Hazardous substance assessment: Citric acid

Important note: Hazardous substance assessments are technical documents produced by Health Canada as educational and informational resources for suppliers of hazardous products under the Hazardous Products Act (HPA) and its regulations. For more information on supplier roles and responsibilities, visit supplier responsibilities.

This hazardous substance assessment was conducted according to the Hazardous Products Regulations (HPR).

Identification

Chemical name:

Citric acid

CAS #:

77-92-9 (anhydrous); 5949-29-1 (monohydrate)

Chemical composition:

C6H8O7 (anhydrous); C6H8O7·H2O (monohydrate)

Synonyms:

1,2,3-Propanetricarboxylic acid, 2-hydroxy-
2-Hydroxy-1,2,3-propanetricarboxylic acid
2-Hydroxypropanetricarboxylic acid
2-Hydroxytricarballylic acid
3-Carboxy-3-hydroxypentane-1,5-dioic acid

UN #:

No chemical-specific UN # available

Pictogram(s):

Figure 1.
Figure 1. - Text Equivalent

The symbol within the pictogram, which applies to pure citric acid (anhydrous or monohydrate) or to 30% or above aqueous solutions of citric acid, is an exclamation mark. This symbol indicates that hazardous products with this pictogram can cause certain health effects for example:

  • skin irritation
  • eye irritation
  • skin sensitization

WHMIS classification

Health hazards:

Physical hazards:

Citric acid does not meet the criteria for classification.

Health hazards

Acute Toxicity (Oral):

Does not meet criteria

Oral median lethal dose (LD50): 11 700 milligrams per kilogram of body weight (mg/kg-bw) (male rats)Footnote 1.

In an acute oral toxicity study in male SD-JCL rats and ICR-JCL mice (6 per species and dose), citric acid of high purity (99.8%) was administered at a dose of 4 820, 5 790 or 7 000 mg/kg-bw in mice or of 10 420, 12 500 or 18 000 mg/kg-bw in rats. The observation period was 7 days and the LD50 values were calculated using the Litchfield and Wilcoxon method. An LD50 value of 11 700 mg/kg-bw was calculated for rats and of 5 790 mg/kg-bw for mice. The study also tested a commercial grade of citric acid in mice for which an LD50 of 5 040 mg/kg-bw was calculated. Clinical signs included spontaneous movement, motor ataxia, mydriasis, a decrease in respiration rate and heart beat and mortality by respiratory failure. The animals which survived from the respiratory failure showed no toxic signs 24 hours after administration. At necropsy, hemorrhage of the gastric mucosa was observedFootnote 1.

The available data do not meet the classification criteria for a category of Acute Toxicity (Oral).

Acute Toxicity (Dermal):

Does not meet criteria

Dermal LD50: >2 000 mg/kg-bw (rats)Footnote 2.

In an Organisation for Economic Co-operation and Development Test Guideline (OECD TG) 402-compliant (Acute Dermal Toxicity) study, Sprague-Dawley rats (5 per sex) were exposed to a dose of solid citric acid of 2 000 mg/kg-bw for 24 hours. The test material was moistened and applied to 10% of the area of the back under semi-occlusive conditions. The animals were observed for deaths and overt signs of toxicity 30 minutes and 1, 2 and 4 hours after dosing, with a total observation period of 14 days. There were no deaths, with a dermal LD50 exceeding 2 000 mg/kg-bw. There were no signs of systemic toxicity nor any abnormalities at necropsyFootnote 2.

The available data do not meet the classification criteria for a category of Acute Toxicity (Dermal).

Acute Toxicity (Inhalation – Gases):

Not applicable

Citric acid is not a gas. The classification criteria for Acute Toxicity (Inhalation – Gases) do not apply to this substance.

Acute Toxicity (Inhalation – Vapours):

No data available

No data are available to determine whether citric acid meets the classification criteria for a category of Acute Toxicity (Inhalation - Vapours).

Acute Toxicity (Inhalation – Dusts and Mists):

No data available

No data are available to determine whether citric acid meets the classification criteria for a category of Acute Toxicity (Inhalation – Dusts and Mists).

