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Toxicity Effects

CAS Registry Number: 6381-77-7

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 2.

Names 1

  • D-Erythro-Hex-2-Enonic Acid, Gamma-Lactone, Monosodium Salt (9ci)
  • Sodium erythorbate (1:1)

Human Toxicity Excerpts

  • GENOTOXICITY: Sodium Erythorbate did not cause chromosomal aberrations or sister chromatid exchanges in cultured human embryo fibroblasts.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • GENOTOXICITY: In mice, Sodium Erythorbate was not mutagenic in the host-mediated assay using S. typhimurium, and it did not increase the mitotic recombination frequency in the host-mediated S. cerevisiae D3 assay. Sodium Erythorbate was not mutagenic to five strains of S. typhimurium in the Ames test, with or without metabolic activation. At a concentration of 5%, Sodium Erythorbate did not increase the mitotic recombination frequency of S. cerevisiae D3 in vitro. Dominant lethal tests using rats produced no consistent responses.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • GENOTOXICITY: Sodium Erythorbate (99.8% pure; 5.0 mg/plate) was nonmutagenic in S. typhimurium strains TA92, TA94, TA98, TA100, TA1535, and TA1537 with and without S9 activation. Sodium Erythorbate (0.25 mg/mL plate) was also negative in the chromosomal aberration assay using Chinese hamster fibroblasts; Sodium Erythorbate did not induce the formation of polyploid cells after 48 hours, and caused 1 % chromosomal breaks after 24 hours[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • GENOTOXICITY: Sodium Erythorbate did not induce heritable translocation heterozygosity in male mice when Sodium Erythorbate was added to the diet for 7 weeks.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • GENOTOXICITY: Sodium Erythorbate was not mutagenic in a number of assays, including the Ames test using S. typhimurium strains TA98 and TA199 (with or without activation), rec assay using B. subtilis (with or without activation), and the chromosomal aberration test using Chinese hamster fibroblasts.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • GENOTOXICITY: The compound caused chromosome aberrations in vivo using rat bone marrow cells, but did not cause mutations in silk worms. Sodium Erythorbate was nonmutagenic in the dominant lethal test system using rats and the chromosomal aberration test using Chinese hamster cells.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Sodium Erythorbate powder (100 mg) was instilled into the conjunctival sac of albino rabbits (10 male and 2 female). The eyes of half of the treated rabbits were rinsed after 5 seconds. Reactions were comparable in rinsed and unrinsed eyes, and were slight and transient in nature. One hour after dosing, two of six unrinsed eyes had congestion of the iris, but the iris reacted normally to light. Varying degrees of redness were observed in the lids of all unrinsed eyes. Slight redness of the nictitating membrane or palpebral conjunctiva at the medial canthus was observed in two unrinsed eyes. At one hour, 1+ iritis was observed in one rinsed eye. Five of six rinsed eyes had slight redness that was limited to only the nictitating membrane in three cases. At 24 hours, all eyes were normal, with the exception of one that had slight reddening of the conjunctiva at the medial canthus. All eyes, rinsed and unrinsed, were normal at 48 hours. The mean ocular irritation scores were 0.33/110 (unrinsed eyes) and 0.17/110 (rinsed eyes)[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Sodium Erythorbate powder was applied to the intact and abraded skin of six rabbits as a single 2 g/kg dose. A substantial amount of residual compound was observed 24 hours after dosing. No erythema, edema, or other signs of dermal irritation were observed at five of six test sites. One rabbit (abraded skin) had slight (1+) erythema at 24 hours that cleared by 48 hours.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: F344 male rats (15 per group; 5-week-old) were given powdered basal diet containing various chemicals, including 5% Sodium Erythorbate for 24 weeks. Urine samples were obtained and analyzed during weeks 8, 16, and 24 of treatment. The dietary addition of Sodium Erythorbate increased urinary pH and sodium ion concentration of the urine. Sodium Erythorbate also reduced significantly the osmolality of the urine. The urinary sediments, including the casts, epithelial cells, white and red blood cells, and bacterial contaminants, were similar for treated and control rats. Other parameters (e.g., bilirubin, protein, and glucose) were normal. Rats given Sodium Erythorbate had simple hyperplasia of the urinary bladder epithelium, consisting of diffuse thickening of the epithelium with four to eight layers of transitional epithelial cells. The observed hyperplasia was slight at week 8 and had regressed by week 16. The mucosa appeared normal at week 24. Papillary or nodular hyperplasia did not occur in the urinary bladders of Sodium Erythorbate-treated rats. At week 8, irregularly shaped foci with slight cellular elevation were observed on the luminal surface of the urinary bladder using the scanning electron microscope. Most of the cells in these foci were covered with short, uniform microvilli and with ...microridges. Pleomorphic microvilli were observed on the luminal surface of several cells.