Sodium 2-(1-carboxylatoethoxy)-1-methyl-2-oxoethyl laurate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1969-01-14 to 1969-05-14

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:

study report

Title:

Unnamed

Year:

1969

Report date:

1969

Materials and methods

Objective of study:

distribution

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: In vivo metabolism study in rats to determine the distribution of 14C activity in rat tissues and excreta following oral administration of sodium capryl lactylate-14C

- Short description of test conditions: A single dose of sodium capryl lactylate-14C was administered by stomach tube to each of four male albino rats at the rate of 250 mg/kg. These animals had received unlabeled sodium capryl lactylate at the same dose rate daily for three days prior to the administration of the tagged material.

- Parameters analysed / observed: Selected tissues, urine, feces and expired CO2 were analysed for radioactivity

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Decanoic acid, 2-(1-carboxyethoxy)-1-methyl-2-oxoethyl ester, sodium salt

Cas Number:

13557-74-9

IUPAC Name:

Decanoic acid, 2-(1-carboxyethoxy)-1-methyl-2-oxoethyl ester, sodium salt

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL (sodium capryl lactylate-14C)
- Source and lot/batch No.of test material: C.j. Patterson Company

RADIOLABELLING INFORMATION (if applicable)
- A primary standard was made by dissolving 11.2 mg of the compound in 10 mL methyl alcohol. The specific activity, as determined in this test system, was found to be 401.464 cpm/mg, which, after correction for 78% instrument efficiency, yields a value of 514.697 dpm/mg or 0.232 µc/mg.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The dose formulation was prepared by suspending 0.5150 g sodium capryl lactylate-14C in 19.5 mL distilled H2O

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

CD-1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc.
- Housing: Animals were housed in standard wire mesh cages. After receiving the last dose of unlabeled compound, four rats were individually placed onto modified Roth all-glass metabolism cages and conditioned for 24 hours prior to administration of the tagged material.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: two weeks

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: A primary standard was made by dissolving 11.2 mg of the compound in 10 mL methyl alcohol. The specific activity, as determined in this test system, was found to be 401,464 cpm/mg, which, after correction for 78% instrument efficiency, yields a value of 514,697 dpm/mg or 0.232 uc/mg. The dose formulation was prepared by suspending 0.5150 g sodium capryl lactylate in 19.5 mL distilled H2O.

Duration and frequency of treatment / exposure:

Unlabeled compound: once per day for three days
Labeled compound: single treatment

Doses / concentrations

Dose / conc.:

250 mg/kg bw/day (nominal)

No. of animals per sex per dose / concentration:

4

Control animals:

no

Details on study design:

- Rationale for animal assignment (if not random): After receiving the last dose of unlabelled compound, four rats were individually placed into modified Roth all-glass metabolism cages and condition for 24 hours prior to administration of the tagged material. Selection was based on general performance during the acclimation period, such as body-weight gain, food consumption, and appearance.

Details on dosing and sampling:

TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, tissues, gastrointestinal tract contents, CO2.
- Time and frequency of sampling: Two animals were sacrificed 24 hours after dosing, and the remaining two at 48 hours. Thus, the entire experimental period lasted 48 hours. During this period, samples were collected at 8-hour intervals.

Results and discussion

Main ADME results

Main ADME results 1

Type:

metabolism

Results:

Between the four rats, the range of metabolism into carbon dioxide was 68.98-71.23%

Main ADME results 2

Type:

excretion

Results:

Between the four rats, the range of dose cleared through urine was 18.62-23.88%

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The compound is almost completely absorbed, and approximately 20% of the dose is cleared through the urine. Very little of the radioactivity was excreted in the feces or retained in the gastrointestinal tract contents.

The compound is rapidly metabolized, the major portion of the dose being converted to CO2 , primarily within 24 hours after administration.

Metabolite characterisation studies

Metabolites identified:

no

Any other information on results incl. tables

Approximately 16 hours after dosing, one rat died. An autopsy was performed which revealed severe necrosis of the stomach. This condition was also found in the other three experimental animals at sacrifice and was especially prominent in another rat. In these animals there was extensive ulceration and is some areas the stomach wall was almost perforated. Although the death of this rat could not be definitely attributed to this condition, it is evident that sodium capryl lactylate at the concentration used caused tissue damage in all animals, and apparently exerts an irritant effect similar to that of a caustic alkali.

Percent of compound that is metabolized and converted into CO₂is below.

Hours	Rat No. 1	Rat No. 2	Rat No. 3	Rat No. 7
8	51.23 %	66.86 %	63.93%	92.37%
16	16.70%	2.10%	5.05%	7.05%
24 hours	1.44%	0.74%		1.81%
24-hour total	69.37%	69.70%	68.98%	71.23%

 

Percent of compound that is absorbed and cleared through the urine.

Hours	Rat No. 1	Rat No. 2	Rat No. 3	Rat No. 7
8	10.18%	17.41%	21.76%	16.26%
16	9.18%	1.57%	2.12%	2.13%
24	0.33%	0.11%		0.23%
24-hour total	19.69%	19.09%	23.88%	18.62%

 

The total recovery of the administered dose amounted to 94.4% for rat No. 1; 94.0% for rat No. 2; 97.0% for rat No. 3 and 93.1% for rat No. 7.

Applicant's summary and conclusion

Conclusions:

Sodium capryl lactylate after oral exposure is almost completely absorbed and rapidly metabolised in the rat with the major portion of the dose being converted to CO2 primarily within 24 hours after administration. The recovery of the administered dose (radioactivity) for the 4 rats at 48 hours after dosing ranged from 93 to 97%.

Executive summary:

A single dose of sodium capryl lactylate-¹⁴C was administered by stomach tube to each of four male albino rats at the rate of 250 mg/kg. These animals had received unlabelled sodium capryl lactylate at the same dose rate daily for three days prior to the administration of the tagged material. Samples of urine, faeces and expired CO₂, collected periodically from each rat until sacrifice, and selected tissues obtained at necropsy were analysed for radioactivity.

Sodium capryl lactylate after oral exposure is almost completely absorbed and rapidly metabolised in the rat with the major portion of the dose being converted to CO₂ primarily within 24 hours after administration. The major portions of the radioactivity were recovered in the CO₂ and urine, primarily within 8 hours after dosing. The recovery of the administered dose (radioactivity) for the 4 rats at 48 hours after dosing ranged from 93 to 97%.