ANOXOMER Explanation This compound has not previously been reviewed by the Joint FAO/WHO Expert Committee on Food Additives. Anoxomer is a complex polymeric substance with an average molecular weight of 4500-5000. No more than 5% of the polymer can be greater than 50 000 daltons and no more than 1% of the polymer can be less than 500 daltons. Anoxomer is to be used as an antioxidant at a level no greater than 0.5% of the fat and oil content of foods. It is an off-white powder with the following structure:BIOLOGICAL DATA BIOCHEMICAL ASPECTS Absorption, distribution and excretion Single oral doses of C14-anoxomer, 10 mg in Sprague-Dawley rats, 1.8 mg in IRC/SM mice, 0.5 mg in Hartley guinea-pigs and 0.6 mg in Dutch-belted rabbits indicated that only 0.2-0.6% of the administered compound is absorbed. The recovery of radioactivity in these studies varied from 78 to 110% (Halladay et al., 1978; Parkinson et al., 1978; Enderlin & Halladay, 1977a, 1977b). Absorption of a single dose of C14-anoxomer was no greater in Sprague-Dawley rats fed 5% anoxomer for 90 days than in rats given C14-anoxomer acutely (Enderlin & Halladay, 1977c). Following oral dosing of 10 mg of C14-anoxomer, the residual radioactivity was assessed in the mesenteric lymph nodes 30 days later. There was some indication from this study that anoxomer was selectively partitioning in lipid stores (Enderlin & Halladay, 1977c). Effects on enzymes and other biochemical parameters 2.8 and 5 g/kg of anoxomer was added to the basal diet of male Sprague-Dawley rats for 90 and 60 days, respectively. The level of cytochrome P-450, cytochrome C reductase activity and microsomal mixed-function oxygenase (MFO) activity for aminopyrine demethylase (APDM), p-nitroanisole demethylase (NADM), hexobarbital oxidase (HO) and benzo[alpha]pyrene hydroxylase (BH) were measured in the hepatic S-9 homogenates. There were no differences between control and anoxomer-fed animals, with regard to liver weights and in hepatic homogenates. There were no differences in the activity of cytochrome P-450, cytochrome C reductase or any of the MFO enzymes (Ryerson et al., 1977). In another study, 2.8 and 5 g/kg of anoxomer was added to the basal diet of male Sprague-Dawley rats for 90 and 60 days, respectively. The levels of cytochrome P-450, cytochrome C reductase activity and microsomal mixed-function oxygenase (MFO) activity for the hydrolysis of indophenol acetate (IPA) and benzo[alpha]-pyrene hydroxylase (BH) was measured in the intestinal S-9 homogenates. Anoxomer caused no alterations in the concentration of cytochrome P-450 and cytochrome C reductase activity over the duration of the 90-day study (Ryerson et al., 1978). TOXICOLOGICAL STUDIES Special studies on blood coagulation During the conduct of the chronic rat feeding study, 4 high-dose (2500 mg/kg bw) male rats suffered unexplained and lethal haemorrhaging of the pelvic region. Thus, a study to assess the influence of anoxomer on blood clotting factors in male rats was conducted. Ten male rats in each of 2 groups received either 0 or 2500 mg/kg bw of anoxomer in basal lab diet for 21 days. There was no statistically significant differences between treated and control animals in prothrombin time, activated partial thromboplastin time, fibrinogen concentration or bleeding time. There was a statistically significant increase in platelet count in treated males (Anon., 1981c). Based on these observations, anoxomer appears to be free of any influence on blood clotting factors. Special studies on dermal irritation Six healthy, New Zealand white rabbits were used in this test. Skin reactions were scored by the Draize system and, since the primary irritation score was 0.2, anoxomer was not judged to be a primary irritant (Anon., 1976b). Special studies on eye irritation In 6 healthy, New Zealand white rabbits, 63 mg of anoxomer was instilled in the conjunctival sac of the left eye with the right eye serving as control. Anoxomer was not judged to be an eye irritant, since findings of irritation were present in only one of 6 test subjects (Anon., 1976a). Special studies on influence on lymphatic tissues Female Sprague-Dawley rats were given 5% anoxomer in the diet for 28 weeks. No gross or microscopic alterations were noted in the mesenteric lymph nodes of any control or high-dose animals that were examined (Anon., 1978). Eighteen female rats (Simonsen strain) were administered 10.74 mg (39 µCi) of 14C-labelled anoxomer by gavage = 50 mg/kg bw. On each of 6 days (days 1, 3, 7, 14, 21 and 28) following dosing, 3 animals were sacrificed and the level of radioactivity assessed in liver, spleen, kidneys, stomach, small intestine, caecum, large