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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older published study conducted prior to development of guidelines and GLP, but scientifically sound and providing relevant information.

Data source

Reference
Reference Type:
publication
Title:
The digestibility of stearyl alcohol, isopropyl citrates, and stearyl citrates, and the effect of these materials on the rate and degree of absorption of margarine fat
Author:
Calbert, C. E., Greenberg, S.M., Kryder, G. and Deuel, H.J.
Year:
1951
Bibliographic source:
Food Research, 16(4): 294-305

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study was conducted prior to development of the guidelines. The study investigated the digestibility of stearyl citrate administered orally to rats.
GLP compliance:
no
Remarks:
conduction prior to GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
The test material was stearyl citrate, a mixture of mono-, di-, and tri-alkyl esters of stearic acid with citric acid (12.5%, 75% and 12.5%, respectively). The material was a commercial product supplied by Best Foods, Inc. Identity was confirmed by analysis at the test facility.
Radiolabelling:
no

Test animals

Species:
rat
Strain:
not specified
Sex:
female
Details on test animals and environmental conditions:
The study animals were female rats from the stock colony at the University of Southern California School of Medicine. They weighed approximately 200 g at study initiation.

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
Rats were fed diets containing stearyl citrate for an initial acclimatisation period of 5 days. Following the acclimatisation period, the rats were maintained on the test diets for a further 8 days. The test diets were composed of casein, margarine fat, sucrose, Osborne-Mendel salt mixture, yeast and appropriate amounts of stearyl citrate. Each diet had a total fat content of 25%.
Duration and frequency of treatment / exposure:
Continuous dietary exosure for 13 days.
Doses / concentrations
Remarks:
Doses / Concentrations:
0.13%, 2.5% and 10.0% stearyl citrate.
No. of animals per sex per dose:
Approximately 10 female rats per group.
Control animals:
yes, plain diet
Positive control:
Not required for this type of study.
Details on study design:
The rats were fed diets containing stearyl citrate for an initial acclimatisation period of 5 days. Following the acclimatisation period, the rats were maintained on the test diets for a further 8 days.
Details on dosing and sampling:
Food consumption was recorded and faeces were collected over the 8 day sampling period. The faeces were analysed for neutral fat and soap; unabsorbed stearyl citrate appears with the neutral fat and/or soap fraction.
Statistics:
Not reported.

Results and discussion

Preliminary studies:
No information available.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Stearyl citrate was poorly absorbed by the rat. When stearyl citrate was added to the diet at levels of 2.5 or 10%, the calculated digestibility of the ester was 5.7 and 19.3% respectively. In these cases, absorption of margarine fat was reduced from 96-97% to approximately 75%. Stearyl citrate in the diet at 0.13% had no effect on fat absorption.
Details on distribution in tissues:
Not determined.
Details on excretion:
See details on absorption.

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
Not determined.

Any other information on results incl. tables

Table 1. Summary of fat consumed and excreted

Category

Stearyl Citrate content in Diet

2.5%

10.0%

0.13%

Number rats

9

10

9

Increase in Weight (g)

-2.0

0

-0.1

Fat eaten (g)

9.6

8.2

16.4

Test substance eaten (g)

1.07

5.45

0.086

Faeces dry weight (g)

5.10

9.30

3.69

Faeces fat; neutral fat (g)

1.257

3.195

0.613

Faeces fat; soaps (g)

2.299

3.787

0.664

Faeces fat; total (g)

3.556

6.982

1.277

Faeces fat, corrected total (g)a

3.357

6.734

1.035

Digestibility of fat alone ± SE

77.1 ± 1.3

71.6 ± 3.0

94.1 ± 0.6

Digestibility of test substance ± SE

5.7 ± 3.9

19.3 ± 4.8

54.3 ± 8.1

aCorrected for metabolic fat 50.5 mg/g dried faeces

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results Data indicate that the intact substance is not absorbed but may be hydrolysed to a limited extent in the gastrointestinal tract to citric acid and fatty alcohol; bioaccumulation is not predicted for the substance or its hydrolysis products.
Stearyl citrate is poorly absorbed by the rat.
Executive summary:

The 'digestibility' of mixed (mono-, di- and tri-) citrate esters of stearic alcohol (C18; stearyl citrate) was investigated in studies in the rat. Animals were administered diets containing various levels of stearyl citrate.

The results of the study indicate that the enzymic hydrolysis of stearyl citrate in the rat is incomplete at low dietary levels and is very limited at higher dose levels; in contrast, the hydrolysis product stearyl alcohol was well absorbed at low dietary levels. The test material was a mixture of mono-, di- and tri-citrate esters of stearic (C18) alcohol: the registered substance consists of tri-ctirate esters of C18, C20 and C22. The limited absorption seen with the test material used in this study is likely to be due largely to the mono-citrate ester, the results therefore indicate that the absorption of the registered substance will be even more limited in the rat.