Skin Corrosion / Irritation:

Does not meet criteria

Humans: A 5% citric acid aqueous solution (pH of 2) was not irritating when applied under occlusive conditions to the backs of 20 patients (14 females and 6 males) 2 times per day for 4 days at a volume of 50 microlitres (µL)Footnote 3.

Animals: In a study conducted similarly to OECD TG 404 (Acute Dermal Irritation/Corrosion), 6 New Zealand White rabbits were exposed under semi-occlusive conditions to 0.5 g of wetted citric acid powder for 4 hours, with observations at 1, 24, 48 and 72 hours after patch removal. The primary dermal irritation index (PDII), as a mean of the irritation scores at 1, 24, 48 and 72 hours post-exposure across the 6 animals, was 0.3 out of 8. The mean Draize scores per animal over 24, 48 and 72 hours post-exposure were 1.67 (1 animal) and 0 (5 animals) out of 4 for erythema and 0.33 (1 animal) and 0 (5 animals) out of 4 for edemaFootnote 2. The mean Draize scores do not meet the criteria of Skin Irritation – Category 2.

A skin corrosion study was conducted in accordance with a United States (U.S.) Department of Transportation (DOT) guideline in 8 New Zealand White rabbits (5 males and 3 females) exposed to 0.5 mL of a 60% citric acid solution for 3 minutes, 60 minutes or 4 hours. The test substance was applied to the intact skin of animals. After a 3- or 60-minute exposure, only very slight erythema was noted immediately after exposure (but not at 24 or 48 hours after exposure) and no edema was observed at any time point. After a 4-hour exposure, very slight-moderate to severe erythema and moderate edema were noted immediately following exposure and at 24 hours post-exposure, which abated to well-defined erythema and no edema at 48 hours post-exposureFootnote 4. Insufficient information is available to evaluate the reaction after the 4-hour exposure for classification purposes.

The available data do not meet the classification criteria for a category or subcategory of Skin Corrosion/Irritation.

Serious Eye Damage / Eye Irritation:

Category 2A

In a study similar in design to OECD TG 405 (Acute Eye Irritation/Corrosion), 0.1 mL of a 10 or 30% citric acid aqueous solution was instilled into the eye of New Zealand White rabbits (3 per concentration). The eyes were not washed and the observation period was up to 14 days following administration. Gradings were conducted at 1, 24, 48 and 72 hours and 7 and 14 days following instillation. For the 10 and 30% solutions, all animals had corneal opacity and iritis scores of 0 at all time points. For the 10% solution, the mean conjunctival redness and chemosis scores per animal over 24, 48 and 72 hours post-instillation were 1 out of 3 (all 3 animals) and 0 out of 4 (all 3 animals), respectively. The ocular effects completely reversed within 24 hours to 7 days post-instillation for all animals. For the 30% solution, the mean scores per animal over 24, 48 and 72 hours post-instillation were 3 out of 3 (all 3 animals) for conjunctival redness and 2.3 (2 animals) and 2.7 (1 animal) out of 4 for chemosis. The effects fully reversed within 14 days post-instillation in all animals except for conjunctival redness in 1 of the animalsFootnote 2. While it was not determined if the conjunctival redness in this animal would fully reverse by 21 days post-instillation, a 30% solution meets at minimum the classification criteria of Eye Irritation – Category 2A.

In a study similar in design to the Draize method, 0.1 mL of a 5% acid solution (pH of 2.1) was placed into an eye of each of 12 New Zealand White rabbits, with observations at 1 hour and 1, 2, 3 and 7 days following a 30-second exposure. An eye wash was performed 30 seconds after instillation for half of the rabbits. No corneal opacities were noted in any of the animals testedFootnote 5.

The available data meet the classification criteria for Eye Irritation – Category 2A [subsection 8.3.2(3) of the HPR] for solutions of citric acid at a concentration of 30% or greater but do not meet the classification criteria of a category or subcategory of Serious Eye Damage / Eye Irritation at a concentration of 10% or lower.

Respiratory Sensitization:

Does not meet criteria

Inhalation exposure of dogs to citric acid at an unspecified concentration caused bronchoconstriction with nonspecific airway hyperreactivityFootnote 6. No further study details are available.

Inhalation exposure of human asthmatics at an unspecified concentration resulted in bronchoconstrictionFootnote 7. No further study details are available. The induction of bronchoconstriction in those with bronchial hyperreactivity may have been an irritant effect.

