mean ± SD) only are presented.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Intravenous and oral dose mass balance studies
In the i.v. study, rats rapidly excreted Propargyl alcohol-derived radioactivity, with 83.9 % of the dose excreted in the first 24 hours after dosing. By 72 hours, 88.4 % of the dose was recovered in excreta, primarily in urine (62.3 %) and as carbon dioxide (19.1 %). Less than 1 % of the dose was recovered in volatile organics traps, and 6.4 % was excreted in faeces. About 5 % of the administered dose remained in the body at 72 hours. However, ca 10 min following dosing, the eyes of the rats started tearing, which resulted in excessive blinking by the animals. After ca 30-45 min, rats remained still with their eyes closed. By 2 hours following dosing, all rats appeared normal.
Similar to the i.v. study, Propargyl alcohol-derived radioactivity from oral doses was rapidly excreted. By 24 hours after dosing, 73.2 % of the dose was excreted. At 72 hours, 90 % of the dose was excreted. As in the i.v. study, major routes of excretion were urine and carbon dioxide. The amount of faecal excretion was greater after an oral compared with an i.v. dose and was likely due to incomplete absorption of the orally administered radioactivity. Very little radioactivity (5.3 %) remained in the tissues at 72 hours.
  
Dermal dose mass balance studies
An average of 14.6 % of the administered dose was recovered in excreta by 24 hours following dosing. An average of 3.0 % of the administered dose was recovered in urine with approximately 0.5 and 0.7 % recovered in faeces and carbon dioxide, respectively. About 10 % of the dose was recovered in volatile organics traps, with most of that collected during the 6-h exposure period. Despite attempts to contain Propargyl alcohol that volatilized from the dose site, used methods may not have been completely foolproof; it is possible that the radioactivity recovered in the volatile organics traps may have escaped the dermal appliance and should be considered unabsorbed. Hence, the majority of the dose (at least 85.9 %) was not absorbed, and most of that was recovered in the charcoal-impregnated trapping material that surrounded the dermal appliance.
 
Inhalation exposure mass balance studies
Inhaled doses were 0.148, 1.45 and 14.8 mg in the 1, 10 and 100 ppm exposure groups, respectively. The per cent of inhaled Propargyl alcohol that was absorbed was similar for the 1 and 10 ppm exposures (55.2 and 62.1 %), then dropped precipitously in the 100 ppm exposure (33.3 %). Consistent with results obtained from i.v. and oral studies, a majority of the absorbed dose was eliminated over 24 hours (82-85 %) following each of the three inhalation exposures. Primary routes of excretion were urine and as carbon dioxide. In contrast to the i.v. and oral studies, a relatively large per cent of the dose was excreted as volatile organics during the first 6 h after exposure, which may have been exhaled Propargyl alcohol. At 24 hours, 13-17 % of the dose was recovered in rat tissues.

Details on distribution in tissues:

TISSUE DISTRIBUTION TIME-COURSE STUDIES
Throughout the entire time-course following i.v. administration of 1 mg/kg bw, the highest concentrations of radioactivity were observed in the organs of excretion (liver, kidney, urinary bladder). Radioactivity in other tissues, with the exception of adipose, was fairly evenly distributed. In most tissues, excluding kidney and urinary bladder, the highest radioactivity content was observed at 0.25 hours following dosing. The concentration of radioactivity in kidney and bladder peaked at 1 hour. By 24 hours following dosing, only 3-6 % of the dose remained in the tissues. A significant amount of radioactivity was present in the gastrointestinal tract after the i.v. dose. Radioactivity present in the small intestine (including lumen contents) reached a maximum of 30 % of administered dose (1 hour time point), then quickly dropped to 4 % by 4 hours following dosing. As the percent dose in the small intestine decreased, radioactivity in the caecum and large intestine increased but by a substantially lesser amount. This is likely due to enterohepatic circulation.

