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BENZALDEHYDE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Benzaldehyde is found naturally in almonds and is used in the pharmaceutical, perfume, photographic, and flavoring industries.
    B) It is an intermediate metabolite of toluene (O'Donoghue, 1985) and amygdalin (Baselt & Cravey, 1989).

Specific Substances

    1) CAS 100-52-7
    2) NIOSH/RTECS CU 4375000
    3) Benzaldehyde
    4) Benzoic aldehyde
    5) Benzene carboxaldehyde
    6) Artificial oil of almond
    1.2.1) MOLECULAR FORMULA
    1) C7-H6-O

Available Forms Sources

    A) SOURCES
    1) Occurs naturally in kernels of bitter almonds (Budavari, 1996).
    B) USES
    1) Used in the production of dyes, cinnamic acid, and perfumes. Also used as a solvent, in flavors, and photographic agents (Budavari, 1996).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Although benzaldehyde has been used extensively, there is little human exposure case data available. Most sources state it may be a mild irritant of the eyes, lungs, and the GI tract; a narcotic and respiratory depressant in moderate doses; and a convulsant in higher doses. It may also cause contact dermatitis. It is absorbed through intact skin.
    0.2.6) RESPIRATORY
    A) May be a respiratory irritant and cause respiratory failure in high doses.
    0.2.7) NEUROLOGIC
    A) May cause CNS depression in moderate doses, which may lead to paralysis and seizures as the dose increases.
    0.2.8) GASTROINTESTINAL
    A) May cause irritation of the mouth and throat. Ingestion of significant amounts may cause nausea, vomiting, and abdominal pain.
    0.2.10) GENITOURINARY
    A) One animal study showed that chronic, high dose exposure could cause kidney damage.
    0.2.14) DERMATOLOGIC
    A) Benzaldehyde may cause allergic reactions and contact dermatitis, it is also a strong sensitizer.
    0.2.19) IMMUNOLOGIC
    A) Vanillin and benzaldehyde have been shown, in a few cases, to cause allergic skin and respiratory reactions.
    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) No specific laboratory measures are indicated. For significant exposure, monitor kidney function tests.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Large doses may cause seizures. If large amounts have been ingested, EMESIS SHOULD NOT BE INDUCED.
    B) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) LD50's in various animal species are quite variable (e.g. oral) LD50 for rat and mouse is 1300 mg/kg and 28 mg/kg, respectively.
    B) An estimated lethal dose (undocumented) in human cases is 2 ounces.

Clinical Effects

Summary Of Exposure

    A) Although benzaldehyde has been used extensively, there is little human exposure case data available. Most sources state it may be a mild irritant of the eyes, lungs, and the GI tract; a narcotic and respiratory depressant in moderate doses; and a convulsant in higher doses. It may also cause contact dermatitis. It is absorbed through intact skin.

Heent

    3.4.3) EYES
    A) IRRITANT - Although benzaldehyde vapor does NOT cause irritation to human eyes, when exposed with ozone and nitrogen dioxide in bright light it forms peroxybenzoyl nitrate which is highly irritating to human eyes (Grant & Schuman, 1993).
    3.4.6) THROAT
    A) IRRITATION - Ingestion may cause throat irritation (Prod Info, 1985; (HSDB , 2000).

Respiratory

    3.6.1) SUMMARY
    A) May be a respiratory irritant and cause respiratory failure in high doses.
    3.6.2) CLINICAL EFFECTS
    A) COUGH
    1) IRRITATION - Benzaldehyde is thought to be a respiratory irritant which may cause coughing and shortness of breath (Prod Info, 1985; (HSDB , 2000).
    B) DYSPNEA
    1) Respiratory distress and failure may be seen with ingestions of large doses (Prod Info, 1985; (HSDB , 2000).

Neurologic

    3.7.1) SUMMARY
    A) May cause CNS depression in moderate doses, which may lead to paralysis and seizures as the dose increases.
    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) Large doses of benzaldehyde can produce seizures (HSDB , 2000).
    B) CENTRAL NERVOUS SYSTEM DEFICIT
    1) Small doses may produce CNS depression (HSDB , 2000).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SEIZURES
    a) Seizures have been seen in poisoned animals (Gosselin et al, 1984; O'Donoghue, 1985; NFPA, 1986; Lewis, 1996).
    2) CNS DEPRESSION
    a) CNS depression has been seen in poisoned animals following small doses (Macht, 1923; Lewis, 1996).
    3) AGITATION
    a) Hyperexcitability was seen in rats given 800 mg/kg acutely. Rats given 800 mg/kg/day, 5 days/week for 13 weeks showed trembling, hyperactivity, or inactivity. This dose induced brain lesions including cerebellar cellular degeneration and necrosis and hippocampal lesions (Kluwe et al, 1983).

