1,4-dioxane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

The dose-dependent fate of 1,4-dioxane in rats

Author:

Young, J. D., Braun W.H., Gehring P.J.

Year:

1978

Bibliographic source:

Journal of environmental Pathology and Toxicology 2: 263-282

Materials and methods

Objective of study:

absorption

excretion

metabolism

toxicokinetics

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,4-dioxane

EC Number:

204-661-8

EC Name:

1,4-dioxane

Cas Number:

123-91-1

Molecular formula:

C4H8O2

IUPAC Name:

1,4-dioxane

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

unchanged (no vehicle)

Details on exposure:

TYPE OF INHALATION EXPOSURE:
head only

GENERATION OF TEST ATMOSPHERE / CHAMPER DESCRIPTION
The dioxane vapour was pumped from the a Saran bag (Anspec) to the chamber via the 3-way connector, where it was diluted with room air to a total flow rate of 8 liters/min. The flow rate was adjusted to give a chamber concentration of 50 ppm. The ai exiting was continously moonitored using Wilks Miran I infrared analyzer equipment.

Duration and frequency of treatment / exposure:

once for 6 hr

Doses / concentrations

Dose / conc.:

50 ppm

No. of animals per sex per dose / concentration:

4

Control animals:

no

Details on study design:

Four male Sprague-Dawley rats with jugular vein cannulas were placed in a 1 litre “head-only” chamber under dynamic air flow conditions. The flow rate of 1,4-dioxane vapour was adjusted to give a chamber concentration of 180 mg/m3 (50 ppm).

Details on dosing and sampling:

During and after the 6-hour exposure urine was collected and analysed.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

When estimated from the total 1,4-dioxane (6.8 μg) and 1,4-dioxane equivalents of HEAA (21271 μg [= ratio of molecular weights]) excreted in urine, the rats absorbed at least 72 mg 1,4-dioxane/kg bw during the 6-hour exposure period. Assuming a respiratory minute volume of 240 mL/min for rats, these data indicate complete absorption.

Details on excretion:

The radioactivity expressed as 1,4-dioxane in plasma at the end of exposure was 7.3 μg/mL. Thereafter, the plasma concentration of 1,4-dioxane decreased in a log-linear manner until it was not detectable (<0.3 μg/mL) at 11 hours after the start of the experiment. A t½ of 1.01 hours was calculated.

The amounts of 1,4-dioxane and β-hydroxyethoxyacetic acid (HEAA) in urine during exposure (0-6 h) were 5.1 and 7613 μg, respectively, and afterward (6-48 h) 1.7 and 13659 μg, respectively. Hence, more than 99.9% of the total urinary excretion of the inhaled 1,4-dioxane was HEAA.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

The amounts of 1,4-dioxane and β-hydroxyethoxyacetic acid (HEAA) in urine during exposure (0-6 h) were 5.1 and 7613 μg, respectively, and afterwards (6-48 h) 1.7 and 13659 μg, respectively. Hence, more than 99.9% of the total urinary excretion of the inhaled 1,4-dioxane was HEAA.

Any other information on results incl. tables

Pharmacokinetics of 50 ppm 1,4-dioxane vapour inhaled for 6 hr by 4 male rats.

	Amount excreted in urine (µg), mean ± SD
Time (hr)	Dioxane	HEAA
0-6	5.1 ± 1.9	7613 ± 3540
6-48	1.7 ± 1.3	13659 ± 7071
0-48	6.8 ± 3.14	21271 ± 4810

Time (hr)	Plasma concentration of dioxane (mg/mL), mean ± SD
6	7.3 ± 2.0
7	4.5 ± 1.2
8	2.2 ± 0.7
9	1.0 ± 0.2
10	0.48 ± 0.12
11	0.3

Parameter	Value mean ± SD
rat weight, kg	0.215 ± 0.011
dose, mgEq	15535 ± 3511
dose, mg/kg	71.9 ± 3.6
K. hr^-1	0.6838 ± 0.1040
t1/2	1.01 ± 0.15