The data are inadequate to meet the classification criteria for a category or subcategory of Respiratory Sensitization.

Skin Sensitization:

Does not meet criteria

Diagnostic patch testing of 221 patients (201 females; 20 males) with contact dermatitis or other dermatologic diseases in Munich, Germany was conducted over a 15-month period. A series of substances were tested, with readings made at 24 hours (upon patch removal) and at 48 and 72 hours after patch application. Only 1 patient (female) reacted to a 1% citric acid solutionFootnote 8. In a case study of a 7-year-old female patient with atopic dermatitis, patch testing was conducted with a series of substances. Readings were made on days 2 and 3. The patient only reacted to a topical cream containing pimecrolimus, a drug used to treat eczema. Patch testing of a mixture of all the cream's excipients, including citric acid, and of citric acid individually (1% aqueous solution) showed no reactionFootnote 9.

In a skin prick test of 91 patients with chronic urticaria or angioedema, 3 patients reacted to a 2.5% aqueous citric acid solutionFootnote 3.

In an investigation into a high incidence of occupational contact dermatitis in a shrimp packing factory, affecting 127 of the 635 workers, patch tests were conducted with several test materials, including citric acid (a component of a shrimp preservative agent used). Readings were made at 4 and 72 hours after patch application. No reactions were reported to a 1% citric acid solutionFootnote 10.

Positive reactions to citric acid were noted in 2 studies of patients with atopic symptoms following oral or dermal challengeFootnote 11Footnote 12. However, the patients were suspected to have been sensitized through the diet and thus these studies do not inform evaluation of skin sensitization.

The available data do not meet the classification criteria for Skin Sensitization.

Germ Cell Mutagenicity:

Does not meet criteria

In vivo: Negative results were obtained in a cytogenetic study and dominant lethal assay where citric acid was administered to rats by gavage at a dose of 1.2, 12 or 120 mg/kg-bw (once or daily for 5 days), or of 500 or 3 500 mg/kg-bw (once) or of 300 or 3 000 mg/kg-bw (daily for 5 days)Footnote 13.

In vitro: In an Ames test performed in accordance with OECD TG 471 (Bacterial Reverse Mutation Test), exposure to an aqueous solution of citric acid at a concentration of 500, 1 000 or 2 000 micrograms (µg) per plate was not mutagenic to Salmonella typhimurium strains TA 97, TA 98, TA 100 and TA 104, with or without metabolic activationFootnote 14. In another study that included an Ames test with and without metabolic activation in Salmonella typhimurium strains TA 92, TA 94, TA 98, TA 100, TA 1535 and TA 1537 and a chromosomal aberration test without metabolic activation in Chinese hamster fibroblasts, exposure to citric acid was not mutagenic nor caused chromosomal aberrationsFootnote 15. In a genotoxicity and cytotoxicity study of root canal irrigants, exposure of murine fibroblasts to serial dilutions of citric acid for 3 hours at 37°C did not produce genotoxicity at any concentration tested based on a comet assay, but reduced cell viability at a concentration of 10.5 or 21%Footnote 16. In a study performed similarly to OECD TG 487 (In Vitro Mammalian Cell Micronucleus Test), exposure to aqueous solutions of citric acid resulted in a statistically significant dose-dependent increase in the percentage of human peripheral lymphocytes containing micronuclei at the concentrations tested, in the absence of metabolic activationFootnote 2.

The available data do not meet the classification criteria for a category or subcategory of Germ Cell Mutagenicity.

Carcinogenicity:

Does not meet criteria

Citric acid has not been reviewed by the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), or the American Conference of Governmental Industrial Hygienists (ACGIH).

In a feeding study in rats, animals exposed to a citric acid concentration of 5% in the diet did not show an excess of tumours relative to control animals when exposed over a 2-year periodFootnote 2.

The available data do not meet the classification criteria for a category or subcategory of Carcinogenicity.

