| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 99.6% (245 of 246) of all reports.Not ClassifiedAggregated GHS information provided per 246 reports by companies from 3 notifications to the ECHA C&L Inventory.This chemical does not meet GHS hazard criteria for 92.2% (214 of 232) of all reports.Aggregated GHS information provided per 232 reports by companies from 2 notifications to the ECHA C&L Inventory. |
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| Regulatorische Informationen | Chemical: L-ThreonineChemical: DL-ThreonineRegulation (EC) No 1831/2003 (amended)Status: Active Update: 07-04-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/16986L-Threonine: Does not have an individual approval but may be used under an appropriate group standardThreonine, (2R,3S)-rel-: Does not have an individual approval but may be used under an appropriate group standard |
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| Weitere Sicherheitsinformationen | IMAP assessments - DL-Threonine: Environment tier I assessmentIMAP assessments - L-Threonine: Environment tier I assessment |
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| Gefahrenübersicht | May cause irritation[Sigma-Aldrich MSDS] |
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| FDA-Anforderungen | L-Threonine is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity of the substance added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) any substance intended for use in or on food is of appropriate food grade and is prepared and handled as a food ingredient.Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: threonine is included in weight control drug products.Threonine used as a nutrient and/or dietary supplement in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice. |
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| Special Reports | NAS, Food and Nutrition Board, Institute of MedicineDietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C. (2009).[Available from, as of March 10, 2010: http://www.nap.edu/catalog/10490.html] |
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| Hazard Classes and Categories | Not Classified |
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| Entsorgungsverfahren | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
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| Wechselwirkungen | A methionine-threonine-supplemented low (8.5%) casein diet (8.5CMT) reduced symptoms such as proteinuria in nephritic rats without severe protein malnutrition. ... This study ... examined whether or not L-arginine supplementation to 8.5CMT would exacerbate proteinuria and other symptoms in nephritic rats. Male Wistar rats with glomerulonephritis induced by a single intravenous injection of nephrotoxic serum were fed either a 20% casein diet (control), 8.5% casein diet, 8.5CMT, or L-arginine-supplemented 8.5CMT (8.5CMTA) for 16 days. The 8.5CMTA, as compared with the 8.5CMT, aggravated proteinuria and glomerulonephritis. Administration of L-N(G)-nitroarginine methyl ester, an inhibitor of nitric oxide synthase, to 8.5CMTA-fed nephritic rats by drinking water for 14 days canceled the adverse effect of L-arginine on proteinuria and histopathological damage in glomeruli. These results suggest that the supplementation of L-arginine makes exacerbation via nitric oxide production in glomerulonephritis.Rats fed a low-protein diet and administered 2-(2-nitro-4-trifluoromethylbenzoyl)cyclohexane-1,3-dione (NTBC) orally at 30 umol/kg/day (10 mg/kg/day) or fed a low-protein diet containing 5 ppm NTBC develop lesions to the cornea of the eye within 3-8 days of exposure with an incidence of about 80%. This treatment also produces a marked inhibition of both hepatic and renal 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity, an induction of hepatic but not renal tyrosine amino transferase activity, and a marked tyrosinemia in the plasma and aqueous humor. The extent of tyrosinemia and changes in the activity of tyrosine catabolic enzymes are similar to those reported for rats fed a normal protein diet and administered NTBC orally at 30 mumol/kg/day. However, the onset of corneal lesions occurs much earlier in rats fed a low-protein diet. The adverse ocular effects of NTBC can be alleviated by supplementing the low-protein diet with 1% w/w threonine. The protection afforded by threonine inclusion in the diet was not due to any amelioration in the extent of inhibition of hepatic HPPD activity or reduction in the extent of the tyrosinemia as measured 8 days after treatment. Rats fed L-tyrosine at 5% w/w in a low-protein diet rapidly develop lesions to the cornea of the eye, which are associated with a marked tyrosinemia, increased hepatic tyrosine aminotransferase activity, and about a 50% reduction in the activity of hepatic HPPD. The onset of corneal lesions produced by feeding a high tyrosine diet could be delayed, but not prevented, by inclusion of 1% w/w threonine in the low-protein diet. The basis for the beneficial effect of dietary supplementation of threonine in alleviating the corneal lesions produced by NTBC is unclear. However, our findings do illustrate that protein deficiency limits the ability of the rat to respond to a tyrosine load produced by inhibition of HPPD. |
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| Milk Concentrations | The threonine content of most of the infant formulas currently on the market is approximately 20% higher than the threonine concentration in human milk. Due to this high threonine content the plasma threonine concentrations are up to twice as high in premature infants fed these formulas than in infants fed human milk. To study the effect of different threonine intakes on plasma and tissue amino acid concentrations, 24 young male Wistar rats were fed three experimental diets based on a mixture of bovine proteins with a whey protein/casein ratio of 60/40 with different threonine contents [group A, 0.86 g of threonine/100 g (n = 8)group B, 1.03 g of threonine/100 g (n = 8)group C, 2.21 g of threonine/100 g (n = 8)]. Eight animals were fed a typical rat diet based on bovine casein as controls. After a feeding period of 15 d, amino acids were measured in plasma and in homogenates of the cerebral cortex, brain stem, liver, and muscle. There was a significant correlation between threonine intake and plasma threonine levels (r = 0.687, p < 0.001). The plasma threonine concentration correlated significantly with the threonine concentration in the cortex (r = 0.821, p < 0.01) and the brain stem (r = 0.882, p < 0.01). There was a positive significant correlation between threonine and glycine concentrations in the cortex (r = 0.673, p < 0.01), and the brain stem (r = 0.575, p < 0.01), whereas the glycine concentration decreased with increasing threonine intakes in the liver and muscle. The presented data indicate that increasing the threonine in plasma leads to increasing brain glycine and thereby affects the neurotransmitter balance in the brain. This may have consequences for brain development during early postnatal life. Therefore, excessive threonine intake during infant feeding should be avoided. |
