2,2'-ethylenedioxydiethyl bis(2-ethylhexanoate)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Materials and methods are described, but not all details (e.g. No. of animals) are available.

Data source

Reference

Reference Type:

publication

Title:

Distribution of 2-Ethylhexanoic acid in mice and rats after an intraperitoneal injection

Author:

Pennanen S. and Manninen A.

Year:

1991

Bibliographic source:

Pharmacology & Toxicology 1991, 68, p. 57-59

Materials and methods

Objective of study:

distribution

Principles of method if other than guideline:

Whole-body autoradiography was performed according to the method described by Ullberg (1977).
Ullberg, S., The technique of whole-body radiography. Cryosection of large specimens. Science Tools. The LKB Instrument Journal. Special Issue on Whole-Body Autoradiography 1977, 2-29.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexanoic acid

EC Number:

205-743-6

EC Name:

2-ethylhexanoic acid

Cas Number:

149-57-5

Molecular formula:

C8H16O2

IUPAC Name:

2-ethylhexanoic acid

Details on test material:

2-14C-EHA

Radiolabelling:

yes

Test animals

Species:

mouse

Strain:

Balb/c

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: National Laboratory Animal Center, Kuopio, Finland
- Weight at study initiation: 300-400 g (rats) 22-25 g (mice)
- Diet : standard pellet diet (R3-EWOS)

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +- 1°C
- Humidity: 60%

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

Single dose

Doses / concentrations

Remarks:

Doses / Concentrations:
5 µCi/mouse (specific activity 6.7 mCi/mmol, Sigma Chemical Compaiiy, Saint Louis, Missouri, U.S.A.)

Control animals:

no

Details on study design:

Thirty min., 1 hr and 6 hr after adininistration of 2-14C-EHA the animals were anaesthetized with carbon dioxide and frozen in liquid nitrogen. Frozen bodies were embedded in carboxymethyl cellulose (2%) and cut into 20-µm-thick sections by a microtome (PVM, Cryo-Microtome, Type 450 P, LKB, Stockholm, Sweden). The tape-bearing sections were then freeze-dried for one day at -20°. Ten sections from each anima1 were placed on the
film (Kodak X-Omat AR Film, Eastlman Kodak Co., Rochester, NY) and exposed for 6 weeks at -20°. The films and photographs were exposed by the conventional dark-room procedure.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

After the first time point, 30 min., the greatest amount of radioactivity over the background was observed at the kidney and liver and the gastrointestinal contents. The radioactivity was also clearly visible in the lung. One hr after administration radioactivity was present most in the kidney and liver. Salivary gland as well as skin also contained radioactivity. A slight amount of radioactivity was visible in the olfactory bulb but not in the brain.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
2-EHA was shown to have a rapid distribution and excretion. Tlie highest concentrations were attained in the liver and kidney.

Executive summary:

The distribution of 2-ethylhexanoic acid (2-EHA) was studied in mice and rats. 2-14C-EHA in blood, brain, liver and kidney was quantitated by liquid scintillation analysis and by wholebody autoradiography in mice. A single intraperitoneal dose of 2-14C-EHA was injected. Animals were sacrifïced 30 min., 2 and 6 hr after the administration of 2-EHA. The highest uptake of 2-EHA was observed in the liver, kidney and blood of mice. In contrast, low uptake of 2-EHA was seen in the brain. 2-EHA was wel1 detectable in the olfactory bulb and in the salivary gland.