(-)-Nicotine hydrogen (+)-tartrate

462.41

462.148560

200-607-2

7892ZN5G41

0521

1659

White plates

246.25000

-2.45900

white to off-white powder

89 °C

508ºC(e)

101.7ºC

H2O: 50 mg/mL

Desiccate at RT

Oral-rat LD50: 65 mg/kg; Oral-Mouse LD50: 65 mg/kg

D20 +26° (c = 10)

Crystals; very soluble in water or alcohol. Specific optical rotation: +26 deg at 20 °C/D (c= 10); mp: 90 °C /Dihydrate/

244 °C

II

6.1(a)

UN 1659 6.1/PG 2

2

26/27/28-51/53

13-28-45-61

QT0350000

T+,N

The warehouse is ventilated, low temperature and dry; stored and transported separately from food materials

Stable under normal temperatures and pressures.

Missing Phrase - N15.00950417-P260-P262-P280-P302 + P352 + P310-P304 + P340 + P310

H300 + H310 + H330-H411

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number P075, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

Dangerous Prop Indust Mat Rpts 5 (6): 75-7 (1985). Review nicotine tartrate hazard; Health hazard of nicotine tartrate; Safety of nicotine tartrate.

Combustible. Gives off irritating or toxic fumes (or gases) in a fire.

|Danger|H300 (86.27%): Fatal if swallowed [Danger Acute toxicity, oral]|P260, P262, P264, P270, P271, P273, P280, P284, P301+P310, P302+P350, P304+P340, P310, P320, P321, P322, P330, P361, P363, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 51 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]|P260, P262, P264, P270, P271, P280, P284, P301+P310, P302+P350, P304+P340, P310, P320, P321, P322, P330, P361, P363, P403+P233, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Wear appropriate chemical protective gloves, boots and goggles.

Wear positive-pressure self-contained breathing apparatus when fighting fires involving this material.|If material is on fire or involved in a fire: Extinguish fire using agent suitable for type of surrounding fire. Material itself does not burn or burns with difficulty. Use water in flooding quantities as fog. Use "alcohol" foam, dry chemical or carbon dioxide.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|Avoid breathing dusts and fumes from burning material. Keep upwind. Avoid bodily contact with the material.|Do not handle broken packages unless wearing appropriate personal protective clothing. Wash away any material which may have contacted the body with copious amounts of water or soap and water.|If material is not on fire and not involved in a fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers.|SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.

/GUIDE 151: SUBSTANCES - TOXIC (Non-combustible)/ Fire or Explosion: Non-combustible, substance itself does not burn but may decompose upon heating to produce corrosive and/or toxic fumes. Containers may explode when heated. Runoff may pollute waterways.|/GUIDE 151: SUBSTANCES - TOXIC (Non-combustible)/ Health: Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution.|/GUIDE 151: SUBSTANCES - TOXIC (Non-combustible)/ Public Safety: CALL Emergency Response Telephone Number on Shipping Paper first. If Shipping Paper not available or no answer, refer to appropriate telephone number listed on the inside back cover. As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. Keep unauthorized personnel away. Stay upwind. Keep out of low areas.|/GUIDE 151: SUBSTANCES - TOXIC (Non-combustible)/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible.|For more DOT Emergency Guidelines (Complete) data for NICOTINE TARTRATE (8 total), please visit the HSDB record page.

No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./|The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials.|The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.

Personal protection: complete protective clothing including self-contained breathing apparatus. Do NOT wash away into sewer. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Then store and dispose of according to local regulations.

Provision to contain effluent from fire extinguishing. Separated from strong oxidants and food and feedstuffs.

Evaporation at 20 °C is negligible; a harmful concentration of airborne particles can, however, be reached quickly when dispersed.

The substance is irritating to the eyes and skin. The substance may cause effects on the central nervous system. This may result in convulsions and respiratory failure. Exposure at high concentrations could cause death. The effects may be delayed. Medical observation is indicated.

Animal tests show that this substance possibly causes toxic effects upon human reproduction.

NO open flames.

PREVENT DISPERSION OF DUST! AVOID EXPOSURE OF (PREGNANT) WOMEN! IN ALL CASES CONSULT A DOCTOR!

