FORMALDEHYDE. ChemWatch Material Safety Data Sheet (REVIEW) CHEMWATCH 64715 Issue Date: Fri 2-Jul-2004 CD 2004/3 Page 9 of 11 Section 9 - PHYSICAL AND CHEMICAL PROPERTIES ... Solution on standing may become cloudy if temperature is low; as at low temperatures a precipitate of trioxymethylene is formed. The formaldehyde vaporizes readily from solution and is flammable in air. Warming or heating solution increases formaldehyde generation. Section 10 - CHEMICAL STABILITY AND REACTIVITY INFORMATION CONDITIONS CONTRIBUTING TO INSTABILITY • Presence of incompatible materials. • Product is considered stable. • Hazardous polymerisation will not occur. Section 11 - TOXICOLOGICAL INFORMATION formaldehyde. TOXICITY IRRITATION Oral (woman)LDLo: 108mg/kg Skin(human): 0.15mg/3d-I mild Oral (man) TDLo: 643mg/kg Skin(rabbit): 2mg/24HSEVERE Oral (rat)LD50: 100mg/kg Eye(human): 4ppm/5m Inhalation(human): TCLo17mg/m3/30M Eye(rabbit): 0.75mg/24HSEVERE Inhalation(man) TCLo: 0.3mg/m3 Inhalation(rat)LC50: 203mg/m3 Dermal (rabbit)LD50: 270mg/kg WARNING: ThissubstancehasbeenclassifiedbytheIARCasGroup1: CARCINOGENIC TOHUMANS. TenthAnnual ReportonCarcinogens: SubstanceanticipatedtobeCarcinogen [National ToxicologyProgram: U.S. Dep. ofHealth&HumanServices2002]
FORMALDEHYDE. ChemWatch Material Safety Data Sheet (REVIEW) CHEMWATCH 64715 Issue Date: Fri 2-Jul-2004 CD 2004/3 Page 2 of 11 Section 3 - HAZARDS IDENTIFICATION STATEMENT OF HAZARDOUS NATURE
CONSIDERED A DANGEROUS SUBSTANCE ACCORDING TO DIRECTIVE 67/548/EEC, POINT 4; AND HAZARDOUS ACCORDING TO OSHA 29 CFR 1910.1200 (USA). POTENTIAL HEALTH EFFECTS ACUTE HEALTH EFFECTS SWALLOWED Toxic effects may result from the accidental ingestion of the material; animal experiments indicate that ingestion of less than 40 gram may be fatal or may produce serious damage to the health of the individual. The material can produce chemical burns within the oral cavity and gastrointestinal tract following ingestion. EYE The material can produce chemical burns to the eye following direct contact. Vapours or mists may be extremely irritating. When applied to the eye(s) of animals, the material produces severe ocular lesions which are present twenty-four hours or more after instillation. SKIN Skin contact with the material may produce toxic effects; systemic effects may result following absorption. The material can produce chemical burns following direct contact with the skin. INHALED Toxic by inhalation. Evidence shows, or practical experience predicts, that the material produces irritation of the respiratory system in a substantial number of individuals following inhalation. CHRONIC HEALTH EFFECTS On the basis, primarily, of animal experiments, concern has been expressed that the material may produce carcinogenic or mutagenic effects; in respect of the available information, however, there presently exists inadequate data for making a satisfactory assessment. Limited evidence shows that inhalation of the material is capable of inducing a sensitisation reaction in a significant number of individuals at a greater frequency than would be expected from the response of a normal population. Pulmonary sensitisation, resulting in hyperactive airway dysfunction and pulmonary allergy may be accompanied by fatigue, malaise and aching. Significant symptoms of exposure may persist for extended periods, even after exposure ceases. Symptoms can be activated by a variety of nonspecific environmental stimuli such as automobile exhaust, perfumes and passive smoking. Practical experience shows that skin contact with the material is capable either of inducing a sensitisation reaction in a substantial number of individuals, and/or of producing a positive response in experimental animals. Principal routes of exposure are usually by inhalation of vapour and skin contact/absorption Sensitisation