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CHAPARRAL

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Chaparral is from a group of closely related wild shrubs located in arid regions of Southwestern United States and Mexico. The herbal medicine generally consists of leaflets and twigs. Nordihydroguaiaretic acid (NDGA) is the active constituent believed responsible for its biologic activity. Chronic ingestions of chaparral have resulted in hepatotoxicity.

Specific Substances

    1) Chaparral
    2) Creosote bush
    3) Dihydronorguaiaretic Acid
    4) Greasewood
    5) Hediondilla
    6) Larrea divaricata
    7) Larrea glutinosa
    8) Larrea tridentata
    9) NDGA
    10) Nordihydroguaiaretic acid
    11) Norguaiaretic acid, dihydro-
    12) Pyrocatechol, 4,4-(2,3-dimethyltetramethylene)di-
    13) Molecular Formula: C18-H22-O4
    14) CAS 27686-84-6
    15) CAS 500-38-9

Available Forms Sources

    A) USES
    1) Native Americans have used an aqueous extract of the leaves and twigs (chaparral tea) as a remedy for the treatment of bronchitis and the common cold, to relieve rheumatic pain, cancer, venereal diseases, tuberculosis, stomach pain, chicken pox and snake bite pain. A burn salve has been prepared from a strong tea from the leaves which has been mixed with oil (Tyler, 1993; Batchelor et al, 1995).
    2) Chaparral is currently promoted as an antioxidant or "free radical scavenger" and for treatment of a variety of skin conditions, including acne (CDC, 1992).
    3) Prior to 1967 NDGA was used in the United States as a food additive to prevent fermentation and decomposition (Batchelor et al, 1995; Fleiss, 1995). In 1992, the United States Food and Drug Administration issued warnings concerning hepatotoxic effects of chaparral (Smith & Desmond, 1993).

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Chronic ingestion of chaparral has been associated with liver damage and possibly cystic renal disease.
    B) Nordihydroguaiaretic acid (NDGA), a constituent of chaparral and an antioxidant, has been reported to produce lesions in the mesenteric lymph nodes and kidneys in chronic toxicity studies in animals.
    C) Contact dermatitis has been induced by the creosote bush.
    0.2.7) NEUROLOGIC
    A) Fatigue may result as a consequence of liver injury due to chaparral.
    0.2.8) GASTROINTESTINAL
    A) Ingestion of large amounts of NDGA or chaparral may result in gastritis.
    0.2.9) HEPATIC
    A) Ingestion of nordihydroguaiaretic acid and chaparral tea have been associated with toxic hepatitis.
    0.2.10) GENITOURINARY
    A) Kidney cysts have been associated with consumption of chaparral tea.
    B) Dark urine has been reported following chronic ingestions.
    0.2.13) HEMATOLOGIC
    A) Coagulation disorders, including decreased prothrombin and factor V, may occur in patients developing chaparral-induced hepatitis.
    0.2.14) DERMATOLOGIC
    A) Contact dermatitis may occur.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Laboratory Monitoring

    A) Determine the SGOT (AST), SGPT (ALT), total bilirubin, and INR (or PT) for all symptomatic patients. If significant abnormalities in liver function are present, monitor creatinine, BUN, urinalysis, electrolytes, glucose, hemoglobin, hematocrit, amylase, and ECG as clinically indicated.
    B) Monitor vital signs.
    C) Monitor weight, abdominal girth, fluid intake, and urine output in patients with hepatotoxicity and ascites.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Most reported cases of toxicity have involved chronic ingestion of chaparral or nordihydroguaiaretic acid; GI decontamination is generally not warranted. Consider activated charcoal after recent, large ingestions.
    B) Treatment is supportive and directed at signs and symptoms of hepatitis, renal dysfunction and possible coagulation disorders.

Range Of Toxicity

    A) Hepatotoxicity has been associated with the ingestion of 15 chaparral tablets per day for 3 months.
    B) Consumption of 1500 milligrams of chaparral daily for 6 weeks has been reported to result in hepatic dysfunction.
    C) There are no published reports of single acute ingestions resulting in toxicity.

Summary Of Exposure

    A) Chronic ingestion of chaparral has been associated with liver damage and possibly cystic renal disease.
    B) Nordihydroguaiaretic acid (NDGA), a constituent of chaparral and an antioxidant, has been reported to produce lesions in the mesenteric lymph nodes and kidneys in chronic toxicity studies in animals.
    C) Contact dermatitis has been induced by the creosote bush.

