Physiological Effects of Food Carbohydrates - ACS Publications

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Downloaded by MICHIGAN STATE UNIV on February 19, 2015 | http://pubs.acs.org Publication Date: June 1, 1975 | doi: 10.1021/bk-1975-0015.ch017

The Physiological Effects of Alginates and Xanthan Gum W. H. McNEELY and PETER KOVACS Kelco Company, San Diego, Calif.

Alginates

Algin, found in all species of brown algae where it functions as an important constituent of cell walls, was discovered by Stanford in 1881. (1) The largest source of algin for actual commercial extraction is Macrocystis pyrifera, although other species are also used. (2) After 1935, alginates became widely used in the food industry as stabilizers, emulsifiers, and viscosity-adjusting agents. Alginates are commercially supplied to the food industry as the sodium, potassium, ammonium, and calcium salts of alginic acid, along with propylene glycol alginate. As indicated in Figure 1, alginic acid is a linear glycuronan consisting of ß-D-mannuronic acid and α-L-guluronic acid units linked throughC and C . For Macrocystis pyrifera, the alginic acid is composed of approximately 60 percent mannuronic acid and 40 percent guluronic acid. (2) The fine structure of the alginic acid molecule has been shown by graded acid hydrolysis and p.m.r. spectroscopy to consist of blocks of polymannuronic acid units and blocks of polyguluronic acid units linked by segments in which the two uronic acid residues alternate. (3,4) 1

4

The most recent acute o r a l t o x i c i t y study conducted by Woodard and co-workers on r a t s i n d i c a t e d t h a t the maximum amount o f sodium a l g i n a t e t h a t could be administered by o r a l i n t u b a t i o n was 5 g/kg f o r one day. T h i s feeding l e v e l caused no m o r t a l i t i e s . Gross necropsy f i n d i n g s , coupled with general observations, i n d i c a t e d t h a t sodium a l g i n a t e i s non-toxic with respect to acute t o x i c i t y by the o r a l route. (5) A number o f acute t o x i c i t y studies have been conducted on a v a r i e t y o f animals by intravenous o r i n t r a p e r i t o n e a l injections of alginate solutions. Arora and co-workers reported that i n t r a p e r i t o n e a l i n j e c t i o n s o f sodium a l g i n a t e t o r a t s a t up t o 1000 mg/kg caused no m o r t a l i t y , while some m o r t a l i t y occurred among the

269 In Physiological Effects of Food Carbohydrates; Jeanes, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1975.

PHYSIOLOGICAL EFFFCTS OF FOOD CARBOHYDRATES


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In Physiological Effects of Food Carbohydrates; Jeanes, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1975.


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mice upon 500 mg/kg dosage a d m i n i s t r a t i o n . (6) Intravenous i n j e c t i o n s o f sodium a l g i n a t e performed by Solandt to mice a t the 200-500 mg/kg l e v e l proved f a t a l i n 1 minute to 12 hours.(7) The LD-50 t o r a t s by t h i s method was determined by Sokow as 1000 mg/kg. (8) The LD-50 of sodium a l g i n a t e by the intravenous route to r a b b i t s was found t o be 100 mg/kg. I t was p o s t u l a t e d that the t o x i c i t y caused by the intravenous a d m i n i s t r a t i o n of sodium a l g i n a t e was due to the formation and p r e c i p i t a t i o n of the i n s o l u b l e calcium a l g i n a t e . (J) Due to i t s known r e a c t i v i t y with calcium ions to form i n s o l u b l e calcium a l g i n a t e , a l g i n has never been recommended f o r use i n intravenous i n j e c t i o n s . The LD-50 o f propylene g l y c o l a l g i n a t e determined by o r a l i n t u b a t i o n was found t o be above the 5 g/kg l e v e l . No mort a l i t y occurred and no signs of t o x i c i t y or changes i n the v i s c e r a of the t r e a t e d r a t s were found. (5) The o r a l a d m i n i s t r a t i o n of 10 g/kg propylene g l y c o l a l g i n a t e to r a t s was a l s o found t o be harmless by Newell and Maxwell with the exception of some t r a n s i e n t depression. (9) Intravenous a d m i n i s t r a t i o n of a l g i n i c a c i d by Thienes and co-workers (10) and calcium a l g i n a t e by Sokow (8) produced r e s u l t s s i m i l a r t o t h a t o f sodium a l g i n a t e ; namely, low LD-50 l e v e l s and s i g n i f i c a n t m o r t a l i t y . I t was suggested that the m o r t a l i t y was caused by embolism, as calcium a l g i n a t e as w e l l as a l g i n i c a c i d i s i n s o l u b l e i n water. A number o f short-term s t u d i e s have been conducted on sodium a l g i n a t e . A 10-day study was conducted by V i o l a and co-workers on r a t s where 0, 5, and 10 percent of the t e s t animals d i e t c o n s i s t e d of sodium a l g i n a t e . No apparent e f f e c t was found a t the 5 percent l e v e l , but at 10 percent l e v e l s , depressions i n calcium absorption were noted, while the u t i l i z a t i o n of p r o t e i n was not s i g n i f i c a n t l y a f f e c t e d . (11) In a 10-week experiment, the d a i l y d i e t s o f four groups of r a t s , each c o n s i s t i n g of s i x animals, were supplemented with 5, 10, 20, and 30 percent sodium a l g i n a t e . The t e s t s r e s u l t s are shown i n Table I. 1