may give severe responses to very low levels of exposure, i.e. hypersensitivity. Sensitised persons should not be allowed to work in situations where exposure may occur. Prolonged or repeated skin contact may cause drying with cracking, irritation and possible dermatitis following. Minor but regular methanol exposures may effect the central nervous system, optic nerves and retinae. Symptoms may be delayed, with headache, fatigue, nausea, blurring of vision and double vision. FORMALDEHYDE. ChemWatch Material Safety Data Sheet (REVIEW) CHEMWATCH 64715 Issue Date: Fri 2-Jul-2004 CD 2004/3 Page 3 of 11 Section 3 - HAZARDS IDENTIFICATION ... or severe exposures may cause damage to optic nerves, which may become severe with permanent visual impairment even blindness resulting. WARNING: Methanol is only slowly eliminated from the body and should be regarded as a cumulative poison which cannot be made non-harmful [CCINFO] When administered by inhalation, formaldehyde induced squamous cell carcinomas of the nasal cavity in rats of both sexes. Although excess occurrence of a number of cancers has been reported, the evidence for a possible involvement of formaldehyde is strongest for nasal and nasopharangeal cancer. The occurrence of these cancers showed an exposure-response gradient in more than one study, but the numbers of exposed cases were often small and some studies did not show excesses
Section 4 - FIRST AID MEASURES SWALLOWED Rinse mouth out with plenty of water. If poisoning occurs, contact a doctor or Poisons Information Centre. • If swallowed do NOT induce vomiting. • If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain open airway and prevent aspiration. • Immediately give a glass of water. EYE If this product comes in contact with the eyes: • Immediately hold eyelids apart and flush the eye continuously with running water. • Ensure complete irrigation of the eye by keeping eyelids apart and away from eye and moving the eyelids by occasionally lifting the upper and lower lids. • Continue flushing until advised to stop by the Poisons Information Centre or a doctor, or for at least 15 minutes. • Transport to hospital or doctor without delay. • Removal of contact lenses after an eye injury should only be undertaken by skilled personnel. SKIN If skin or hair contact occurs: • Immediately flush body and clothes with large amounts of water, using safety shower if available. • Quickly remove all contaminated clothing, including footwear. • Wash skin and hair with running water. Continue flushing with water until advised to stop by the Poisons Information Centre. • Transport to hospital, or doctor.INHALED • If fumes or combustion products are inhaled remove from contaminated area. • Lay patient down. Keep warm and rested. • Prostheses such as false teeth, which may block airway, should be removed, where possible, prior to initiating first aid procedures. • Apply artificial respiration if not breathing, preferably with a demand valve resuscitator, bag-valve mask device, or pocket mask as trained. Perform CPR if necessary. • Transport to hospital, or doctor, without delay.
WARNING:
NOTES TO PHYSICIAN For acute or short-term repeated exposures to formaldehyde:
INGESTION [as a breakdown product of methanol in aspartame] :
• Patients present early with severe corrosion of the gastro-intestinal tract and systemic effects.
• Inflammation and ulceration may progress to strictures.
FORMALDEHYDE. ChemWatch Material Safety Data Sheet (REVIEW) CHEMWATCH 64715 Issue Date: Fri 2-Jul-2004 CD 2004/3 Page 4 of 11 Section 4 - FIRST AID MEASURES ... • Severe acidosis results from rapid conversion of formaldehyde to formic acid. Coma, hypotension, renal failure and apnoea complicate ingestion. • Decontaminate by dilution with milk or water containing ammonium acetate; vomitingshouldbeinduced.