Neurologic

    3.7.1) SUMMARY
    A) Fatigue may result as a consequence of liver injury due to chaparral.
    3.7.2) CLINICAL EFFECTS
    A) FATIGUE
    1) Fatigue may be expected in patients with liver damage due to chronic chaparral ingestions (Katz & Saibil, 1990).

Gastrointestinal

    3.8.1) SUMMARY
    A) Ingestion of large amounts of NDGA or chaparral may result in gastritis.
    3.8.2) CLINICAL EFFECTS
    A) GASTRITIS
    1) Ingesting large amounts of NDGA or chaparral may result in nausea, vomiting, abdominal pain, and loss of appetite (Katz & Saibil, 1990).
    B) INFLUENZA-LIKE SYMPTOMS
    1) Nausea and flu-like illness have been reported in patients who developed hepatotoxicity following chronic chaparral ingestions (Batchelor et al, 1995; Gordon et al, 1995).
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CYST
    a) Single and multiple mesenteric cysts were induced in rat studies at higher dose oral feedings of NDGA. Hemorrhage into the cecum was observed in up to 50% of the animals (Cranston et al, 1947; Grice et al, 1968).

Hepatic

    3.9.1) SUMMARY
    A) Ingestion of nordihydroguaiaretic acid and chaparral tea have been associated with toxic hepatitis.
    3.9.2) CLINICAL EFFECTS
    A) TOXIC HEPATITIS
    1) Several cases of toxic hepatitis have been associated with consumption of nordihydroguaiaretic acid and chaparral tea (Smith et al, 1994; Gordon et al, 1995; Batchelor et al, 1995; Gordon et al, 1995; CDC, 1992; Smith & Desmond, 1993). In one case, ascites was associated with hepatitis and the liver biopsy showed mild to moderate hepatocellular necrosis, mild cholestasis, and mild fibrous septation (Batchelor et al, 1995).
    2) CASE REPORT - Subacute hepatic necrosis, with ascites and coagulopathy, following 3 months of ingesting 15 chaparral tablets per day, is reported in a previously healthy 33-year-old female. All signs/symptoms eventually regressed following discontinuation of the chaparral tablets (Katz & Saibil, 1990).
    3) CASE REPORT - Severe cholestatic, cholangiolitic hepatitis, with marked elevation of serum hepatic enzyme levels, is reported in a 45-year-old female after 2 months of ingesting 160 mg/day of chaparral tablets. She had a history of alcoholism, but had not consumed any for 2 months. Prior to starting chaparral she had taken lovastatin. She had begun taking chaparral tablets for treatment of alcohol withdrawal (Alderman et al, 1994).
    a) Following therapy with corticosteroids, her hepatotoxicity resolved (Alderman et al, 1994). An actual causal relationship, however, has not been established. The authors suggested that chaparral may have potentiated pre-existing liver damage.
    4) CASE REPORT - A 60-year-old female presented with signs/symptoms of hepatitis following 10 months of daily chaparral use (1 to 2 capsules). Liver biopsy revealed severe acute hepatitis and areas of lobular collapse and nodular regeneration. Also present was mixed portal inflammation and significant bile ductular proliferation. Liver biopsy supported the theory that an acute injury evolving to chronic liver damage had occurred.
    a) Liver failure progressed, requiring a liver transplant. It should be noted that in addition to chaparral, the patient had been taking diltiazem, atenolol, aspirin, nitroglycerin, and occasional acetaminophen (Gordon et al, 1995).
    5) CASE REPORT - A 69-year-old male who had taken 14 chaparral compound tablets/day for 6 weeks, developed pruritus, nausea, anorexia, weight loss and jaundice associated with abnormal liver tests. His only other medication was metoprolol, and there was no recent history of any medication or events that would alter liver function.
    a) Abnormal lab tests included elevated serum liver enzymes, abnormal albumin and protein. There was no lab evidence for hepatitis A, B, or C, cytomegalovirus or Epstein-Barr virus. Following discontinuance of the herbal containing chaparral, the patient's symptoms and lab abnormalities progressively improved and were normal at 8 weeks. The presence of multiple agents in the herbal preparation and the absence of a re-challenge with chaparral precludes assigning causation to this agent (Shad et al, 1999).
    6) CASE SERIES - In a series of 13 cases of hepatotoxicity associated with chaparral ingestions, clinical presentations occurred within 3 to 52 weeks following chronic ingestions. Toxic or drug-induced cholestatic hepatitis was the main presentation, with progression to cirrhosis in 4 patients and acute fulminant hepatic failure in 2 patients (Sheikh et al, 1997).
    7) CASE REPORT - A 22-year-old woman presented to the hospital with a one-week history of progressive jaundice and mild abdominal pain. Liver enzyme levels were elevated (ALT 2871 units/L, AST 1773 units/L, alkaline phosphatase 511 units/L). The liver enzyme levels improved and she was discharged 2 weeks post-admission. Two weeks post-discharge, she presented with increased jaundice, fatigue, nausea, pruritus, and epigastric pain. Liver enzyme levels were again elevated (ALT 1084 units/L, AST 862 units/L, alkaline phosphatase 379 units/L). A liver biopsy showed inflammatory infiltration with severe parenchymal damage.
    a) She admitted to consuming an herbal preparation containing 61.9% chaparral powder, 2 tablets daily for approximately 8 weeks prior to her first hospitalization. During her first hospitalization, she had discontinued taking the preparation, but 5 days post-discharge she restarted at the same dose. The liver enzyme levels began to gradually normalize and the patient was discharged 5 weeks post-admission. Approximately 9 months after the first liver biopsy was performed, a second biopsy showed mild hepatic fibrosis and inflammation of the portal tract (Kauma et al, 2004).

