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1753. Turning a blind eye to chromium
270
THE CHEMICAL ENVIRONMENT
THE CHEMICAL ENVIRONMENT 1751. Fluoride in food Ericsson, Y. (1968). Influence of sodium chloride and certain other food components on fluoride absorption in the rat. J. Nutr. 96, 60. The pros and cons of adding fluoride (F) to local water supplies have evoked heated argument at many a Town Council meeting. But what if the responsibility for fluoridation were transferred from the local to the national level and F were added to a staple food, such as salt, as is done in Switzerland ? Ericsson (cited above) has studied the effect of certain food components such as salt and wheat flour on the intestinal absorption and skeletal fixation of F in the rat, with a view to the possible addition of F to food. Fasting rats were given in quick succession two 4-ml doses of 4 ppm F in one of the test foods, the F in the first dose only being in the form of the lSF isomer. The doses were given by stomach tube and the rats were sacrificed after 4 hr. F remaining in the digestive tract was assumed to reflect unabsorbed F and F deposited in the femur to reflect absorbed F. Femoral uptake of F was found to be greater after the ingestion of flour, egg yolk or carboxymethyl cellulose (CMC) than after the ingestion of water. Addition of 350 m-mole salt reduced femoral uptake of F from water and flour slurry but not from egg yolk. Increased skeletal utilization of F ingested with pure starch, like that observed with flour and CMC, is probably due to the physical consistency of these foodstuffs. The fixation associated with egg yolk may also be a result of its consistency, since egg components such as glutamic acid, aspartic acid, lecithin, lysine, cholesterol, orthophosphate or fat in the form of olive oil failed to increase skeletal uptake of F, despite more complete intestinal absorption. Rats given a diet rich in calcium phosphate prior to the ingestion of F retained more in the intestine and less in the skeleton when the F was ingested with water only but not when a viscous vehicle was used. Skeletal fixation of parenteraUy administered F was not measurably influenced by the simultaneous ingestion of egg yolk, olive oil or cholesterol. 1752. How essential is chromium? Sehroeder, H. A. (1968). The role of chromium in mammalian nutrition. Am. J. clin. Nutr. 21, 230. The question whether chromium (Cr) is an essential micronutrient still provokes much speculation, but its important role in glucose metabolism and its ability to alleviate human diseases resulting from disturbances in such metabolism remind us of its benevolence if not of its essentiality (Cited in F.C.T. 1968, 6, 422). This question has been raised again in an extensive review of the role of Cr in mammalian nutrition. It is considered, on the evidence available from studies of growth, longevity, glucose and lipid metabolism and protein synthesis, that trivalent Cr is essential to rats and probably to mice. Unequivocal proof of the essentiality of Cr in man would depend on showing that a deficiency state impairs glucose tolerance, leading possibly to diabetes mellitus, induces hypercholesterolaemia and tends towards atherosclerosis. Data so far obtained in man are inconclusive and only by analogy with animals can a role of essentiality be assigned to Cr at present. 1753. Turning a blind eye to chromium Roglnski, E. E. & Mertz, W. (1967). An eye lesion in rats fed low chromium diets. J. Nutr. 93, 249.
THE CHEMICAL ENVIRONMENT
271
The number of chemical and therapeutic agents known to evoke adverse effects in the eyes of man and animals is increasing (Marzulli, Fd Cosmet. Toxicol. 1968, 6, 221) and toxic changes in this organ can result from the local or systemic application of many of these agents. A deficiency or excess in vitamin-A intake can also lead to untoward ocular effects. In support of evidence, mentioned in the previous abstract, for the essentiality of trivalent chromium (Cr) in rats, it has recently been discovered that rats fed diets with a low Cr content develop a pronounced opacity of the cornea and congestion of the iridal vessels. Diets containing less than 100 ppb (b = 109) Cr were fed for a minimum of 10 wk and the first pathological changes were seen as early as wk 2 or 3 of the test. Cr supplementation (2 ppm in the drinking water) prevented the development of this lesion but did not completely reverse the established lesion in rats previously given low Cr diets. [Our understanding of the mechanism of eye toxicity is scanty to say the least. Drugs, not food additives, are the chief offenders and nutritionists and food-additive toxicologists will undoubtedly lean heavily on drug-toxicity studies for fundamental progress in this somewhat neglected field.] 1754. The skin chronicles of chromium continued