Reproductive Toxicity:

Does not meet criteria

Teratologic studies were performed on pregnant CD-1 mice (22 to 24 per dose), Wistar rats (19 to 24 per dose), golden hamsters (22 to 23 per dose) and Dutch-belted rabbits (9 to 14 per dose) that were gavaged aqueous citric acid solutions at a citric acid dose of 2.41, 11.2, 52 or 241 mg/kg-bw/day (mice), of 2.95, 13.7, 63.6 or 295 mg/kg-bw/day (rats), of 2.72, 12.6, 58.7 or 272 mg/kg-bw/day (hamsters) or of 4.25, 19.75, 91.7 or 425 mg/kg-bw/day (rabbits) from gestation day (GD) 6 to 15 (mice and rats), 6 to 10 (hamsters) or 6 to 18 (rabbits). No effects were observed on nidation, on maternal or fetal survival or on the number of abnormalities in either soft or skeletal tissues of the offspring compared to controlsFootnote 17.

A study in which female mice and rats (6 per species) were administered citric acid at a dietary concentration of 5% prior to, during and subsequent to mating demonstrated no effect on the number of offspring born or their subsequent survival up to weaningFootnote 18.

In a non-guideline reproductive toxicity study involving 2 rounds of mating of the same parental animals, namely at 32 weeks of age and at 11 weeks thereafter, citric acid was administered in the diet of male and female rats at a concentration of 1.2% by weight (about 600 mg/kg-bw/day) for 90 days. There was no indication of reproductive effects nor adverse effect on the growth of the 2 successive generations of offspringFootnote 2Footnote 7.

In a study in which pregnant hamsters were dosed with 272 mg/kg-bw of citric acid, presumably daily, from GD 6 to 10, there was no evidence of reproductive or developmental toxicityFootnote 7. In another study in which pregnant rabbits were administered doses up to 425 mg/kg-bw/day of citric acid from GD 6 to 18, there was no evidence of reproductive or developmental toxicityFootnote 6.

The available data do not meet the classification criteria for a category or subcategory of Reproductive Toxicity.

Specific Target Organ Toxicity – Single Exposure:

Does not meet criteria

Oral Route of Exposure:

Human data: Ingestion of 25 grams (g) of citric acid, corresponding to a dose of approximately 417 mg/kg-bw, caused vomiting and almost led to death in 1 womanFootnote 6.

Animal data: In an acute oral toxicity study in male SD-JCL rats and ICR-JCL mice (6 per species and dose), citric acid of high purity (99.8%) was administered at a dose of 4 820, 5 790 or 7 000 mg/kg-bw in mice or of 10 420, 12 500 or 18 000 mg/kg-bw in rats. The observation period was 7 days. Clinical signs included spontaneous movement, motor ataxia, mydriasis, a decrease in respiration rate and heart beat and mortality by respiratory failure. The animals which survived from the respiratory failure showed no toxic signs 24 hours after administration. At necropsy, hemorrhage of the gastric mucosa was observedFootnote 1.

Dermal Route of Exposure:

In an OECD TG 402-compliant (Acute Dermal Toxicity) study, Sprague-Dawley rats (5 per sex) were exposed to a dose of solid citric acid of 2 000 mg/kg-bw for 24 hours. The test material was moistened and applied to 10% of the area of the back under semi-occlusive conditions. The animals were observed for deaths and overt signs of toxicity 30 minutes and 1, 2 and 4 hours after dosing, with a total observation period of 14 days. There were no deaths or signs of systemic toxicity, nor were there any abnormalities at necropsyFootnote 2.

Inhalation Route of Exposure:

Inhalation exposure of 10 anesthetized inbred MFL rats that had bronchial hyperreactivity to a respirable aerosol of citric acid in distilled water at a concentration of 10% by weight per volume for 2 sequential challenges of 2 minutes, separated by 20 minutes, produced reversible increases in respiratory rate and pleural pressure relative to baseline and hypotension during both exposure periods, and also bradycardia during the first exposure period. The same exposure to 10 anesthetized Fischer rats, which did not exhibit such pulmonary hyperresponsiveness, produced no discernible result. These pulmonary and cardiovascular changes are similar to exaggerated responses to irritant stimuli, including to citric acid, observed in hyperreactive dogs and asthmatic humansFootnote 19.

