| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Acetic acid | 64-19-7 | 82 | 1977 | 1 | 184.1005 |
SCOGS Opinion:
Acetates are common constituents of plant and animal tissues. They are normal metabolic intermediates produced in relatively large quantities during the digestion and metabolism of foods.
Although the Select Committee is not aware of any long-term feeding studies of acetic acid or the acetates, short term studies have revealed no untoward effects at concentrations far exceeding those consumed in the normal diet and do not suggests that adverse effects might be revealed by longer term studies.
No data on carcinogenic evaluation of acetic acid and the acetate salts have come to the attention of the Select Committee. Limited data indicate that acetic acid is not teratogenic in vivo; sodium acetate is not mutagenic and acetic acid is probably not mutagenic in vitro.
No reports of biological studies on sodium diacetate have been found, but since this substance dissociates in the body to sodium acetate and acetic acid, neither of which elicits adverse effects under current conditions of use, the Select Committee beleives that use of sodium diacetate can be considered to be without adverse effects.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on acetic acid, sodium acetate, and sodium diacetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American diet, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added food
ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Acid hydrolyzed proteins | There is no ID Code | 37b | 1980 | 1 | There is no CFR citation. |
SCOGS Opinion:
The average level of consumption of protein hydrolyzates for flavoring purposes is less than 3 mg per kg per day. Protein hydrolyzates are not used for flavoring purposes in commercially processed baby foods wich formerly may have contained about 2 percent by weight. The Select Committee was unable to locate reports of experimentally demostrable adverse effects of high concentrations of glutamate in dietary mixtures.
In light of the above, and assuming that appropriate product specifications are adopted, the Select Commitee concludes that:
There is no evidence in the available information on acid hydrolyzed proteins, enzymatically hydrolyzed protein, yeast autolysates, and soy sauces, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as flavoring agents at levels that are now current or that might reasonably be expected in the future.
The situation is different regarding the use of enzymatic casein hydrolyzates as nutrients. These hydrolyzates are consumed or administered in much higher doses, frequently as the sole source of dietary protein in products that are used as special dietary foods.
Decades of clinical experience have revealed no reports of untoward effects when casein hydrolyzates are administered orally in combination with other nutrients such as glucose. Adverse effects of the dicarboxylic amino acid components have been reported only in rodents under unusual conditions of administration (e.g., gavage or subcutaneous injection) and are not considered relevant to the use of casein hydrolyzates by humans.
The Select Commitee therefore concludes that: There is no evidence in the available information on enzymatically hydrolyzed casein that demostrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a nutrient in special dietary foods at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Acid Modified Starch | 65996-63-6 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Aconitic Acid | 499-12-7 | 41 | 1974 | 1 | 184.1007 |
SCOGS Opinion:
The limited data on trans-aconitic acid indicate it to be less toxic than citric acid. Trans-aconitate salts appear to be excreted readily by the kidneys. There is no direct evidence that trans-aconitic acid is utilized as is the cis-aconitic acid isomer in mammalian metabolism although non-specific oxidation probably occurs. The Select Committee has weighed all of the foregoing and concludes that: There is no evidence in the available information on aconitic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Adipic acid | 124-04-9 | 80 | 1976 | 1 | 184.1009 |
SCOGS Opinion:
Investigations on animals and humans show that adipic acid is readily absorbed from the alimentary tract. Much of the absorbed compound is rapidly excreted in the urine but a substantial portion is oxidized to carbon dioxide. The intermediate products formed indicate that it is metabolized by the same route as the fatty acids.
The tolerance of animals to adipic acid is comparable to that of certain normal metabolites such as citric acid. Adipic acid caused no harmful effects in animals in long-term tests in which it was added to the diet in amounts up to at least 1 percent (500mg per kg body weight per day). This is over 500 times the daily per capita intake estimated from the poundage reported to be used in food in 1970. The available evidence suggests that the metabolism of adipic acid in man is comparable to that of laboratory animals.