Gastrointestinal

    3.8.1) SUMMARY
    A) May cause irritation of the mouth and throat. Ingestion of significant amounts may cause nausea, vomiting, and abdominal pain.
    3.8.2) CLINICAL EFFECTS
    A) INDIGESTION
    1) PEPTIC ACTIVITY - Administration of benzaldehyde to normal and ulcer patients showed a decrease in peptic activity as measured by edestin digestion and hemoglobin (Kleeberg, 1959).
    B) ABDOMINAL PAIN
    1) Abdominal pain and nausea as well as sore throat may be seen after ingestion (Prod Info, 1985).

Genitourinary

    3.10.1) SUMMARY
    A) One animal study showed that chronic, high dose exposure could cause kidney damage.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RENAL FUNCTION ABNORMAL
    a) RENAL EPITHELIAL DEGENERATION - Was seen in rats given 800 mg/kg/day, 5 days a week for 13 weeks (Kluwe et al, 1983).

Dermatologic

    3.14.1) SUMMARY
    A) Benzaldehyde may cause allergic reactions and contact dermatitis, it is also a strong sensitizer.
    3.14.2) CLINICAL EFFECTS
    A) CONTACT DERMATITIS
    1) Contact dermatitis may be seen with dermal benzaldehyde exposure (Prod Info, 1985; (Lewis, 1996). It is also a strong sensitizer (HSDB , 2000).
    B) ERUPTION
    1) Prolonged skin contact can cause irritation (CHRIS , 1985). Benzaldehyde is absorbed through intact skin (Sittig, 1985; JEF Reynolds , 2000; HSDB , 2000).

Immunologic

    3.19.1) SUMMARY
    A) Vanillin and benzaldehyde have been shown, in a few cases, to cause allergic skin and respiratory reactions.
    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) ALLERGENICITY - p-Hydroxybenzaldehyde (vanillin) has been known to cause allergic reactions (van Assendelft, 1984). Allergic contact urticaria has also been reported (Forsbeck & Skog, 1977).

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 INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    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

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS100-52-7 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.4) ANIMAL STUDIES
    A) GASTRIC CARCINOMA
    1) Gastrointestinal tumors were noted in mice receiving 154 g/kg orally for 2 years (RTECS , 2000).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory measures are indicated. For significant exposure, monitor kidney function tests.
    4.1.2) SERUM/BLOOD
    A) OTHER
    1) No specific laboratory evaluation is available.
    4.1.3) URINE
    A) OTHER
    1) A chronic, high dose study in animals showed renal damage. Patients should be monitored for normal renal function.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.
    2) PULMONARY FUNCTION TESTS
    a) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) If respiratory tract irritation is present, monitor chest x-ray.

Methods

    A) CHROMATOGRAPHY
    1) Benzaldehyde can be detected in blood by liquid chromatography following oral administration (HSDB , 1991).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) No specific laboratory measures are indicated. For significant exposure, monitor kidney function tests.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED -
    1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for seizures.
    B) ACTIVATED CHARCOAL -
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    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).
    6.5.2) PREVENTION OF ABSORPTION
    A) 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).
    B) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) SUPPORT
    1) There is no specific treatment. Treatment is symptomatic and supportive.
    B) OBSERVATION REGIMES
    1) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

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

Range Of Toxicity

Summary

    A) LD50's in various animal species are quite variable (e.g. oral) LD50 for rat and mouse is 1300 mg/kg and 28 mg/kg, respectively.
    B) An estimated lethal dose (undocumented) in human cases is 2 ounces.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) Estimated lethal dose in humans has been estimated to be 2 ounces (Gosselin et al, 1984; HSDB , 2000), but this has not been confirmed with any case studies.
    B) ANIMAL DATA
    1) Oral LD50 for the rat is 1300 mg/kg and 28 mg/kg in the mouse (RTECS , 2000).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.

Workplace Standards

    A) ACGIH TLV Values for CAS100-52-7 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS100-52-7 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS100-52-7 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Benzaldehyde
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS100-52-7 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 2000
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 9 mg/kg
    2) LD50- (ORAL)MOUSE:
    a) 28 mg/kg
    3) LD50- (ORAL)RAT:
    a) 1300 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

    A) Benzaldehyde is thought to be an irritant of mucous membranes.

Physicochemical

Physical Characteristics

    A) Benzaldehyde is a clear or yellowish liquid with an almond odor and a burning, aromatic taste (JEF Reynolds , 2000).
    B) Benzaldehyde is a combustible, refractive, volatile, colorless to yellowish oily to watery liquid with an easily appreciated almond-like odor and a burning, aromatic taste (NFPA, 1986; Lewis, 1996; JEF Reynolds , 2000; HSDB , 2000).
    C) The material is initially colorless, but develops a yellow color on storage and oxidizes in air to benzoic acid (JEF Reynolds , 2000).

Molecular Weight

    A) 106.13 (Lewis, 1996)

Other

    A) ODOR THRESHOLD
    1) 0.042 ppm (CHRIS , 2002)

References

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