Table I Short-Term, High-Level Sodium A l g i n a t e Feeding Studies with Rats Sodium A l g i n a t e Level 5% 10% 20% 30%

Mean D a i l y Weight Gain 3.81 3.47 2.91 2.35

g g g g

Food Consumed Gain i n Weight 3.20 3.31 3.48 3.87

g g g g

Water Consumed Gain i n Weight 5.84 6.28 8.83 13.47


g g g g


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At the h i g h e s t feeding l e v e l , only two r a t s s u r v i v e d . The m o r t a l i t y was a t t r i b u t e d t o the low n u t r i t i o n a l q u a l i t y o f the b a s a l d i e t and not t o any t o x i c e f f e c t s of the sodium a l g i n a t e . (12) In an unpublished i n v e s t i g a t i o n by Woodard and co-workers, the e f f e c t of feeding 5 and 15 percent sodium a l g i n a t e and propylene g l y c o l a l g i n a t e t o purebred beagles f o r a p e r i o d o f one year was determined, A f t e r one year the animals were s a c r i f i c e d , and gross h i s t o p a t h o l o g i c a l examinations were made on the important organs. The r e s u l t s o f t h i s study i n d i cated t h a t the dogs t o l e r a t e d l e v e l s as high as 15 percent sodium a l g i n a t e and propylene g l y c o l a l g i n a t e . Animals even at the h i g h e s t amount o f a l g i n a t e gained weight, as d i d the c o n t r o l s . V a r i a b l e s t o o l c o n s i s t e n c i e s at the 15 percent feeding l e v e l s i n d i c a t e d the presence o f unabsorbed c o l l o i d . Hemograms and blood chemistry values were g e n e r a l l y w i t h i n normal l i m i t s and showed no trends which could be r e l a t e d t o the a d m i n i s t r a t i o n o f the t e s t m a t e r i a l s . Based on the above, i t was concluded that both sodium a l g i n a t e and propylene g l y c o l a l g i n a t e were devoid of any harmful o r d e l e t e r i o u s e f f e c t s . (13) For a p e r i o d o f one year, propylene g l y c o l a l g i n a t e was fed t o mice by N i l s o n and Wagner a t 0, 5, 10, 15, and 25 percent by weight of the d i e t . No s i g n s o f t o x i c i t y were noted, but a t the two h i g h e s t feeding l e v e l s , smaller weight gains and i n c r e a s e d m o r t a l i t y r a t e s were noted. T h i s was a t t r i b u t e d t o the water a b s o r p t i o n q u a l i t y o f the d i e t l i m i t i n g the e s s e n t i a l n u t r i e n t intake. (12) By the same workers, propylene g l y c o l a l g i n a t e was added t o the d i e t o f guinea p i g s at 0, 5, 10, and 15 percent l e v e l s . A f t e r 26 weeks, no untoward e f f e c t s were noted which could be a t t r i b u t e d t o the propylene g l y c o l a l g i n a t e . (12) In a feeding study by N i l s o n and Wagner, c a t s were f e d 0, 5, 10, and 15 percent propylene g l y c o l a l g i n a t e as p a r t o f t h e i r d i e t f o r up to 111 days. Although the c a t s r e c e i v i n g propylene g l y c o l a l g i n a t e i n t h e i r d i e t had apparent problems i n swallowing and e a t i n g and consequently l o s t weight when compared t o the c o n t r o l animals, no i n d i c a t i o n s o f c h r o n i c t o x i c i t y were noted. Gross and h i s t o p a t h o l o g i c a l examinations of organs o f these animals revealed no l e s i o n s which could be a t t r i b u t e d t o any s p e c i f i c problems. (12) Table I I i n d i c a t e s the r e s u l t s o f a study where, f o r a p e r i o d o f two months, a l g i n i c a c i d was f e d t o r a t s a t 0, 5, 10, and 20 percent o f t h e i r d i e t . As shown i n t h i s t a b l e , at up t o 10 percent c o n c e n t r a t i o n s , no s i g n i f i c a n t e f f e c t on growth o r food consumption was noted. At the 20 percent l e v e l , however, a s i g n i f i c a n t decrease i n weight g a i n was observed. (10)


