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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
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.

Data source

Reference
Reference Type:
publication
Title:
The digestibility of stearyl alochol, 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 dogs.
GLP compliance:
no
Remarks:
conduction prior to GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
The test compound 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 test compound was a commercial product supplied by Best Foods, Inc. Identity was confirmed by analysis at the test facility.
Specific details on test material used for the study:
Stearyl citrate was obtained from the Best Foods, Inc..The identity of the product was estabilished by analysis in the laboratory.
Radiolabelling:
no

Test animals

Species:
dog
Strain:
other: Cocker and mixed-breed
Sex:
female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
The dogs were fed either plain diet, or diet containing 3% stearyl citrate. The diets were made up of casein, sucrose, dextrin, margarine fat, cold liver oil, cellu flour, salt mixture and dried brewers yeast. Both the plain diet and the test diet had a total fat content of 23.3%.
Duration and frequency of treatment / exposure:
Continuous dietary exposure for 12 days. The digestibility experiments on dogs were made over a 12-day period during the last third of a 12-week toxicological test.
Doses / concentrations
Remarks:
Doses / Concentrations:
0% or 3% stearyl citrate in the diet (14.8 % of the fat).
No. of animals per sex per dose:
3 dogs/group; control: fat with no additives,
Control animals:
yes, plain diet
Positive control:
Not required.
Details on study design:
In order to determine whether the stearyl citrates could be hydrolysed by the dog, samples of fresh feces were removed from the cage in the period directly after the completion of the digestibility tests. These were stored in the deep freeze until analyses could be completed. An aliquot was removed for the determination of the dried stool aqueous extract. Another aliquot was used for the determination of any citric acid in an aqueous extract. Citric acid was also determined in the aqueous extract following saponification of another aliquot. The content of stearyl citrates in the stool was calculated on the basis that the citric acid makes up the same proportion of the ester mixture as in the original stearyl citrate preparation fed. Any stearyl alcohol remaining over and above that accounted for in ester form was considered to be present as the free alcohol.
Details on dosing and sampling:
The digestibility study was conducted over a 12 day period during the last third of a 12 week toxciological study. Food consumption was recorded and faeces were collected over the 8 day sampling period. The faeces were separated by the use of carmine markers which were fed on the 1st and 13th days of the test. The faeces were analysed for neutral fat and soap; unabsorbed stearyl citrate appears with the neutral fat and/or soap fraction.
In order to determine whether stearyl citrate could be hydrolysed by the dog, samples of fresh faeces were collected directly after completion of the digestibility study.
Statistics:
Not reported.

Results and discussion

Preliminary studies:
No information available.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Free stearyl alcohol was found in the faeces of the dogs fed the test diets, indicating that stearyl citrate was hydrolysed in the gastrointestinal tract. It was calculated that 50% of the stearyl citrate administered in the diet was digested by the dogs, and there was no significant effect on the absorption of margarine fat.
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. Fat consumed in diet and excreted in the faeces

Parameter

Control Diet

3% Stearyl Citrate Diet

Sex

M

F

M

F

F

M

Food eaten (g)

980

980

3962

968

968

2870

Fat eaten (g)

228.3

228.3

923.1

196.5

196.5

582.6

Stearyl citrate eaten (g)

-

-

-

29.1

29.1

86.1

Faeces dry weight (g)

49.1

68.7

284.7

86.8

103.7

221.6

Faeces corrected dry weight (g)1

-

-

-

72.4

87.7

187.4

Neutral fat extracted (g)

4.40

4.59

36.9

26.7

35.8

69.1

Soaps extracted (g)

3.60

3.35

29.3

10.5

12.1

30.1

Total lipid extracted (g)

8.00

7.94

66.2

37.2

47.9

99.2

  Corrected for metabolic fat (g)2

0.00

0.00

9.2

-

-

-

  Corrected for stearyl citrate and stearyl alcohol (g)

-

-

-

22.8

31.9

65.0

  Corrected for stearyl citrate, stearyl alcohol and metabolic fat (g)

-

-

-

8.5

14.5

27.8

1Corrected by subtracting the weight of stearyl citrate plus stearyl alcohol from total weight of dried faeces

2Corrected for metabolic fat by multiplying corrected dried faeces weight by 0.198

Table 2. Determination of the proportion of stearyl citrate and stearyl alcohol excreted in the faeces following dietary exposure

Sex

F

F

M

M

Parameter

Stearyl alcohol excreted (mg/g dried faeces)

225

186

-

197

Citric acid excreted

 

 

 

 

 - as free acid (before hydrolysis) (mg/g dried faeces)

0

0

-

0

 - combined (after hydrolysis) (mg/g dried faeces)

46(1)

49(4)

-

50(2)

Distribution of stearyl alcohol

 

 

 

 

 - Total (mg/g dried faeces)

225

186

-

197

 - Combined (mg/g dried faeces)

129

138

-

140

 - Free (mg/g dried faeces)

96

48

-

57

Calculation of stearyl citrate hydrolysed

 

 

 

 

 - Total stearyl alcohol as stearyl citrate (mg/g dried faeces)

290

240

-

254

 - Unhydrolysed stearyl citrate (mg/g dried faeces)

166

178

-

181

 - Hydrolysed (mg/g dried faeces)

124

62

-

73

 - Hydrolysed (%)

42.8

25.8

-

28.7

Calculation of stearyl citrate and stearyl alcohol content of faeces (g)

14.4

16.0

34.2

-

Numbers in parantheses indicate number of determinations preceded by the average

Applicant's summary and conclusion

Conclusions:
At a level of 3 % in the ration fully 50 % stearyl citrate is digested and no significant interference with the absorption of margarine fat occurs.
Executive summary:

The 'digestibility' of mixed (mono-, di- and tri-) citrate esters of stearic alcohol (C18; stearyl citrate) was investigated in studies in the dog. Animals were administered diets containing various levels of stearyl citrate. At a level of 3 % in the ration fully 50 % stearyl citrate is digested and no significant interference with the absorption of margarine fat occurs.