An inhalation exposure study was conducted in 5 anesthetized Ascaris-sensitive Basenji-Greyhound (BG) dogs with bronchial hyperreactivity that received a challenge of each of 5 different treatments, one of which was solely of citric acid, in a random order and at a minimum interval of 1 week between challenges. The citric acid-alone treatment involved a 5-minute exposure to a 10% aqueous solution of citric acid nebulized into a respirable aerosol at a delivery rate of 0.5 to 1 mL per minute (mL/min). The citric acid challenge increased the activity of the slow-reacting substance of anaphylaxis (SRS-A) in the plasma, but not the concentration of histamine, and increased pulmonary resistance and dynamic complianceFootnote 20.

In another inhalation exposure study, 6 unanesthetized Dunkin-Hartley guinea pigs of both sexes were exposed to a nebulized aqueous solution of 0.40 molar (M) citric acid, at an average delivery rate 0.54 mL/min, for up to 7 mins. Exposure to citric acid caused both cough and reflex airway obstructionFootnote 21.

In a prospective randomized double-blinded case and auto-control study, 9 healthy human volunteers (5 male; 4 female), who were non-smokers with no evidence of respiratory disease or infection, were exposed while awake to citric acid for 7 vital capacity inspirations on 3 separate occasions that were 2 to 3 days apart, 1 with and 1 without superior laryngeal nerve conduction blockade and a third following a sham procedure. Exposures were through a mouthpiece to nebulized citric acid solutions at an average delivery rate of 0.295 mL/min. The cough threshold was measured using stepwise increases in the concentration of nebulized citric acid solution, namely 0, 2, 5, 10, 20, 35 and 50 grams per 100 millilitres (g/100 mL), during inspirations at intervals of approximately 90 seconds. Of the 9 subjects, 4 showed no change in cough threshold after nerve blockade, 3 showed increased cough threshold after nerve blockade, and 2 showed decreased cough threshold after nerve blockade compared to no blockade. Of those with a change in cough threshold, none had a change greater than 1 increment of the citric acid concentration. Neither nerve blockade nor the sham treatment resulted in a statistically significant difference in the geometric means of the cough thresholdsFootnote 22.

Coughing was reported in guinea pigs exposed for 30 minutes to an aerosolized 6% citric acid solution at an airborne citric acid concentration of 81 milligrams per cubic metre (mg/m³). Exposure of guinea pigs for 3 minutes to an airborne concentration of 75 milligrams per millilitre (mg/mL) of aerosolized citric acid also resulted in coughingFootnote 6.

These inhalation effects are indicative of sensory irritation rather than of local cytotoxicity.

The available data do not meet the classification criteria for a category of Specific Target Organ Toxicity – Single Exposure.

Specific Target Organ Toxicity – Repeated Exposure:

Does not meet criteria

Oral Route of Exposure:

In a longer-term study, 60 male New Zealand White rabbits were divided into 4 groups of 15 animals each. Citric acid, sodium salt (5% free citric acid) was added to the diets of the test animals at a concentration of 7.7%. The diet was fed to the animals for 150 days. No significant gross or histopathological changes were noted nor any differences in growth or survival compared to the control animalsFootnote 4.

A subacute 6-week feeding study was conducted in male SD-JCL rats (5 per concentration) at a dietary concentration of citric acid of 1.2, 2.4 or 4.8% (corresponding to a mean citric acid intake of 1 150, 2 260 or 4 670 mg/kg-bw/day, respectively). No behavioural abnormalities were noted at any concentration tested. Slight depressions of body weight gain and food intake were noted at all concentrations tested compared to controls, although a dose-response relationship was only apparent for the latter observation. The high-concentration group had a statistically significant decrease in the mean plasma cholesterol level and an increase in the mean serum aspartate aminotransferase activity. A decrease in mean total plasma protein content was observed at all concentrations tested, but was only statistically significant at the intermediate concentration. The biochemical findings in blood were considered mild. Some morphological abnormalities were observed in the testes and liver of some treated animals. Decreases in mean absolute thymus and spleen weights were noted at the high concentration, although only that of the thymus was statistically significant. Increases in mean absolute prostate and thyroid gland weights were noted at the low and high concentrations, respectively, although only that of the prostate was statistically significant. Histopathological examination revealed slight atrophy of the cortex of the thymus and of splenic lymph follicles at the high concentration but the effect was not considered deleteriousFootnote 1. The mean citric acid intakes exceed the guidance values for the categories of this hazard class, adjusted for exposure duration.

