Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 2451-62-9 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • 1,3,5-Triglycidyl isocyanurate
  • GLYCIDYL ISOCYANURATE
  • 1,3,5-TRIAZINE-2,4,6(1H,3H,5H)-TRIONE,1,3,5-TRIS(OXIRANYLMETHYL)- (9CI)
  • ARALDITE MT 9523
  • S-(TRIAZINE-2,4,6(1H,3H,5H)-TRIONE,1,3,5-TRIS(2,3-EPOXYPROPYL)-(8CI)
  • ARAKOTE 4000B
  • TETEROXIRONE
  • TEPIC
  • N,N,N"-TRICLYCIDYL ISOCYANURATE
  • TRIS(2,3-EPOXYPROPYL)ISOCYANURATE
  • TRIALLYL ISOCYANURATE EPOXIDE

Human Toxicity Excerpts

  • HUMAN EXPOSURE STUDIES: Allergic contact dermatitis has been reported in several case-studies of exposure to triglycidyl isocyanurate and powder coatings containing triglycidyl isocyanurate. ...Symptoms included dermatitis, itchy rashes, and swelling on the face, hands, arms, neck, and thighs. All subjects tested positive to patch testing with triglycidyl isocyanurate. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Human trials were performed during clinical development of alpha-triglycidyl isocyanurate as an antitumor agent. In these studies, alpha-triglycidyl isocyanurate was administered iv to cancer patients at doses up to 900 mg/kg bw using a variety of dosing regimes. Toxic signs included myelosuppression, nausea and vomiting, and, rarely, alopecia and leucopenia at high doses (>600 mg/kg bw). Owing to its severe local toxicity (thrombophlebitis) at the site of injection, the use of alpha-triglycidyl isocyanurate as an antitumor agent was not pursued. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: In 1991 in an Australian factory manufacturing powder coating, two employees had allergic dermatitis and two employees had intrinsic asthma which were being aggravated by TGIC. The two employees with allergic dermatitis were found to be positive when patch tested with TGIC. Medical examination of a further 28 employees showed respiratory effects were present or reported in five employees and irritant effects in eight employees. Irritant effects included nasal, eye and throat irritation, skin rash and nose bleeds. The company reported that stricter controls were implemented which resulted in the elimination of these occupational health effects among employees. [National Occupational Health and Safety Commission, Australian Goverment; Exposure Standards: Triglycidylisocyanurate (TGIC) (1994). Available from: http://www.nohsc.gov.au/OHSInformation/Databases/ExposureStandards/az/Triglycidylisocyanurate_TGIC.htm m#ref as of March 10, 2004. ]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Two schedules of teroxirone, a triazine triepoxide, were evaluated in a phase I study. Twenty-six patients were treated on 1 day every 5 weeks at doses of 36-2250 mg/sq m. At doses greater than or equal to 1500 mg/sq m, severe thrombophlebitis was seen without cytotoxic effect, and this schedule was closed. Twenty-seven patients were treated on 5 days every 5 weeks at daily doses of 16-450 mg/sq m. Mild thrombophlebitis and moderate leukopenia were encountered. [Rubin J et al; Cancer Treat Rep 71 (5): 489-92 (1987) ]**PEER REVIEWED**
  • CASE REPORTS: The case is presented of a man with allergic contact dermatitis and occupational asthma due to triglycidylisocyanurate (TGIC), which is used as a hardener in thermosetting powder paint. The contact dermatitis was confirmed by patch testing (TGIC 0.5% and 5% in petrolatum), and the occupational asthma was confirmed by bronchial provocation testing: two challenges to an aerosol of lactose containing TGIC (0.05% and 0.1%, w/w, each for 0.5+1+2+4 min) led to a maximal decrease in FEV1 /(forced expiratory volume in 1 second)/ of 22% and 31% after 6 and 4 hr, respectively. [Meuleman L et al; Allergy 54 (7): 752-6 (1999) ]**PEER REVIEWED**
  • CASE REPORTS: A case of a 31-yr-old color paint factory worker who developed contact dermatitis of the face and forearms on exposure to triglycidyl isocyanurate is reported. Patch testing showed a positive allergic reaction to only 5% triglycidyl isocyanurate in methyl ethyl ketone. [Wigger-Alberti W et al; Am J Contact Dermat 8 (2): 106-7 (1997) ]**PEER REVIEWED**