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: F344/DuCrj rats of both sexes (6-week-old) were given 1.25% or 2.5% Sodium Erythorbate in drinking water for 104 weeks and untreated water for 8 additional weeks. Rats of the control group were given untreated water only. Each group consisted of 52 male and 50 female rats. Cumulative consumption of Sodium Erythorbate by male rats was 217 g/rat (1.25%) and 430 g/rat (2.5%). Consumption by females was 206 g/rat (1.25%) and 583 g/rat (2.5%). Body weight of rats given 2.5% Sodium Erythorbate was reduced by 8.5% for males and 15.5% for females at weeks 88 and 85, respectively, compared to controls. Body weight gain was normal in rats of the low dose group. All male treated and control rats (except two of the high-dose group) had testicular interstitial cell tumors. Various tumors occurred in 80% of control males, 69% of males given the low dose, and 78% of males given the high dose. A 6-18% incidence of leukemia, pheochromocytoma, mammary fibroadenoma, and mesothelioma was observed. Of the females of the control, 1.25%, and 2.5% dose groups, 94%, 88%, and 78% had tumors, respectively. Twenty to 43% of females (all groups) had leukemia, mammary fibroadenoma, endometrial stromal polyp and/or pituitary adenoma. Females given 2.5% Sodium Erythorbate had significantly fewer tumors than control females. The pattern of occurrence of the various types of tumors was similar among the groups. Sodium Erythorbate did not enhance the development of rare spontaneous tumors or transform benign tumors (e.g., solid adenoma of the thyroid) to carcinomas. The investigators concluded that Sodium Erythorbate was not carcinogenic in F344 rats.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Male 6-week-old F344 rats were given doses of 5% Sodium Erythorbate in feed for 168 days. Parameters of urinary excretion were investigated and the urinary bladder epithelium was examined using light and scanning electron microscopy at weeks 8, 16, and 24. The urine of rats fed Sodium Erythorbate had increased pH, elevated content of crystals and sodium, and decreased osmolality; however, no morphological alterations such as hyperplasia were detected in the mucosa. The urine values and urinary bladder mucosa were similar to controls at doses below 5 g/kg/day.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Sodium Erythorbate was administered in drinking water to male B6C3Fi mice at concentrations of 1.25% and 2.5% (the MTD; see Animal Toxicology-Short-Term Toxicity in this report). Female mice received 2.5% and 5% (MTD). Each group contained 50 mice. Treatment continued for 96 weeks; the study was terminated at week 110. Feed and water were available ad libitum. No significant difference was observed between groups in the amount of water intake. As a consequence, the males in the high dose group received a dose of Sodium Erythorbate that was approximately 1.5 times greater than that of the low-dose group. For the female groups, Sodium Erythorbate intake by the high-dose group was approximately 1.8 times greater than that of the low-dose group. The average body weights of the treated mice were similar to controls. Nine male and seven female mice died accidentally within week 21 and were excluded when the percent survivals were determined. Of the male mice (without tumors) that survived beyond week 43, dose-dependent reductions in the heart and brain weights were observed. The weights of the heart, lungs, kidneys, and brain of female mice (without tumors) were significantly different between the highdose group and the control group. The tumors observed in the male mice were hepatocellular tumors, subcutaneous sarcoma, adenoma and carcinoma of the lungs, and lymphoma/leukemia. The time-adjusted analysis of tumor incidence was performed on the hepatocellular tumors and subcutaneous sarcomas, the incidence of which was significant. The lymphoma/leukemia had the highest incidence in female mice treated with Sodium Erythorbate, but this was not significant. Overall, tumor incidence, time to death with tumors, and the distribution of tumors in treated mice did not differ significantly from mice of the control group[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: ...0.05, 0.5, or 5.0% Sodium Erythorbate /was fed/ to mated female Wistar rats on days 7-14 of gestation. The rats were weighed daily and feed consumption was determined. Five to seven rats per group were killed on day 20. The peritoneal cavity was opened, and the numbers and positions of live and dead fetuses and resorptions were noted. The fetuses were removed by caesarean section, weighed, sexed, and examined for external anomalies. Half of the fetuses were examined for skeletal defects; the remaining fetuses were examined for visceral anomalies. Five pregnant rats of the 5% and 0.05% treatment groups were allowed to deliver spontaneously. The numbers of live and dead pups were recorded. Live pups were sexed, weighed, and examined for external anomalies. The litter size was culled to eight offspring (four males, four females). The offspring were weighed weekly and weaned on day 21 after birth, when the dams were killed. The number of implantation remnants was determined. Offspring were weighed weekly until 10 weeks after birth. Body weight gain of pregnant rats given 0.5% and 5% Sodium Erythorbate was comparable to that of the control group. Body weight gain of dams given 0.05% Sodium Erythorbate was greater than that of the control group. Feed consumption did not differ between groups. No clinical signs of toxicity were observed in dams of any group. The incidence of intrauterine fetal death, number of live fetuses/dam, sex ratio of the fetuses, fetal body weight of both sexes, and the placental weight did not differ from controls. External skeletal and internal visceral examinations of the fetuses produced no evidence of teratogenesis in any group. Offspring delivered normally had a high survival rate and normal growth rate.