In a 2-year feeding study, male rats (20 per concentration) were fed a diet containing a citric acid concentration of 3 or 5%, which corresponded to a citric acid dose of approximately 1 200 or 2 000 mg/kg-bw/day, respectively. Slightly decreased growth at the higher dose was observed, although this was accompanied by a reduction in food consumed. No abnormalities in the tissues of major organs were observedFootnote 7. The citric acid doses exceed the guidance values for the categories of this hazard class, adjusted for exposure duration.

Dermal Route of Exposure: No data available

Inhalation Route of Exposure: No data available

The available data do not meet the classification criteria for a category of Specific Target Organ Toxicity – Repeated Exposure.

Aspiration Hazard:

No data available

No human data are available and the substance is not a liquid hydrocarbon.

Biohazardous Infectious Materials:

Not applicable

Citric acid is not a microorganism, protein or nucleic acid.

Physical hazards

Explosives:

Not evaluated*

* Explosives are excluded from the Hazardous Products Act and its regulations. Explosives are regulated under the Explosives Act. For more information, visit Natural Resources Canada .

Flammable Gases:

Not applicable

Citric acid is not a gas. The classification criteria for Flammable Gases do not apply to this substance.

Aerosols:

Not evaluated

Classification of a hazardous product in the Aerosols hazard class is product dependent.

Oxidizing Gases:

Not applicable

Citric acid is not a gas. The classification criteria for Oxidizing Gases do not apply to this substance.

Gases Under Pressure:

Not applicable

Citric acid is not a gas. The classification criteria for Gases Under Pressure do not apply to this substance.

Flammable Liquids:

Not applicable

Neither anhydrous nor monohydrate forms of citric acid are a liquid. The classification criteria for Flammable Liquids do not apply to either. Furthermore, no flash point was available for aqueous solutions of citric acid.

Flammable Solids:

Does not meet criteria

Citric acid as a deposited dust did not ignite in a burning test but rather melted and evaporated. The study was conducted according to a national standard method but was not in accordance with good laboratory practice (GLP)Footnote 2.

The available data do not meet the classification criteria for Flammable Solids.

Self-reactive Substances and Mixtures:

Does not meet criteria

Anhydrous and monohydrate forms of citric acid have melting points of 153 and 135°C, respectivelyFootnote 23Footnote 24.

Self-reactive substances and mixtures must have a self-accelerating decomposition temperature (SADT) of 75°C or lower to meet minimum classification criteria. As the melting points exceed this limit, citric acid is not classified in a category of Self-reactive Substances and Mixtures.

Pyrophoric Liquids:

Not applicable

Neither anhydrous nor monohydrate forms of citric acid are a liquid. The classification criteria for Pyrophoric Liquids do not apply to either. Furthermore, no data were available to evaluate the ignitability of aqueous solutions of citric acid exposed to air.

Pyrophoric Solids:

Does not meet criteria

Citric acid as a deposited dust did not ignite in a burning test but rather melted and evaporatedFootnote 2. As burning tests involve exposure to air, such as via a fume cupboard draught, the result suggests a lack of pyrophoricity.

The available data do not meet the classification criteria for a category of Pyrophoric Solids.

Self-heating Substances and Mixtures:

Does not meet criteria

Anhydrous and monohydrate forms of citric acid have melting points of 153 and 135°C, respectivelyFootnote 23Footnote 24. As such, citric acid does not spontaneously combust at a temperature of 50°C or lower and is consequently excluded from classification.

The available data do not meet the classification criteria for a category of Self-heating Substances and Mixtures.

Substances and Mixtures which, in Contact with Water, Emit Flammable Gases:

Excluded from classification

Citric acid is soluble in water and forms a stable mixture, with a water solubility of 59.2% at 20°CFootnote 24. Furthermore, it does not have a chemical structure containing metals or metalloids. On these bases, it is excluded from classification [HPR 7.12.1(1)(a) and (c)].

Oxidizing Liquids:

Not applicable

Neither anhydrous nor monohydrate forms of citric acid are a liquid. The classification criteria for Oxidizing Liquids do not apply to either. Furthermore, data on the oxidizing properties of aqueous solutions of citric acid were not available.