Details on excretion:

BILIARY EXCRETION STUDY
About 62 % of the intravenously administered radioactivity was excreted in bile by 4 hours post-dosing. Excretion of radioactivity in bile was essentially complete by 2.5 hours following dosing with ca. 59 % of the dose being excreted in bile during this period.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

BILIARY AND URINARY METABOLITE PROFILES
No parent Propargyl alcohol was found in either urine or bile. Chromatographic analysis of bile samples obtained from 4 rats after an i.v. dose revealed a striking peculiarity. Peaks eluting in the 10-12 min time interval were missing in 2/4 rats. This difference was consistent for each bile collection period. The reason for the observed variability is unknown. The presence of 6 to 11 distinct peaks in the chromatogram indicates that Propargyl alcohol was extensively metabolized. Analysis of urine further indicated that Propargyl alcohol was extensively metabolized.
Chromatographic profiles of rat urine obtained after inhalation exposure were qualitatively similar to those observed after i.v. and oral exposure. At least 10 metabolites were present in rat urine. Urine sampled after an oral dose was used to isolate radiolabelled metabolites for identification. Up to 22 peaks were detected in some urine samples. Individual metabolite fractions were collected from a semipreparative column, then neutralized and concentrated under a gentle stream of nitrogen. Recovery of radioactivity was determined at each step. Overall recovery of radioactivity was 73-100 % in all but two metabolite fractions in which only 42-44 % of the original radioactivity was recovered. These two metabolites are suspected to be volatile.
With the exception of the peak that eluted at ca 36 min (Tsp), no radiolabelled metabolites were identified. For some of the other metabolites, purification resulted in too little mass for mass and NMR spectrometric analysis. In other cases, residual TFA and/or TEA prohibited obtaining definitive spectra. Mass spectrometric analysis of peak Tsp using electrospray ionization resulted in the production of a prominent M+ H ion at m/z 383. Ion-neutral interactions between the non-charged molecule and its protonated form resulted in the production of an additional ion at m/z 765. An additional ion with relative intensity >20 % was seen at m/z 220. Since this ion was the base-ion produced upon MS/MS analysis of the ion at m/z 383, it appears that this ion at m/z 220 is the result of thermally induced fragmentation of the parent compound. Isolation and MS/MS analysis of the ion at m/z 383 resulted in the production of daughter ions at m/z 220, 202, 190, 160 and 148. This fragmentation pattern is consistent with the structure of 3,3-bis[(2-(acetylamino)-2-carboxyethyl)thio]-1-propanol, a urinary metabolite of Propargyl alcohol reported by Banijamali et al. (1999). These daughter ions could be rationalized in part by the cleavage patterns. While the simple fragmentation patterns in some instances result in ions that differ by one mass unit (or in the case of m/z 162, two units) from those observed, it is likely that the fragmentation pathways shown produced the observed ions, albeit with the addition of a proton transfer or a more complex intramolecular rearrangement.

Applicant's summary and conclusion

Executive summary:

In a toxicokinetic study, Propargyl alcohol (99 % a.i.; 90 -95 % radiochemical purity; location of [14 -C] label: C2, C3) was administered to groups of 4 -5 male Fischer 344 rats per group or per group and timepoint via the intravenous (1 mg/kg bw), oral (50 mg/kg bw), dermal (5 mg/kg bw) and inhalation (1, 10 or 100 ppm) routes. By 72 hours following a single intravenous or oral dose, about 90 % of the dose was excreted. Major routes of excretion were urine (50 -62 %), carbon dioxide (19 -26 %) and faeces (6 -14 %). Less than 6 % of the dose remained in tissues at 72 hours. Biliary excretion of radioactivity (62 % in 4 hours) was much greater than elimination in faeces (6 % in 72 hours), indicating that Propargyl alcohol metabolites underwent extensive enterohepatic recycling. Dermal exposure studies demonstrated minimal absorption due to the inherent volatility of Propargyl alcohol. Owing to the volatility of Propargyl alcohol, the risk to humans from dermal exposure is likely to be minimal unless dermal contact is prolonged. In the inhalation studies (1, 10 or 100 ppm for 6 hours), 33.3 -62.1 % of the radioactivity to which animals were exposed was absorbed. The primary route of excretion was urine (38 -53 %), and a significant portion was exhaled as volatile organics (17 -21 %). Propargyl alcohol was extensively metabolised. One metabolite was indentified as 3,3 -bis[2 -(acetylamino)-2 -carboxyethyl)thio]-1 -propanol.

This toxicokinetics study in the rat is classified acceptable and satisfies the guideline requirement for a toxicokinetic study (OECD 417) in rats.