OECD SIDS

CITRIC ACIDFOREWORDINTRODUCTION

CITRIC ACID
CAS N°:77–92–9

UNEP PUBLICATIONS

1OECD SIDS

CITRIC ACIDSIDS Initial Assessment Reportfor11th SIAM(Orlando, Fla., January 2001)
C h e mical Name:

Citric acid

CAS No.:77– 92–9

Sponsor Country:

Switzerland

National SIDS Contact Point
in Sponsor Country:

Dr Georg Karlaganis
Swiss Agency for the Environment, Forests andLandscapeC H–3003 Berne, Switzerland
georg.karlaganis@buwal.admin.ch

HISTORY:
The chemical was chosen by the Sponsor Company and the Swiss authorities in
the frame of the ICCA Initiative.
no testing
testing(X)( )COMMENTS:
Deadline for Circulation:

10 November 2000

Date of Circulation:

10 November 2000

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UNEP PUBLICATIONSOECD SIDS

CITRIC ACIDSIDS INITIAL ASSESSMENT PROFILECAS No.

77-92-9

Chemical Name

Citric acid

CH 2COOH
Structural Formula

HOCCOOH
CH 2COOH

RECOMMENDATIONS
The chemical is currently of low priority for further work .

SUMMARY CONCLUSIONS OF THE SIAR
Human Health
Based on many experimen tal data in animals and on human experience, citric acid is of low acutetoxicity. The NOAEL for repeated dose toxicity for rats is 1200 mg/kg/d. The major, reversible(sub)chronic toxic effects seem to be limited to changes in blood chemistry and metal
absorption/excretion kinetics. Citric acid is not suspected of being a carcinogen nor a reprotoxic or
teratogenic agent. The NOAEL for reproductive toxicity for rats is 2500 mg/kg/d. Further, it is not
mutagenic in vitro and in vivo. Also, the sensitising potential is seen as low. In contrast, irritation, inparticular of the eyes but also of the respiratory pathways and the skin, is the major toxicologicalhazard presented by citric acid; this conclusion is confirmed by a series of reports relating to eye an dskin irritation.
Environment
Due to its physico -chemical characteristics citric acid is highly mobile in the environment and will
partition to the aquatic compartment. Citric acid is rapidly degraded in both sewage works and surface
waters and in soil. Citric acid is of low acute toxicity to freshwater fish, daphnia and algae and also to
the few marine species tested; longer -term tests show comparable effect values. Similarly, citric acidhas no obvious toxic potential against protozoans and many specie s or strains of bacteria including
activated sludge micro-organisms. Based on the available data, citric acid is not judged to be a
substance that presents a hazard to the environment.
Exposure
Citric acid is a water soluble organic solid. It is a natural substance that appears as an intermediate in
the basic physiological citric acid or Krebs cycle in every eukaryote cell. Citric acid has been produced
for many years in high volumes, current global production is estimated to approach 1,000,000 t/a. It
has wide dispersive use, being added to processed food and beverages, used in pharmaceuticalpreparations and in household cleaners as well as in special technical applications.

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OECD SIDS

CITRIC ACID

A large body of physico-chemical, toxicological and environmentally relevant data exists for citricacid, many of which are relatively old and some located only in standard reference works and reviews.
While the quality of a single result often may be hard or even impossible to assess, the sheer volume
and high congruence of the data result in a uniform picture all the same.

NATURE OF FURTHER WORK RECOMMENDED
No further work recommended.

