National Toxicology Program

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

Names (NTP)

• CYCLIC DEXADIENE
• ACITENE A
• 2,6,6-TRIMETHYLBICYCLO[3.1.1]HEPT-2-ENE
• 2-PINENE
• alpha-Pinene

Human Toxicity Excerpts

• IRRITATES SKIN, MUCOUS MEMBRANES. CAUSES SKIN ERUPTION, GI IRRITATION, DELIRIUM, ATAXIA, KIDNEY DAMAGE, COMA. INHALATION CAUSES PALPITATION, DIZZINESS, NERVOUS DISTURBANCES, CHEST PAIN, BRONCHITIS, NEPHRITIS. BENIGN SKIN TUMORS FROM CHRONIC CONTACT. [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1545]**PEER REVIEWED**
  
• FATAL DOSE ABOUT 180 G ORALLY AS TURPENTINE /WHICH CONTAINS 58-65% ALPHA-PINENE/. [The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 969]**PEER REVIEWED**
  
• SYMPTOMATOLOGY: 1. BURNING PAIN IN MOUTH & THROAT, ABDOMINAL PAIN, NAUSEA, VOMITING & OCCASIONALLY DIARRHEA. 2. MILD RESPIRATORY TRACT SYMPTOMS ARE OFTEN NOTED ... COUGHING, CHOKING, DYSPNEA & EVEN CYANOSIS. ASPIRATION OR ... SYSTEMIC ABSORPTION MAY LEAD TO PULMONARY EDEMA & PNEUMONITIS. /TURPENTINE/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-395]**PEER REVIEWED**
  
• SYMPTOMATOLOGY: 3. TRANSIENT EXCITEMENT, ATAXIA, CONFUSION & FINALLY STUPOR, WHICH IS COMMONEST SEVERE SYMPTOM. CONVULSIONS OCCUR OCCASIONALLY, USUALLY NOT UNTIL SEVERAL HR AFTER INGESTION, WHEN THEY MAY INTERRUPT A DEEP COMA. /TURPENTINE/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-394]**PEER REVIEWED**
  
• SYMPTOMATOLOGY: 4. OCCASIONALLY PAINFUL URINATION, ALBUMINURIA, HEMATURIA. URINE MAY HAVE ODOR RESEMBLING ... VIOLETS ... RENAL LESION IS USUALLY TRANSIENT. 5. ODOR OF TURPENTINE ON BREATH & IN VOMITUS. 6. FEVER & TACHYCARDIA ARE COMMON. 7. DEATH IS USUALLY DUE TO RESPIRATORY FAILURE. /TURPENTINE/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-394]**PEER REVIEWED**
  
• ... /IT HAS/ ESSENTIALLY THE SAME TOXICITY AS TURPENTINE. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-259]**PEER REVIEWED**
  
• AS LITTLE AS 15 ML (1/2 OZ) HAS PROVED FATAL TO A CHILD, BUT A FEW CHILDREN HAVE SURVIVED 2 & EVEN 3 OZ. MEAN LETHAL DOSE IN ADULT PROBABLY LIES BETWEEN 4 & 6 OZ. /TURPENTINE/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-393]**PEER REVIEWED**
  

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Non-Human Toxicity Excerpts

• TURPENTINE TREATMENT INCR THE AFFINITY OF LIVER MICROSOMAL CYTOCHROME P450 TO ALPHA-PINENE (THE MAIN COMPONENT OF TURPENTINE). [JARVISALO J, VAINIO H; ACTA PHARMACOL TOXICOL 46 (1): 32 (1980)]**PEER REVIEWED**
  
• Camphor, alpha-pinene (the major component of turpentine), and thujone (a constituent in the liqueur called absinthe) produced an increase in porphyrin production in primary cultures of chick embryo liver cells. In the presence of desferrioxamine (an iron chelator which inhibits heme synthesis and thereby mimics the effect of the block associated with acute porphyria), the terpenes enhanced porphyrin accumulation 5 to 20 fold. They also induced synthesis of the rate-controlling enzyme for the pathway, 5-aminolevulinic acid synthase. These effects are shared by well-known porphyrogenic chemicals such as phenobarbital and glutethimide. Camphor and glutethimide alone led to the accumulation of mostly uro- and heptacarboxylporphyrins, whereas alpha-pinene and thujone resulted in lesser accumulations of porphyrins which were predominantly copro- and protoporphyrins. In the presence of desferrioxamine, plus any of the three terpenes, the major product that accumulated was protoporphyrin. The terpenes tested are porphyrogenic and hazardous to patients with underlying defects in hepatic heme synthesis. [Bonkovsky HL et al; Biochem Pharmacol 43 (11): 2359-68 (1992)]**PEER REVIEWED**
  