Genitourinary

    3.10.1) SUMMARY
    A) Kidney cysts have been associated with consumption of chaparral tea.
    B) Dark urine has been reported following chronic ingestions.
    3.10.2) CLINICAL EFFECTS
    A) SIMPLE RENAL CYST
    1) Microscopic and macroscopic renal cysts have been reported following chronic ingestions of chaparral tea (Smith et al, 1994).
    2) CASE REPORT - Smith et al (1994) report the case of a 56-year-old female who was diagnosed with numerous microscopic and macroscopic cysts in her kidneys. The patient had a history of consuming 3 to 4 cups daily of chaparral tea in a 3-month period approximately 1 and 1/2 years prior to her surgery.
    B) ABNORMAL URINE
    1) Darkened urine, in association with hepatic toxicity, has been reported following chronic ingestions of chaparral leaf (Katz & Saibil, 1990).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RENAL FUNCTION ABNORMAL
    a) Long-term feeding studies with nordihydroguaiaretic acid (0.5% to 1%) in rats induced lesions in the mesenteric lymph nodes and kidney tubular epithelium (CDC, 1992; Grice et al, 1968). Renal disorders induced by NDGA included hydronephrosis, chronic pyelonephritis and nephrocalcinosis (Grice et al, 1968; Evan & Gardner, 1979).

Hematologic

    3.13.1) SUMMARY
    A) Coagulation disorders, including decreased prothrombin and factor V, may occur in patients developing chaparral-induced hepatitis.
    3.13.2) CLINICAL EFFECTS
    A) BLOOD COAGULATION PATHWAY FINDING
    1) Patients with chaparral-induced liver damage may have coagulation or bleeding disorders, and should be monitored for these (Gordon et al, 1995).
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEMORRHAGE
    a) Toxicity tests with rats given NDGA in the diet demonstrated that 0.5% concentration caused inflammatory cecal lesions and slight cystic enlargement of paracecal lymph nodes. Massive cecal hemorrhages resulted with single and multiple mesenteric cysts (Grice et al, 1968; Cranston et al, 1947).

Dermatologic

    3.14.1) SUMMARY
    A) Contact dermatitis may occur.
    3.14.2) CLINICAL EFFECTS
    A) CONTACT DERMATITIS
    1) Contact dermatitis may occur following exposure to the creosote bush.

Immunologic

    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LYMPHADENOPATHY
    a) Long term feeding studies with nordihydroguaiaretic acid in rats induced lesions in the mesenteric lymph nodes and kidneys (CDC, 1992; Grice et al, 1968).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) DeSesso and Goeringer (1990) gave rabbits 950 mg per kg of NDGA subcutaneously on day 12 and found no increase in defects. This antioxidant was associated with a significant increase in body weight.
    2) DeSesso & Goeringer (1990) demonstrated in animal studies that NDGA acted as a protectant against hydroxyurea-induced teratogenicity when administered prior to hydroxyurea in pregnant rabbits.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) RENAL CARCINOMA
    1) Smith et al (1994) reported a case of cystic renal cell carcinoma in a 56-year-old female following protracted ingestion of NDGA in the form of chaparral tea in a concentration and duration (3 to 4 cups daily for 3 months) considerably greater than that used to induce cystic renal disease in animals.