Oxidizing Solids:

Excluded from classification

Citric acid is an organic solid that contains oxygen that is chemically bonded only to carbon or hydrogen and is therefore excluded from classification [paragraph 7.14.1(1)(b) of the HPR].

Organic Peroxides:

Not applicable

Citric acid is not an organic peroxide. The classification criteria for Organic Peroxides do not apply to this substance.

Corrosive to Metals:

Does not meet criteria

A weight loss study was conducted on samples of mild steel immersed for 2 hours at room temperature in an aqueous solution of citric acid at a concentration of 1 or 2 normal (N). At these respective concentrations, the corrosion rates were 29.5343 and 33.7694 millimetres per year (mm/yr), in the absence of a corrosion inhibitorFootnote 25. Given the positive relationship between corrosion rates and temperature, these rates would exceed 6.25 mm/yr at a temperature of 55°C. However, the method employed in the study differs from that required in the HPR, including discrepancies in sample size, in pre-exposure chemical surface modifications, in post-exposure sample treatment, in exposure duration and temperature, and in the use of replicates and of unexposed controls. While not all of the discrepancies limit the classification evaluation, the exposure duration, which falls significantly short of the 1-week minimum required, renders the results unsuitable for evaluation.

The Handbook of Corrosion Data indicates that, at ambient temperature, aluminum-manganese alloys and stainless steel of types 304, 316, 409, 410 and 430 exhibit corrosion resistance to solutions containing citric acid at a concentration of 6 to 50%. Corrosion rates did not exceed 0.260 mm/yr, significantly lower than 6.25 mm/yr at a temperature of 55°CFootnote 26.

The available data are either insufficient for evaluation or do not meet the classification criteria for a category of Corrosive to Metals.

Combustible Dusts:

No data available

No data are available to determine whether citric acid meets the classification criteria for a category of Combustible Dusts. While several secondary sources in the literature state that citric acid is a combustible dust, supporting information is not available.

Simple Asphyxiants:

Not applicable

Citric acid is not a gas. The classification criteria for Simple Asphyxiants do not apply to this substance.

Chemicals Under Pressure:

Not evaluated

Classification of a hazardous product in the Chemicals Under Pressure hazard class is product dependent.

Regulatory and other information

Regulatory information:

Hazardous substance assessments are prepared by Health Canada as educational and information resources. Under the HPA, suppliers of hazardous products must, upon the sale or importation of a hazardous product, provide a safety data sheet and label that meet the requirements set out in the HPR.

Other information:

The information and classifications contained in these hazardous substance assessments are based on publicly available sources, such as peer-reviewed literature or reports by international bodies. New information, including proprietary information, could have an impact on the classification of substances or hazardous products containing them. It is the responsibility of the supplier to ensure the accuracy, sufficiency and reliability of their hazardous product classifications.

Last updated:

2025

Prepared by:

Workplace Hazardous Materials Bureau, Health Canada

References

Footnote 1

Yokotani, H., et al (1971) Acute and subacute toxicological studies of TAKEDA-citric acid in mice and rats. Journal of the Takeda Research Laboratory 30(1):25–31.

Return to footnote 1 referrer

Footnote 2

European Chemicals Agency (2025) Citric acid CAS# 77-92-9 - REACH dossier. Available at: https://www.echa.europa.eu.

Return to footnote 2 referrer

Footnote 3

Cosmetic Ingredient Review Expert Panel, et al (2014) Safety assessment of citric acid, inorganic citrate salts, and alkyl citrate esters as used in cosmetics. International Journal of Toxicology 33:16S–46S.

Return to footnote 3 referrer

Footnote 4

HPVIS (2001) Assessment Plan for Acetic Acid and Salts Category. U.S. High Production Volume (HPV) Chemical Challenge Program. Prepared by: American Chemistry Council, Acetic Acid and Salts Panel

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Footnote 5

Murphy, J. C., Osterberg, R. E., Seabaugh, V. M. and Bierbower, G. W. (1982) Ocular irritancy responses to various pHs of acids and bases with and without irrigation. Toxicology 23:281–291.

Return to footnote 5 referrer

Footnote 6

NICNAS (2013) Citric Acid: Human health tier II assessment, https://services.industrialchemicals.gov.au/search-assessments/.

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Footnote 7

OECD SIDS (2001) Citric acid. CAS No: 77-92-9. UNEP Publications.