Use ventilation (not if powder), local exhaust or breathing protection.

Protective gloves. Protective clothing.

Wear face shield or eye protection in combination with breathing protection if powder.

P075; An acute hazardous waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 100 lb or 45.4 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b). /Nicotine and salts/

P075; As stipulated in 40 CFR 261.33, when nicotine and salts, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to federal and/or state hazardous waste regulations. Also defined as a hazardous waste is any container or inner liner used to hold this waste or any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5(e)). /Nicotine and salts/

highly toxic

... Twelve cigarette smokers were studied while receiving transdermal mecamylamine 6 mg/24 hr and placebo patches for 7 days each. On the fifth day of patch use, subjects received a combined infusion of deuterium-labeled nicotine and cotinine, with measurement of disposition kinetics of nicotine and cotinine, and cardiovascular and plasma catecholamine responses to nicotine. Half of the subjects were studied under alkaline urine conditions and the other half under acidic urine conditions. Steady-state plasma mecamylamine concentrations were twice as high (mean, 12.2 versus 6.3 ng/mL), consistent with lower renal clearance (2.1 versus 5.8 mL/min/kg) during alkaline compared with acidic urine conditions. Mecamylamine did not significantly affect the clearances of nicotine or cotinine. Mecamylamine significantly reduced the volume of distribution and inhibited the cardioacceleratory and epinephrine-releasing effects of nicotine. Mecamylamine has little effect on the clearance of nicotine and is not expected to affect steady-state levels during transdermal nicotine dosing. The reduction of the volume of distribution of nicotine by mecamylamine suggests that part of the antagonism of nicotinic central nervous system effects by mecamylamine may be due to a pharmacokinetic interaction-most likely decreased transport of nicotine into the brain or decreased binding to nicotine receptors. Mecamylamine may decrease the potential adverse cardiovascular effects of coadministered nicotine.|...The present study demonstrates that the opiate antagonist naloxone can precipitate an abstinence syndrome in nicotine-dependent rats. Fourteen rats were infused for 7 days with 9 mg/kg/day nicotine tartrate in saline via an Alzet osmotic minipump. Fourteen rats were sham-operated and remained nicotine-naive. Half of each group received 4.5 mg/kg naloxone SC immediately before a "blind" 15-min observation, while the other half received saline alone. ANOVA revealed significant nicotine infusion, naloxone injection and interaction effects. Post-hoc analysis showed that the nicotine-infused rats injected with naloxone had significantly more signs than all other groups (P < 0.01). ...|Antihistamines are being increasingly administered in combination with various other agents, with adverse drug reactions the frequent result. The present study consisted of two experiments. Experiment 1 examined the toxicological response of rats to nicotine tartrate (0.0, 2.0, 4.0, and 8.0 mg/kg) in combination with either of two H1-histamine receptor antagonists, the ethylene diamine tripelennamine HCl (0.0, 16.0, 32.0, and 64.0 mg/kg) or the aminoethyl ether diphenhydramine HCl (0.0, 32.0, 64.0, and 96.0 mg/kg). Adult female rats received intraperitoneal injections when housed 12 per cage and toxicological response (number dead per group) was assessed 24 hours post-treatment. The results showed that over the dose ranges employed, and when given alone, nicotine was completely non-lethal, tripelennamine was virtually non-lethal and diphenhydramine was toxic only at the highest dose (5 of 12, at 96.0 mg/kg). However, when nicotine and the antihistamines were delivered in combinations, the toxicological response was markedly altered. Tripelennamine in combination with nicotine yielded supra-additive interaction, with the degree of potentiation being a simple linear function of nicotine within each dose of tripelennamine. The interaction between nicotine and diphenhydramine was more complicated, with certain dose combinations yielding supra-additivity, yet with others yielding antagonism. It was suggested that seizure-precipitated cardiopulmonary collapse was the immediate cause of death, plausibly mediated by central mechanisms. As such, Experiment 2 examined the influence of adding the proconvulsant pentylenetetrazole (PTZ) (0.0, 10.0, and 20.0 mg/kg) to nicotine (0.0, 2.0, 4.0, and 8.0 mg/kg)-tripelennamine (0.0 and 32.0 mg/kg) combination treatments. Effects were assessed both at 1.0 and 24.0 hours post-injection.|The effect of pretreatment with nicotine bitartrate and/or caffeine sodium benzoate (nicotine 2.5 mg % and caffeine 30 mg % in drinking water for 21 days) on the gastric mucosal damage induced by aspirin, phenylbutazone, and reserpine was studied in rats. When given alone, nicotine, caffeine, and their concurrent administration did not produce any visible discernible gastric lesions. Pretreatment with nicotine, caffeine, their combination increased the gastric ulcers produced by aspirin, phenylbutazone, and reserpine.|For more Interactions (Complete) data for NICOTINE TARTRATE (7 total), please visit the HSDB record page.