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UNEP PUBLICATIONSOECD SIDS

CITRIC ACID

Full SIDS Summary
CAS No. 77–92–9
2.1

Physical-Chemical
Melting Point

2.2

Boi ling Point

2.3
2.4

Relative Density
Vapour Pressure

2.5
2.6

2.11
2.12

SpeciesProtocolResultsNANA

152 –159 °C~153 °C
none; decomposition > 175 °C

NA

1.665 at 20 °C
no studies located
7.3 x 10- 7 Pa (25 °C)
logPow = –1.72 at 20 °C
576 –771 g/l at 20 °C/room
temperature, data from 4 sources
1330 g/l, “cold water”

pH ValueNANA

2.2 at 0.1 N~1.8 at 50 g/l and 25 °C

Dissociation Constants
Oxidation/Reduction
Potential
Additional Data:
Henry’s Law ConstantNA

pK a 1 = 3.13, pK a 2 = 4.76, pK a 3 = 6.4
no studies locatedcalculated

K H = 2.3 x 10 - 7 Pam 3/mol

Partition Coefficient
Water solubilityNAcalculated
NA
NA

Environmental Fate andPathway
3.1.1 Photodegradation
3.1.2 Stability in Water
3.1.3 Stability in Soil
3.2

Monitoring Data

calculated
calculatedNAbackgroundconcentration
measurement

3.3.1 Transport
3.3.2 Distribution

no studies locatedt ½ = 2.3 days in the atmospheret ½ = 72.9 years at pH 1, stable“substantial disappearance of citratefrom soil within 7 days”<0.04 –0.2 mg/l, river surface water
0.025 –0.145 mg/l, Atlantic coast
seawaterup
10 mg/l,raw sewage
no to
studies
located

calculated:fugacity level III(dynamic)emission 33% each to water, soil andair: 55.76% to water, 44.2% to soil,
0.02% t o sediment, 0.02% to air

calculated:fugacity level I(static)

static equilibrium concentrations:99.99% to water, <0.01% to soil,<0.01% to sediment, <0.01% to air

3.4

Mode of Degradation in
Actual Use

NA

3.5

Biodegradation

Modified Sturm
test
Closed Bottle test
Closed Bottle test
Closed Bottle test
Closed Bottle test

synthesised and metabolised by all
eukaryote cells in the Krebs cycle;
easily oxidised by common oxidising
agents97% (CO 2 evolution), readily
biodegradable
B O D 30/COD = 90%, readily
biodegradable
B O D 5 = 526 mg, COD = 728 mg,
B O D 5 /COD = 0 .72, readily
biodegradable
B
O D 5 /ThOD = 58% –61%
(3 publications), readily
biodegradable
B O D 1 /ThOD = 13%

Closed Bottle test B O D 20/ThOD = 98%, readily
biodegradable

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5OECD SIDS
CAS No. 77–92–9

CITRIC ACID
SpeciesProtocolResul ts

Zahn-Wellens
test

85%, 1 day
98%, 7 days; inherently
biodegradable

Coupled Unitstest

93% (COD removal), ultimately
biodegradable

Carassius
auratusNA

LC 0 = 625 mg/l, LC 100 = 894 mg/l,“long-time exposure in hard water”

Lepomismacrochirus
Leuciscus
idus
Daphniamagna
Daphniamagna

NA

LC 50 = 1516 mg/l, 96 h

NA

LC 50 = 440 –760 mg/l, 96 h,“solution was not neutralised”
EC 0 = 80 mg/l, EC 100 = 120 mg/l,“long-time exposure in soft water”

NA

EC 0 = 1206 mg/l, EC 50 = 1535 mg/l,
EC 100 = 2083 mg/l (neutralised)
EC 0 = 73 mg/l, EC 50 = 85 mg/l,
EC 100 = 98 mg/l (not neutralised)

Carcinus
maenas (crab)
Scenedesmus
quadricauda
Pavlovalutheri(saltwater
chrysophytes)
Chaetoceros
gracilis
Microcystis
aeruginosa
Nitrosomonassp.
Pseudomonas
putidaNA

LC 50 = 160 mg/l, 48 h

NA

EC 0 = 640 mg/l, 7 daysNA

TLC (7d) = 1 – 300 mg/l

NA

TLC (7d) = 1 – 300 mg/l

NA

EC 0 = 80 mg/l, 8 daysNAno inhibition on NH 3 oxidation at
100 mg/l
EC 0 > 10,000 mg/l, 16 h