In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on adipic acid that demonstrates , or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Agar-agar | 9002-18-0 | 23 | 1973 | 2 | 184.1115 |
SCOGS Opinion:
Agar-agar has relatively little effect when added to the diets of animals in amounts considerably greater than those present in the human diet. The observed increases in intestinal weight and length in animals appear to be related to the bulking and hydrocolloidal properties of the material, and these changes occur only at relatively high concentrations of agar-agar. Although no specific studies of the carcinogenicity or other long-term investigtions of agar-agar have been made, this material has a long history of use as a gelling agent and bulk component of experimental animal diets. Because 2 to 5 percent of this material has been used routinely in control diets in numerous studies witout reported significant effects, it is reasonable to conclude that even at these high levels, agar-agar produces no significant chronic effects. However, there is one report that agar-agar, fed at relatively high levels (400 to 1570 mg per kg per
day), is lethal to many pregnant mice and rabbits but not to pregnant rats and hamsters fed at equivalent levels (650 to 1140 mg per kg per day). Significant numbers of material deaths occurred in pregnant mice and rabbits fed agar-agar at levels 110 fold greater (mice) and 30 fold greater (rabbits), than the maximum level estimated to be consumed by adults (13.2 mg per kg per day) in the daily diet, but no toxic effects were observed in pregnant mice and rabbits fed levels 25 fold greater (mice) and 9 fold greater (rabbits) than the estimated adult human intake level. With respect to these comparisons it should be emphasized that the Select Committee believes the intake estimate of 13.2 mg per kg per day (Table II) is overstated by a considerable margin, which could make the foregoing differences in each case even larger. It is noteworthy that similar toxic effects have been observed in identical tests on a number of other polysacchardies (gum arabic, sterculia gum, carob bean gum,
guar gum, gum ghatti, gum tragacanth, carrageenan, propylene glycol alginate, and methyl cellulose) fed at very high levels. The relative sensitivity of the seveeral animal species to these effects varies depending on the particular polysaccharide tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude that unrestricted use of such substances in food would be without harzard. Agar-agar is a product extracted from marine algae. The possibility exists that harmful concentrations of certain metals such as mercury, may be accumulated in the commercial product if algae are harvested from coastal waters contaminated with significant levels of such heavy metals (26). Current specifications for food grade agar-agar (4) place a limitation on the content of "heavy metals as lead." Because modern methods of analysis are capable of distinguishing between and measuring the amounts of the several metal
elements, it would appear advisable to make the specifications for agar-agar more specific with respoect to allowable concentrations of potentially toxic heavy metals, such as mercury. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on agar-agar that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
Tocopherols are a natural constituent of many foods. The average daily dietary intake of tocopherols in the United States is approximately 5 to 20 mg. The quantity of tocopherols added to foods as antioxidants is estimated to be equivalent to an average adult daily intake of 0.6 mg. The several tocopherols used in foods as antioxidants are readily absorbed and metabolized. They are relatively non-toxic. LD50 values for acute oral toxicity of several animal species are in excess of 2000 mg per kg. Hypervitaminosis E has been reported in humans only at oral dosage levels in excess of 400 mg per day. Investigations on mutagenic, carcinogenic, and teratogenic effects of tocopherols have not revealed any deleterious or pathologic alterations, although some reproductive system effects have been observed in young animals fed or administered dosage levels that exceed by manyfold, the quantitites added to food or present in the daily
diet. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on tocopherols and alpha-tocopheryl acetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| alpha-Tocopherols | 59-02-9 | 36 | 1975 | 1 | 184.1890 |
SCOGS Opinion:
Tocopherols are a natural constituent of many foods. The average daily dietary intake of tocopherols in the United States is approximately 5 to 20 mg. The quantity of tocopherols added to foods as antioxidants is estimated to be equivalent to an average adult daily intake of 0.6 mg. The several tocopherols used in foods as antioxidants are readily absorbed and metabolized. They are relatively non-toxic. LD50 values for acute oral toxicity of several animal species are in excess of 2000 mg per kg. Hypervitaminosis E has been reported in humans only at oral dosage levels in excess of 400 mg per day. Investigations on mutagenic, carcinogenic, and teratogenic effects of tocopherols have not revealed any deleterious or pathologic alterations, although some reproductive system effects have been observed in young animals fed or administered dosage levels that exceed by manyfold, the quantitites added to food or present in the daily
diet. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on tocopherols and alpha-tocopheryl acetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Aluminum hydroxide | 21645-51-2 | 43 | 1975 | 1 | 184.1139 |
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Aluminum sulfate | 10043-01-3 | 43 | 1975 | 1 | 182.1125 |