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Sodium Erythorbate /was given/ via oral intubation to mated female albino Wistar rats on days 6 to 15 of gestation in a similar study. The positive control was 250 mg/kg of aspirin. The dams were dosed with 9.0 mg/kg, 41.8 mg/kg, 194.0 mg/kg, or 900.0 mg/kg. Of the mated rats, 20 of 24 (negative control), 20 of 22 (positive control), 20 of 20 (9.0 mg/kg and 41.8 mg/kg), 20 of 21 ( 194.0 mg/kg), and 20 of 24 (900.0 mg/kg) became pregnant; all survived to term. All dams were subjected to caesarean section on day 20, and the dams and fetuses were examined. No soft tissue abnormalities were observed in rats of the negative control group or in rats given Sodium Erythorbate. Abnormalities were observed in rats given aspirin. The investigators concluded that the administration of up to 900 mg/kg (body weight) of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Various dosages of Sodium Erythorbate were administered via gastric intubation to mated female albino CD-1 outbred mice on days 6-15 of gestation. The test volume was 10 ml/kg in water. The positive control was 150.0 mg/kg of aspirin. Body weights were recorded on days 0, 6, 11, 15, and 17 of gestation. The mice were observed for appearance and behavior, as well as feed consumption. All control and test mice survived to term. Of the negative control mice, 21 of 30 became pregnant. Twenty-one of 23 mice of the positive control group were pregnant. Of the mice given Sodium Erythorbate, the number of pregnant females per group was 22 of 25 (10.3 mg/kg), 20 of 25 (47.8 mg/kg and 1030.0 mg/kg), and 21 of 28 (221.9 mg/kg), respectively. All dams were subjected to caesarean section on day 17, and the numbers of implantation sites, resorption sites, and the number of live and dead fetuses were recorded. The body weights of the live pups were determined. The fetuses were examined for the presence of external (gross) congenital abnormalities, and one-third of the fetuses underwent detailed visceral examination. The remaining fetuses were examined for skeletal defects. One pup of a dam of the positive control group had exophthalmos, encephalomeningocele, and gastroschisis. A cleft palate was observed in a pup of the 1030.0 mg/kg treatment group. The investigators concluded that the administration of up to 1030 mg/kg of [Sodium Erythorbate] to pregnant mice for 10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Male and female B6C3F1 mice (10 per sex per group) were given drinking water containing 0.625%, 1.25%, 2.5%, 5.0%, or 10% Sodium Erythrobate for 10 weeks. Water and feed were available ad libitum. The untreated control group consisted of 20 male and 20 female mice. By the end of the 1st week of treatment, six male mice and one female mouse of the 10% dosing group had died. Of the male mice given 5.0% Sodium Erythrobate, the average weekly body weight gain was slightly less than 90% that of the control female mice. Body weight gain was increased in female mice given Sodium Erythrobate at a concentration of 5.0%, compared to that of control mice. The maximum tolerated dose (MTD) of Sodium Erythrobate in drinking water was 2.5% for male mice and 5.0% for female mice. Mice given doses greater than the MTD had marked atrophy of both hepatocytes and splenic lymphoid follicles, as well as hydropic degeneration of the renal tubular epithelium. No significant changes were observed in the visceral organs of untreated mice or mice given the dose less than or equal to the MTD of Sodium Erythrobate.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Sodium Erythorbate powder (2 g/kg) was applied to the intact and abraded skin of six rabbits. Each test site was moistened with physiological saline just prior to dosing. After application of the test material, the exposure area was covered with a double layer of surgical gauze and a piece of rubber dam. The trunk of each rabbit was wrapped in a stockinette, which was secured to the body with tape. The dressings were removed after 24 hour, and the amount of residual sample and signs of localized irritation were noted. The exposure area was cleaned by thorough wiping, and the rabbits were observed for signs of toxicity for 14 days. At 72 hours, a significant amount of residual compound was found at the exposure site of each rabbit. Behavior, body weight gain, and consumption of feed and water were normal, and no signs of toxicity were observed.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Rats oral > 5 g/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1596] **PEER REVIEWED**