intestine, intestinal contents, lymph nodes (mesenteric, axillary, cervical and inguinofemoral), fat (from mesenteric, peri-uterine and subcutaneous regions) and muscle (gracilis). Specimens from blood, urine and faeces were also collected and analysed for radioactivity. Control (undosed) animals were used to determine the limits of detection of the radiolabelled anoxomer. The levels initially detected were negligible in all tissues but the gastrointestinal tract. Even the initially high levels found in the stomach and large and small intestine declined rapidly. This study gave no evidence of a selective tissue accumulation of anoxomer (Enderlin, 1981). This contrasts with the earlier metabolism studies (Enderlin & Halladay, 1977c) which suggested anoxomer concentrations in fat tissue. This earlier observation may have been due to measurement uncertainties (error) related to counts per minute extrapolations from small tissue samples (50 mg). At the many-fold higher doses used in the subchronic and lifetime animal studies (10 g/kg bw), some abnormal or selective accumulation in fat or lymphoid tissue may occur: however, at the doses used in this study (about 50 mg/kg bw), there is no evidence of selective accumulation of anoxomer in either fat or lymphoid tissues. Special studies on mutagenicity Anoxomer, in concentrations up to 5 mg/plate, was neither mutagenic nor cytotoxic in the Ames test using 5 strains of his- Salmonella typhimurium (strains used were sensitive for both base- pair and frame-shift mutations) either with or without activation by rat microsomal preparation. Four strains of trp-Escherichia coli were employed to test anoxomer in concentrations up to 1 mg/plate with and without metabolic activation. Anoxomer was nonmutagenic in this bacterial test system (Dietrich et al., 1977). Anoxomer was evaluated for its ability to induce mitotic crossing over or intergenic recombination and reverse mutation of Saccharomyces cerevisiae. Anoxomer was tested in concentrations up to 5 mg/ml and at time periods up to 16 hours with and without metabolic activation. No dose- or time-related effects were seen with any of these endpoints (Dietrich et al., 1977). The potential mutagenicity of anoxomer in mammalian cells was tested in L5178Y mice lymphoma cells. There were no effects on forward point mutations at the thymidine kinase locus, sister chromatid exchanges or chromosome aberrations (Anon., 1977). The validity of this particular study is questioned at doses above 0.32 mg/ml because of precipitation of the test materials, and because the incidence of chromosomal aberrations was not different between the positive and solvent controls. Special studies on reproduction A 3-generation reproduction and teratology study was conducted with anoxomer in Sprague-Dawley rats. Control animals received basal diets while test animals received 0.5, 1.58 or 5% of anoxomer in basal diet throughout the study. Each parental generation consisted of 30 males and 30 females. There was a statistically significant decrease in neonatal survival index in the 1.58 and 5% offspring and in the weaning survival index of all 3 treated groups in the F1a litters. There was a significant decrease in male birth weight and in male and female weaning weights at the 5% level in the F1b litters. The neonatal and weaning survival indices as well as weaning weights were significantly reduced in the 5% groups of the F2a litters. Weaning survival was decreased in the 0.5 and 5% offspring, and weaning weight of all males in the same groups was decreased. In the F3a, F3b and F3c litters, the pregnancy rate was low in all groups including the control animals. However, none of these effects were observed consistently during the successive generations, nor was there any indication that these effects were more marked during the successive breedings. Based on all the information from the study, the no-effect level on reproductive performance and indices was determined to be 1.58% of the diet. The F3d litters were utilized for the teratology phase of this study. The test animals were sacrificed on day 19. There was no effect on numbers of corpora lutea, implantations, resorptions, liver of dead foetuses for any of the groups. In addition, there was no treatment- related effects on body weight or size or on the incidences of visceral or skeletal anomalies (Anon., 1979a). Special studies on teratogenicity Thirty female Sprague-Dawley rats, each of 4 treatment groups, were fed anoxomer at 0, 250, 800 or 2500 mg/kg bw per day on days 6-15 of gestation. The test animals were sacrificed on gestation day 20. No compound-related effects were found in maternal