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Orally administered licorice and licorice derivatives are absorbed to some extent and the principal metabolic products are excreted through the bile, but most of an ingested dose is hydrolyzed in the digestive tract and the products excreted through the feces. Acute and short-term substances of a very low order of toxicity, capable of eliciting a variety of pharmacological effects but only at levels considerably higher than are likely to be achieved in usual diets. None of these effects suggests cause for convern at current or foreseeable dietary levels of consumption. However, the capacity of licorice and licorice derivatives to elicit transitory hypertensive effects, at higher dosage levels in animals and man, requires more definitive clarification as far as its practical implications are concerned. This would be particularly important for the unknown number but probably few individuals who may indulge themselves with excessive
intakes of licorice-containing candies and/or beverages. The Select Committee has found no long-term toxicological data on licorice-related products administered to animals or man. Until the long-term as well as the acute dose relationships of the hypertensive effect are clarified, it appears inappropriate to conclude that unrestricted use of licorice and licorice derivatives in food would be without hazard to consumers in general. In the light of the foregoing and the information elsewhere in this report, the Select Committee concludes that: There is no evidence in the available information on licorice, glycyrrhiza, and ammoniated glycyrrhizin that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium alginate | 9005-34-9 | 24 | 1973 | 2 | 184.1133 |
SCOGS Opinion:
The available information on the alginates reveals no significant adverse toxicological effects from oral administration in non-pregnant animals or humans in daily amounts greatly exceeding those currently consumed in the diet. However, in pregnant mice, very large doses of propylene glycol alginate, while not teratogenic, cause a significant increase in maternal mortality. Such increased maternal toxicity does not occur at a dose of propylene glycol alginate which is 26-fold or more greater than that estimated to be the average daily adult dietary intake. No respect but studies of propylene glycol, made by the same investigators and is without maternal toxicity even at very large doses. This indicates that the adverse effects reported for propylene glycol alginate may be due to the alginate moiety. It is noteworthy that similar toxic effects have been observed in identical tests on a large number of other polysaccarides (gum
arabic, sterculia gum, carob bean gum, guar gum, gum ghatti, gum tragacanth, carrageenan, methyl cellulose, and agar-agar) fed at very high levels. The relative sensitivity of the several animal species to these effects, varies depending on the particular polysaccaride tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude that unrestricted use of such substances in food would be withou hazard. The Select Committee has weighed all of the foregoing and concludes that: There is no evidence in the available information on ammonium, calcium, potassium, sodium, and propylene glycol alginates that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption of these substances would
constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium bicarbonate | 1066-33-7 | 34 | 1974 | 1 | There is no CFR citation. |
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium carbonate | 8000-73-5 | 34 | 1974 | 1 | 184.1137 |
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium chloride | 12125-02-9 | 34 | 1974 | 1 | 184.1138 |
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium citrate | 7632-50-0 | 84 | 1977 | 1 | 184.1140 |
SCOGS Opinion:
The citrate ion is widely distributed in plants and animals and is a naturally occurring component of the diet. It is a common metabolite in oxidative metabolism and an important component of bone. Exogenous citrate administered to infants and adults as a component of commonly consumed diets is considered completely metabolizable. The addition of citric acid to foods is considered equivalent to adding citrate salts except in foods of very high acidity. The amount of citrate added to foods by foods processors is about 500mg per person per day. This amount occurs naturally in 2 ounces of orange juice and does not constitute a significant addition to the total body load. Although data on acute and chronic effects of orally administered sodium citrate, calcium citrate and potassium citrate are limited, no biological effects of the citrate-containing substances evaluated in this report cause concern about the safety of these GRAS
substances used in reasonable amounts and in accordance with prescribed tolerances and limitations.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on citric acid, sodium citrate, potassium citrate, calcium citrate, ammonium citrate, isopropyl citrate, stearyl citrate, and triethyl citrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium hydroxide | 1336-21-6 | 34 | 1974 | 1 | 184.1139 |
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium sulfate | 7783-20-2 | 34 | 1974 | 1 | 184.1143 |
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Arrowroot Starch | 977000-09-1 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
