Food Additives & Contaminants

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Dietary effects of propylene glycol alginate in humans D. M. W. Anderson , W. G. Brydon , M. A. Eastwood & D. M. Sedgwick To cite this article: D. M. W. Anderson , W. G. Brydon , M. A. Eastwood & D. M. Sedgwick (1991) Dietary effects of propylene glycol alginate in humans, Food Additives & Contaminants, 8:3, 225-236, DOI: 10.1080/02652039109373973 To link to this article: https://doi.org/10.1080/02652039109373973

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FOOD ADDITIVES AND CONTAMINANTS, 1991, VOL. 8, NO. 3, 2 2 5 - 2 3 6

Dietary effects of propylene glycol alginate in humans D. M. W. ANDERSON†, W. G. BRYDON‡, M. A. EASTWOOD‡ and D. M. SEDGWICK‡ †Chemistry Department, The University, Edinburgh EH9 3JJ, UK; ‡Gastrointestinal Unit, Western General Hospital, Edinburgh EH4 2XU, UK (Received 30 August 1990; revised 22 November 1990; accepted 21 December 1990) Following a 7-day control period, five male volunteers consumed a weight of propylene glycol alginate corresponding to 175 mg/kg body weight for 7 days, followed by 200 mg propylene glycol alginate per kg body weight for a further 16 days. Measurements before and at the end of the 23-day period of dietary supplementation showed that propylene glycol alginate had little effect on faecal parameters (pH, water content, daily wet and dry weights). The dietary transit time remained constant for three volunteers, increased for one, and decreased for one. The ingestion of propylene glycol alginate had no significant effect on (a) haematological indices, (b) plasma biochemistry parameters, (c) urinalysis parameters, (d) blood glucose and plasma insulin concentrations, (e) breath hydrogen concentrations. No allergic responses were reported by, nor observed in, any of the volunteers. The study therefore indicates that the ingestion of propylene glycol alginate at a high level for 23 days caused no adverse dietary or physiological effects; in particular, the enzymatic and other sensitive indicators of adverse toxicological effects remained unchanged. Keywords: propylene glycol alginate, dietary effects, transit time

Introduction

Propylene glycol alginate has been approved for use as a food additive by all of the major international regulatory authorities since the inception of the present positive-list principle. In recent years there has been a tendency, welcomed and encouraged by the regulatory authorities and consumers, for direct evidence of the dietary effects of food hydrocolloids to be obtained in man to supplement the evidence derived from animal-based experiments. Such studies (Anderson etal. 1986, Eastwood et al. 1987) have had positive effects in terms of upward revisions of the Acceptable Daily Intake (ADI) originally assigned to the most widely used emulsifiers, stabilizers, and thickeners. This study of propylene glycol alginate in humans was therefore commissioned. The objectives were: (a) to demonstrate that daily consumption of propylene glycol alginate at about 30 times the maximum actual average daily human exposure is tolerated without gastric upset or allergic response; (b) to determine the extent and nature, if any, of the dietary, biochemical, haematological and physiological changes resulting from the consumption of propylene glycol alginate. The study was conducted in conformity with all regulatory requirements currently in force in Great Britain, and with the prior consideration and approval 0265-203X/91 $3.00 © 1991 Taylor & Francis Ltd.

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D. M. W. Anderson et al.

of the appropriate authority i.e. the Ethics of Research Committee of the North Lothians District, Edinburgh, UK. Materials and methods

The test article Propylene glycol alginate, Lot EX5759, was supplied by the Kelco Division of Merck & Co. Inc., San Diego, USA. The Test Article is retained in the Chemistry Department, University of Edinburgh, UK, for reference purposes. Preliminary study in the rat As required by the Ethics of Research Committee, the Test Article was fed to 15 mature male rats at a dietary supplementation of 5% (w/w) for 30 days. The animals thrived and remained active and alert throughout. There was no incidence of diarrhoea nor loss of normal bowel habit. Urine was collected from each animal during the fourth week of dietary supplementation; there were no abnormal values for any of the standard urinalysis parameters. The official Animal House Veterinary Officer (Mr David Shannon, BSc, MRCVS, DTVM) conducted full post-mortem examinations on all animals and certified that 'the rats were in good health and condition immediately prior to post-mortem examination: five rats showed mild distension of a portion of the ileum; all rats showed distension of the caecum compared with the control animals; twelve rats showed distension of the colon to some degree, with soft contents; ten rats showed soft/ill-formed faecal pellets'. Study in humans Five males (Volunteers A-E), all normal in health and free from gastrointestinal disease, participated; their ages ranged from 23-43 years with initial body weights ranging from 67 • 6-88 • 3 kg and subsequent weights as shown in table 1. The study involved a 7-day initial control period, during which a volume of orange juice, equal to that to be used later to flavour/dilute the gel containing the Test Article, was consumed by all volunteers. Thereafter, each volunteer consumed, for the first 7 days of the test period, a weight of propylene glycol alginate equal to 175 mg/kg body weight; this was increased to 200 mg/kg body weight for the remainder of the 23 days of dietary supplementation. In order to simulate the use of propylene glycol alginate as a food additive as closely as possible, each volunteer consumed his pre-calculated daily allocation of propylene glycol alginate in three measured portions at intervals each day. The individual portions for each participant were prepared in advance in 250 ml 'polypots', fitted with lids, by adding the weighed aliquots of propylene glycol alginate, with rapid stirring, to 220 ml cold distilled water. The hydrocolloid was then allowed to hydrate fully for 24 h to give a thick, but fluid gel, to which each volunteer then added the pre-determined amount of orange juice immediately prior to consumption. During the initial control week (Day 3), each volunteer was interviewed to ascertain any past history of allergenicity. During the period of dietary supplementation, consumption of the Test Article was ensured by daily contact with one or other of the authors of this Report, and enquiries were made concerning any apparent allergic responses. Diet diaries were maintained by all volunteers during the control and dietary supplementation weeks.