Followwithgastriclavageusingaweakammonia solution(convertsformaldehyde to relatively inert pentamethylenetetramine) • Gastric lavage is warranted only in first 15 minutes following ingestion. SKIN: • Formaldehyde can combine with epidermal protein to produce a hapten-protein couplecapableofsensitisingT-lymphocytes. Subsequent exposures cause a type IV hypersensitivity reaction(i.e allergic contact dermatitis). [Ellenhorn& Barceloux: Medical Toxicology]
S e c t i o n 8 - E X P O S U R E C O N T R O L S / P E R S O N A L P R O T E C T I O N E X P O S U R E C O N T R O L S T L V C : 0 . 3 p p m , 0 . 3 7 m g / m0¶ ( A 2 ) S E N S I T I S E R W A R N I N G : T h i s s u b s t a n c e h a s b e e n c l a s s i f i e d b y t h e A C G I H a s A 2 S u s p e c t e d H u m a n C a r c i n o g e n . E S T W A : 1 p p m , 1 . 2 m g / m0¶ ; S T E L : 2 p p m , 2 . 5 m g / m0¶ S E N S I T I S E R ( U n d e r r e v i e w ) W A R N I N G : T h i s s u b s t a n c e i s c l a s s i f i e d b y t h e N O H S C a s C a t e g o r y 2 P r o b a b l e H u m a n C a r c i n o g e n P R O P O S E D C H A N G E E S P e a k 0 . 3 p p m , 0 . 3 7 m g / m0¶ S E N S I T I S E R C a t e g o r y 2 P r o b a b l e H u m a n C a r c i n o g e n M E L T W A : 2 p p m , 2 . 5 m g / m0¶ ; S T E L : 2 p p m , 2 . 5 m g / m0¶ O d o u r T h r e s h o l d V a l u e : 0 . 9 8 p p m ( r e c o g n i t i o n ) I D L H L e v e l : 2 0 p p m N O T E : D e t e c t o r t u b e s f o r f o r m a l d e h y d e , m e a s u r i n g i n e x c e s s o f 0 . 2 p p m a r e a v a i l a b l e c o m m e r c i a l l y . F o r m a l d e h y d e v a p o u r e x p o s u r e : P r i m a r y i r r i t a t i o n i s d e p e n d e n t o n d u r a t i o n o f e x p o s u r e a n d i n d i v i d u a l s u s c e p t i b i l i t y . T h e f o l l o w i n g a r e t y p i c a l s y m p t o m s e n c o u n t e r e d a t v a r i o u s e x p o s u r e l e v e l s . 0 . 1 p p m - L o w e r l e v e l o f m u c o u s e y e , n o s e a n d t h r o a t i r r i t a t i o n 0 . 8 p p m - T y p i c a l t h r e s h o l d o f p e r c e p t i o n 1 - 2 p p m - T y p i c a l t h r e s h o l d o f i r r i t a t i o n 2 - 3 p p m - I r r i t a t i o n o f e y e s , n o s e a n d t h r o a t
Section 9 - PHYSICAL AND CHEMICAL PROPERTIES PHYSICAL PROPERTIES Liquid. Mixes with water. Toxic or noxious vapours/gas. Molecular Weight: Not applicable. Boiling Range (°C): -19.5 gas Melting Range (°C): -92 gas Specific Gravity (water=1): 1.09-1.14 Solubility in water (g/L): Miscible pH (as supplied): Not applicable pH (1% solution): Not available. Vapour Pressure (kPa): > 100 Volatile Component (%vol): 100 Evaporation Rate: Not applicable Relative Vapour Density (air=1): 1.1 Flash Point (°C): 69 water soln. Lower Explosive Limit (%): 7 Upper Explosive Limit (%): 73 Autoignition Temp (°C): 430 Decomposition Temp (°C): Not available. State: Liquid APPEARANCE Formaldehyde is a gas; however all references in this document are to the commercially available form of the material, i.e. a solution of the gas in water; which is a clear, water-white liquid with a suffocating pungent highly irritating odour. Mixes with water, alcohol, acetone.