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Gum

Table II Short-Term A l g i n i c A c i d Feeding Studies with Rats


Dietary Algin % 0 5 10 20

Average Weight Gain Initial Final 66 66 64 63

Average D a i l y Food Consumption g/100 g.b.w. 10.8 12.6 12.1 8.8

156 154 156 116

In a d e t a i l e d two-year, three-generation reproduction study by Morgan, et a l . , r a t s were p l a c e d on a d i e t c o n t a i n i n g 5 percent sodium a l g i n a t e and propylene g l y c o l a l g i n a t e . When the animals were f i v e t o s i x months o f age, they were mated, and the o f f s p r i n g , the F-^ generation, were grouped, as were the parent animals, and fed the same d i e t s . When the F i generation r a t s were about four months o l d , they were a l s o mated, and the r e s u l t i n g o f f s p r i n g , the F generation, were d i v i d e d , as the parent generations were, and p l a c e d on the same d i e t . Table III shows the body weight data f o r the three generations of c o n t r o l animals and those r e c e i v i n g 5 percent sodium a l g i n a t e and propylene g l y c o l a l g i n a t e . As i n d i c a t e d i n t h i s t a b l e , there were no s i g n i f i c a n t d i f ferences between the c o n t r o l and t r e a t e d groups or between the e f f e c t s of sodium a l g i n a t e and propylene g l y c o l a l g i n a t e . The c o n c l u s i o n s of t h i s study revealed t h a t the feeding of sodium a l g i n a t e and propylene g l y c o l a l g i n a t e t o r a t s f o r the p e r i o d o f two years at 5 percent l e v e l s of t h e i r d i e t s d i d not a f f e c t the growth r a t e of the parent generation and t h e i r progeny f o r two generations when compared t o the c o n t r o l group. No gross p a t h o l o g i c a l or hematological changes were noted i n the t e s t animals. A s l i g h t change i n the b a c t e r i a l f l o r a of the g a s t r o i n t e s t i n a l t r a c t was observed, but these were not s i g n i f i c a n t enough t o cause changes i n the d i g e s t i v e process or t o r e t a r d the h e a l t h of the animals. (15) Pregnant mice, r a t s , and hamsters i n d i c a t e d no signs of t e r a t o g e n i c e f f e c t s when they were administered by o r a l i n t u b a t i o n propylene g l y c o l a l g i n a t e i n doses of 780, 720, and 700 mg/kg during g e s t a t i o n . (16) While i n v e s t i g a t i n g the c a r c i n o g e n i c i t y of s e v e r a l c o l l o i d s , E p s t e i n reported t h a t no change i n the frequency o f tumors i n i n f a n t mice occurred a f t e r repeated subcutaneous i n j e c t i o n s o f a l g i n i c a c i d . (17) E a r l i e r p u b l i c a t i o n s on the d i g e s t i b i l i t y of a l g i n c a r r i e d out on v a r i o u s animal species by N i l s o n and co-workers (12, 20) tended t o show t h a t a l g i n was p a r t i a l l y d i g e s t i b l e . 2