Jansen, L. H. & Berrens, L. (1968). Sensitization and partial desensitization of guinea-pigs to trivalent and hexavalent chromium. Dermatologica 137, 65. Gross, P. R., Katz, S. A. & Samitz, M. H. (1968). Sensitization of guinea pigs to chromium salts. J. invest. Derm. 50, 424. Scheidegger, J. P., Schwarz-Speck, M., Schwarz, K. & Storck, H. (1967). Experimentelles Ekzem auf Kaliumbichromat im Tierversuch. Dermatologica 135, 382. The question of sensitization to chromium (Cr) salts arises from time to time (Cited in F.C.T. 1969, 7, 91). Jansen & Berrens (cited above) have reported that guinea-pigs could be sensitized to Cr by two subcutaneous injections (1 wk apart) of an aqueous solution of 0-03 ~ potassium dichromate ( K z C r 2 0 7 ) o r chromic sulphate (Cr2(SO4)a) emulsified in Freund's adjuvant. Animals became sensitized to Cr in both the trivalent (Cr m) and hexavalent (Cr v~) forms after total doses of 2 mg K2Cr207 or of 4-5 or 22-5 mg Cr2(SO~)a, and challenge with either compound gave similar results. Total doses of I0 mg K2Cr2OT, however, introduced an anomaly, since the development of sensitization was then temporarily inhibited. The specificity of the inhibition was demonstrated by inducing hypersensitivity to 2,4-dinitrochlorobenzene in animals still in a state of inhibition regarding Cr sensitivity. Further experiments will be necessary to explain and possibly make use of this phenomenon. Differences in sensitization to Cr m and Cr v~ are demonstrated in the study of Gross et al. (cited above). After receiving three subcutaneous injections of 0-5 ml of 3.4 × 10-3M K2Cr207 with 0.5 ml Freund's adjuvant at weekly intervals, 26 of 27 guinea-pigs gave positive skin tests with Cr vt. With chromic chloride as sensitizer, ten of 13 reacted. All animals sensitized to Cr v~ also reacted to Cr m, while of the ten sensitized to Cr m, eight reacted to Cr w. Animals highly reactive to K2Cr207 gave significant reactions when challenged with Cr acetate, chloride, nitrate or sulphate, but doubtful ones to the oxalate, possibly because of its low dissociation. Attempts to induce sensitization to conjugates of K2Cr207 with guinea-pig serum albumin or globulin or skin extract were unsuccessful. A new aspect of Cr sensitivity is described by Scheidegger et al. (cited above), who determined the effect of an anti-inflammatory compound, 1-methyl-4-dimethylaminocarbostyril sulphate (G 35905 S), on the incidence of sensitization. Guinea-pigs were sensitized to
THE CHEMICAL ENVIRONMENT
THE CHEMICAL ENVIRONMENT 1751. Fluoride in food Ericsson, Y. (1968). Influence of sodium chloride and certain other food components on fluoride absorption in the rat. J. Nutr. 96, 60. The pros and cons of adding fluoride (F) to local water supplies have evoked heated argument at many a Town Council meeting. But what if the responsibility for fluoridation were transferred from the local to the national level and F were added to a staple food, such as salt, as is done in Switzerland ? Ericsson (cited above) has studied the effect of certain food components such as salt and wheat flour on the intestinal absorption and skeletal fixation of F in the rat, with a view to the possible addition of F to food. Fasting rats were given in quick succession two 4-ml doses of 4 ppm F in one of the test foods, the F in the first dose only being in the form of the lSF isomer. The doses were given by stomach tube and the rats were sacrificed after 4 hr. F remaining in the digestive tract was assumed to reflect unabsorbed F and F deposited in the femur to reflect absorbed F. Femoral uptake of F was found to be greater after the ingestion of flour, egg yolk or carboxymethyl cellulose (CMC) than after the ingestion of water. Addition of 350 m-mole salt reduced femoral uptake of F from water and flour slurry but not from egg yolk. Increased skeletal utilization of F ingested with pure starch, like that observed with flour and CMC, is probably due to the physical consistency of these foodstuffs. The fixation associated with egg yolk may also be a result of its consistency, since egg components such as glutamic acid, aspartic acid, lecithin, lysine, cholesterol, orthophosphate or fat in the form of olive oil failed to increase skeletal uptake of F, despite more complete intestinal absorption. Rats given a diet rich in calcium phosphate prior to the ingestion of F retained more in the intestine and less in the skeleton when the F was ingested with water only but not when a viscous vehicle was used. Skeletal fixation of parenteraUy administered F was not measurably influenced by the simultaneous ingestion of egg yolk, olive oil or cholesterol. 1752. How essential is chromium? Sehroeder, H. A. (1968). The role of chromium in mammalian nutrition. Am. J. clin. Nutr. 21, 230. The question whether chromium (Cr) is an essential micronutrient still provokes much speculation, but its important role in glucose metabolism and its ability to alleviate human diseases resulting from disturbances in such metabolism remind us of its benevolence if not of its essentiality (Cited in F.C.T. 1968, 6, 422). This question has been raised again in an extensive review of the role of Cr in mammalian nutrition. It is considered, on the evidence available from studies of growth, longevity, glucose and lipid metabolism and protein synthesis, that trivalent Cr is essential to rats and probably to mice. Unequivocal proof of the essentiality of Cr in man would depend on showing that a deficiency state impairs glucose tolerance, leading possibly to diabetes mellitus, induces hypercholesterolaemia and tends towards atherosclerosis. Data so far obtained in man are inconclusive and only by analogy with animals can a role of essentiality be assigned to Cr at present. 1753. Turning a blind eye to chromium Roglnski, E. E. & Mertz, W. (1967). An eye lesion in rats fed low chromium diets. J. Nutr. 93, 249.