RISK Toxic by inhalation, in contact with skin and if swallowed. Causes burns. Limited evidence of a carcinogenic effect. Risk of serious damage to eyes. May cause SENSITISATION by skin contact. Name Score WGK formaldehyde. 2 Source: VwVwS
FORMALDEHYDE. ChemWatch Material Safety Data Sheet (REVIEW) CHEMWATCH 64715 Issue Date: Fri 2-Jul-2004 CD 2004/3 Page 11 of 11 Section 16 - OTHER INFORMATION ... R41 Riskofseriousdamagetoeyes. R43 MaycauseSENSITISATION by skin contact.
_________________________________________________________________________________
Pharmacol Toxicol. 1987 Mar; 60(3): 217-20.
Elimination half-life of methanol during hangover.
Jones AW.
Department of Forensic Toxicology, University Hospital, SE-581 85 Linkoping,
Sweden. wayne.jones@RMV.se
This paper reports the elimination half-life of methanol in human
volunteers. Experiments were made during the morning after the subjects had
consumed 1000-1500 ml red wine (9.5% w/v ethanol, 100 mg/l methanol)
the previous evening. [ 100 to 150 mg methanol ]
The washout of methanol from the body coincided with the onset of hangover.
The concentrations of ethanol and methanol in blood were determined
indirectly by analysis of end-expired alveolar air.
In the morning when blood-ethanol dropped below the Km of liver alcohol
dehydrogenase (ADH) of about 100 mg/l (2.2 mM), the disappearance half-life
of ethanol was 21, 22, 18 and 15 min. in 4 test subjects respectively.
The corresponding elimination half-lives of methanol were 213, 110, 133 and
142 min. in these same individuals.
The experimental design outlined in this paper can be used to obtain useful
data on elimination kinetics of methanol in human volunteers without undue
ethical limitations.
Circumstantial evidence is presented to link methanol or its toxic metabolic
products, formaldehyde and formic acid, with the pathogenesis of hangover.
PMID: 3588516
Jones has suggested that it is the metabolism of methanol to formaldehyde
and formic acid that causes symptoms of hangover, with quicker methanol
metabolisers suffering more.(7) The justification for this suggestion is
threefold:
the types of drink associated with more severe hangovers contain higher
levels of methanol;
the time course of methanol metabolism corresponds to the onset of symptoms;
and a small dose of ethanol, which blocks the formation of formaldehyde and
formic acid, provides an effective treatment for hangovers ("the hair of the
dog").
Many pathophysiological disturbances occur during hangover, including
dehydration; metabolic acidosis; hypoglycaemia; disturbed prostaglandin
synthesis; abnormal secretion of vasopressin, cortisol, aldosterone,
renin, and testosterone; increased cardiac output; tachycardia; and
vasodilatation.
Table 1-Typical neotame concentrations in various products when used as a
sweetener
Product Typical concentration (ppm)
Carbonated soft drinks 2-50
Cola 17
Lemon-lime 14
Root beer 20
Flavored water 15
Still beverages 2-20
Red punch 15
Lemonade 16
Ready-to-drink tea 8
Powdered soft drink, as is 200-2,000
Lemon-flavored 16
Tabletop sweetener, as is 800-4,000
Lemon tea 12
Bakery products 6-130
Cookie 25
Yellow cake 35
Chocolate cake 125
Fillings 25
Frosting 25
Dairy products 5-50
Yogurt 15
Ice cream 15
Other frozen desserts 30
Chewing gum 10-1,600
Confections 1-200
Hard candy 5-75
Cereals 10-500
Extruded 23
Frosting 20
Edible gels 10-1,000
Nutraceuticals 15-250
Pharmaceuticals 1-1,000
Liquid sweetener 10-10,000
Sweetener tablets 50-12,000
REFERENCES
Bishay, I., Fotos, J., Desai, N., Cleary, M., and Schroeder, S. 2000a. The
use of cyclodextrin to stabilize
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester.
PCT intl. applic. WO 00/15049.
Bishay, I., Prakash, I., Desai, N., and Gelman, Y. 2000b. Modification of
the taste and physicochemical properties of neotame using hydrophobic
additives. PCT intl. applic. WO 00/69282.