body weights, deaths or pathology at necropsy. No compound-related differences were observed in pregnancy rate, number of corpora lutea, implantations, resorptions, live foetuses, foetal body weight or length (Anon., 1981a). The mean number of visceral and skeletal variants increased in the treated groups, but the increase did not appear to be dose related. In 2 studies, A and B, 20 or 25 female rabbits, respectively in each of 4 treatment groups received anoxomer at 0, 250, 500 or 1000 mg/kg bw per day by oral intubation from day 6 through day 18 and sacrifice was on gestation day 29. In both studies, maternal gross pathology did not indicate any treatment-related effects. No effect was apparent in the number of dead foetuses, live foetuses, or sex ratio. There appeared to be no treatment-related increase in skeletal problems in both studies. In study A, there was a dose-related increase in dilated pelvises and ectopic kidneys in all groups. Study B utilized the same protocol, but did not confirm the renal effects (Anon., 1979, 1981a). Acute toxicity LD50 Reference Animal Route (g/kg bw) Mouse Oral 10 Anon., 1981c i.p. 10 Jorgenson & Rushbrook, 1976 Rat (Sprague-Dawley) Oral 10 Jorgenson & Rushbrook, 1976 i.p. 10 Jorgenson & Rushbrook, 1976 Dog Oral 10 Jorgenson & Rushbrook, 1976 i.p. 5 Jorgenson & Rushbrook, 1976 Short-term studies Rat Fifty young, adult Sprague-Dawley rats (25 males and 25 females) in 4 different groups were fed 0, 0.5, 1.58 or 5% anoxomer in rat diet for 90 days. Water intake, activity and behaviour were normal and comparable for all groups. Body weights and food consumption for males and females in all groups remained in the normal ranges for the duration of the study. The haematology, differential counts, platelet counts and reticulocyte counts of all groups were also within normal limits. The serum enzyme and biochemistry were within the expected limits of biological variation. Gross necropsy revealed a 15-20% incidence of emphysema, slight haemorrhaging and/or congestion of the lungs in all groups, including controls. This was probably the result of handling and CO2 asphyxiation and not the result of treatment. Two control males and 2 0.5% dose level females had cataracts. No dose- response effects were evident and the gross findings were within normal ranges for this strain of rat. All organ weights and organ-to- body weight ratios were comparable between groups. Slight to moderate hyperplasia of the lymph node was seen in 2 high-dose rats and haemorrhage of the lymph node was observed in another high-dose rat. Slight focal haemorrhage and slight focal congestion was found in the thymus, respectively, in 2 high-dose rats (Jorgenson & Rushbrook, 1977). Long-term studies Mouse One hundred and seventy-five sexually mature HAM/ICR mice were selected on the basis of good health and randomly assigned either to one of two control groups or to treatment groups and fed 0, 0.5, 1.58 and 5% anoxomer for 104 weeks to assess the chronic toxicity and carcinogenicity potential of this substance. After 1 week, animals were mated. Female mice were maintained on control or test diet throughout gestation, delivery and lactation. Fifty animals per sex per dose were then randomly assigned to the chronic feeding phase of the present study. There were no compound-related effects indicated by the survival data from the test and control groups. While the high-dose male and female groups' mean weights were decreased during the first 6 months of the study, by the end of the first year, there were no significant differences in body weights of the offspring of the high-dose F0 groups. The early decreased body weight would appear to reflect the test animals exposure in utero to the test compound. Thus, the decreased body weights of the high-dose males and females in the early phase were considered treatment related. This effect on offspring body weight may have been due to simple dilution of the nutritive value of the diet because of the presence of the diet compound. Problems of food spillage, however, made food consumption data of questionable reliability (Anon., 1980a). At termination of the study at 104 weeks, gross pathology was characterized in large measure as being comparable across treatment and control groups. Certain lesions occurred with nearly equal frequency across all treatment groups, e.g., discoloration of the lungs, enlarged spleens and darkened areas or lobes of the liver. The results of histopathological findings were essentially comparable between the high-dose treatment group and control group 1. The more common incidental findings observed were: chronic murine pneumonia, hydronephrosis, focal