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Human Toxicity Values

• None found

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Non-Human Toxicity Values

• LD50 Rat oral 3700 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2707]**PEER REVIEWED**
  
• LCL0 Rat inhalation 625 ug/cu m [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2707]**PEER REVIEWED**
  
• LCL0 Guinea pig inhalation 572 ug/cu m [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2707]**PEER REVIEWED**
  
• LCL0 Mouse inhalation 364 ug/cu m [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2707]**PEER REVIEWED**
  

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Absorption, Distribution and Excretion

• ABSORBED THROUGH SKIN, LUNGS, INTESTINE. [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1545]**PEER REVIEWED**
  
• The toxicokinetics of alpha-pinene (a-pinene) were studied in humans. The study group consisted of eight healthy males, average age 31 years. They were exposed to 0, 10, 225, or 450 mg/cu m (+)-alpha-pinene or 450 mg/cu m (-)-alpha-pinene for 2 hr in an inhalation chamber. During exposure they exercised on a cycle ergometer at the rate 50 watts. Average pulmonary uptake of (+)-alpha-pinene and (-)-alpha-pinene amounted to 59% of the exposure concn. Absolute uptake increased linearly with concn. Blood alpha-pinene concn increased rapidly at first then tapered off. Mean blood concn at the end of exposure were linearly related to inhaled concn. Elimination of alpha-pinene from the blood was triphasic. Half times for elimination of inhaled (+)-alpha-pinene from the blood during the three phases were 4.8, 39, and 695 minutes. Elimination half times fo (-)-alpha-pinene were 5.6, 40, and 555 minutes. Cumulative urinary excretion of unchanged alpha-pinene amounted to less than 0.001% of each dose. Respiratory elimination of (+)-alpha-pinene and (-)-alpha-pinene was 7.7 and 7.5% of total uptake, respectively. Five subjects complained of eye, nose, and throat irritation. No exposure related changes in lung function were seen. At the concn tested the capacity of the liver to metabolize alpha-pinene is not exceeded. (+)-alpha-Pinene and (-)-alpha-pinene show similar pharmacokinetic behavior. alpha-Pinene is readily metabolized and elimination of unchanged alpha-pinene is very low. [Falk AA et al; Scand J Work Environ Health 16 (5): 372-8 (1990)]**PEER REVIEWED**
  

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Metabolism/Metabolites

• The urinary excretion of verbenols after inhalation of alpha-pinene enantiomers was studied. Healthy male subjects were exposed to 10, 225, or 450 mg/cu m (+)alpha-pinene or 450 mg/cu m (-)alpha-pinene for 2 hr while performing light exercise. Exhaled air samples were collected after exposure, and urine samples were obtained before and after pinene exposure. Respiratory elimination of both pinenes was similar; at a concn of 450 mg/cu m, 7.7% of the total uptake of (+)alpha-pinene and 7.5% of the total uptake of (-)alpha-pinene was eliminated. Urinary excretion of verbenol 4 hr after exposure to (+)alpha-pinene ranged from 1.7% at 450 mg/cu m to 3.8% at a dose of 10 mg/cu m. Urinary excretion of (-)alpha-pinene was similar. A semilogarithmic plot of the excretion data suggested the existence of more than one rate constant for the elimination of (+)alpha-pinene and (-)alpha-pinene. Most of the verbenols were eliminated within 20 hr after a 2 hr exposure. The renal excretion of unchanged alpha-pinene was less than 0.001%. The determination of urinary verbenols may be useful as a biological exposure index for exposure to terpenes. [Levin JO et al; Int Arch Occup Environ Health 63 (8): 571-3 (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.