Chinn, B., Solter, S., Ponakala, S., Ziegler, J., Bakhoum, M., Jarrett, T.,
Paeschke, T., and Corliss, G. 1999. Use of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester in
baked goods, frostings and bakery fillings. PCT intl. applic. WO 99/30566.
Dron, A. 2001. Process for making granulated
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-Lphenylalanine 1-methyl ester. PCT
intl. applic. WO 01/60842.
Dron, A., Bishay, I., Fotos, J., and Trione, M. 2000. Spheronization of
neotame with and without binders. PCT intl. applic. WO 00/57725.
DuBois, G., Walters, D, Schiffman, S., Warwick, Z., Booth, B., Pecore, S.,
Gibes, K., Carr, B., and Brands, L. 1991. Concentration-response
relationships of sweeteners.
Chpt. 20 in "Sweeteners Discovery, Molecular Design, and Chemoreception,"
ed. D.E. Walters, F.T. Orthoefer, and G.E. DuBois, pp. 261-276. Am. Chem.
Soc., Washington, D.C.
FDA. 1998. Monsanto Co.: Filing a food additive petition. FAP 8A4580. Food
and Drug Admin., Fed. Reg. 63: 6762.
FDA. 1999. Monsanto Co.: Filing a food additive petition. FAP 9A4643. Food
and Drug Admin., Fed. Reg. 64: 6100.
Fotos, J. and Bishay, I. 2001. Process for preparing an
N-[N-(3,3-dimethylbutyl)-L-aaspartyl]-L-phenylalanine 1-methyl ester
agglomerate. U.S. patent 6,180,157.
Fotos, J., Bishay, I., Prakash, I., Wachholder, K., and Desai, N. 2001.
Co-crystallization of sugar and
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester.
U.S. patent 6,214,402.
Gaughan, W., Gerlat, P., Ziegler, J., Walters, G., Logli, L., Corliss, G.,
and Finley, J. 1999. Neotame sweetener for dairy products and dairy product
substitutes. PCT intl. applic. WO 99/30578.
Gerlat, P., Hatchwell, L., Walters, G., Miragilo, A., and Sawer, H. 2000.
Use of N-neohexyl-a-aspartyl-L-phenylalanine methyl ester as flavor
modifier. U.S. patent applic. 09/465,837.
Gerlat, P., Milovanovic, S., Ponakala, S., Ziegler, J., Sawyer, H., and
Walters, G. 1999. Neotame-based sweeteners for beverages. PCT intl. applic.
WO 99/30576.
Gerlat, P., Walters, G., Bishay, I., Prakash, I., Jarrett, T., Desai, N.,
Sawer, H., and Bechert, C.-L. 2000.
Use of additives to modify the taste characteristics of
N-neohexyl-a-aspartyl-L-phenylalanine methyl ester. PCT intl. applic. WO
00/69283.
Jarrett, T. 2001. Confectionery food products sweetened with
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester. PCT
intl. applic. WO 01/010236.
Lavia, A. and Hill, J. 1972. Sweeteners with masked saccharin aftertaste.
French patent 2,087,843.
Nofre, C. and Tinti, J.-M. 1996a. Method of preparing a compound derived
from aspartame, useful as a sweetening agent. U.S. patent 5,510,508.
Nofre, C. and Tinti, J.-M. 1996b. N-substituted derivatives of aspartame
useful as sweetening agents. U.S. patent 5,480,668.
Nofre, C. and Tinti, J.-M. 2000. Neotame: Discovery, properties, utility.
Food Chem. 69: 245-297.
FOOD TECHNOLOGY 45 VOL. 56, NO. 7 . JULY 2002 DEVELOPING FOODS
Pajor, L. and Gibes, K. 2000.
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester
synergistic sweetener blends. U.S. patent 6,048,999.
Pariza, M., Ponakala, S., Gerlat, P., and Andress, S. 1998. Predicting the
functionality of direct food additives. Food Technol. 52(11): 56-60.
Ponakala, S. 2001. Pharmaceutical compositions containing neotame. PCT intl.
applic. WO 01/028590.