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Absorption, Distribution And Excretion

  • Male F344 rats (five per group, 6-week-old) were given 5% Sodium Erythorbate in feed for 22 weeks. The rats eliminated totals of 203.3 +/- 33.2 mg/100 mL erythorbic acid and 9.0 +/- 5.1 mg/100 mL dehydroerythorbic acid during the study. Ascorbic acid and dehydroascorbic acid were not detected. Urine pH was 6.98 +/-0.31, which was significantly different from that of rats given basal diet alone (6.31 +/- 0.18; p < 0.05). Urine osmolarity also differed significantly from controls; osmolarity was 1378 +/- 277 mOsmol/kg H20 in rats given Sodium Erythorbate and 1756+/- 200 mOsmol/kg H20 in rats of the control group. Crystals were detected in urine of rats given basal diet and Sodium Erythorbate or basal diet alone.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**

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Metabolism/Metabolites

  • Male F344 rats (five per group, 6-week-old) were given 5% Sodium Erythorbate in feed for 22 weeks. The rats eliminated totals of 203.3 +/- 33.2 mg/100 mL erythorbic acid and 9.0 +/- 5.1 mg/100 mL dehydroerythorbic acid during the study. Ascorbic acid and dehydroascorbic acid were not detected.[Cosmetic Ingredient Review; Int. J. Toxicol. 18 (Suppl 3): 1-26 (1999)] **PEER REVIEWED**

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Tsca Test Submissions

  • None found

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Footnotes

1 Source: the NTP's CEBS database.

2 Source: the National Library of Medicine's Hazardous Substance Database, 02/28/2017.

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