243 234

204

304

243 202

204 236

402

323 292

287 268

403

32 3 270

287 272

761

202 202

212 212

761

202 202

212 212

5% A l g i n a t e

Control

5% A l g i n a t e

Control

5% A l g i n a t e

(S A)

291

298

401

401

761

761

Control

209

298

S A

PGA

S A

PGA

Mean Body Weight Female

PGA

Mean Body Weight Male

S A

Diet Level

Propylene G l y c o l A l g i n a t e (PGA)

Sodium A l g i n a t e

Parent

Generation

Day of Termination

Long-Term Sodium A l g i n a t e and Propylene G l y c o l A l g i n a t e Feeding Studies with Rats

Table I I I


a ο

&

Ο

ο

ο r

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Gum

A n a l y t i c a l methods used were based on i s o l a t i o n of the a l g i n from the f e c e s . These methods are not very r e l i a b l e . Recent s t u d i e s by the more accurate r a d i o a c t i v e C method by Humphreys and T r i f f i t t (18) f o r sodium a l g i n a t e and by S h a r r a t t and Dearn (19) f o r propylene g l y c o l a l g i n a t e found n e g l i g i b l e or no absorption of the a l g i n . Numerous published r e p o r t s d e a l i n g with the e f f e c t of sodium a l g i n a t e on the g a s t r o i n t e s t i n a l absorption of r a d i o a c t i v e strontium and s e v e r a l other m e t a l l i c ions are l i s t e d i n a review by Tanaka and Skoryna. (21) While s e v e r a l authors reported t h a t a l g i n i n h i b i t s the r a d i o a c t i v e strontium absorption, much l e s s e r e f f e c t s have been produced on the absorption of calcium, magnesium, i r o n , copper, and z i n c . The current p u b l i c i n t e r e s t created by the a l l e g e d d e t o x i f i c a t i o n p r o p e r t i e s of sodium a l g i n a t e with respect to lead does not appear to be j u s t i f i e d . In a recent study by H a r r i s o n , et a l . , human volunteers were administered 5 g of sodium a l g i n a t e , which d i d not change the l e v e l of lead i n t h e i r systems.(22) Based on a human feeding study, Carr, et a l . , reported t h a t sodium a l g i n a t e does not a f f e c t the abs o r p t i o n of sodium, potassium, magnesium, and phosphorous i n the g a s t r o i n t e s t i n a l t r a c t . (23) The e f f e c t of a l g i n i c a c i d on the c a t i o n absorption i n humans was reported e a r l i e r by Feldman and co-workers. Four a d u l t males were maintained on a c o n t r o l d i e t c o n t a i n i n g 500 mg sodium per day f o r seven days. A f t e r that time, 15 g of a l g i n i c a c i d , three times d a i l y , was administered f o r seven days. In three p a t i e n t s t h i s study was repeated with 1500 mg d a i l y intake of sodium. The a l g i n i c a c i d was w e l l t o l e r a t e d by the subjects with the exception of m i l d l a x a t i v e e f f e c t s . (14) In a calciumbalance experiment performed on s i x a d u l t humans by M i l l s and Reed, the r e s u l t s i n d i c a t e d that sodium a l g i n a t e does not i n t e r f e r e with the calcium absorption of the normal v a r i e d d i e t . (24) 1 4


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Xanthan

Gum

Xanthan gum, a r e l a t i v e l y r e c e n t l y developed p o l y saccharide produced by the b a c t e r i a l fermentation of glucose with the organism Xanthomonas campestris, was approved by the FDA as a food a d d i t i v e i n 1969. Since t h a t time, xanthan gum has been widely accepted by the food i n d u s t r i e s of many c o u n t r i e s as a general purpose s t a b i l i z e r - t h i c k e n e r . The commercial success of xanthan gum was r e c e n t l y manifested by the p r e s e n t a t i o n of the 1974 IFT Food Technology I n d u s t r i a l Achievement Award to Kelco Company and the Northern Regional Research Laboratory of the USDA. (25) As i n d i c a t e d i n Figure 2, xanthan gum i s a heteropolysaccharide with main b u i l d i n g b l o c k s c o n s i s t i n g of D-glucose, Dj-mannose, and D-glucuronic a c i d r e s i d u e s . (26) The polymer


In Physiological Effects of Food Carbohydrates; Jeanes, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1975. Figure 2.