37 strains of
acidophilic
bacteriaNA

positive growth on all strains with
500 mg citric acid/l as sole C sourcefor 30 days at pH 3

Arthrobacter
globiformis,
10 strains
Entosiphon
sulcatum
Tetraselmis
tetrathele(saltwater)
Tetramitus
rostratus(freshwater)
Uronemaparduzci
Carassius
auratus
Daphniamagna

NA

good degradation of citric acid as sole
C source over 5 days

NA

EC 0 = 485 mg/l, 72 h

NA

TLC (7d) = 1 – 300 mg/l

NA

TLC (35hrs) ≤ 108 mg/l

NA

TLC = 622 mg/l

NA

LC 0 = 625 mg/l, LC 100 = 894 mg/l,“long-time exposure in hard water”
EC 0 = 80 mg/l, EC 100 = 120 mg/l,“long-time exposure in soft water”

Ecotoxicology
4.1

4.2

4.3

4.4

Acute/Prolonged
Toxicity to Fish

Acute Toxicity to
Aquatic Invertebrates

Toxicity to Aquatic
Plants, eg Algae

Toxicity to Micro organis ms, eg Bacteria

4.5.1 Chronic Toxicity toFish
4.5.2 Chronic Toxicity to
Aquatic Invertebrates

6

NA

NA

NA

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CITRIC ACID

CAS No. 77–92–9
Species
4.6.1 Toxicity to SoilDwelling Organisms
4.6.2 Toxicity to Terrestrial
Plants
4.6.3 Toxicity to Other NonMamm. Terrestrial
Species
4.8
Biotransformation
andKinetics
4.9

ProtocolResul ts
no studies located
all plants produce citric acidno studies locatedcitric acid is an intermediate in the
Krebs cycle which takes place inevery eukaryote cell
citric acid is “extremely widespreadin nature”

Additional Remarks

citric acid is “widely distributed inplants and animal tissues and fluids”
in man, during 24 h approximately
2000 g of citric acid are formed andfurther metabolised as intermediatesof the Krebs cycle in adults
Toxicity
5.1.1 Acute Oral Toxicity

5.1.2 Acute Inhalation
Toxicity
5.1.3 Acute Dermal Toxicity
5.1.4 Acute Toxicity, Other
Routes

5.2.1 Skin Irritation

rat
rat

NA
NA

LD 50 = 3,000 mg/kg
LD 50 = 5,000 mg/kg

rat
rat

NA
NA

LD 50 ≥ 6,730 mg/kg
LD 50 = 12,000 mg/kg

mouse

NA

LD 50 = 5,400 mg/kg for males andfemales; 5 males, 5 fem ales, gavage,
5 concent rations in water, controls

rabbitNAlethal dose = 7,000 mg/kg (probably
lowest lethal dose)no studies locatedno studies located
LD 50 = 5,500 mg/kg by s.c.
application
LD 50 = 2,700 mg/kg by s.c.
application

rat

NA

mouse

NA

rabbitNAdose = 500 mg/24 h; slightly
irritating, effects reported as “mild”

rabbitOECD 404

rabbitDraize test

according to guideline; slightly
irritating, avg. erythema score = 0.33,
oedema = 0
0.5 ml of 30% aq. solution for 4 h
under occlusive patch produced noeffect in intact skin, slight to welldefined effect in abraded skin; prim.
irritation index = 0.84

manclinical reportmanclinical reportmanclinical reportmanclinical report

UNEP PUBLICATIONS

irritant skin dermatitis in waiters andbakers attributed to citric acidin solution the acid may produce pain
if applied to abraded skina 0.3 N solution (~2%) can “sting”
intact skinpatch testing of 60 eczema patientswith 2.5% citric acid in petrolatum(probably 24-h covered contact) did
not produce any irritant reactions

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CAS No. 77–92–9
5.2.2 Eye Irritation