  • CASE REPORTS: ...Triglycidyl isocyanurate (TGIC), an epoxy compound, is often used as a hardener. ...A 36-yr-old non-smoking man who worked mainly as a spray painter, using a polyester powder paint containing 4% TGIC /was examined/. During painting he used protective clothing and a motorized breathing protector. After 4 years he developed eczema on his hands, face and body, and an occupational allergic eczema caused by TGIC was diagnosed. He also suffered from powder-paint-related asthmatic symptoms. ...Spirometry showed slight obstruction; the blood eosinophils and serum IgE value were elevated. Skin-prick tests with common environmental allergens were negative. The challenge test with lactose powder was also negative. A challenge test with a paint containing TGIC (4%) induced a dual reaction in PEF /(peak expiratory flow)/ and a late 23% fall in FEV1. A test with TGIC (4%) mixed with lactose induced a dual PEF reaction, and also dual changes in spirometry. The PD15 /(provocative dose causing a 15% fall in FEV1)/ in the histamine challenge test decreased significantly after the challenge tests. [Piirila P et al; Clin Exp Allergy 27 (5): 510-4 (1997) ]**PEER REVIEWED**
  • CASE REPORTS: ...Leukopenia occurred regularly at dose levels above 1,800 mg/sq m and resulted in life-threatening leukopenia in one patient, and in a toxic death at 2,700 mg/sq m in another patient. Other toxic side-effects included moderate reversible thrombocytopenia, nausea, and vomiting. [Dombernowsky P et al; Cancer Chemother Pharmacol 11 (1): 59-61 (1983) ]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • LABORATORY ANIMALS: Acute Exposure: In rat inhalation (nose-only) studies (650 mg/cu m), ...slight inflammation of the nasal mucosa in the upper dose groups was observed. There were no substance-related gross organ changes in sacrificed animals, and partial hemorrhage only was observed in the lungs of animals who died during the study. ...Clinical signs /in mice after/ An LC50 of 2000 mg/cu m (whole-body exposure to dust, particle size range 3.2 to 3.9 um) and included hypoactivity and ocular and respiratory irritation. Pathological observations included perinasal/periocular/perioral encrustation and lung discoloration. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: ...Clinical signs of toxicity observed /in laboratory animals/ prior to death included sedation, dyspnoea, and emaciation. Pathological findings included edematous and hemorrhagic lungs, hemorrhagic thymus, intestines, and testes, involuted testes, and enlarged kidney. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: In several rabbit studies, triglycidyl isocyanurate caused slight skin irritation, with both very slight erythema and very slight edema observed in the intact skin of some animals up to 72 hr post-application. Triglycidyl isocyanurate caused serious eye damage in rabbits, including severe corneal opacity and chemosis. Triglycidyl isocyanurate (commercial grade) was positive for skin sensitization in guinea-pigs in two modified Magnusson and Kligman studies. In both studies, groups of 10 male and 10 female guinea-pigs were initially exposed to triglycidyl isocyanurate and challenged 2 weeks after induction. Positive responses were observed in 25% of the test animals in one study and in 60% of the test animals in the other study. No skin reactions were noted in the control group at induction or when challenged with triglycidyl isocyanurate. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: In a study in which male CD-1 mice were exposed (nose-only) to triglycidyl isocyanurate at 0, 10, 40, or 140 mg/cu m, 6 hr/day for 5 days, mortality, body weight loss, and lung damage occurred at the highest concentrations (40 and 140 mg/cu m). No exposure-related effects were observed at 10 mg/cu m. Clinical signs of toxicity observed in the intermediate- and high-concentration groups included lethargy, ptosis, decreased respiratory rate, and noisy or gasping respiration. Gross pathology and organ weights were recorded for the lungs, liver, kidney, and testes. Pathological findings included dark or reddened lungs, pale liver, pale kidneys, and congestion of the small intestine. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In a 7-day oral rat study, gross pathology was recorded for the lungs, kidney, liver, stomach, and intestines. Renal tubular damage and hemorrhagic and degenerative changes involving the gastric and duodenal mucosa were observed at the high triglycidyl isocyanurate dose (216 mg/kg bw/day for males and 172 mg/kg bw/day for females). Less marked changes to the renal tubules were noted at the low dose (54 mg/kg bw/day for males and 43 mg/kg bw/day for females). [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: In a 13-wk toxicity/fertility study, groups of 10 male rats were given diets containing 0, 10, 30, or 100 ppm (mg/kg) triglycidyl isocyanurate. This study followed a preliminary 19-day range-finding investigation in which signs of toxicity (large mesenteric lymph nodes, small prostate and seminal vesicles) were observed in animals administered diets containing 160 or 640 ppm (mg/kg) triglycidyl isocyanurate. In the full study after 64 days of treatment, each male was placed with two females until mating occurred. The females were then allocated to two subgroups (cesarean or normal delivery) on day 19 of pregnancy. Females from the cesarean group were killed on day 20 of pregnancy and the ovaries and uterus examined to determine number of corpora lutea, live and dead fetuses, resorptions, and implantation sites. The other group was allowed to deliver normally; litter size was noted, pups were examined for presence of clinical signs, and their development was recorded. Between 22 and 25 days postpartum, the females in the normal delivery group were sacrificed, the main thoracic and abdominal organs were examined, and the number of implantation sites was noted. In males at autopsy, all organ weights and macroscopic and microscopic changes were recorded in the control and highest-dose groups, with selected organs examined in the other test groups. No exposure-related clinical effects or deaths were observed. Body weight gain was slightly lower over the first 6 weeks in animals from the 100 ppm (mg/kg) test group. A dose-related reduction in the number of spermatozoa was noted; compared with the unexposed controls, there was a 5%, 13%, and 23% reduction in spermatozoa in males administered diets containing 10, 30, and 100 ppm (mg/kg) triglycidyl isocyanurate, respectively. Spermatozoa viability was similar in the triglycidyl isocyanurate-exposed and control groups. No exposure-related infertility was noted in males, and no effects on embryonic and pup development were observed in the offspring of females mated with triglycidyl isocyanurate-exposed males. However, it should be noted that the highest concentration used in this study (100 ppm; mg/kg) was not a maximum tolerated dose. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • GENOTOXICITY: The results of the mouse spot test were negative when triglycidyl isocyanurate was administered at doses of 13.5, 27, or 54 mg/kg bw in a single intraperitoneal injection to pregnant mice on the 10th day after conception. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • GENOTOXICITY: The genotoxicity of triglycidyl isocyanurate has been investigated in a wide range of in vitro and in vivo assays. Triglycidyl isocyanurate was mutagenic in Salmonella typhimurium and mouse lymphoma cells and clastogenic in Chinese hamster ovary cells in vitro. It induced chromosomal aberrations in bone marrow cells in hamsters and in germ cells in mice following oral administration. Available data also indicate that triglycidyl isocyanurate has the potential to alkylate DNA. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • GENOTOXICITY: In two reverse mutation assays, commercial-grade triglycidyl isocyanurate induced mutations in the presence and absence of metabolic activation in S. typhimurium strains TA1535, TA1538, TA98, and TA100, with the effect more pronounced in the latter two strains. Triglycidyl isocyanurate was not mutagenic in TA1537. In one of these studies, triglycidyl isocyanurate did not induce back mutation in Escherichia coli WP2uvrA, with or without metabolic activation. All studies were well conducted, using appropriate negative and positive controls, with the results indicating that triglycidyl isocyanurate is a direct-acting mutagen. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • GENOTOXICITY: In a mouse lymphoma cell assay, triglycidyl isocyanurate induced forward mutations in the presence of metabolic activation at 6.0 ug/mL and in the absence of metabolic activation at 2.8 ug/mL. Triglycidyl isocyanurate with and without metabolic activation induced sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells. Triglycidyl isocyanurate also tested positive for the induction of chromosomal aberrations without metabolic activation in Chinese hamster lung cells but was negative with metabolic activation. In an unscheduled DNA synthesis assay in rat hepatocytes, a clear dose-response relationship was noted for triglycidyl isocyanurate over the range 5-20 ug/mL. However, in a similar study conducted with human fibroblasts, triglycidyl isocyanurate did not induce unscheduled DNA synthesis at concentrations up to 400 ug/mL. In two cell transformation studies in mouse embryo fibroblasts, triglycidyl isocyanurate did not induce any significant increase in either transformed colony number or size in the concentration range 8.8-5000 ng/mL. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • GENOTOXICITY: Triglycidyl isocyanurate did not induce chromosomal aberrations in human lymphocytes at concentrations up to 2500 ng/mL. Only one aberration was reported at each of the two higher concentrations of 5000 and 10,000 ng/mL. Significant numbers of aberrations were observed with the positive controls. As only a very late sampling time was used, the results are considered questionable. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • GENOTOXICITY: In a gavage study, male and female Chinese hamsters were administered 0, 140, 280, or 560 mg triglycidyl isocyanurate/kg bw/day for 2 days. Triglycidyl isocyanurate induced small but significant increases in nuclear anomalies in bone marrow cells at the two highest doses, indicative of clastogenicity. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • GENOTOXICITY: In a dominant lethal test, male TifMAGf(SPF) mice were administered (by gavage) 0, 160, or 480 mg triglycidyl isocyanurate/kg bw. In females mated to the high-dose males, there was a significant increase in the number of embryonic deaths when mating occurred during the 1st week after exposure, but not when mating took place 2-3 weeks after the males were exposed. No increase in embryonic deaths was noted in females mated to the low-dose males 1-3 weeks after exposure. The results of this study are considered equivocal. In a study in which male ICR mice were administered (by gavage) 0, 138, 275, or 550 mg triglycidyl isocyanurate/kg bw, no significant increase in the number of embryonic deaths was observed in the mated females. These studies are of limited value, as the mating periods covered only the first 3 weeks after the males had been exposed. In another study, male CD-1 mice were exposed (by inhalation) to 0.25, 10, or 50 mg triglycidyl isocyanurate/cu m. A reduction in male fertility (i.e. number of sperm-positive and pregnant females) was observed in high-dose males in the first 3 weeks and 6th week post-exposure, as well as in mid-dose males in the 3rd week post-exposure only. No dominant lethal effects were observed; however, the results are suggestive of an effect on mature sperm, maturing spermatids, and Type B spermatogonia. This is the only dominant lethal study in which the mating period covered all stages of the spermatogenic cycle. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • GENOTOXICITY: In a (whole-body) inhalation study, mice were exposed to 0, 2.5, 10, or 50 mg triglycidyl isocyanurate/cu m (particle size range 2.5-3.5 um) for 6 hr/day for 5 days. Effects on mouse spermatogonial cells were measured by the induction of chromosomal aberrations. The results of this study were inconclusive. The number of chromosomal aberrations in the control group was high, there was a very low number of scorable cells at the highest concentrations (10 and 50 mg/cu m), and cytotoxicity was not clearly established, as the cytotoxic ratio was not measured. At 2.5 mg/cu m, the number of chromosomal aberrations was only slightly higher than in the controls, which was unusually high. In an (nose-only) inhalation study, male CD-1 mice were exposed to 0 or 7.8 mg triglycidyl isocyanurate/cu m (mean particle size 1.6 um) for 6 hr/day for 5 days. Chromosomal aberrations were not induced in spermatogonial cells at the single concentration tested. In both these studies, body weight gain was unaffected, no deaths occurred, and no adverse clinical signs were observed. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • GENOTOXICITY: A number of oral studies have been conducted to investigate the potential of triglycidyl isocyanurate to induce chromosomal aberrations in mouse germ cells. In male ICR mice administered 0, 30, 125, or 350 mg triglycidyl isocyanurate/kg bw for 5 days, chromosomal aberrations were induced in spermatogonial cells at the two highest doses. In another study in which male B6D2F1 mice were administered 0, 29, 58, or 115 mg triglycidyl isocyanurate/kg bw for 5 days, chromosomal aberrations in spermatogonial cells were significantly increased at all doses. When male TifMAGf mice were administered 0, 43, or 128 mg triglycidyl isocyanurate/kg bw for 5 days, a dose-related increase in chromosomal aberrations was observed in spermatogonial cells; however, a statistical analysis was not conducted. Chromosomal aberrations were not induced in the spermatocytes of male mice administered (by gavage) 0, 32, or 96 mg triglycidyl isocyanurate/kg bw for 4 days. In a single-dose oral study, chromosomal aberrations were induced in mouse spermatogonia at 115 mg triglycidyl isocyanurate/kg bw. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • GENOTOXICITY: ...In vitro studies have clearly shown that TGIC causes point mutations in bacteria and gene mutations in mammalian cells, both in the presence and absence of an exogeneous metabolic activation systems. Positive results have also been obtained for the induction of unscheduled DNA synthesis in rat hepatocytes in vitro. [Meldrum M; HSE Toxicity Review 27: 14 (1992) ]**PEER REVIEWED**
  • GENOTOXICITY: Two gavage studies were conducted to determine the ability of triglycidyl isocyanurate to induce sister chromatid exchanges in bone marrow cells in male and female Chinese hamsters. In one study, no increase in the number of sister chromatid exchanges was observed in animals administered a single dose of 0, 35, 70, or 140 mg triglycidyl isocyanurate/kg bw. In the study in which triglycidyl isocyanurate was administered at a single dose of 0, 140, 280, or 560 mg/kg bw, a dose-related increase in sister chromatid exchange in bone marrow cells (with statistically significant increases) was observed at all exposures. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: The molecular structure of triglycidyl isocyanurate indicates a potential for alkylating DNA. A dose-dependent increase in triglycidyl isocyanurate-DNA adduct formation was observed in a study in which male TifMAGf(SPF) mice were orally administered 5, 17, or 200 mg triglycidyl isocyanurate/kg bw. DNA alkylation was measured as the covalent binding index. For the highest dose, the ratio of covalent binding indices for the stomach, liver, and testes at 3 hr after exposure was approximately 30:7:1. The highest covalent binding index, for the stomach, was 8.9, compared with covalent binding indices of 20,000 for the potent liver carcinogen aflatoxin B1 and 200 for the moderate carcinogen 2-acetylaminofluorene. In a second DNA alkylation study, male TifRAIf(SPF) rats were pretreated with trans-stilbene oxide at 0, 100, or 400 mg/kg bw to induce epoxide hydrolase activity, followed by triglycidyl isocyanurate administered orally or intraperitoneally (20 mg/kg bw). The dose-dependent increase in liver microsomal epoxide hydrolase activity was associated with a dose-dependent decrease in DNA binding by triglycidyl isocyanurate, calculated as the covalent binding index. However, the relatively low covalent binding indices suggested that only a small proportion of triglycidyl isocyanurate binds to DNA. As mentioned in section 7, microsomal epoxide hydrolase activity with triglycidyl isocyanurate as substrate measured in two human livers was greater than the activity in non-induced rat liver. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Rat dermal >2000 mg/kg bw [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • LD50 Rat (male) oral <100 mg/kg [National Occupational Health and Safety Commission, Australian Goverment; Exposure Standards: Triglycidylisocyanurate (TGIC) (1994). Available from: http://www.nohsc.gov.au/OHSInformation/Databases/ExposureStandards/az/Triglycidylisocyanurate_TGIC.htm m#ref as of March 10, 2004. ]**PEER REVIEWED**