L-ascorbic acid, vitamin C, occurs in nutritionally significant amounts as a natural constituent of many fruits, vegetables, berries, and melons. As a vitamin it is needed in the diet of all age groups. L-ascorbic acid and its sodium salt are antioxidants and they are extensively used as preservatives, color stabilizers and for related functions in various foods and beverages. Calcium ascorbate and ascorbyl palmitate, a derivative of ascorbic acid having greater fat solubility, also are anti-oxidants, but appear not to have significant use in processed foods. In addition to their use in foods as antioxidants, L-ascorbic acid and its salts are added to some foods as a source of vitamin C. These sources constitute a significant proportion of the total ascorbate intake of the general population. Erythorbic acid (D-isoascorbic acid), a stereoisomer of L-ascorbic acid, and its sodium salt, also are effective antioxidants and are used
for this purpose in a number of food products. The quantities used in 1970 were substantially less than for the ascorbates. The vitamin activity of erythorbates is only one -twentieth that of ascorbic acid, and their anti-oxidant effectiveness is not greater than for the ascorbates. For this reason, it would seem desirable, where possible, to use L-ascorbic acid rather than erythorbic acid as an antioxidant. From studies in guinea pigs and man it can be concluded that although erythorbic acid shares the same absorption and tissue uptake system as ascorbic acid it has little antiscorbutic activity. Although competition between ascorbic acid and erythorbic acid has been demosntrated at a biochemical level, there is no firm evidence that such competition will produce a scorbutic state. Whether this biochemical interaction could result in a clinically significant depletion of ascorbic acid remains to be established. Both short- and long-term toxicity studies have demonstrated tolerance
without adverse effects for large amounts of orally administered L-ascorbic acid, sodium L-ascorbate, and erythorbic acid in several species including mice, rats, guinea pigs, rabbits, and dogs. A substantial number of short-term experiments with human subjects ingesting 1 to 4 g of ascorbate daily have generally not revealed any harmful effects. Some subjects have received higher amounts, up to at least 8 to 10 g per day. In most instances no untoward results have been noted. But there is marked paucity of such studies that were well controlled and in which inquiring attention was given to possible harmful effects. In due course, such studies would be desirable. In the various studies on the effect of ingesting excessive amounts of ascorbates, attention has been focused on questions including oxalate excretion and renal tract stones, effets on the utilization of copper, iron, and other metals, need for vitamin B12, blood coagulation,and reproductive performance. The findings indicate
that the tolerance to excessive amounts of ascorbic acid and its sodium salt is high. Several investigators have reported the development of dependency in animals and human after ingestion of large amounts of ascorbates for extended time periods; however, the levels of ascorbates added to foods by 1 to 3 orders of magnitude. It is notable that no data have been found concerning the possible effects of ascorbyl palmitate and calcium ascorbate in humans, and there is practically no information regarding the latter in animals. Information concerning ascorbyl palmitate in animals is almost as limited. The few meaningful experiments suggest that ascorbyl palmitate is tolerated about the same as ascorbic acid and sodium ascorbate. This should be expected. It is reasonable to assume that the tolerance to calcium ascorbate is approximately the same as for sodium ascorbate and this is a high level. In view of the foregoing, The Select Committee concludes that: There is no evidence in the
available information on L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, ascorbyl palmitate (palmitoyl L-ascorbic), erythorbic acid (D-isoascorbic acid), and sodium erythorbate (sodium D-isoascorbate) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as food ingredients at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
There is a paucity of experimental data on the digestion, absortion, metabolism, and short-term or long-term toxicity of beeswax after oral intake by humans or animals; but as a component of comb honey, beeswax has been ingested since ancient times without evidence of harm. Although the composition of beeswax is not digested or absorbed from the alimentary tract in most animals or man. Beeswax containing pollens or oleoresins may be allergenic to sensitive individuals but beeswax alone has not been reported to be allergenic. No studies designed to show teratogenic effects of beeswax have been reported. Numerous injections of beeswax as a vehicle for drugs have nor led to reports of tumors at the injection site. Relatively little comb honey is used as a food in the U.S. The use of beeswax in processed food products decreased fourfold in the decade from 1960-1970 and presently is very small, amounting to an average estimated per
capita daily intake of about 0.16mg. On the basis of the above considerations the Select Commitee concludes that: There is no evidence in the available information on beeswax (yellow or white) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Bentonite | 1302-78-9 | 90 | 1977 | 1 | 184.1155 |
SCOGS Opinion:
Bentonite and clay (kaolin) are readily hydratable aluminium silicates. Bentonite is used to assist in the clarification of juices, beverages, and other food products, as a binding agent for the preparation of pelleted animal feeds, and as an ingredient of coatings and adhesives for food packaging materials. The Select Committee is not aware of any instance in current practice where use of bentonite in the processing or packaging of foods for human consumption results in the retention of more than minute amounts in the final product and assumes the current practice will continue. Nevertheless, food grade standards for bentonite should be established, particularly with respect to soluble constituents and heavy metal cations that may be present in commercial products.