Return to footnote 7 referrer

Footnote 8

Dohn, W. (1980) Dermatological patients not employed in handicraft or factories. Contact Dermatitis 6(2):148–150.

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Footnote 9

Neczyporenko, F. and Blondeel, A. (2010) Allergic contact dermatitis to Elidel cream itself?. Contact Dermatitis 63(3):171–172.

Return to footnote 9 referrer

Footnote 10

Laraqui, C. H., et al (1997) Allergies cutanées dans une usine de décortication de crevettes [Skin allergies in a shrimp shelling factory]. Revue Francaise d'Allergologie Et d'Immunologie Clinique 37(4; PMID:1997264949):438–441.

Return to footnote 10 referrer

Footnote 11

Walsh, W. E. (1979) Atopic dermatitis. Associated with citric and malic acid intolerance. Minnesota Medicine 62(9; PMID:1980011497):637–639.

Return to footnote 11 referrer

Footnote 12

Fuglsang, G., et al (1994) Adverse reactions to food additives in children with atopic symptoms. Allergy 49(1; PMID:8198237):31–37.

Return to footnote 12 referrer

Footnote 13

Litton Bionetics (1975) Mutagenic evaluation of compound FDA 71-54, citric acid.

Return to footnote 13 referrer

Footnote 14

Al-Ani, F. Y. and Al-Lami, S. K. (1988) Absence of mutagenic activity of acidity regulators in the Ames Salmonella/microsome test. Mutation Research 206(4):467–470.

Return to footnote 14 referrer

Footnote 15

Ishidate, M. J., et al (1984) Primary mutagenicity screening of food additives currently used in Japan. Food & Chemical Toxicology 22(8):623–636.

Return to footnote 15 referrer

Footnote 16

Marins, J. S., Sassone, L. M., Fidel, S. R. and Ribeiro, D. A. (2012) In vitro genotoxicity and cytotoxicity in murine fibroblasts exposed to EDTA, NaOCl, MTAD and citric acid. Brazilian Dental Journal 23(5; PMID:23306229):527–533.

Return to footnote 16 referrer

Footnote 17

Food and Drug Research Labs (1973) Teratologic evaluation of FDA 71-54 (citric acid).

Return to footnote 17 referrer

Footnote 18

Wright, E. and Hughes, R. E. (1976) The influence of dietary citric acid supplement on the reproduction and survival time of mice and rats. Nutrition Reports International 13(6):563–566.

Return to footnote 18 referrer

Footnote 19

Hamel, R. and Ford-Hutchinson, A. W. (1985) Pulmonary and cardiovascular changes in hyperreactive rats from citric acid aerosols. Journal of Applied Physiology 59(2; PMID:4030589):354–359.

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Footnote 20

Hirshman, C. A., et al (1983) Role of mediators in allergic and nonallergic asthma in dogs with hyperreactive airways. Journal of Applied Physiology: Respiratory, Environmental & Exercise Physiology 54(4):1108–1114.

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Footnote 21

Karlsson, J. A., Choudry, N. B., Zackrisson, C. and Fuller, R. W. (1992) A comparison of the effect of inhaled diuretics on airway reflexes in humans and guinea pigs. Journal of Applied Physiology 72(2):434–438.

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Footnote 22

Stockwell, M., et al (1993) Lack of importance of the superior laryngeal nerves in citric acid cough in humans. Journal of Applied Physiology 75(2):613–617.

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Footnote 23

Rumble, J. R. (2025) CRC Handbook of Chemistry and Physics. 106 Edition. CRC Press/Taylor & Francis, Boca Raton, FL.

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Footnote 24

The Merck Index: An encyclopedia of chemicals, drugs and biologicals (2013). 15th Edition. O'Neill, M. J. Royal Society of Chemistry, Merck & Co., Inc, Camdridge, UK.

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Footnote 25

Matheswaran, P. and Ramasamy, A. K. (2012) Corrosion Inhibition of Mild Steel in Citric Acid by Aqueous Extract of Piper Nigrum L. E-Journal of Chemistry 9(1):75–78 Wiley.

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Footnote 26

ASM International (1995) Handbook of Corrosion Data. 2nd Edition. D. B. Craig and D. B. Anderson (Eds.). ASM International.

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