ulceration of the gastric mucosa, malignant lymphoma originating in the thymus, hepatocellular carcinoma and chronic interstitial nephritis. None of these lesions occurred in other than an apparently random distribution. Statistical analysis was performed on the comparative incidences of malignant lymphoma (all types combined alveolar/bronchiolar carcinoma and hepatocellular carcinoma in control group 1 and the high-dose groups. These 3 tumour categories were selected since they were representative of the tumour types occurring most frequently. There was not a statistically significant increase in incidence of these tumours in the treated group compared to control group 1 (Anon., 1980a). An examination of the pattern and occurrence of tumours in other organs and tissues did not reveal a frequency of distribution across treatment groups which is compound related. Rat Fifty animals (Fischer 344 strain) per sex per dose were fed 0, 0.5, 1.58 or 5% anoxomer for 130 weeks in this study to assess the chronic toxicity and carcinogenicity potential of this substance. The parents of these animals had also been fed 0, 0.5, 1.58 or 5% anoxomer. Exposure to anoxomer continued during mating, gestation, delivery and lactation. Survival in all groups at 18 months exceeded the 55% protocol requirement. The higher mortality experienced by the mid-dose males is considered to be incidental and not compound related. Anoxomer administration resulted in statistically significant decreases in body weight gain (growth rates) through week 51 in low- and high-dose males. In addition, during the chronic feeding phase of the study, the mean body weights of the 3 treated male groups were consistently lower than the 2 control groups. This finding is considered to be compound related; however, the decreases were similar across groups and bore no relationship to those observed among the female treatment groups. The slightly lower mean body weight of certain of the treated groups coupled with the increased levels of food consumption by some of the treated groups suggests that the lower body weights were the result of dilution of the nutritive value of the diet due to the presence of anoxomer. Additional evidence of the non-specific rather than toxic nature of the decreased weight was the fact that there were no statistically significant differences in terminal organ or organ-to- body weight ratios observed between treated and control groups. During week 37, some rats exhibited clinical signs of sialodacryoadenitis (SDA) virus. There was no treatment of this normally self-limited disease and no effects were observed which were interpreted as being detrimental to the conduct of the present study. Gross eye findings included a slightly increased frequency of cloudy eyes in high-dose animals during the latter part of the study, e.g., at week 99, the overall incidence ranged from about 2 to 9% for control, low- and mid-dose groups and was 17% for the high-dose group. The presumptive diagnosis of degenerative cataracts secondary to probable senile retinal dystrophy was made. The findings did not provide definite evidence of a compound-related effect in the high- dose group; however, the slightly higher incidence suggested a potential indirect effect on normal geriatric process. The frequency of this finding across treatment groups became virtually the same by the end of the study. Also, during week 37, 4 high-dose males were found moribund, and 3 animals manifested posterior paresis. At necropsy, suggestions of haemorrhage were present with dark red fluid in the urinary bladder of 2 males, and large areas of diffuse redness in the bladder wall of a third animal. A fourth animal found dead during week 37 had haemorrhage and a large haematoma in the pelvic area. Prothrombin determinations and platelet counts made at 55 weeks were comparable to control animals. No additional animals or groups suffered these lesions. Other representative findings were: discoloration of pituitary, lungs, liver, kidneys, adrenals and testes; enlargement, thickened appearance or variations in size of pituitary, liver, spleen and testes; ulcerated areas of the stomach; cloudy or opaque eyes; nodules in various organs; masses in subcutaneous tissue, in body cavities and associated with viscera and enlargement or discoloration of lymph modes. A wide variety of spontaneous neoplasms and lesions were observed. Among the commonly observed neoplasms, such as pituitary "C" cell tumours of the thyroid, pheochromocytoma of the adrenals, mammary fibroadenomas in females, monocytic leukaemia, testicular interstitial cell tumours, and uterine endometrial stromal polyps. Statistical