Generally accepted xanthan gum structure


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Gum

a l s o contains pyruvate attached t o a glucose s i d e chain at an, as yet, undetermined l o c a t i o n . The molecule i s a very long l i n e a r chain with a molecular weight of 5 to 10 m i l l i o n . Xanthan gum i s perhaps the most e x t e n s i v e l y i n v e s t i g a t e d polysaccharide from the standpoint of t o x i c o l o g i c a l and safety properties. The r e s u l t s of the acute t o x i c i t y s t u d i e s are summarized i n Table IV. Table

IV


Acute T o x i c i t y Studies with Xanthan

Gum

Animal

Route

Maximum mg/kg Body Weight Administered

Mouse

Oral Intraperitoneal Intravenous

1000 (21) 150 (27) 100-250 (28)

Rat

Oral

5000

(29)

Dog

Oral

20000

(30)

In the r a t and dog s t u d i e s , the LD-50 l e v e l s are a c t u a l l y r e p r e s e n t a t i v e of the maximum l e v e l s the animals were able t o consume w i t h i n the t e s t p e r i o d . Since no m o r t a l i t i e s or t o x i c manifestations occurred, the true o r a l LD-50 l e v e l s are above those shown i n t h i s t a b l e . There were two short-term feeding s t u d i e s conducted on both r a t s and dogs by Booth, et a l . No untoward e f f e c t s were noted upon the extensive i n v e s t i g a t i o n of r a t s when they were fed xanthan gum f o r a p e r i o d of 99-110 days at 7.5 percent and 10 percent as p a r t of t h e i r d a i l y d i e t . (29) In a 91-day feeding study, normal weight gains were recorded at 3 percent and 6 percent xanthan gum l e v e l s i n the d i e t , while some weight gain r e d u c t i o n was noted at 7.5 percent and 15 percent l e v e l s . No d i f f e r e n c e s i n organ weights, hemog l o b i n concentration, and white and red c e l l counts were found. At the highest dosage l e v e l s , the animals d i d produce abnormally high f e c a l p e l l e t s , but no occurrence of d i a r r h e a was noted. In a p a i r e d feeding t e s t study at 7.5 percent feeding l e v e l , no g r o w t h - i n h i b i t i n g f a c t o r a t t r i b u t a b l e t o xanthan gum was found. (29) Feeding dogs 2 g/kg xanthan gum f o r a p e r i o d of two weeks produced d i a r r h e a i n the t e s t group, while the same d i d not occur at the 1 g/kg feeding l e v e l . Gross h i s t o p a t h o l o g i c a l examination d i d not r e v e a l any organ damage a t t r i b u t a b l e to the i n g e s t i o n of xanthan gum. (31) T h i s occurrence i s not unexpected, as most h y d r o p h i l i c c o l l o i d s , due to t h e i r