Clay (kaolin) is GRAS only as an ingredient of paper and paperboard products used in food packaging. There are no data available concerning the amounts of clay (kaolin) that might migrate to foods from this source but the Select Committee believes the amounts can only be very small.
Apparently, very little, if any, bentonite is absorbed after oral administration and as much as 3 percent in the diet has no observable adverse effects on experimental animals. Diets containing 10 to 25 percent can cause growth retardation both because of dilution of the diet and the tendency of some bentonites to adsorb vitamin A in mixed diets and otherwise interfere with the absortion of this vitamin in the intestinal tract.
Very little, if any, kaolin is absorbed after oral administration. Bowel obstruction occurs at very high doses, about 100g per kg body weight in rats being fatal to 1 percent, about 150 per kg being fatal to 50 percent.
No adverse effects have been observed at dietary levels as high as 12 percent in experimental animals. The human therapeutic dose for diarrhea is about 250 to 1,000 mg per kg.
It is noted that clay (kaolin) administered under conditions that damage mucosal tissues, tends to produce granulomatous lesion. However, the generally high tolerance for kaolin under normal conditions makes it improbable that such effects could result as it is currently used.
Based upon consideration of the data presented in this report and assuming the establishment of appropriate food grade standards fro bentonite, the Select Committee concludes that:
There is no evidence in the available information on bentonite that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when it is used in the manner now practiced or that might reasonably be expected in the future.
There is no evidence in the available information on clay (kaolin) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as an ingredient of food packaging materials in the manner now practiced or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Benzoic Acid | 65-85-0 | 7 | 1973 | 1 | 184.1021 |
SCOGS Opinion:
There are extensive metabolic data on benzoic acid and sodium benzoate in experimental animals and man. It appears that the rat and human have similar metabolic pathways. Short- and long-term feeding studies, as well as teratological investigations, have also been reported in the rat. Interpolation of the rat data and consumer exposure data indicates that the highest no effect level reported in the long-term laboratory feeding study of sodim benzoate is approximately 180 fold the amount usually present in man's daily diet. The highest no effect level reported in laboratoy animal feeding is approximately 90 fold the amount that would be consumed if an individual's diet were to consist only of those foods containng the greatest amoutns of sodium benzoate in current usage. In the light of the foregoing the Select Committee concludes that: There is no evidence in the available information to show that benzoic acid and sodium benzoate
as food ingredients constitute a hazard to the general public when used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Biotin | 58-85-5 | 92 | 1978 | 1 | 182.8159 |
SCOGS Opinion:
Biotin, one of the B complex vitamins, is an essential nutrient functioning as a part of the enzyme systems of the human body that are involved in carboxylation and decarboxylation reactions. It is present in many foods and usual diets of adults probably supply an average of 30 to 40mg daily, with large variation. The difficulty of producing biotin deficiency in mammals without the use of avidin indicates that the usual intakes are in excess of those required for normal maintenance and growth.
Currently the only food use of biotin is in milk-free infant formulas and certain special formulas used in the management of older subjects. Infant formulas are likely to provide approximately 95 mg of biotin per day for a 4 month old (about 20 mg per kg body weight) and an adult receiving 2000 kcal in the form of foods for special dietary use under medical supervision could receive up to 300 mg biotin per day (about 5mg per kg body weight). Considerably larger doses (up to 2mg per kg body weight) have been administered without untoward effects in attempts at treating several disease conditions.