THE CHEMICAL ENVIRONMENT
271
The number of chemical and therapeutic agents known to evoke adverse effects in the eyes of man and animals is increasing (Marzulli, Fd Cosmet. Toxicol. 1968, 6, 221) and toxic changes in this organ can result from the local or systemic application of many of these agents. A deficiency or excess in vitamin-A intake can also lead to untoward ocular effects. In support of evidence, mentioned in the previous abstract, for the essentiality of trivalent chromium (Cr) in rats, it has recently been discovered that rats fed diets with a low Cr content develop a pronounced opacity of the cornea and congestion of the iridal vessels. Diets containing less than 100 ppb (b = 109) Cr were fed for a minimum of 10 wk and the first pathological changes were seen as early as wk 2 or 3 of the test. Cr supplementation (2 ppm in the drinking water) prevented the development of this lesion but did not completely reverse the established lesion in rats previously given low Cr diets. [Our understanding of the mechanism of eye toxicity is scanty to say the least. Drugs, not food additives, are the chief offenders and nutritionists and food-additive toxicologists will undoubtedly lean heavily on drug-toxicity studies for fundamental progress in this somewhat neglected field.] 1754. The skin chronicles of chromium continued
Jansen, L. H. & Berrens, L. (1968). Sensitization and partial desensitization of guinea-pigs to trivalent and hexavalent chromium. Dermatologica 137, 65. Gross, P. R., Katz, S. A. & Samitz, M. H. (1968). Sensitization of guinea pigs to chromium salts. J. invest. Derm. 50, 424. Scheidegger, J. P., Schwarz-Speck, M., Schwarz, K. & Storck, H. (1967). Experimentelles Ekzem auf Kaliumbichromat im Tierversuch. Dermatologica 135, 382. The question of sensitization to chromium (Cr) salts arises from time to time (Cited in F.C.T. 1969, 7, 91). Jansen & Berrens (cited above) have reported that guinea-pigs could be sensitized to Cr by two subcutaneous injections (1 wk apart) of an aqueous solution of 0-03 ~ potassium dichromate ( K z C r 2 0 7 ) o r chromic sulphate (Cr2(SO4)a) emulsified in Freund's adjuvant. Animals became sensitized to Cr in both the trivalent (Cr m) and hexavalent (Cr v~) forms after total doses of 2 mg K2Cr207 or of 4-5 or 22-5 mg Cr2(SO~)a, and challenge with either compound gave similar results. Total doses of I0 mg K2Cr2OT, however, introduced an anomaly, since the development of sensitization was then temporarily inhibited. The specificity of the inhibition was demonstrated by inducing hypersensitivity to 2,4-dinitrochlorobenzene in animals still in a state of inhibition regarding Cr sensitivity. Further experiments will be necessary to explain and possibly make use of this phenomenon. Differences in sensitization to Cr m and Cr v~ are demonstrated in the study of Gross et al. (cited above). After receiving three subcutaneous injections of 0-5 ml of 3.4 × 10-3M K2Cr207 with 0.5 ml Freund's adjuvant at weekly intervals, 26 of 27 guinea-pigs gave positive skin tests with Cr vt. With chromic chloride as sensitizer, ten of 13 reacted. All animals sensitized to Cr v~ also reacted to Cr m, while of the ten sensitized to Cr m, eight reacted to Cr w. Animals highly reactive to K2Cr207 gave significant reactions when challenged with Cr acetate, chloride, nitrate or sulphate, but doubtful ones to the oxalate, possibly because of its low dissociation. Attempts to induce sensitization to conjugates of K2Cr207 with guinea-pig serum albumin or globulin or skin extract were unsuccessful. A new aspect of Cr sensitivity is described by Scheidegger et al. (cited above), who determined the effect of an anti-inflammatory compound, 1-methyl-4-dimethylaminocarbostyril sulphate (G 35905 S), on the incidence of sensitization. Guinea-pigs were sensitized to