Citric acid

Endpoint summary

Description of key information

A reliability 1 key study on skin irritation, which was conducted according to OECD 404, reports that citric acid was not irritating to skin (Haarmaan & Reimer, 1990). The proposal for harmonised classification and labelling has been considered and it is concluded that there is not sufficient evidence for classification of citric acid as irritating to the skin.

The key eye irritation study (Roche, 1984) found the test substance to be an eye irritant within a 14 day observation period and classification as Eye Irritant, Cat 2 has been proposed.

Citric acid is used to induce the cough response in human volunteers in studies to evaluate the use of citric acid as a positive control in the efficacy testing of anti-tussive agents (Bickerman et al., 1954; Winther, 1969; Barros et.al., 1990), and has been shown to cause cough and bronchoconstriction in the guinea pig (Zelenak 1982, Forsberg and Karlsson, 1986), and classification for Specific Target Organ Toxicity, Cat 3 respiratory irritation has been proposed.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted largely in accordance with the OECD guideline and in compliance with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

very minor deviations

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mohican Valley Rabbitry inc., Loudonville, OH, USA
- Age at study initiation: 5 months
- Weight at study initiation: 3.1-3.4 kg
- Housing: 1/suspended cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: duration not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 64-69 deg F
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: not stated

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: covered with patch moistened with water

Controls:

other: untreated skin serves as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g powder

VEHICLE
- Amount(s) applied: none - covered with wetted patch

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48, 72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 6.25 cm2
- % coverage: not stated
- Type of wrap if used: wetted Webril patch held with Blenderm tape; covered with gauze bandage secured with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with tepid water for 3 secs
- Time after start of exposure: 4 h

SCORING SYSTEM: according to OECD 404/Draize; final score given as mean of 1, 24, 48 and 72 h readings

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Remarks:

of 6 animals

Time point:

other: 1, 24, 48, 72 h mean

Score:

0.3

Max. score:

8

Reversibility:

other: very slight effects remaining at final observation at 72 h

Remarks on result:

other: mild skin irritant

Irritation parameter:

overall irritation score

Basis:

mean

Remarks:

of 6 animals

Time point:

other: 24, 48, 72 h mean

Score:

0.3

Max. score:

8

Reversibility:

other: very slight effects remaining at final observation at 72 h

Remarks on result:

other: not irritant according to EU criteria

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks:

slight indication of erythema at final observation at 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Well defined erythema in 1/6 from 1-48 h; mild erythema in the same animal was still evident at 72h when study was terminated. See table 1.

Other effects:

None reported.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Erythema/eschar	Edema
	Max. score: 4	Max. score: 4
1 h	2/0/0/0/0/0	0/0/0/0/0/0
24 h	2/0/0/0/0/0	1/0/0/0/0/0
48 h	2/0/0/0/0/0	0/0/0/0/0/0
72 h	1/0/0/0/0/0	0/0/0/0/0/0
Average given in report: 1h, 24h, 48h, 72h	0.3	0
Average - EU criteria: 24h, 48h, 72h	0.3	0
Reversibility*	c	n/a
Average time for reversion	unclear (likely to be reversible)

* Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

A reliable study conducted largely in accordance with OECD 404 and in compliance with GLP, found the citric acid to be mildly irritating to the skin of rabbits. Current EC criteria would find the material to be non-irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2-16 January 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Remarks:

Study conducted largely in accordance with the OECD guideline and apparently with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

The report notes that study was conducted according to recommended guidelines of Interagency Regulatory Liaison Group and OECD. The specific guideline is not stated.

Deviations:

yes

Remarks:

no data on purity, systemic toxicity observations or housing conditions

GLP compliance:

yes

Remarks:

described as being conducted according to GLP; no details are given

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Fűllinsdorf Breeding Farm (no further details given)
- Age at study initiation: "adult"
- Weight at study initiation: not less than 2 kg
- Housing: 1/cage
- Diet: standard ad libitum
- Water: drinking water ad libitum
- Acclimation period: not stated

ENVIRONMENTAL CONDITIONS
-no details given

IN-LIFE DATES: From: 1984-01-2 To: 1984-01-16

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 ml solution
- Concentration: 10% and 30% aqueous solution

VEHICLE
- Amount(s) applied: sufficient for 0.1 ml solution

Duration of treatment / exposure:

Unwashed. Exposure/observation for up to 14 days following treatment.