CAS No. 77–92–9

5.3

5.4

8

Sensitization

Repeated DoseToxicity

CITRIC ACID
Species
rabbitProtocolNArabbitNA

rabbitOECD 405

according to guideline; avg. cornea
score = 2.8; iris = 0.0; conjunctiva =1.7

Species
rabbitProtocolDraize test

Results
0.1 ml of 10% or 30% aq. solution
placed in lower conjunctival sac of 3
animals for 1 s; 10% sol. caused
moderate to weak conjunctival
irritation for 1 week, avg. Draizescore = 9.3; 30% sol. caused welldefined to moderate conjunctival
irritation in 2/3 animals for 14 d plus
short -lasting superficial lesion of
conjunct. epithelium, avg. Draizescore =16.0

manclinical report

severe eye damage in a man splashedin the eye with saturated aq. solutionmanclinical reportmouth sores, headache, asthma, nasal
blockage, general tiredness. itchinesswere reported after the ingestion offoods containinng citric acidman

clinical report

citric acid might be a skin sensitizer

ratinternal test
F. Hoffmann-La
Roche LtdNOEL = 4,000 mg/kg/d, LD 50 = 5,600± 440mg/kg/d; oral, gavage, once
daily for 5 days, post -exposure
observation 10 days; 10 males, 10
females, avg. weight = 150 g

rat

NA

oral, dietary, feed containing 1.2%
citric acid, probably ad libitum, for
90 weeks; “...no harmful effects on
the growth of two successive
generations. No effect on
reproduction, blood characteristics,
pathology ..., although a slightincrease in dental attrition wasreported”.

rat

NA

oral, dietary, feed containing 5% and3% citric acid for 2 years, slightly
decreased growth was observed but
no tissue abnormalities were found on
examination of the major organs.
NOAEL = 1200 mg/kg/d

rat

NA

oral, dietary, feed containing 1.2, 2.4,
4.8% citric acid for 6 weeks. At the
top dose, slight growth reduction,
mild blood and urine changes andslight degeneration of the thymus
gland and the spleen were observed.

UNEP PUBLICATIONSResul ts
irrigation for 30 min with 0.5% or 2 %aq. solution caused permanent
cloudiness resp. severe dense
opacification
750 µ g for 24 h caused “severe”
effects

OECD SIDS
CAS No. 77–92–9

5.5.A Genetic Toxicity invitro, Bacterial Test

5.5.B Genetic Toxicity invitro, Non -Bacterial
Test

5.6

Genetic Toxicity invivo

CITRIC ACID
Speciesrat

Protocol
NA

rat

NA

mouse

NA

rabbit

NA

dog

NA

guinea pig

NA

pig

NA

sheep

NA

Salmonella
typhimurium

OECD 471

not mutagenic in 4 defined strains
with and without metabolic activation

Salmonella
typhimurium

OECD 471

not mutagenic in 5 defined strains
with and without metabolic activation

yeast“yeast genemutation assay”

not mutagenic with and without
metabolic activation

ChinesehamsterNAno clastogenic effects reported infibroblast culture cells atconcentrations up to 1 mg citricacid/mlrat

dominant lethal
assay

no mutagenic potential after doses of
3 g/kg (possibly per day) for 5 days

rat

NA

no chromosomal damage in bonemarrow of rats fed up to 3 g/kg/d for
5 daysUNEP PUBLICATIONSResul ts
oral, dietary, feed containing 2%
citric acid. The absorption andurinary excretion of calcium andmagnesium were unaffected, althoughurinary zinc excretion was
temporarily elevated.
oral, dietary, feed containing 1.2%
citric acid for 1 year. No adverse
effect were reported (with thepossible exception of slight changes
in tooth structure) in two successive
generations.
oral, dietary, feed containing 5%
citric acid, probably ad libitum, forunspecified period to male mice;decreased growth and lower survival
times in treatment group 11 -12
months as opposed to 16 -17 months
in controls.
oral, dietary, feed containing 7.7%
sodium citrate, probably ad libitum,for 150 days to 15 rabbits; no adverse
effects were reported
oral, dietary, fed 1.38 g citric acid/kg
bw daily to 3 dogs for up to 120 days;
no adverse effects were reported
oral, dietary supplement with 1–5%
citric acid to unknown number ofanimals for up to 60 days; reduced
packed blood cell volume, nohistology was performed
oral, dietary; young pigs fed
cadmium -enriched diet containing 5%
citric acid; only reported effects were
elevated Cd levels in liver andkidneys and decreased zinc level inmuscle6 sheep given 795 mg citric acid/kg
bw daily via ruminal cannula for
uspecified time; no adverse effects
were reported