Although adverse effects of biotin administration on reproductive performance have been reported in limited experimenys in rats, the effective doses have been extremely large (about 50mg of biotin per kg of body weight).
Such doses are orders of magnitude greater than those to which humans could conceivably be exposed by consumption of processed foods containing added biotin.
The Select Committee concludes that:
There is no evidence in the available information on biotin that demonstrates, or suggests reasonable grounds to suspect a hazard to the public when it is added to foods at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Bleached Starch | 9005-25-8 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Brown algae | 977161-38-8 | 38 | 1973 | 1 | 184.1120 |
SCOGS Opinion:
The term, "algae", is too ill-defined to be a meaningful term in the context of the GRAS list. The uncertainty with respect to the source and the nature of these materials makes it imprecise to attempt to evaluate the health aspects of the use of substances that simply bear the designation brown algae, red algae, or algae. This is particularly pertinent because of the variation in the chemical constituency of the several species of algae that have been reported to be used in food. In addition, the fact that there are no data available on the usage or consuption of algae, kelp and dulse, raises a question as to whether or not any of these materials are now being used in foods in the United States.
The Select Commitee believes that the extent of actual use of algae, kelp, and dulse in food should be ascertained. If they are found to be used to any considerable extent, it would be advisable to identify them more definitely for regulatory purposes. Further, in view of the probable absortion of metals by algae from pollutes waters, permissible levels of mercury and other heavy metals should be specified for the materials so identified.
However, within this context, and in the light of available biological data, an interim conclusion can be drawn. The biological information available with respect to algae, dulse, and kelp and certain substances derived from the, is limited to studies on laminine monocitatrate and laminarin sulfate, and to feeding trials involving fooder containing dehydrated algal meals and dried seaweed prepared from several species of brown and red algae. These investigations, involving several animals species have revealed no evidence of adverse effects from the feeding the algal species tested or their derived products at levels that are orders of magnitude above those presumed to be used in foods in this country as ingredients of spices, seasonings, and flavorings.
The Select Commitee has weighed the foregoing and concludes that: There is no evidence in the available information on the brown algae (Laminaria sp. and Nereocystis sp.), also referred to as kelp, and the red algae, Porphyra sp. and Rhodymenia palmata (L.)Grev., also referred to as dulse, and the materials derived from these species, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that now seem to be current or that might reasonably be expected in future if their use is confined to ingredients of spices, seasonings, and flavorings as is now stated in the Code of Federal Regulations.
SCOGS Opinion:
The absorption and metabolism of BHA by several animal species and by man are well documented. Man excretes a minute quantity of BHA as the free phenol and an ethereal sulfate while the major portion is conjugated with glucoronic acid. In the rat, a larger percentage of administered doses is excreted as the free phenol and an ethereal sulfate. In rats, dogs, monkeys, and man, none of the metabolic products of BHA are antioxidants while in these species, metabolic products of BHT have antioxidant properties. The acute toxicity (LD 5 0) of BHA is about 2g per kg for mice, rats, and rabbits. The no-effect level for short-term effects in the rat has been estimated at 25mg per kg. If this value should be approximately applicable to man, it is 125 to 500 times the estimated daily intake of 0.05 to 0.2mg per kg. Doses of the order of 50 mg per kg or more when fed chronically to animals produced significant liver hypertrophy accompanied by proliferation of endoplasmic reticulum and a
nonspecific stimilation of the synthesis of drug-metabolizing systems. Such effects disappeared on cessation of BHA intake but remained as long as the compound continued to be ingested. Two monkeys fed BHA at the 50mg per kg level had marginal proliferation of the endoplasmic reticulum and stimulation of mixed function oxidases. It was noteworthy that at both the 50mg and 500mg per kg level BHA had a more pronounced effect on liver weight in monkeys than BHT. It is not clear that liver hypertrophy per se is a manifestation of microsomal enzyme induction. Liver hypertrophy is a gross measure of enzyme induction, but its absence may not necessarily mean that enzyme induction is absent. In addition, the findings from studies with rats, monkeys, and man suggest that BHA metabolism may vary among animal species. Recent studies show that BHA action on enzyme systems in vitro occurs at very low concentrations. BHA can conceivably affect drug metabolizing enzymes in vivo which are the natural
effectors of steroid hydroxylations and prostaglandin synthetases. In addition, there are reports that very low concentrations of BHA interfere with the action of bradykinin and prostaglandin synthesis. It would be desirable to determine whether BHA tissue levels resulting from chronic intake affect metabolic rates of natural substrates such as androgenic, progestational and adrenal steroids, pyridine nucleotides and cytochromes. In addition, the effects on metabolism of common drugs and oral contraceptives should be investigated. In man single doses of BHA requires 10 days for elimination probably due to the solubility and retention of the compound in fat. Thus, with a typical American diet which provides a regular intake of BHA, the chronic tissue level should be determined for man. The evidence indicates that BHA is not mutagenic. While there are teratogenic effects of BHA in the avian embryo test system, several investigations using three mammalian species have failed to establish