LD50 Mouse iv 300 ug/kg|LD50 Mouse sc 53 mg/kg|LD50 Mouse ip 9.15 mg/kg at pH 3.2.|LD50 Rat oral 65 mg/kg|For more Non-Human Toxicity Values (Complete) data for NICOTINE TARTRATE (7 total), please visit the HSDB record page.

/EXPL THER/ To determine the safety and clinical response of nicotine tartrate liquid enemas for active left-side ulcerative colitis in a pilot study. Ten non-smoking patients with mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy were treated in an open protocol with nightly nicotine tartrate liquid enemas at a dose of 3 mg nicotine base for 1 week then 6 mg for 3 weeks. Clinical assessments were determined at baseline and 4 weeks by endoscopy, physician assessment and a patient diary of daily symptoms. Peak and trough serum nicotine and trough plasma cotinine were determined by gas chromatography/mass spectrometry and high performance liquid chromatography, respectively. After 4 weeks of treatment, 5/7 patients (71%) showed clinical and sigmoidoscopic improvement (per protocol analysis). The other three patients discontinued therapy within 7 days because of inability to retain the liquid enemas. No patients showed histologic improvement. Six of the patients who completed the 4-week study had peak and trough serum nicotine concentration determined, only 1 of 6 patients had a detectable peak nicotine concentration (value 2.3 ng/mL), and all six patients had undetectable trough nicotine concentrations. The mean trough plasma cotinine concentration was 13 +/- 10 ng/mL. Transient and mild adverse events occurred in 4/10 patients (nausea, lightheadedness, tremor, sleep disturbance). Given the low or undetectable serum nicotine concentrations, these adverse events are not likely to be related to the nicotine enemas. Nicotine tartrate liquid enemas administrated at a dose of 3 mg nicotine base/day for 1 week and then 6 mg/day for 3 weeks are safe and appear to result in clinical improvement in some patients with mildly to moderately active, left-sided ulcerative colitis unresponsive to first-line therapy. Placebo-controlled trials are warranted to confirm these preliminary findings.