Observation period (in vivo):

For 14 days following treatment.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: unwashed

SCORING SYSTEM: Draize (max 110)

TOOL USED TO ASSESS SCORE: not clear

Irritation parameter:

overall irritation score

Remarks:

mean maximum Draize score for 10% solution

Basis:

mean

Remarks:

of 3 animals

Time point:

other: at 1, 24, 48 or 72 h

Score:

9.3

Max. score:

110

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: score achieved at 1 h

Irritation parameter:

overall irritation score

Remarks:

mean maximum Draize score for 30% solution

Basis:

mean

Remarks:

of 3 animals

Time point:

other: at 1, 24, 48 or 72 h

Score:

16

Max. score:

110

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: score achieved at 1 h

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

30% solution

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

30% solution

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

30% solution

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

30% solution

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

30% solution

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

30% solution

Irritant / corrosive response data:

30% Aqueous solution of test substance: Conjunctival redness grade 3/3 in 3/3 animals at 1, 24, 48, 72 h; at grade 1/3 in 3/3 at 7 days; at grade 1/3 in 1/3 at 14 days. Chemosis grade 2-3/4 in 3/3 animals at 1, 24, 48, 72 h; at 1/3 in 3/3 at 7 days and in none at 14 days. These effects are reported as well defined to moderate irritation, whereas effects from the 10% solution are reported as moderate to weak.

Other effects:

No details are given of clinical observations on systemic toxicity or body weights at study completion.

Table 1: Test with 30% aqueous solution

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

	Cornea				Iris	Conjunctivae				Discharge
Score at time point / Reversibility	Opacity	Area of opacity	Ulceration visible to the naked eye	Positive stain retention			Redness	Chemosis	Ulceration (u)
	Max. score: 4	Max. score: 4	-	-	Max. score: 2		Max. score: 3	Max. score: 4	-	Max. score: 3
1 h	0/0/0	-	0/0/0	0/0/0	0/0/0		3/3/3	3/3/3	0/0/0	2/2/2
24 h	0/0/0	-	0/0/0	0/0/0	0/0/0		3/3/3	3/3/3	u/u/u	2/2/2
48 h	0/0/0	-	0/0/0	0/0/0	0/0/0		3/3/3	2/3/2	u/u/u	2/2/2
72 h	0/0/0	-	0/0/0	0/0/0	0/0/0		3/3/3	2/2/2	u/u/u	2/2/2
7 days	0/0/0	-	0/0/0	0/0/0	0/0/0		1/1/1	1/1/1	0/0/0	0/0/0
14 days	0/0/0	-	0/0/0	0/0/0	0/0/0		0/1/0	0/0/0	0/0/0	0/0/0
Average 24h, 48h, 72h	0/0/0	-	-	-	0/0/0		3/3/3	2.3/2.7/2.3	0/0/0	2/2/2
Draize maximum average score @ 1, 24, 48 or 72 h	0		-	-	0		16
Reversibility**	-	-	-	-	-		n.c.	c	-	c
Time for reversion							by 14 days	by 14 days		by 7 days

 * The Draize scoring method is as follows:

Cornea: opacity value x area value x 5. (Max = 80)

Iris: value x 5. (Max = 10)

Conjunctiva: (redness + chemosis + discharge) x 2. (Max = 20)

Total maximum value = 110

** Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Table 2: Test with 10% aqueous solution

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

	Cornea				Iris	Conjunctivae				Discharge
Score at time point / Reversibility	Opacity	Area of opacity	Ulceration visible to the naked eye	Positive stain retention		Redness		Chemosis	Ulceration
	Max. score: 4	Max. score: 4	-	-	Max. score: 2	Max. score: 3		Max. score: 4	-	Max. score: 3
1 h	0/0/0	-	0/0/0	0/0/0	0/0/0	2/2/2		2/1/2	0/0/0	1/1/1
24 h	0/0/0	-	0/0/0	0/0/0	0/0/0	1/1/1		0/0/0	0/0/0	0/0/0
48 h	0/0/0	-	0/0/0	0/0/0	0/0/0	1/1/1		0/0/0	0/0/0	0/0/0
72 h	0/0/0	-	0/0/0	0/0/0	0/0/0	1/1/1		0/0/0	0/0/0	0/0/0
7 days	0/0/0	-	0/0/0	0/0/0	0/0/0	0/0/0		0/0/0	0/0/0	0/0/0
14 days	0/0/0	-	0/0/0	0/0/0	0/0/0	0/0/0		0/0/0	0/0/0	0/0/0
Average 24h, 48h, 72h	0/0/0		-	-	0/0/0		1/1/1	0/0/0	0/0/0	0/0/0
Draize maximum average score @ 1, 24, 48 or 72 h	0		-	-	0		9.3
Reversibility**	-	-	-	-	-		c	c	-	c
Time for reversion							7 days	24 h		24 h

 * The Draize scoring method is as follows:

Cornea: opacity value x area value x 5. (Max = 80)

Iris: value x 5. (Max = 10)