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CAS No. 77–92–9
5.8
Toxicity to
Reproduction

5.9

5.10

10

Developmental
Toxicity/
Teratogenicity

Other relevant
information

CITRIC ACID
Speciesrat

ProtocolNA

Resul ts
2-generation study over 90 weeks,oral, dietary, feed containing 1.2%(w/w) citric acid; no harmful effects
on growth of two successive
generations nor on reprod uction
parameters, pathology, blood charac teristics or calcium levels, only slightdental attrition was reported

rat

NA

oral, dietary, feed cont aining 1.2%
citric acid plus 0.1% sodium citrate
for 29 weeks prior to mating and thenfor “another few months”; no harmful
effects reported

rat

NA

rat

NA

rat

NA

oral, dietary, feed containing 5%
citric acid to female rats prior, during
and subsequent to mating; no harmful
effects reported
NOEL = 2500 mg/kg/d
oral, 295 mg citric acid/kg/d given tofemale rats during days 6 –15 ofpregnancy; no teratogenic or harmful
effects reported
oral, 241 mg citric acid/kg/d given tofemale rats during days 6 –15 ofpregnancy; no teratogenic or harmful
effects reported

mouse

NA

oral, dietary, feed containing 5%
citric acid to female mice prior,during and subsequent to mating;litter size and survival of offspringwere unaffected
NOEL = 7500 mg/kg/d

rabbitNA

hamster

NA

rat

NA

rats and miceNA

up to 425 mg citric acid/kg given tofemale rabbits during days 6–18 ofpregnancy; no teratogenic or harmful
effects reported
NOEL = 425 mg/kg/d
up to 272 mg citric acid/kg given tofemale hamsters during days 6 –10 ofpregnancy; no teratogenic or harmful
effects reported
oral, > 241 mg citric acid/kg/d given
to female rats during days 6 –15 ofpregnancy; no indication of adverse
effects on nidation, foetal survival or
abnormalities
oral, diet, feed contianing 5% citricacid given for unspecified time; nonegative effect on litter size or
subrvival up to weaning of pups

rats, mice,
rabbitsNA

citric acid and its salts injected byvarious routes caused nervous system,
lung, spleen and liver effects

rat

NA

intravenous infusion with sodium
citrate solution was shown to increasecalcium excretion

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CAS No. 77–92–9

CITRIC ACID
Specieshorse

ProtocolNA

Resul ts
int ravenous injection with 0.56 mg
sodium citrate/kg bw did not cause
any cardiovascular effects or effects
on blood composition

rats, mice,
rabbits

NA

Severe damage to the stomach lining
and nervous system effects werereported with high doses of citric acidcitric acid is a powerful chelating
agent and there is evidence that
dietary citric acid may reduce thebiological avilability of iron andcalcium
it has been shown in an in vitro
system for the development ofartificial caries that the application of
citric acid to teeth may make themmore susceptible to decay
citric acid and its salts may increase
the absorption and retention ofingested metals such as aluminium,tin, cadmium and lead

dog

NA

severe ulceration and tissue damage
occured in dogs receiving tongue
application of 0.1 ml of 50% citricacid solution for 5 minutes

dog

NA

broncvhoconstriction was inducedwith citric acidguinea-pigs

NA

Coughing was reported when guinea pigs were exposed for 30 minutes toatmospheric citric acid concentrationof 81 mg/m 3