Dietary effects of propylene glycol alginate in humans

227

Following an overnight fast, blood was taken for glucose (Kadish et al. 1968) and insulin (Ashby and Speake 1975) measurements on the third day of the initial control period immediately prior to consumption of 50 g glucose in 200 ml water. Thereafter, blood was taken at 30-min intervals for 4h. Fasting blood samples were also taken, prior to consumption of the glucose, for (a) serum lipid estimation of cholesterol and HDL cholesterol (Sigma 1982), (b) triglycérides (Egstein 1966), (c) haematological indices, (d) plasma chemistry analyses (urea, electrolytes, bicarbonate, alkaline phosphatase, calcium, phosphate, creatinine, uric acid, total protein, albumin, bilirubin, lactate dehydrogenase (LDH) and aspartate amino transferase (AST) using SMAC-2 (Technicon Instruments Co., Basingstoke, UK). During the glucose tolerance test, end alveolar air samples were taken at 30-min intervals for hydrogen determinations (Tadesse et al. 1979). All of these tests were repeated on the last day of the dietary supplementation period (Day 31) and on the final day of the second control period (Day 38). A 24 h urine sample was taken by each volunteer for routine urinalysis during the initial control week and during the third week of dietary supplementation with propylene glycol alginate. Complete 5-day faecal collections were made during Days 2-6 of the initial control period, and Days 16-20 of the dietary supplementation period, after consumption (1700 h) of a bolus of 40 radio-opaque markers to assess completeness of collection and gastrointestinal transit time, which was taken as the time for 80% of the markers to appear in the faeces (Hinton et al. 1969). The individual stools were weighed and homogenized in a known volume of water. Daily dry weight was determined from dried aliquots which were subsequently analysed for bile acids (Evrard and Janssen 1968), neutral sterols (Miettinen et al. 1965), fat (Varley 1962), and volatile fatty acids (Spiller et al. 1980); pH was determined on an aliquot of homogenized faeces. Faecal occult blood was determined on two separate aliquots of faeces (control and test periods) using Haemoccult test envelopes (Roehm Ltd, Derby, UK). Plasma glucose concentrations were estimated by an automated glucose oxidase method (Kadish et al. 1968); blood glucose concentration was estimated from this value using the haematocrit. Plasma insulin concentrations were estimated by a radio-immunoassay technique (Ashby and Speake 1975). A full blood analysis was made (automated Coulter S Counter and manual methods). Results Analysis of the diet diary records confirmed that all volunteers had maintained a uniform pattern of living, as stipulated in the Study Protocol. The volunteers' individual intakes of protein, fat, sugar, carbohydrate, fibre and alcohol in the final week of dietary supplementation did not differ significantly from those recorded for the control weeks. The volunteers showed small increases in body weight after the period of dietary supplementation. The faecal measurements before and after dietary supplementation with propylene glycol alginate are shown in tables 2,3 and 12-14. The effects on the haematological indices are shown for each volunteer in table 4 (Day 3, initial control week), table 5 (Day 31, final dietary supplementation week), table 6 (Day 38, final control week) and table 7 (comparison of the mean values (n = 5) for Days 3,31 and 38).