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e f f i c i e n t water-absorbing p r o p e r t i e s , are known t o cause d i a r r h e a a t high feeding l e v e l s . In long-term feeding s t u d i e s by Woodard, e t a l . , a group of 30 male and 30 female r a t s was fed xanthan gum at 0, 0.25, 0.5, and 1.0 g/kg as p a r t of t h e i r d a i l y d i e t f o r a p e r i o d of 104 weeks. No abnormalities were found which could be a t t r i b u t e d to the i n g e s t i o n of the product. S u r v i v a l r a t e , body weight gain, food consumption, behavior, and appearance were normal when compared to the c o n t r o l group. Hemat o l o g i c a l values, organ weights, and tumor occurrence showed no s i g n i f i c a n t v a r i a t i o n . S l i g h t l y s o f t e r s t o o l s were noted i n the middle- and h i g h - l e v e l t e s t animals, but the d i f f e r e n c e from the c o n t r o l was not s t a t i s t i c a l l y s i g n i f i c a n t . (32) In a 107-week-long study on a group of four male and four female beagle dogs, 0, 0.25, 0.37, and 1 g/kg xanthan gum was fed to the animals as p a r t of t h e i r d a i l y d i e t . No adverse e f f e c t s were noted i n the t e s t animals with respect to s u r v i v a l , food intake, body weight gain, electrocardiograms, blood pressures, hemograms, organ weights, gross necropsy observations, and h i s t o p a t h o l o g i c a l observations. At the h i g h e s t feeding l e v e l , a d o s e - r e l a t e d increase i n f e c a l weights and a measurable increase i n the s p e c i f i c g r a v i t y of the u r i n e and more frequent presence of u r i n a r y albumin were noted. T h i s t e s t revealed no untoward e f f e c t s caused by the treatment of xanthan gum a t any dosage l e v e l s . (32) The feeding of xanthan gum was a l s o examined i n a threegeneration reproduction study by Woodard, et a l . , using 10 male and 20 female r a t s i n the f i r s t generation and 20 male and 20 female r a t s i n subsequent generations. Dosage l e v e l s were 0, 0.25, and 0.5 g/kg as p a r t of the animals' d i e t . The t e s t r e s u l t s were evaluated f o r s u r v i v a l , body weights, general appearance, behavior, reproductive performance, p h y s i c a l c o n d i t i o n of the o f f s p r i n g , and the s u r v i v a l of the o f f s p r i n g . With respect to a l l c r i t e r i a , no adverse e f f e c t s were noted i n t h i s study which would be a t t r i b u t a b l e to the presence of xanthan gum i n the d i e t of the animals. (32) According to a t e s t conducted by the c a l o r i c a v a i l a b i l i t y method, the d i g e s t i b i l i t y of xanthan gum was found to be zero. T h i s c o n c l u s i o n was s u b s t a n t i a t e d i n a r e p o r t by Booth and coworkers which found that p r a c t i c a l l y a l l xanthan gum fed f o r a p e r i o d of seven days could be recovered i n the s t o o l of the animals. (27) In another study, conducted by the more accurate r a d i o a c t i v e t r a c e r method, the d i g e s t i b i l i t y of xanthan gum was found to be approximately 15 percent. The p o l y s a c c h a r i d e c o n s t i t u e n t s d i d not accumulate i n the t i s s u e s , and they were metabolized by the expected route as carbohydrates. In v i t r o t e s t s i n d i c a t e d t h a t non-enzymatic h y d r o l y s i s and the a c t i o n of microorganisms were r e s p o n s i b l e f o r the i n i t i a l breakdown of the molecule. Based on the above s t u d i e s , the approximate c a l o r i c value of xanthan gum i s 0.5 k i l o -


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279

c a l o r i e s per gram.


Conclusion The foregoing, o f course, i s an abridged summary o f the t o x i c o l o g i c a l studies conducted on a l g i n a t e s and xanthan gum. There i s a b s o l u t e l y no information a v a i l a b l e i n d i c a t i n g t h a t the consumption o f these products a t t h e i r normal usage l e v e l s would present any h e a l t h hazards. Furthermore, i t should be emphasized t h a t the f u n c t i o n a l l e v e l s and the per c a p i t a consumption o f a l g i n a t e s and xanthan gum are orders of magnitude below the feeding l e v e l s used t o e s t a b l i s h t h e i r s a f e t y as food a d d i t i v e s . "Literature Cited"

1 Stanford, E. C. C , J. Soc. Chem. Ind., (1886) 5, 218. 2 McNeely, W. H. and Pettitt, D. J., in "Industrial Gums," 2nd Ed., pp. 49-81, Academic Press, New York, New York, 1973. 3 Haug, Α., Larsen, G., Smidsrød, O., Acta. Chem. Scand., (1967) 21, 691. 4 Penman, A. and Sanderson, G., Carb. Res., (1972) 25, 273. 5 Knott, W. B. and Johnston, C. D., "Sodium and Propylene Glycol Alginate Acute Oral Toxicity to Rats," Woodard Research Corporation unpublished report, 1972. 6 Arora, C. Κ., Chandhury, S. K., Chanha, P. S., Indian J. Physiol. Pharmacol., (1968) 12 (3) 129-30. 7 Solandt, Ο. Μ., Quart. J. Exp. Physiol., (1941) 31, 25-40. 8 Sokov, L. Α., Radioactivnye Izotopy Vo Vneshnei Srede i Organizme (Russian), (1970) 247-51. 9 Stanford Research Institute, "Study of Mutagenic Effects of Propylene Glycol Alginate (71-18)," PB 221 826, Ν.T.I.S., 1972. 10 Thienes, C. H., Skillen, R. G., Meredith, Ο. Μ., Fairchild, M. D., McCandless, R. S., Thienes, R. P., Arch. Intern. Pharmacodyn., (1957) 111 (2) 167-81. 11 Viola, S., Zimmerman, G., Mokady, S., Nutr. Rep. Int., (1970) 1 (6) 367-76.


