2
830 PROCESSING AND PACKAGING CONTAMINANTS Triton (I) has been shown to decrease fat absorption, as assessed by serum esterified fatty acid (EFA) levels (Cited in F.C.T. 1966, 4, 115). For this reason taking I with a meal would be expected to reduce calorie intake. But before advocating this measure for slim- ming, it is important to establish that I is not absorbed (since intravenous injection of I produces a deleterious elevation of blood lipids) and also that fat retention as well as fat absorption is decreased by I. This has now been tested in rats fed diets containing 20 70 corn oil supplemented or not with I in the food and/or drinking water. It was found that the total body fat of rats fed 2-5 70 1 was considerably less than that of untreated animals. The reduction in serum EFA at the end of the 12-wk experimental period showed that I was not absorbed. Moreover, the normal growth and well-being of the rats suggested a low toxicity for I. 1439. UK plastics toxicity symposium Transactions and Journal of the Plastics Institute (1967). Symposium on Toxicity in Plastics. ibid 35, 447. A brief account has already been given in these pages of the proceedings of the Symposium on Toxicity in Plastics, organized by the National College of Rubber Technology, London and held in December 1966 (Cited hz F.C.T. 1967, 5, 400). Summaries of nine of the ten papers have now been published as an official record of the proceedings of the Symposium. 1440. Fate and toxicity of 2,6-dioctadecyl-p-cresol Terhaar, C. J., Roudabush, R. L., Fassett, D. W. & Weinberg, M. S. (1967). Physiologic effects of 2,6-dioctadecyl-p-cresol (DOPC) in the rat and dog. Toxic. appl. Pharmac. 10, 401. Astill, B. D. & Fassett, D. W. (1967). Fate of 2,6-bis-(1 '-methylheptadecyl)-p-cresol (DOPC) in rats. Toxic. appl. Pharmac. 10, 400. 2,6-Dioctadecyl-p-cresol (DOPC) is an antioxidant with potential use as a stabilizer in food-packaging material. Preliminary reports on its toxicity and fate in the body have now been published. Terhaar et al. (cited above) have found a low acute oral toxicity, doses of 6400 and 3200 mg/kg being well tolerated by rats and mice respectively. It produced very slight skin irrita- tion in guinea-pigs. Short-term dietary administration of 0-1% DOPC to rats had no effect on the appearance or behaviour of the animals or on food utilization, haematology, clinical chemistry or histology. The only adverse effect observed was a slight growth reduction in males at the 1% level. Dogs, too, tolerated 0-1 70 DOPC in the diet for 90 days apart from a slight, transient food refusal and weight loss. The low oral toxicity is not surprising since Astill & Fassett (cited above) have found that rats given DOPC orally excrete most of the dose in the faeces. After administration of a single oral dose (190-860) mg/kg), labelled with carbon-14 (~4C) in the l'-methyl groups, 96-99 % of the 14C was eliminated in the faeces and less than 1 Yo in the urine, while none was detected in the expired air. Similar results were obtained with a dietary level of 0.01 Yo given for 15 days. Only traces of 14C were found in the tissues (in the liver and brain after dietary administration, in the liver after low single doses and in the liver, brain, kidney and fat after high single doses), but these traces were eliminated at different rates from the body. 1441. Concerning triaryl phosphates Pegum, J. S. (1966). Contact dermatitis from plastics containing tri-aryl phosphates. Br. J. Derm. 78, 626. Seward, C. R., Vaughan, G., Shue, G. M. & Hove, E. L. (1966). Accentuation of essential fatty acid deficiency by dietary tri-o-cresyl phosphate. J. Nutr. 90, 245.

1441. Concerning triaryl phosphates

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Page 1: 1441. Concerning triaryl phosphates

830 PROCESSING AND PACKAGING CONTAMINANTS

Triton (I) has been shown to decrease fat absorption, as assessed by serum esterified fatty acid (EFA) levels (Cited in F.C.T. 1966, 4, 115). For this reason taking I with a meal would be expected to reduce calorie intake. But before advocating this measure for slim- ming, it is important to establish that I is not absorbed (since intravenous injection of I produces a deleterious elevation of blood lipids) and also that fat retention as well as fat absorption is decreased by I.

This has now been tested in rats fed diets containing 20 70 corn oil supplemented or not with I in the food and/or drinking water. It was found that the total body fat of rats fed 2-5 70 1 was considerably less than that of untreated animals. The reduction in serum EFA at the end of the 12-wk experimental period showed that I was not absorbed. Moreover, the normal growth and well-being of the rats suggested a low toxicity for I.

1439. UK plastics toxicity symposium Transactions and Journal of the Plastics Institute (1967). Symposium on Toxicity in Plastics. ibid 35, 447.

A brief account has already been given in these pages of the proceedings of the Symposium on Toxicity in Plastics, organized by the National College of Rubber Technology, London and held in December 1966 (Cited hz F.C.T. 1967, 5, 400). Summaries of nine of the ten papers have now been published as an official record of the proceedings of the Symposium.

1440. Fate and toxicity of 2,6-dioctadecyl-p-cresol Terhaar, C. J., Roudabush, R. L., Fassett, D. W. & Weinberg, M. S. (1967). Physiologic effects of 2,6-dioctadecyl-p-cresol (DOPC) in the rat and dog. Toxic. appl. Pharmac. 10, 401.

Astill, B. D. & Fassett, D. W. (1967). Fate of 2,6-bis-(1 '-methylheptadecyl)-p-cresol (DOPC) in rats. Toxic. appl. Pharmac. 10, 400.