  • LD50 Rat (female) oral 255 mg/kg [National Occupational Health and Safety Commission, Australian Goverment; Exposure Standards: Triglycidylisocyanurate (TGIC) (1994). Available from: http://www.nohsc.gov.au/OHSInformation/Databases/ExposureStandards/az/Triglycidylisocyanurate_TGIC.htm m#ref as of March 10, 2004. ]**PEER REVIEWED**
  • LC50 Rat (male) inhalation >650 mg/cu m/4 hr [National Occupational Health and Safety Commission, Australian Goverment; Exposure Standards: Triglycidylisocyanurate (TGIC) (1994). Available from: http://www.nohsc.gov.au/OHSInformation/Databases/ExposureStandards/az/Triglycidylisocyanurate_TGIC.htm m#ref as of March 10, 2004. ]**PEER REVIEWED**
  • LC50 Rat (female) inhalation 650 mg/cu m/4 hr [National Occupational Health and Safety Commission, Australian Goverment; Exposure Standards: Triglycidylisocyanurate (TGIC) (1994). Available from: http://www.nohsc.gov.au/OHSInformation/Databases/ExposureStandards/az/Triglycidylisocyanurate_TGIC.htm m#ref as of March 10, 2004. ]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • In an oral (gavage) study in mice, at least 17% of the administered dose was absorbed within 24 hr, with blood analysis indicating that the absorption of triglycidyl isocyanurate administered in aqueous solution was twice that of triglycidyl isocyanurate in sesame oil. Triglycidyl isocyanurate was distributed to the liver, stomach, and testes (the only tissues studied). [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • The only available human data are from clinical trials with alpha-triglycidyl isocyanurate (intravenous administration), which indicate that alpha-triglycidyl isocyanurate has... total body clearance of 5.7 L/min. Less than 1% of the administered dose was recovered unchanged in urine within 24 hr. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • In oral (gavage) and intravenous studies with [14C]alpha-triglycidyl isocyanurate in rabbits, the radioactivity recovered in urine within 24 hr was approximately 30% and 60-70%, respectively. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • Following absorption, systemic distribution to the liver, stomach and testes has been demonstrated. Hydrolysis of the reactive epoxy groups occurs both spontaneously in the low pH conditions of the stomach and enzymatically in the liver (epoxide hydrolases). [National Occupational Health and Safety Commission, Australian Goverment; Exposure Standards: Triglycidylisocyanurate (TGIC) (1994). Available from: http://www.nohsc.gov.au/OHSInformation/Databases/ExposureStandards/az/Triglycidylisocyanurate_TGIC.htm m#ref as of March 10, 2004. ]**PEER REVIEWED**

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Metabolism/Metabolites

  • In an oral (gavage) study in mice, ...blood plasma analysis indicated that triglycidyl isocyanurate was metabolized by hydrolysis to the diol diepoxide, the bis-diol epoxide, and the fully hydrolysed tris-diol, with no free triglycidyl isocyanurate detected 8 hr after treatment. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • In in vitro studies, rapid hydrolysis of triglycidyl isocyanurate involving the enzyme epoxide hydrolase was observed in mouse liver preparations. Hydrolysis was also observed in rat liver preparations but not in rat lung preparations. Microsomal epoxide hydrolase activity with triglycidyl isocyanurate as substrate measured in two human livers obtained from kidney donors was found to be greater than the activity in rat liver. [International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 8: Triglycidyl Isocyanurate (1998). Available from http://www.inchem.org/pages/cicads.html as of March 3, 2004. ]**PEER REVIEWED**
  • ...Metabolism of TGIC involves hydrolysis of the epoxy functions, leading to the formation of the trisdiol derivative, and is promoted by hepatic but not pulmonary epoxide hydrolase. Non-enzymatic hydrolysis of the epoxy functions occurs under conditions of low pH. Further mechanisms for the metabolism of TGIC have not been investigated. Excretion of TGIC and/or its metabolites is largely via the urine. Urinary metabolites of TGIC have not been identified. [Meldrum M; HSE Toxicity Review 27: 14 (1992) ]**PEER REVIEWED**

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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