Genotoxicity

    A) In vivo and in vitro induction of sister-chromatid exchanges, with a dose-dependent response, was demonstrated with nordihydroguaiaretic acid (NDGA), indicating that NDGA can produce genotoxic and cytotoxic effects (Madrigal-Bujaidar et al, 1998).

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Determine the SGOT (AST), SGPT (ALT), total bilirubin, and INR (or PT) for all symptomatic patients. If significant abnormalities in liver function are present, monitor creatinine, BUN, urinalysis, electrolytes, glucose, hemoglobin, hematocrit, amylase, and ECG as clinically indicated.
    B) Monitor vital signs.
    C) Monitor weight, abdominal girth, fluid intake, and urine output in patients with hepatotoxicity and ascites.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Overdose experience is limited. It may be advisable to monitor serum liver function tests as hepatotoxicity has been associated with the therapeutic use of chaparral.
    2) Serum creatinine and blood urea nitrogen should be measured in symptomatic patients.
    3) Monitor serum electrolytes in symptomatic patients.
    4) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    B) HEMATOLOGIC
    1) Monitor PT or INR and PTT and monitor for bleeding in all symptomatic patients. Patients with hepatic dysfunction and portal hypertension with ascites may be prone to esophageal varices.

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients who develop significant hepatic or renal function impairment should be admitted to an intensive care setting.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Consumption of chaparral or nordihydroguaiaretic acid in alternative or herbal medicines can result in moderate to severe hepatic or renal failure within several months of chronic ingestion. Hemodialysis may be necessary in some cases of severe renal failure.

Monitoring

    A) Determine the SGOT (AST), SGPT (ALT), total bilirubin, and INR (or PT) for all symptomatic patients. If significant abnormalities in liver function are present, monitor creatinine, BUN, urinalysis, electrolytes, glucose, hemoglobin, hematocrit, amylase, and ECG as clinically indicated.
    B) Monitor vital signs.
    C) Monitor weight, abdominal girth, fluid intake, and urine output in patients with hepatotoxicity and ascites.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY - Most cases of toxicity reported have involved chronic ingestion of chaparral or nordihydroguaiaretic acid, and GI decontamination is not generally warranted. Consider activated charcoal after recent, large ingestions.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Most reported cases of toxicity have involved chronic ingestion of chaparral or nordihydroguaiaretic acid; GI decontamination is generally not warranted. Consider activated charcoal after recent, large ingestions.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) Most reported cases of toxicity have involved chronic ingestion of chaparral contained in alternative or herbal medicine sources. Treatment is supportive and directed at signs and symptoms of progressive hepatitis and possible renal dysfunction.
    2) Corticosteroids have empirically been used to treat chaparral-induced hepatitis (Alderman et al, 1994), but there is no direct evidence that this is beneficial.
    B) MONITORING OF PATIENT
    1) Decreased pulmonary function may occur and should be monitored following chronic or acute toxic ingestions. All symptomatic patients should have liver and renal function tests monitored.
    2) Because of the possibility of progressive hepatitis following chronic use of chaparral, all symptomatic patients should be monitored for portal hypertension, ascites, and possible bleeding or coagulation disorders. When ascites is present, fluid restriction should be initiated along with monitoring the patient's weight and abdominal girth.