analyses were conducted on the comparative incidences of monocytic leukaemia, pituitary adenoma, adrenal pheochromocytoma and mammary fibroadenoma in control group 1 and the high-dose group. The overall incidence of these tumour types did not differ significantly between the high-dose groups and their respective controls. An examination of the pattern and occurrence of tumours in other organs and tissues reveals no evidence of compound-related effects (Anon., 1980b). Dog Eight male and 8 female adult, pure-bred beagles were fed 0, 0.5, 1.58 or 5% anoxomer for 52 weeks. No deaths occurred during the experimental period. Clinical observations were occasional instances of emesis, soft stools and diarrhoea, but these were observed in both treated and control groups. The consistently lower weight gains of the high-dose animals are considered to be treatment related. Food consumption of the treatment groups did not vary significantly from controls; however, absolute levels of food ingested were slightly depressed in the low- and mid- dose males. Haematology and clinical chemistry evaluations were made on weeks 4, 13, 26 and 52 and no findings suggesting a compound- related effect were discovered in any test group. There were no compound-related findings with regard to urinalysis data. There were no treatment-related ocular changes in any of the test subjects. At 13 weeks, 2 males and 2 females from each treatment group were sacrificed and at 52 weeks 6 additional animals per test group were terminated and subjected to gross and histopathological examination. With respect to histomorphological alterations, there were only occasional spontaneous disease lesions found and these were not systematically associated with compound administration (Anon., 1979b). OBSERVATIONS IN MAN Six healthy, male human subjects received 13.8 mg or 50 µCi of radiolabelled anoxomer orally. Urinary and faecal excretion were 0.02% and 95%, respectively. Based upon data from blood and urine, intestinal absorption was estimated to be less than 0.1% of the administered dose. Comments Various metabolic studies show that no more than 0.2% of an orally administered dose of anoxomer is absorbed in mice, rats, rabbits, guinea-pigs and man. In spite of having a lipophilic structure, anoxomer does not appear to selectively accumulate in either lymph tissues or lipid-rich regions of the organism. Acute oral toxicity studies in mice, rats and dogs with anoxomer suggest that the LD50 for all these species is greater than 10 g/kg bw. A multigeneration reproduction study in rats did not show any consistent effects during the successive breedings, nor was there any indication that the effects were more marked in successive generation. Based on all the information from this study, the no-effect level on reproductive performance and indices was determined to be 1.58% of the diet. The no-effect levels for teratogenicity studies in rats and rabbits were, respectively, 2.5 g/kg and 1.0 g/kg bw per day. Anoxomer was not mutagenic in a series of bacterial tests. It was not carcinogenic in lifetime studies in both rats and mice. No other significant compound-related effects were observed in these studies, except in the rat study where there was an increase in the occurrence of cloudy eyes, in the high-dose groups (5% of the diet) at week 99. However, the frequency of the occurrence of this effect, which has been tentatively diagnosed as degenerative cataracts secondary to probable senile retinal dystrophy, became virtually the same in all groups at termination of the study (week 104). Additional studies are presently under way to determine if there is an anoxomer-related increase in lenticular opacities. A 1-year feeding study in dogs showed no compound-related effects, except liver weight gains in dogs, maintained on diets containing 5% anoxomer. No lenticular opacities were observed in any of the test groups. EVALUATION Level causing no toxicological effect 15 800 ppm (1.58%) in the diet equivalent to 800 mg/kg bw. Estimate of temporary acceptable daily intake for man 0-8 mg/kg bw. FURTHER WORK OR INFORMATION Required by 1984 Further information about the occurrence of senile cataract in rats exposed to high levels of anoxomer in the diet. REFERENCES Anon. (1976a) Final report. Acute eye irritation potential study in rabbits. Unpublished study by Hazelton Laboratories of America, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Anon. (1976b) Final report. Primary skin irritation study in rabbits. Unpublished study by Hazelton Laboratories of America, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Anon. (1977) Mutagenicity evaluation of D00079 (Lot No. 0314) in