any teratogenic or embryotoxic potential when BHA is fed to young or adult and pregnant animals at dosages that greatly exceed estimates of human consumption. Data from several studies indicate that BHA is not a carcinogenic substance. There is evidence that BHA may interfere with synthesis of natural carcinogens and suppress or retard growth of tumors induced by known chemical carcinogens. The Select Committee in its report on BHT identified areas of concern regarding the properties of BHT and indicated that additional studies are needed. Although the concentrations at which these responses occur are generally lower with BHA than with BHT, the qualitative effects are comparable. Concern was expressed about the possible enzyme inductive properties of BHT in extrahepatic tissues, particularly the intestine. Questions were also raised regarding the effect of induction of hepatic enzymes on the metabolism of steroids. The long-term effects of continuously maintained liver hypertrophy from
multiple stimuli were also raised. This is a part of the general problem of adaptive responses of the liver which develop after the ingestion of many foreign substances including drugs, hormone analogues, insecticides, alkaloids, and carcinogenic polycyclic hydrocarbons. While available data suggest that BHA in food is ingested at levels many times below that which produces short-term effects, several of these questions remain. The Select Committee concludes that studies on the tissue levels of BHA attained in man by chronic ingestion and the contribution of BHA to the general problem of enzyme induction should be assessed. Finally, chronic feeding studies with BHA at dosages equivalent to human exposure and use levels should be conducted in primates to determine the long-term effects of BHA on liver mixed function oxidase systems. The Select Committee regards these questions as less urgent for BHA than for BHT and concludes that: While no evidence in the available information on
butylated hydroxyanisole (BHA) demonstrates a hazard to the public when it is used at levels that are now current and in the manner now practiced, uncertaintied exist requiring that additional studies be conducted.
SCOGS Opinion:
The information on the metabolism and toxicology of BHT is extensive. There is ample evidence of efficacy of this compound as an antioxidant. It has been suggested that BHT in fatty tissue may even have some effect similar to that of vitamin E. There are some data to indicate that BHT in diets reduces the incidence of certain tumors and the rate of absorption in the rat. The available evidence does not support the view that BHT interferes in any specific way with cellular metabolism. There is no evidence that demonstrates that BHT causes frank biochemical lesions in the liver; moreover, it is obvious that high doses of BHT are needed to induce biochemical alterations. With 0.1% BHT in the diet in rats there are differening data in the literature concerning the effect of such treatment on liver growth and liver enzymes. At 0.05 % in the dit, no toxic effects are discernible. This "no-effect level" is equivalent to 50 mg per kg per
day. However, BHT increases the level of microsomal enzymes in the liver. The significance of this increase raises certain questions. The liver weight of animals fed BHT is increased and some interpret this enlargement as hypertrophy which is fully reversible and without apparent toxicological significance. But a point could occur at which adaptation fails, a new condition is created, and injury commences. It does not appear that "fully adapted" livers have been challenged by additional doses of BHT or, more importantly, other chemicals. In view of the widespread use, for example, of oral contraceptives, it is felt that informatoin should be available on the effect of challenging fully adapted livers with compounds which are themselves metabolized by microsomal hydroxylases. Therefore, there is the need to determine the effects of BHT at levels now present in foods under conditions where steroid hormones or oral contraceptives are being ingested. Other tissues such as lung and the
gastrointestinal mucosa, in addition to liver, can respond to enzyme inducing agents. More information is required on the inducing properties of BHT on extra hepatic organs. If induction should be found to occur, it would be necessary to determine the effect of such enzymes on the conversion of other ingeted materials into toxic substances or carcinogens. The Select Committee has weighed the foregoring and concludes that: While no evidence in the available information on BHT demonstrates a hazard to the public when it is used at levels that are now current and in the manner now practiced, uncertainties exist requiring that additional studies should be conducted.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Caffeine | 58-08-2 | 89 | 1978 | 3,4 | 182.1180 |
SCOGS Opinion:
Caffeine has been consumed by man for centuries in coffee and tea. This opinion is not concerned with such naturally ocurring caffeine in foods. It is addressed solely to caffeine as commercially added to food commodities. Cola beverages comprise the largest and only significant source of caffeine in this latter group. Such beverages have been in use for decades.