2,6-Dioctadecyl-p-cresol (DOPC) is an antioxidant with potential use as a stabilizer in food-packaging material. Preliminary reports on its toxicity and fate in the body have now been published.

Terhaar et al. (cited above) have found a low acute oral toxicity, doses of 6400 and 3200 mg/kg being well tolerated by rats and mice respectively. It produced very slight skin irrita- tion in guinea-pigs. Short-term dietary administration of 0-1% DOPC to rats had no effect on the appearance or behaviour of the animals or on food utilization, haematology, clinical chemistry or histology. The only adverse effect observed was a slight growth reduction in males at the 1% level. Dogs, too, tolerated 0-1 70 DOPC in the diet for 90 days apart from a slight, transient food refusal and weight loss.

The low oral toxicity is not surprising since Astill & Fassett (cited above) have found that rats given DOPC orally excrete most of the dose in the faeces. After administration of a single oral dose (190-860) mg/kg), labelled with carbon-14 (~4C) in the l '-methyl groups, 96-99 % of the 14C was eliminated in the faeces and less than 1 Yo in the urine, while none was detected in the expired air. Similar results were obtained with a dietary level of 0.01 Yo given for 15 days. Only traces of 14C were found in the tissues (in the liver and brain after dietary administration, in the liver after low single doses and in the liver, brain, kidney and fat after high single doses), but these traces were eliminated at different rates from the body.

1441. Concerning triaryl phosphates Pegum, J. S. (1966). Contact dermatitis from plastics containing tri-aryl phosphates. Br. J. Derm. 78, 626. Seward, C. R., Vaughan, G., Shue, G. M. & Hove, E. L. (1966). Accentuation of essential fatty acid deficiency by dietary tri-o-cresyl phosphate. J. Nutr. 90, 245.

Page 2: 1441. Concerning triaryl phosphates

THE CHEMICAL ENVIRONMENT 831

Tricresyl phosphate (TCP) and triphenyl phosphate (TPP) are both used as plasti- cizers (Cited in F.C.T. 1964, 2, 755). Although sensitivity to these triaryl phosphates is relatively rare, it can be a considerable problem when it does occur, as exemplified by a recent case report (Pegum, cited above). A woman with severe eczema gave a strongly posi- tive reaction to the PVC-containing surgical tape used in applying the patch tests, as well as her spectacle frames made from cellulose acetate (CA), and the reaction was shown to be due to sensitivity to both TCP and TPP. She also reacted to a variety of household articles made from PVC and CA. Following cessation of exposure to as many of the offending products as possible (the PVC floor tiles and chairs remained), her dermatitis improved con- siderably but some lichenified eczema still persisted.

A biochemical study on tri-o-cresylphosphate (o-TCP) is reported by Seward et aL (cited above). When o-TCP was fed to rats receiving a diet free from essential fatty acids (EFA), signs of EFA deficiency developed more quickly and increased in severity. Thus dietary levels of 0.05 or 0.1 ~o o-TCP were found to accelerate the appearance and severity of dermal lesions, to accentuate alterations in liver lipids (a rise in total lipids, in cholesterol and in the ratio of trienoic to tetraenoic fatty acids) and to cause a further depression of oxidative phosphorylation in liver mitochondria, o-TCP also depressed growth in both EFA-deficient and control rats and altered the above FA ratio in the livers of control animals, o-TCP has been reported to increase the requirement for vitamin E (Hove, Am. J. clin. Nutr. 1955, 3, 328) and to cause vitamin A deficiency in rats (Hands et al. Biochem. J. 1965, 94, 279), although the latter effect was not noted in the present investigation. These effects, as well as the accentuation of EFA deficiency demonstrated in the present study, are probably all related to the known ability of o-TCP to oxidize unsaturated lipids.

THE CHEMICAL ENVIRONMENT

1442. Intestinal absorption of chromium Donaldson, R. M. & Berreras, R. F. (1966). Intestinal absorption of trace quantities of chromium. J. Lab. clin. Med. 68, 484.

Ingested chromium (Cr) is known to be poorly absorbed, being largely eliminated in the faeces (Cited in F.C.T. 1963, 1, 301; ibid 1966, 4, 540). Little is known about the relative absorption of the trivalent (Cr m) and hexavalent (Cr vr) forms, although red blood cells have been shown in vitro to take up Cr vt readily but not Cr m.

A study has therefore been conducted of the intestinal absorption of trace amounts of 51Cr-labelled Cr trichloride or sodium chromate in human subjects and rats. When given orally to man or rats, both forms were excreted virtually quantitatively in the faeces. When introduced directly into the small intestine, absorption of Cr ux was still almost negligible but about 50 ~o of Cr vx was absorbed (as judged by the faecal excretion of 51Cr) and as much as 10 ~o of the dose was recovered in the urine. In vitro experiments with everted rat-intes- tinal preparations also showed that Cr vx was absorbed very much more readily than Cr ux. In addition, patients with achlorhydria or pernicious anaemia were found to absorb con- siderably more orally-administered 51Cr vx than normal subjects, suggesting that acid gastric juice may inhibit intestinal absorption of Cr va. This possibility receives further support from the finding that treatment of Cr vx with acid gastric juice inhibited its subsequent absorption following introduction into the duodenum and also reduced in vitro uptake of Cr by the everted intestine. This is attributable mainly to the reduction of Cr vx to the poorly absorbed Cr m, but in addition a small proportion of the Cr v~ was absorbed on to macromolecular components of the gastric juice.

It is concluded that oral ingestion of Cr w may be hazardous in achlorhydric subjects or in those in whom gastric contents are neutralized at the time of Cr vx ingestion, o