man

5.11

Experience with
Human Exposure

the lowest concentration of inhaledcitric acid required to produce
involuntary coughing ranged from 0.5
to 32 mg/ml
reference booktotal daily consump tion of citric acidfrom natural sources and foodadditives may exceed 500 mg/kg

clinical report

after ingesting a single dose of 25 g
citric acid (approx. 417 mg/kg) a
young woman vomited and almost
diedclinical report,
various sourcess y s temic effects after single exposure
through i.v. transfusion of large
amounts of citrated blood: depletionof body calcium, effetcs on blood
composition, nausea, exacerbation,muscle weakness, breathingdifficulties up to cardiac arrest

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CAS No. 77–92–9

CITRIC ACID
SpeciesProtocolclinical report,
various sources

textbookreference book

Resul ts
systemic effects after repeatedexposure through oral doses ofpotassium citrate, either solid or
dissolved in water: minor
gastrointestinal disturbances,
diarrhoea, indigestion, nausea,“burning”
potassium and sodium ci trate havebeen used in doses of up to 15 g/d as
medications presumably without any
marked side effects
excretion of citric acid in 82 adults
ranges from 1.5 to 3.68 mmol/d (total
range 0.4–8.80 mmol/d) respectively
from 290 to 707 mg/d (total range
80–1,690 mg/d)

NA = Not available; most of these data are from widely accepted, peer-reviewed secondary sources.

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CITRIC ACIDSIDS Initial Assessment Report
1.

IDENTITY

Name

Citric acid

CAS No.

77– 92–9

Chemical Name

2-Hydroxy-1,2,3-propanetricarboxylic acid

Synonyms

β -Hydroxytricarballylic acid
2-Hydroxypropanetricarboxylic acid

Structure

CH2 COOH
H O-CCOOH
CH2 COOH

Empirical FormulaC 6H 8 O 7Molecular Weight

192.12 g/mol

Purity> 99 % w/w

Melting Point~153 °C

Boiling Point

not applicable, de composition above 175 °C

Water Solubility≥ 576 g/l (20 °C)

Dissociation constants

p Ka1 = 3.13, p Ka 2 = 4.76, pKa 3 = 6.4 (25 °C)

n-Octanol/waterpartition coefficientlog POW = –1.72 (20 °C)

Vapour Pressure

known to be nonvolatile; no precise data located
QSAR estimation: 7.3 x 10 -7 Pa at 25 °C

Classification

classified as irritating to eyes

Citric acid is a water soluble organic solid with a melting point of approximately 153 °C.
It is an ubiquitous natural substance that appears as an in termediate in the basic
physiological citric acid cycle in every eukaryote cell. Citric acid has been produced formany years in high volumes and added to processed food and beverages, used inpharmaceutical preparations and in household cleaners as well as in special technicalapplications.

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13OECD SIDS2.

EXPOSURE

2.1

General Discussion

CITRIC ACID

Between 100,000 and 500,0000 tonnes/annum of citric acid is estimated to have been
produced in Europe, including Eastern Europe and Israel, in 1999. Global production isestimated by industry to be approaching 1,000,000 t/a. Worldwide, citric acid production
is mainly through microbio logical fermentation of molasses and sugar solutions, while
extraction from lemon juice or chemical synthesis is negligible. Dilute citric acid fromfiltered fermentation broths is precipitated with milk of lime (calcium hydroxide) as
practically insoluble calcium citrate, which is then reacted with sulfuric acid to form citricacid and calcium sulfate (gypsum) as a recoverable and valorisable by-product.
Approximately 50% of the production is estimated to be used by the beverage and softdrinks industry, another 20% in food processing industry and around 10% in
pharmaceutical industry, where citric acid is used as an acidulant, buffering agent, tasteenhancer and synergist in antioxidant mixtures. Thus, approximately four fifths are
destined for human consumption and have a very wide dispersive use. The remainder issplit between technical applications in various industries as a complex-forming agent,cle aning agent, softening agent, decalcifying agent, derusting agent, corrosive agent andsynergist in antioxidant mixtures; many of those applic ations also have wide dispersiveuse, eg, washing powders and detergents. Last, small fractions are used in special applic ations such as citrate buffering of whole blood samples for transfusion.