The Select Committe's opinion on the health aspects of caffeine as a commercially-added food ingredients rests primarily upon the integrated interpretation of a cluster of eight factors. These are:
1. Levels of consumption of caffeine as a commercially-added food ingredient: Three points of reference have been used: (a) the total amount of caffeine added to foods in the United States supplies about 0.2 mg per kg per day for the population as a whole; (b) most cola drinkers consume about 0.3 mg of caffeine per kg per day from this source with a few in the 1 to 5 years range consuming as much as 1.8 mg per kg per day; (c) the consumption of a 12-ounce container of cola beverage containing 0.01 percent caffeine represents a dose of about 0.9 mg per kg for a 40kg child, for example, or about 0.6 mg per kg for an adult. It is to be noted that these figures represent the amount of caffeine solely form cola drinks. They, therefore, represent the minimum levels of caffeine consumption on the part of individuals consuming a range of caffeine-containing foods and beverages.
2. History of cola consumption: Despite widespread human consumption of cola beverages over many years, the literature contains no definitive studies of possible long-term effects.
3. Mutagenicity: Caffeine causes chromosomal damage in certain microbial and other non-mammalian test systems, and caffeine has similar effects at high concentrations on mammalian cells in culture in several in vitro tests. However, in vivo tests utilizing mice and rats have failed to demonstrate mutagenic effects of caffeine.
4. Teratogenicity: Many animal tests showed that teratogenic effects are generally absent at caffeine doses up to 50 mg per kg body weight. At doses up to 75 mg per kg of body weight, teratogenic effects of caffeine are neither striking nor consistently demonstrated. At bolus doses greater than 75 mg per kg terratogenic effects are apparent. Two retrospective studies of more than 14,000 mothers on whom caffeine consumption histories were obtained, revealed no association between caffeine intakes and abnormalities in offspring.
5. Carcinogenicity: A very recent and as yet unpublished report has indicated that rats given caffeine orally at daily doses of 150 to 250 mg per kg for 15 months develop cancer of several organs. Epidemiological studies suggest that there is no casual relationship between drinking coffee or the caffeine contained in it and cancer.
6. Long term feeding studies
Two to four generation studies with rats intubated daily with up to 30 mg per kg body weight of caffeine or supplied the same dosage in drinking water, showed no consistent dose-related effects. Mice given 250 mg caffeine per kg body weight daily in drinking water throughout life, continued to breed satisfactorily. Fertility of eggs from pullets fed 80mg caffeine per kg per day was not impaired but embryonic losses were about 16 percent compared to 5 percent in controls. Marked but reversible reduction in sperm output and concentration was found in roosters after 3 weeks feeding of 160mg caffeine per kg per day.
7.Dose effects in humans. The pharmacological dose of caffeine used to stimulate central nervous system activity in humans is about 3 mg per kg and is observable at about 2 mg per kg. The acute human fatal dose of caffeine appears to be greater than 170 mg per kg. Oral administration of caffeine (4 mg per kg) has been found to increase blood pressure in fasted individuals.
8. Behavioral effects on children: Concerns with respect to behavioral effects are less for adults, particularly when the amount of caffeine consumed as cola beverages is compared to that consumed in coffee, tea or other natural sources of caffeine, than for children where there can be chronic consumption of caffeine in colatype beverages during the period of brain growth and development. It is during this period of plasticity that the developing ce