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Case Reports

    A) ADULT
    1) Batchelor et al (1995) reported that a 43-year-old female presented with jaundice, flu-like illness, and nausea after a 6 to 8 week history of ingesting chaparral leaf tablets. No risk factors for hepatitis could be identified.
    a) Laboratory examination showed elevated serum liver enzymes (AST, 1612 International Units/L; ALP, 129 International Units/L; bilirubin 166 mcmol/L), PT of 11 seconds, and albumin of 33 g/L. Antihepatitis A, HBsAg, HBsAb, and HBcAb were negative. Anti-HCV was negative. Chest x-ray and abdominal ultrasound were within normal limits.
    b) Chaparral tablets were discontinued. Occasional aspirin was taken for tension headaches. Four months following the onset of her initial symptoms, liver enzyme levels normalized and she gradually improved with no further medical problems. Chaparral re-challenge was not attempted.
    2) A 71-year-old male presented to the hospital with a flu-like illness, jaundice, and ascites after 3 month history of daily chaparral leaf ingestion. The only risk factor for hepatitis was a history of daily consumption of about 14 ounces of wine daily for many years. Serum hepatic enzymes were markedly elevated.
    a) Following discontinuation of the wine and chaparral tablets, all symptoms resolved within 2 months. He began taking chaparral again, 3 months later, remaining abstinent from alcohol, and his hepatic signs/symptoms returned. Liver biopsy revealed diffuse mild to moderate hepatocellular necrosis with inflammation, portal tract expansion, mild cholestasis, and mild fibrous septation. No steatosis and Mallory bodies were present.
    b) Complete resolution of his symptoms and serum aminotransferases, PT, and bilirubin occurred after discontinuing chaparral again. During follow-up, the patient remained well while not taking chaparral (Batchelor et al, 1995).
    3) A 69-year-old man who had been taking 14 tablets per day for 6 weeks of a mixed herbal preparation containing chaparral developed pruritus, nausea, anorexia, weight loss and jaundice associated with abnormal liver tests. His only medication was metoprolol and there was no history of blood transfusion, intravenous drug use, infectious contacts, foreign travel or alcohol abuse.
    a) Abnormal lab tests included total bilirubin 27.2 mg/dL, alkaline phosphatase 272 Units/L, AST 833 Units/L, ALT 1081 Units/L, LDH 383 Units/L, albumin 2.3 g/dL, total protein 5.6 g/dL and prothrombin time 15.6 seconds. There was no laboratory evidence for hepatitis A, B, or C, cytomegalovirus or Epstein-Barr virus.
    b) The patient's symptoms and laboratory abnormalities progressively improved following discontinuation of the herbal preparation and he was asymptomatic and had normal laboratory values at 8 weeks.
    c) The presence of multiple agents in the herbal preparation and the absence of a re-challenge with chaparral precludes assigning causation to this agent (Shad et al, 1999).

Summary

    A) Hepatotoxicity has been associated with the ingestion of 15 chaparral tablets per day for 3 months.
    B) Consumption of 1500 milligrams of chaparral daily for 6 weeks has been reported to result in hepatic dysfunction.
    C) There are no published reports of single acute ingestions resulting in toxicity.

Therapeutic Dose

    7.2.1) ADULT
    A) ROUTE OF ADMINISTRATION
    1) ORAL - A 42-year-old male reported taking three 500 milligram capsules of chaparral daily as a "free radical scavenger" (CDC, 1992).
    2) ORAL - An 85-year-old male took an estimated 200 to 250 milligrams of nordihydroguaiaretic acid, contained in the leaves and stems of Larrea divaricata, daily for 10 months for treatment of a malignant melanoma (Smart et al, 1969).

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) Ingestion of 15 chaparral tablets per day for 3 months resulted in dark urine, abdominal pain, nausea and anorexia in a 33-year-old female. After reducing her dosage from 15 to 1 tablet per day, her symptoms disappeared. On rechallenge with 7 tablets per day, symptoms returned with the additional signs/symptoms of scleral icterus, fatigue, pedal edema, and increased abdominal girth (Katz & Saibil, 1990).
    a) Serum hepatic enzyme levels were markedly elevated, prothrombin time was prolonged (19 seconds) and albumin was 28 grams/liter. Percutaneous liver biopsy showed loss of 60% of parenchymatous tissue without significant inflammatory infiltration. All signs/symptoms of the subacute hepatic necrosis eventually regressed with supportive care and abstinence from the herbal.
    2) Ingestion of 1500 milligrams daily for 6 weeks was reported to result in toxic hepatitis in a 42-year-old male. Liver enzyme levels returned to normal within 3 weeks of discontinuing chaparral (CDC, 1992).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) (nordihydroguaiaretic acid)
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 550 mg/kg ((RTECS, 1998))
    2) LD50- (ORAL)MOUSE:
    a) 2 gm/kg ((RTECS, 1998))
    3) LD50- (ORAL)RAT:
    a) 2 gm/kg ((RTECS, 1998))

Toxicologic Mechanism

    A) Nordihydroguaiaretic acid (NDGA), an active agent in chaparral leaf, is a powerful antioxidant acting as a cyclooxygenase and lipoxygenase pathway inhibitor (Gimeno et al, 1983; (Nakadate et al, 1982). Platelet aggregation is decreased by NDGA. At concentrations that inhibit cyclooxygenase pathways, NDGA may possibly cause a shift favoring proinflammatory mediators and thus potentiate liver toxicity (Gordon et al, 1995).
    1) Animal studies have shown that cancer extract-induced leukocyte adherence inhibition depends on the release of arachidonic acid metabolites, and can be significantly antagonized by NDGA (Bracco et al, 1984). Long-term feeding in animals has resulted in renal cysts and mesenteric lymphadenopathy (Evan & Gardner, 1979)