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PHYSIOLOGICAL EFFECTS OF FOOD CARBOHYDRATES

12 Nilson, H. W. and Wagner, J. Η., Proc. Soc. Exp. Biol. Med., (1951) 76 (4) 630-5. 13 Dardin, V. J., "Feeding of KELGIN or KELCOLOID to Dogs for One Year," Woodard Research Corporation unpublished report, 1959.


14 Feldman, H. S., Urbach, K., Naegle, C. F., Regan, F. D., Doerner, Α. Α., Proc. Soc. Exp. Biol. Med., (1952) 79, 439-41. 15 Morgan, C. F., Farber, J. E. Jr., Dardin, V.J.,"The Effects of Algin Products on the Rat," Georgetown Univer sity Medical School unpublished report, 1959. 16 Food and Drug Research Laboratories, "Teratological Evaluation of Propylene Glycol Alginate," PB 221 786, Ν.T.I.S., 1972. 17 Epstein, S. S., Toxicol. Appl. Pharmacol., (1970) 16, 321-4. 18 Humphreys, Ε. R. and Triffitt, J. T., Nature, (1968) 219, 1172-3. 19 Sharratt, M. and Dearn, P., Food Cosmet. Toxicol., (1972) 10 (1) 35-40. 20 Nilson, H. W. and Lemon, J. Μ., "Metabolism Studies with Algin and Gelatin," pp. 1-9, U.S. Fish and Wildlife Serv. Research Report No. 4, 1942. 21 Tanaka, Y. and Skoryna, S. C., in "Intestinal Absorption of Metal Ions, Trace Elements, and Radionuclides," pp. 10114, Pergamon Press, New York, New York, 1971. 22 Harrison, G. E., Carr, T. E. F., Sutton, Α., Humphreys, E. R., Nature, (1969) 224, 1115-6. 23 Carr, T. E. F., Harrison, G. Ε., Humphreys, E. R., Sutton, Α., Int. J. Radiat. Biol., (1968) 14 (3) 225-33. 24 Millis, J. and Reed, F. Β., Biochem J., (1947) 41, 273-5. 25 Anonymous, Food Technol., (1974) 28 (6) 18-21. 26 Sloneker, J. H., Orentes, D. G., Jeanes, Α., Can.J.Chem., (1964) 42, 1261-9.


17.

MC

NEELY

AND

KOVACS

Alginates

and

Xanthan

Gum

21 Booth, A. N., Hendrickson, A. P., DeEds, F., Toxicol. Appl. Pharmacol., (1963) 5, 478-84. 28 Hendrickson, A. P. and Booth, Α. Ν., "Supplementary Acute Toxicological Studies of Polysaccharide B-1459," Western Reaional Research Laboratory Research Report, Albany, California, 1964.


29 Jackson, N. N., Woodard, M. W., Woodard, G., "Xanthan Gum Acute Oral Toxicity to Rats," Woodard Research Corporation unpublished report, 1968. 30 Jackson, Ν. Ν., Woodard, M. W., Woodard, G., "Xanthan Gum Acute Oral Toxicity to Dogs," Woodard Research Cor poration unpublished report, 1968. 31 Robbins, D. J., Moulton, J. Ε., Booth, Α. Ν., Food Cosmet. Toxicol., (1964)2,545. 32 Woodard, G., Woodard, M. W., McNeely, W. Η., Kovacs, P., Cronin, M. T. I., Toxicol. Appl. Pharmacol., (1973) 24, 30-6.


Physiological Effects of Food Carbohydrates - ACS Publications

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