2-ethylbutyric acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1948

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

The Metabolism of Some Branched Chain Aliphatic Acids

Author:

Dziewiatkowski, D. D., Venkataraman, A. and Lewis, H. B.

Year:

1949

Bibliographic source:

Dziewiatkowski, D. D., Venkataraman, A. and Lewis, H. B. (1949). The Metabolism of Some Branched Chain Aliphatic Acids. Journal of Biological Chemistry, 178(1), 169 - 177.

Materials and methods

Objective of study:

metabolism

Principles of method if other than guideline:

No guideline was available at the time the study was undertaken. Young male rabbits (2 - 4 kg) were housed in metabolism cages and were provided with a uniform diet of commercial rabbit chow or oat and cabbage. The sodium salt of the registered substance was injected subcutaneously or provided orally on day 0 at 1 g and urine was collected at 24-hour intervals (for at least 4 days). 0.1 g of the sodium salt of the registered substance was administered to rats. Standard procedures were used to analyse the urine, including modified Kjeldahl (total nitrogen), Folin (creatinine), Folin and Benedict-Denis (partition of urinary sulfur), and the procedure of Maughan, Evelyn, and Browne (1938). See Dominic, Dziewiatkowski, and Howard (1945) for a detailed description of the methodology.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylbutyric acid

EC Number:

201-796-4

EC Name:

2-ethylbutyric acid

Cas Number:

88-09-5

Molecular formula:

C6H12O2

IUPAC Name:

2-ethylbutyric acid

Test material form:

not specified

Radiolabelling:

no

Test animals

Species:

rabbit

Sex:

male

Administration / exposure

Route of administration:

other: Oral and subcutaneous injection

Vehicle:

water

Duration and frequency of treatment / exposure:

Daily administration for a period of 4 days.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Remarks:

Control

Doses / concentrations 2

Dose / conc.:

0.1 other: g

Remarks:

As sodium salt / rats

Doses / concentrations 3

Dose / conc.:

1 other: g

Remarks:

As sodium salt / rabbits

Control animals:

yes

Details on dosing and sampling:

Urine collected in 24-hour periods for analysis.

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Large amounts of glucuronic acid were excreted in rabbit urine that corresponded to 25 - 52 % of the 1 g 2-ethylbutyric acid ingested. Ketone derivatives, such as methylpropyl ketone, were not isolated in urine in increased amounts. At 0.1 g, glucuronic acid excretion in rats was increased by 22 to 49 %.

Applicant's summary and conclusion

Conclusions:

The sodium salt of 2-ethylbutyric acid was administered to male rabbits and rats orally or by subcutaneous injection in a 4-day in vivo experiment. 2-Ethylbutyric acid was discovered to be excreted unchanged in the urine in combination with glucuronic acid at 22 - 52 % of the total amount ingested. This result is suggestive of the registered substance being somewhat difficult to oxidise. Ketone derivatives such as methylpropyl were not identified, however, the possibility of catabolism occurring by such pathways was not ruled out.