Physical Characteristics

    A) Nordihydroguaiaretic acid is a lipoxygenase inhibitor occurring as the mesoform in the resinous exudate of the creosote bush, Larrea divaricata. It is soluble in ethanol, methanol, ether, and concentrated H2SO4. It is slightly soluble in hot water and chloroform. It is soluble in dilute alkalies and forms a deep red color (Budavari, 1996).

Molecular Weight

    A) 302.40 (nordihydroguaiaretic acid)

General Bibliography

    1) Batchelor WB, Heathcote J, & Wanless IR: Chaparral-induced hepatic injury. Amer J Gastroenterol 1995; 90:831-833.
    2) Bracco MM, Sterin-Borda L, & Fink S: Stimulatory effect of lymphocytes from Chagas' patients on spontaneously beating rat atria. Clin Exp Immunol 1984; 55:405-412.
    3) Budavari S: The Merck Index, 12th ed, Merck & Co, Inc, Whitehouse Station, NJ, 1996.
    4) CDC: Chaparral-induced toxic hepatitis - California and Texas, 1992. CDC: MMWR 1992; 41:812-814.
    5) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    6) Cranston EM, Jensen HV, & Moren A: The acute and chronic toxicity of nordihydroguaiaretic acid. Fed Proc 1947; 6:318-319.
    7) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    8) Evan AP & Gardner KD: Nephron obstruction in nordihydroguaiaretic acid-induced renal cystic disease. Kid Internat 1979; 15:7-19.
    9) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    10) Fleiss PM: Chaparral and liver toxicity (letter). J Amer Med Assoc 1995; 274:871.
    11) Gisvold O & Thaker E: Lignans from Larrea divaricata. J Pharm Sci 1974; 63:1905-1907.
    12) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    13) Gordon DW, Rosenthal G, & Hart J: Chaparral ingestion - The broadening spectrum of liver injury caused by herbal medications. J Amer Med Assoc 1995; 273:489-490.
    14) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    15) Grice HC, Becking G, & Goodman T: Toxic properties of nordihydroguaiaretic acid. Food Cosmet Toxic 1968; 6:155-161.
    16) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    17) Katz M & Saibil F: Herbal hepatitis: subacute hepatic necrosis secondary to chaparral leaf. J Clin Gastroenterol 1990; 12:203-206.
    18) Kauma H, Koskela R, Makisalo H, et al: Toxic acute hepatitis and hepatic fibrosis after consumption of chaparral tablets. Scand J Gastroenterol 2004; 11:1168-1171.
    19) Madrigal-Bujaidar E, Barriga SD, & Cassani M: In vivo and in vitro induction of sister-chromatid exchanges by nordihydroguaiaretic acid. Mutation Res 1998; 412:139-144.
    20) Nakadate T, Yamamoto S, & Ishii M: Inhibitiion of 12-O- tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity by phospholipase A2 inhibitors and lipoxygenase inhibitor. Cancer Res 1982; 42:2841-2845.
    21) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    22) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    23) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 1998; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    24) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    25) Shad JA, Chinn CG, & Brann OS: Acute hepatitis after ingestion of herbs. South Med J 1999; 92:1095-1097.
    26) Sheikh NM, Philen RM, & Love LA: Chaparral-associated hepatotoxicity. Arch Intern Med 1997; 157:913-919.
    27) Smart CR, Hogle HH, & Robins RK: An interesting observation on nordihydroguaiaretic acid (NSC-4291; NDGA) and a patient with malignant melanoma - a preliminary report. Cancer Chemother Rep 1969; 53:147-151.
    28) Smith AY, Feddersen RM, & Gardner KD: Cystic renal cell carcinoma and acquired renal cystic disease associated with consumption of chaparral tea: a case report. J Urol 1994; 152:2089-2091.
    29) Smith BC & Desmond PV: Acute hepatitis induced by ingestion of the herbal medication chaparral. Aust NZ J Med 1993; 23:526.
    30) Tyler VE: Chaparral: In: The Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies, 3rd ed, Pharmaceutical Products Press, NY, New York, NY, 1993.