the mouse lymphoma multiple endpoint test (MET). Unpublished study by Dynapol, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Anon. (1978) Gross and microscopic evaluation of mesenteric lymph nodes in female rats. D00079. Unpublished study by Hazelton Laboratories of America, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Anon. (1979a) A three-generation reproduction and teratology study in rats, D00079, final report. Unpublished study by Hazelton Laboratories of America, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Anon. (1979b) Final report. Chronic dietary administration in dogs. Unpublished study by Hazelton Laboratories of America, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Anon. (1980a) Chronic dietary administration in mice, D00079, final report. Unpublished study by Hazelton Laboratories of America, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Anon. (1980b) Chronic toxicity study in mice, D00079, final report. Unpublished study by Hazelton Laboratories of America, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Anon. (1981a) Teratology study in rats, D00079, final report. Unpublished study by Hazelton Laboratories of America, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Anon. (1981b) Teratology study in rabbits, D00079, final report. Unpublished study by Hazelton Laboratories of America, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Anon. (1981c) Hematological evaluations in male rats, D00079, final report. Unpublished study by Hazelton Laboratories of America, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Dietrich, P. S., Brown, J. P. & Bakner, C. M. (1977) Phase II mutagenicity testing of Poly AOTM-79: Microbial tests with Salmonella/microsome assay, Escherichia coli and Saccharomyces cerevisiae. Unpublished study by Dynapol, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Enderlin, F. E. & Halladay, S. C. (1977a) Urinary and fecal excretion of the polymeric antioxidant [14C]-D00079 in guinea pigs. Unpublished study by Dynapol, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Enderlin, F. E. & Halladay, S. C. (1977b) Urinary and fecal excretion of the polymeric antioxidant [14C]-D00079 in rabbits. Unpublished study by Dynapol, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Enderlin, F. E. & Halladay, S. C. (1977c) Intestinal absorption of the polymeric antioxidant [14C]-D00079 in rat. V. Absorption in rats previously maintained for 90 days on 5% D00079 in the diet. Unpublished study by Dynapol, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Enderlin, F. E. (1981) Distribution of radioactivity in internal organs and tissues of the rat after oral administration of a high activity dose of Poly AOTM79-[14C]. II. Determined at six different times between 1 and 28 days after dosing. Unpublished study by Dynapol, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Halladay, S. C. et al. (1978) The bile duct ligated animal: A model for determining total intestinal absorption, Drug Chem. Toxicol., 1, 203-213 Jorgenson, T. A. & Rushbrook, C. J. (1976) (1) Acute oral toxicity studies in rats, mice and dogs; (2) Acute intraperitoneal toxicity in rats, mice and dogs; (3) Maximum tolerated dose study in rats. Unpublished study by Stanford Research Institute, submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Jorgenson, T. A. & Rushbrook, C. J. (1977) Toxicity study of D00079, A ninety-day subacute study in rats. Unpublished study by Stanford Research Institute, submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Parkinson, T. M., Honohan, T. & Enderlin, F. E. (1978) Intestinal absorption, distribution and excretion of an orally administered polymeric antioxidant in rats and mice, Fd. Cosmet. Toxicol., 16, 321-330 Ryerson, B. A., Halladay, S. C. & Dollar, L. A. (1977) Effects of orally administered D00079 and butylated hydroxytoluene on microsomal mixed function oxygenase activity, cytochrome C reductase and cytochrome P-450 in hepatic tissues of rats. Unpublished study by Dynapol, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Ryerson, B. A., Halladay, S. C. & Dollar, L. A. (1978) Effects of orally administered D00079 and butylated hydroxytoluene on microsomal mixed function oxygenase activity, cytochrome C reductase and cytochrome P-450 in intestinal tissues of rats. Unpublished study by Dynapol, Inc., submitted to the World Health Organization by Dynapol, Inc., Palo Alto, California, USA Walson, P. D. et al. (1979) Intestinal absorption of two potential polymeric food additives in man, Fd. Cosmet Toxicol., 17, 201-203
See Also: Toxicological Abbreviations Anoxomer (WHO Food Additives Series 19) ANOXOMER (JECFA Evaluation)