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| Toxizitätsübersicht | Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.orgL-Threonine is a precursor to the amino acids glycine and serine. It acts as a lipotropic in controlling fat build-up in the liver. May help combat mental illness and may be very useful in indigestion and intestinal malfunctions. Also, threonine prevents excessive liver fat. Nutrients are more readily absorbed when threonine is present. |
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| Plant Concentrations | Plants with the highest amount of Threonine(1). [Table#7477] |
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| Natural Pollution Sources | (L)-Threoniine is one of the nine indispensable amino acids that cannot be synthesized to meet body needs in animals and therefore must be provided in the diet(1). It has been identified in oat protein(2). |
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| Human Toxicity Excerpts | /OTHER TOXICITY INFORMATION/ Threonine also has been studied in low birth weight infants. In a study of 163 low birth weight infants, threonine serum concentrations were directly related to the threonine concentrations of the formula. The authors suggested that threonine intakes should not exceed about 140 mg/kg body weight/day for premature infants./OTHER TOXICITY INFORMATION/ There is no evidence that amino acids derived from usual or even high intakes of protein from foodstuffs present any risk./OTHER TOXICITY INFORMATION/ Serum threonine concentration was determined during the first month of life in 163 low birthweight infants fed on either human milk, various adapted formulae, or total parenteral nutrition. On the pooled data, a significant positive relationship was found between the serum threonine concentration and threonine intake. However, the increase of the serum threonine level is more marked in the infants with the lowest actual gestational agewith a high threonine intake, the most premature infants have serum threonine levels twice as high (58.1 vs 31.7 uM/dL) as term infants. Therefore, threonine metabolism seems to be impeded in preterm infants. Considering the cord blood concentration of threonine (26.8 +/- 5.1 uM/dL) and the possible hazardous effect of hyperthreoninemia, it is suggested that threonine intake should not exceed 1200 uM (143 mg)/kg bodyweight/day in premature infants and that the amino acid composition of the diet should probably be modified in order to satisfy their protein requirement./OTHER TOXICITY INFORMATION/ The threonine content of most of the infant formulas currently on the market is approximately 20% higher than the threonine concentration in human milk. Due to this high threonine content the plasma threonine concentrations are up to twice as high in premature infants fed these formulas than in infants fed human milk. Increasing the threonine in plasma leads to increasing brain glycine and thereby affects the neurotransmitter balance in the brain. This may have consequences for brain development during early postnatal life. Therefore, excessive threonine intake during infant feeding should be avoided. |
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| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
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| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Acute Exposure/ The purpose of this study was to determine whether an addition of dietary limiting amino acids affected urea synthesis in rats fed a low gluten diet. Experiments were done on three groups of rats given diets containing 10% gluten, 10% gluten +0.5% L-lysine or 10% gluten+0.5% L-lysine, 0.2% L-threonine and 0.2% L-methionine for 10 d. The urinary excretion of urea, and the liver concentrations of serine and ornithine decreased with the addition of dietary L-lysine, L-threonine and L-methionine. The fractional and absolute rates of protein synthesis in tissues increased with the treatment of limiting amino acids. The activities of hepatic urea-cycle enzymes was not related to the urea excretion. These results suggest that the addition of limiting amino acids for the low gluten diet controls the protein synthesis in tissues and hepatic ornithine and decline in urea synthesis./LABORATORY ANIMALS: Acute Exposure/ Rats quickly recognize and reject diets deficient in an essential amino acid. The purpose of this study was to determine whether the anterior piriform cortex (APC), the site traditionally recognized as the amino acid chemosensor, plays a role in this early behavior. Rats had cannulae implanted bilaterally into the APC, and were injected with either saline vehicle or 2 nmoles of threonine (n = 6 per group). All rats were then fed a diet imbalanced with respect to threonine. The threonine-injected group had first meals of longer duration and consumed more food. These data conformed to expectations derived from earlier studies of responses to the first meal of an amino acid imbalanced diet. /It was concluded/ that the concentration of the dietary limiting amino acid in the APC regulates acceptance and rejection of amino acid deficient diets./LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In weanling pigs, adding 0.5, 1, 2, or 4% L-threonine to a 20% crude protein diet did not change weight gain, food intake, and gain:feed ratios in comparison to the controls./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The results of neurochemical and behavioral studies in the developing rat suggest that despite numerous possible effects of threonine on brain constituents, moderate hyperthreoninemia does not impair markedly the development of the central nervous system./OTHER TOXICITY INFORMATION/ In rats fed 5% threonine added to a 10% casein diet, weight gain was reduced compared to controls fed casein alone but there were no changes in liver weight or hepatic DNA, RNA, or protein content. |
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| Probable Routes of Human Exposure | NIOSH (NOES Survey 1981-1983) has statistically estimated that 18,524 workers (13,980 of these were female) were potentially exposed to threonine in the US(1). |
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| Antidote and Emergency Treatment | /SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B//SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B//SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/ |
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| Non-Human Toxicity Values | LD50 rat ip 3098 mg/kg |
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