Ponakala, S. and Corliss, G. 2000. Cereals and cereal-based food sweetened
with neotame. PCT intl. applic. WO 00/056175.
Ponakala, S., Ziegler, J., Patterson, K., Brahmbhatt, D., Lui, P., Corliss,
G., Chaudhary, V., Towb, A., Bishay, I., and Ansay, A., R. 1999.
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester as a
sweetener in chewing gum. U.S. patent applic. No. 09/465,402.
Ponakala, S., Walters, G., Gerlat, P., and Hatchwell, L. 2000a.
Nutraceuticals having
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester. PCT
intl. applic. WO 00/057726.
Ponakala, S., Walters, G., and Schroeder, S. 2000b. Manufacture of edible
gels sweetened with neotame. PCT intl. applic. WO 00/056176.
Prakash, I. 1998. Method for preparing and purifying an N-alkylated
aspartame derivative. U.S. patent 5,728,862.
Prakash, I. 2001. Synthesis of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester using
oxazolidinone derivatives. PCT intl. applic. WO 01/90138.
Prakash, I. and Chapeau, M.-C. 2000. N-3,3-Dimethylbutyl-L-aspartic acid and
esters thereof, the process of preparing the same, and the process for
preparing
N-(N-(3,3-dimethylbutyl)- L-a-aspartyl)-L-phenylalanine 1-methyl ester
therefrom. U.S. patent 6,077,962.
Prakash, I., and Guo, Z., 2000a. Metal complexes of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester. U.S.
patent 6,146,680.
Prakash, I., and Guo, Z., 2000b. Sweetener salts of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester. U.S.
patent 6,129,942.
Prakash, I., and Wachholder, K. 2001a. Acid salts of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester. U.S.
patent 6,180,156.
Prakash, I. and Wachholder, K. 2001b. Basic salts of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester. U.S.
patent 6,291,004.
Prakash, I., Bishay, I., and Schroeder, S. 1999. Neotame: synthesis,
stereochemistry and sweetness. Synthetic Commun. 29: 4461-4467.
Prakash, I., Bishay, I., Desai, N., and Walters, D. 2001a. Modifying the
temporal profile of the high-potency sweetener neotame. J. Agric. Food Chem.
49: 786-78.
Prakash, I., Scaros, M., Orlovskii, V., and Moore, C. 2001b. A method for
the preparation of N-neohexyl-L-a-aspartyl-L-phenylalanine methyl ester from
imidazolidin-4-one intermediates. PCT intl. applic. WO 01/87927.
Roefer, W. 2002. Unpublished data. Dept. of Analytical Chemistry, The
NutraSweet Co., Mt. Prospect, Ill.
Schiffman, S., Booth, B., Carr, B., Losee, M., Sattely-Miller, E., and
Graham, B. 1995. Investigation of synergism in binary mixtures of
sweeteners. Brain Research Bull. 38(2): 105-120.
Schroeder, S. and Wang, R. 2001a. Amorphous
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]- L-phenylalanine 1-methyl ester. U.S.
patent 6,331,646.
Schroeder, S. and Wang, R. 2001b. Stability enhancement of sweeteners using
salts containing divalent or trivalent cations. PCT intl. applic. WO
01/70049.
Schroeder, S., Wang, R., Ponakala, S., and Choudhary, V. 2000. Method of
preparing liquid compositions for delivery of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester in
food and beverage systems. PCT intl. applic. WO 02/05661.
Scott, D. 1971. Saccharin-dipeptide sweetening compositions. British patent
1,256,995.
Towb, A., Dron, A., and Walters, G. 2002. Drying of neotame with co-agents.
PCT intl. applic. WO 02/05660.
Verdi, R.J. and Hood, L.L. 1993. Advantages of alternative sweetener blends.
Food Technol. 47(6): 94-101.
Walters, E. 1993. High intensity sweetener blends. Food Prod. Design 3(6):
83-92. l