Studies were conducted to localize the antinociceptive action of nicotine ditartrate within the central nervous system. Antinociceptive and biodispositional studies were carried out after the injection of (3)H-nicotine sc and intracerebroventricularly into the common carotid and vertebral arteries and into the subarachnoid space. (3)H-nicotine was more potent when given into the subarachnoid space than by any other route of administration. Further, disposition studies showed that (3)H-nicotine was almost entirely contained in the thoracic and lumbar areas. Apparently, the spinal cord is an important site for antinociception induced by nicotine.|...The purpose of the current study was to determine the bioavailability and pharmacokinetic parameters of nicotine after administration by hydrophilic liquid enema (acidic and basic), hydrophobic liquid enema (acidic and basic), and by oral and intravenous routes. Thirty healthy volunteers received 45 ug nicotine base/kg (as nicotine tartrate) in one of five formulations (each n = 6): hydrophilic acidic liquid enema, hydrophilic basic liquid enema, hydrophobic acidic liquid enema, hydrophobic basic liquid enema, and oral solution. All participants also received 15 ug nicotine base/kg (as nicotine tartrate) intravenously during a separate study period. Serum concentrations of nicotine were determined by gas chromatography with mass spectrometry. The mean (+/-SD) bioavailabilities of nicotine after administration in the liquid enema formulations (hydrophilic acidic 17 +/- 18%, hydrophilic basic 16 +/- 16%, hydrophobic acidic 25 +/- 17%, hydrophobic basic 15 +/- 12%) were similar to the bioavailability of nicotine after administration by oral solution (20 +/- 25%). The bioavailabilities of nicotine for all five nonintravenous formulations were significantly less than for intravenous nicotine (100%). Serum concentrations of nicotine did not predict adverse reactions. Nicotine tartrate administered as either a liquid enema or as an oral solution had low bioavailability and was well tolerated. ...|Experiments were done to compare the time-courses of the nicotine concentration in the blood, heart, and brain of infant and adult mice after small and large single doses of radioactive nicotine tartrate. In some experiments the nicotine receptors were blocked with mecamylamine or hexamethonium, and their effects on nicotine levels were measured. The nicotine-induced tremor was allowed visually, and its effects on the heart rate were measured by ECG. In adult mice the peak levels of brain nicotine occurred at 10 min, whereas in infant mice the brain nicotine levels were still rising at 20 min. In the latter the blood and heart nicotine levels were higher than the respective brain levels, and the nicotine level in the brain stem exceeded the hemisphere level. The results were reversed in adult mice. A remarkable accumulation of nicotine in the infant heart was measured. Pretreatment with mecamylamine lowered brain nicotine levels in adult mice, and in infant mice the nicotine levels in blood and heart were lowered as well. This pretreatment abolished the nicotine tremor and its effects on the heart rate similarly in both age groups. This suggests that the difference in nicotine levels after mecamylamine in infant and adult mice may not depend solely on possible differences in circulatory changes but can represent differences in "receptor population" as well. Hexamethonium did not abolish the central depressant effect of nicotine on the heart rate nor did it lower the brain nicotine levels. ...

In man, nicotine is metabolized to cotinine, hydroxycotinine, desmethylcotinine, and other unidentified compounds ... In other studies with (14)C-labeled nicotine, nicotine isomethonium ion was isolated from urine after iv administration.

Fresh air, rest. Refer for medical attention.

Remove contaminated clothes. Rinse and then wash skin with water and soap. Refer for medical attention .

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

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 as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on 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. /Nicotine and Related Compounds/|Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Aggressive airway management may be needed. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. 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. Administer activated charcoal ... . /Nicotine and Related Compounds/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or is in respiratory distress. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) 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 ... . /Nicotine and Related Compounds/|Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat seizures, coma, hypotension, hypertension, and arrhythmias if they occur. observe for at least 4-6 hours to rule out delayed toxicity, especially after skin exposure. For ingestion of intact gum tablets or transdermal patches, observe for a longer period (up to 12-24 hours). /Nicotine/|For more Antidote and Emergency Treatment (Complete) data for NICOTINE TARTRATE (7 total), please visit the HSDB record page.

/ALTERNATIVE and IN VITRO TESTS/ Fragments of human adipose tissue were maintained in culture for 1 week in a medium containing 1 mU/mL insulin and 100 ng/mL dexamethasone. Under these conditions lipoprotein lipase activity was present in human adipose tissue fragments which converted [14C]glucose to 14CO2 and [14C]triglyceride. Both metabolic parameters studied were affected by human tumor necrosis factor and brefeldin A. When fragments of human adipose tissue after 1 week in culture were incubated with nicotine tartrate for 20 hr, a slight but significant increase in lipoprotein lipase activity was observed, and an increased conversion of [14C]glucose to 14CO2 and [14C]triglyceride occurred. Nicotine was taken up by human adipose tissue, but no conversion to cotinine was observed. Our data demonstrate a direct effect of nicotine on human adipose tissue metabolism. Furthermore, it is suggested that weight loss in smokers is a multifactorial phenomenon, and one of the important factors to be considered is the direct effect of nicotine within the tissue.

The substance can be absorbed into the body by inhalation of its aerosol, through the skin and by ingestion.

Nausea. Vomiting. Abdominal pain. Headache. Convulsions.

MAY BE ABSORBED! Redness. Pain. See Inhalation.

Pain. Redness.