Conjunctiva: (redness + chemosis + discharge) x 2. (Max = 20)

Total maximum value = 110

** Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

A generally reliable study, apparently conducted according to OECD 405 and GLP, reported that a 30% aqueous solution of the test substance caused well defined to moderate conjunctival irritation that had not fully resolved after 14 days. A 10% solution was associated with weak to moderate conjunctival effects, resolved after 7 days. Given the 30% solution effects would have been allowed to dissipate for 21 days, it is likely the test substance would not be considered irritating to the eyes according to EU criteria (please see attached expert letter as reference).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation

The key study reports citric acid to be not irritating as assessed by a 4-hour semiocclusive application to intact skin (Haarmaan & Reimer, 1990). This is further supported by three reliability 2 supporting studies which are all equivalent or similar to guideline and also concluded that citric acid is not irritating to skin (Miles, 1979; Roche 1984).

Consideration of classification and labelling for skin irritation

The harmonised classification and labelling (CLH) report (Belgium, 2018) proposes an entry in Annex VI of Regulation (EC) No 1272/2008 (CLP) which includes Skin Irrit. 2, H315. This conclusion is based on the pH of citric acid in aqueous solution (as reported in IUCLID 2000 and in a solubility study), supported by:

1.       OECD SIDS observations on dermatitis in bakers.

2.       Use in anti-aging cosmetics as a chemical peel.

3.       The difference in results in the Registration dossier between neat substance applied semi-occlusively and a 30% solution applied to scarified skin.

Classification based on pH

According to Regulation (EC) No 1272/2008, pH can be used for classification: “In the absence of any other information, a substance is considered as corrosive to skin (Skin Corrosion Category 1) if it has a pH ≤ 2 or a pH ≥ 11,5.”

In the tiered approach to classification under Regulation (EC) No 1272/2008, emphasis is placed human data followed by animal data, so where data exists pH is not sufficient to classify.

Observations of dermatitis

There is no information about what other substances the bakers have been exposed to, so this evidence is not sufficient to classify. The OECD SIDS reports that patch testing of 60 eczema patients with 2.5% citric acid in petrolatum did not produce any irritant or allergic response.

Use as a chemical peel

The harmonised classification and labelling (CLH) report references Yates, 1999 for evidence of use of citric acid as a chemical peel. This publication indicates the presence of citric acid in 4 salon or commercial skin-peel products. No toxicity data are included in the paper. Since there is no information on which other substances were present in the products, this paper is not evidence of use of citric acid as the effective ingredient in skin peel. Therefore, this is not grounds for classification.

Results of animal studies

The in vivo skin irritation guideline, OECD TG 404, requires that “care should be taken to avoid abrading the skin, and only animals with healthy, intact skin should be used.” The application of a 30% solution of citric acid to scarified skin (Roche, 1984) is not appropriate justification for classification for skin irritation and should be discounted from the overall conclusions on classification. This study has been evaluated in a Cosmetic Ingredient Review, which concluded that the substance is not a primary irritant (CIR, 2012). In a study conducted according to OECD TG 404 and in compliance with GLP neat citric acid was applied semi-occlusively, with results which do not trigger classification for skin irritation (Haarmaan & Reimer, 1990). Supporting studies tested 30% and 50% solutions on intact skin and concluded that these concentrated solutions are not irritating (Miles, 1979; Roche 1984).

Therefore, it is concluded that there is not sufficient evidence for classification of citric acid as irritating to the skin.

Citric acid is used as a cosmetic ingredient. A Cosmetic Ingredient Review (CIR) of available information on citric acid and citrate concluded that citric acid is not irritant in formulations at a concentration of 4%, based on repeated insult patch testing (Cosmetic Ingredient Review, 2012). Data are presented on formulated products; these data cannot be used for classification as there is no information on the other ingredients. The CIR review presents animal data which has been considered for classification. One study using leads to the tentative conclusion that citric acid is irritant to the skin. 100% citric acid was applied to the skin of 10 rabbits in an acute dermal study using a dose of 5 g/kg bw (RIFM, 2011, as cited in Cosmetic Ingredient Review, 2012). The OECD TG 404 indicates that the appropriate dose for in vivo skin irritation testing is 0.5 g/kg bw. Therefore, this study, which is not available for evaluation, cannot be used to conclude on classification.