D. M. W. Anderson et al.

228

Table 1. Propylene volunteers.

glycol

alginate:

age/weight

of

:Body weight (kg)

Pre-dosing

Post-dosing

Age

Volunteer A B C

D E Mean

(years)

Day 3

Day 8

Day 31

31 24 23 43 42 33

88-3 76-2 85-7 71-0 67-6 77-7

88-4 77-3 86-0 71-5 68-4 78-3

90-3 78-9 87-0 71-2 70-0 79-5

The effects on the plasma chemistry parameters are shown in table 8 (Day 3, initial control week), table 9 (Day 31, final dietary supplementation week), table 10 (Day 38, final control week) and table 11 (comparison of the mean values (« = 5) for Days 3,31 and 38). Breath hydrogen concentrations for each volunteer remained unchanged at below 15 ppm and urinalysis parameters remained unchanged and within normal ranges for each volunteer throughout the study; data are therefore not presented. None of the volunteers reported any allergic responses, gastrointestinal disturbances, feelings of distension or abdominal discomfort, or unusual looseness of bowel during the period of dietary supplementation with propylene glycol alginate. None of the volunteers had any previous history of allergenicity. The completeness of faecal collections was confirmed by the recovery of more than 90% of the markers in all collections. No occult blood was present in any sample. The blood glucose and serum insulin responses were essentially unchanged after the dietary supplementation period. Discussion On average, the 24 h faecal wet and dry weights and faecal water content (table 2) showed little change after the period of dietary supplementation with propylene glycol alginate, although the volunteers differed in the extent and nature of their individual responses, as is frequently the case in such studies (Eastwood etal. 1986). Although there was an increase in the mean intestinal transit time from 48 to 61 h, this arose because of an unusually large increase, from 50 to 120 h, shown by Volunteer A; in contrast, three volunteers showed no effective change and Volunteer C showed a slight decrease, from 41 to 31 h. Faecal pH fell slightly for all volunteers, resulting in the mean value decreasing from pH 6-57 to pH 6-31 (table 2). There were no significant changes in faecal total and individual volatile fatty acids (tables 3 and 12), nor in faecal total and individual bile acids (tables 3 and 13), but faecal total neutral sterols (table 3) and cholesterol (table 14) decreased to a variable extent for each volunteer.

Table 2. The effect of ingestion of propylene glycol alginate on faecal measurements After 23 days

Control period

Volunteer

Volunteer A PH

Transit time (h) Wet weight (g/24h) Dry weight (g/24h) Water (%)

6-71 50 181 54 70

B

C

6-73 66 193 51 74

D

6- 88 41 271 63 77

6-69 44 202 44 78

E

5-85 41 290 52 82

X

6-57 48 227 53 76

SD

0-41 10 49 7 4

A

6-38 120 183 56 69

B

6-23 66 243 54 78

C

D

6-61

6-67

31 160 37 77

45 243 58 76

E

5-66 41 229 53 77

X

6-31 61 212 52 75

SD

0-40 36 38

8 4

3 Table 3. The effect of ingestion of propylene glycol alginate on faecal measurements

Volunteer

Volunteer D

Fat (mmol/24h) Total volatile fatty acids (mmol/24h) Total bile acids (mmol/24h) Total neutral sterols (mmol/24h)

I

After 23 days

Control period

5' D

SD

SD

22-0

16-7

19-1

10-9

20-1

7-7

24-9

25-3

6-9

25-0

10-7

18-6

9-0

5-74

12-06

17-28

12-97

18-71

13-35

5-1

12-14

15-81

9-49

19-38

12-46

13-86

3-8

1-17

2-54

0-94

1-06

0-69

1-28

0-73

1-86

2-47

0-67

1-47

0-87

1-47

0-73

2-55

1-76

2-28

1-80

1-94

2-07

0-34

1-37

1-02

1-20

1-77

1-77

1-43

0-34

31-6

a-

I

I

&



230

D. M. W. Anderson et al.

Table 4. Propylene glycol alginate: haematology, Day 3 (control). Volunteer

WBC (x 109/O RBC (x 1012/O Hb (side) Hct

MCV (ft) MCH (pg) MCHC (g/df) RDW

Platelets (x 109/O

A

B

6-4

4-7

4-66 15-2 44-1 94-6 32-6 34-5 12-5

4-93 15-3 44-1 89-4 31-0 34-7 11-7

227

Neutrophils (%) (x 109/O Lymphocytes (%) (x 109/0 Monocytes (%) (x 109/£) Eosinophils (%)

(x 109/0 Basophils (%) (x 109/f)

64 4-1 27 1-7 6 0-4 3 0-2 0 0

249

52 2-4 35 1-7

9 0-4 3 0-1 0 0

C

D

E

4-8

5-5

8-5

4-90 15-2 44-4 90-6 31-0 34-2 12-4

4-64 14-9 43-0 92-7 32-1 34-6 12-9

5-20 15-3 44-8 86-1 29-4 34-2 12-2

244 55 2-6 36 1-7 8 0-4 1

Dietary effects of propylene glycol alginate in humans.

Following a 7-day control period, five male volunteers consumed a weight of propylene glycol alginate corresponding to 175 mg/kg body weight for 7 day...
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