Eye irritation

The key study for eye irritation reports that a 30% aqueous solution of citric acid caused well-defined to moderate conjunctival irritation that had not fully resolved after 14 days. A 10% solution was associated with weak to moderate conjunctival effects, resolved after 7 days (Roche, 1984). The reported eye reaction data was re-evaluated with respect to the recovery period and whether there would have been complete recovery at the 30% concentration if a longer recovery period had been used (21 days rather than 14 days). It was found that the score level of 1 for conjunctival redness in 1/3 animals in day 14 would have completely resolved if there had been a further 7 day observation period. This opinion was based on the recovery profile in the 2 other rabbits at this concentration and the ongoing recovery profile for the rabbit in question (significant recovery had already occurred by day 14 with only a low grade of conjunctival redness remaining). The evaluation report is included in the study record. Based on these results with a 30% aqueous solution, classification as Eye Irritant, Cat 2 has been proposed.

Respiratory irritation

In a study preliminary to the evaluation of antitussive agents, citric acid was chosen as most consistent in the cough response elicited as measured by the mean number of coughs produced with five inhalations in human volunteers (Bickerman et al., 1954). 10% citric acid gave the highest number of positive reactors.

In a study to develop a method for the use of citric acid in testing antitussive medicines with human volunteers, a training period was used to determine the concentration of citric acid solution able to produce 3-6 coughs after one inhalation (Winther, 1969). There were three test periods one hour apart. 5 inhalations were administered at 3-minute intervals in each test period. The number of coughs was counted after each inhalation. Each subject was given a placebo tablet after the first test period, but was informed that they could receive either a placebo or an anti-tussive tablet.

The total number of coughs after each inspiration over the three test periods was compared among subjects and between test periods and inspirations. Statistical variance and F-values were analysed.

The concentration of citric acid producing between 3 and 6 coughs after a single inhalation was found to vary from 5% to 25%. Adaptation to the citric acid aerosol occurred during the initial training period, but further adaptation during the test period was low, except between the first and second inhalation.

Some reduction in response between the first and second test periods might be attributable to a placebo reaction. It was concluded that the administration of citric acid to induce coughing using the method described would be useful in evaluating antitussive medicines, providing that a double-blind trial using a placebo was used.

A study was conducted to evaluate the effect of inspiratory flow rate on the cough response in humans to citric acid (Barros et.al., 1990). It was considered by the authors that the cough response to citric acid is produced mainly by irritation of the larynx and trachea. Variations in the inspiratory flow rate might lead to changes in deposition of the drug, and consequently in the cough threshold. The effect of inspiratory flow rate was studied in 11 healthy non-smoking volunteers aged 23 to 29 years (9 male, 2 female). The test substance was administered by inhalation of a nebulised solution via apparatus which limited and measured the inspiratory flow rate to 50, 100 and 150 l/minute of increasing concentrations of citric acid.

The test was finished when a cough was produced after each inhalation at one concentration (cough threshold) or the maximum concentration was reached. Each concentration was given at three different flow rates. The exposures were repeated on 3 days at least 48 hours apart.

The mean cough threshold was determined to be 21 (±9-54) mg/l at an inspiratory flow rate of 50 l/min and 43 (±13-141) mg/l at 150 l/minute. It was concluded that inspiratory flow rate should be controlled when cough challenges with citric acid are performed.

On the basis of these studies, classification for specific target organ transient respiratory tract irritation, Cat 3 has been proposed. Classification is supported by acute inhalation studies in the guinea pig. Inhalation of citric acid was shown to cause cough and bronchoconstriction in the guinea pig. The bronchoconstriction seems to involve cholinergic and capsaicin sensitive neurons (Forsberg & Karlsson, 1986).

Citric acid was seen to elicit a cough response in the guinea pig (Zelenak, 1982) in a study in which the time-response relationship observed with citric acid showed a maximum response around 5 to 10 minutes of exposure for isolated coughs and a fade in response as the exposure continued.

References

Belgium, 2018. CLH report. Proposal for Harmonised Classification and Labelling. Citric acid EC Number: 201-069-1, CAS Number: 77-92-9. https://echa.europa.eu/documents/10162/477e07c3-6404-d921-b1d3-d5d512e7e02e

RIFM 2011. Research Institute for Fragrance Materials (RIFM). RIFM data synopsis on citric acid. 2011. Unpublished document submitted by RIFM on March 21, 2011, as cited in Cosmetic Ingredient Review, 2012.

Yates R.L and Havery D.C., 1999. Determination of Phenol, Resorcinol, Salicylic Acid and α-Hydroxy Acids in Cosmetic Products and Salon Preparations, Journal of Cosmetic Science, vol. 50, pp. 315-325

Justification for classification or non-classification

Based on the available in vivo eye irritation data for a 30% aqueous solution of citric acid, classification as eye irritant, Category 2, with the hazard phrase H319 (Causes serious eye irritation), is proposed for citric acid according to Regulation (EC) No. 1272/2008.

Based on the information from human volunteers, classification for specific target organ transient respiratory tract irritation STOT SE3 H335 is considered appropriate according to Regulation (EC) No. 1272/2008.