2.2

Environmental Partitioning and Fate

Citric acid is exceedingly soluble in water, has relatively low acid dissociation constants
that ensure that the substance is at least partly deprotonated in aqueous solution at allenvironmentally relevant pH values. Additionally, it has a low n-octanol/water partition
coefficient; no precise information was found on vapour pressure but the melting point isaround 153 °C. The re sult of a QSAR estimation is 7.3 x 10 -7 Pa at 25 °C. These
properties of citric acid indicate that it is likely to partition mainly into the water phase,with very little distributing into the atmosphere. In addition, due to the high watersolubility the substance is unlikely to adsorb onto soil or sediment. Using a level III
generic fugacity model (see Table 1) it is predicted that if citric acid is released to water,
it is unlikely to partition into other environmental compartments. Release of citric acid to
air is likely to lead to distribution into soil and water through deposition processes, while
release or deposition onto soil is predicted to lead to redistribution into the aquaticcompartment. In corroboration of this prediction, a pure equilibrium partitioning model
reflecting only distribution based on free intermedia exchange (but neglecting emission,
advection or reaction; Mackay et al.: EQC Model v. 1.0, Level I, Environmental
Modelling Centre, Trent University, Canada) results in the partitioning of 99.99% to theaquatic compartment.

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CITRIC ACID

Table 1: Environmental distribution of citric acid using a level III generic fugacity model[Mackay et al.: Level III, Fugacity-based Environmental Equilibrium Partitioning Model,
v. 2.2, Environmental Modelling Centre, Trent University, Canada].
Compartment R e l e a s e :100 % to air 100 % to water 100 % to soil
33 % each to air,water and soil
Air
Water
Sediment

0.06 %
38.41 %
0.01 %< 0.01 %99.96 %
0.04 %< 0.01 %36.28 %
0.01 %

0.02 %
55.76 %
0.02 %

Soil

61.51 %

< 0.01 %63.70 %

44.20 %In the aquatic compartment, citric acid may be expected to be rapidly degraded as it is
known to be well biodegradable from several ready and inherent aerobic biodegrada tion
tests (Table 2).
Table 2: Biodegradation test data for citric acid.
Test system
Results
Modified Sturm
97% (CO 2 evolution)
Test
100% (DOC removal)
Closed Bottle TestB O D 30 /COD = 90%
BOD 5 /COD Ratio
B O D 5= 526 mg
C O D = 728 mg
B O D 5/ C O D = 0.72
BOD 5 /ThOD Ratio B O D 5/ThOD = 58% –61%
BOD 1 /ThOD Ratio B O D 1/ThOD = 13%
BOD 20/ThOD Ratio BO D 20 /ThOD = 98%
Z a h n -Wellens Test
Z a h n -Wellens Test
Coupled Units Test

85%, 1 day (DOC
removal)98%, 7 days (DOC
removal)93% (COD removal)

Notes
readily biodegradable; exposure period
not statedreadily biodegradable
readily biodegradable;
concentration of test substance andactivated sludge not statedreadily biodegradable; data fromthree publications
readily biodegradable; initial test
substance concentration 720 mg/l
inherently biodegradable
inherently biodegradable
ultimately biodegradable; exposure
period not stated

The prediction of extensive and rapid degradation, both in sewage treatment plants and innatural water bodies, is borne out by experimental data confirming double to three times
the degradation of low concentrations of citric acid in lake water at pH 8 as compared toin distilled water. Monitor ing data show that while raw sewage contains up to 10 mg
citrate/l, background concentrations in river water range between < 0.04 and maximally
0.2 mg/l, respectively in Atlantic coast surface seawater between 0.025 and 0.145 mg/l.
Regarding these surface water concentrations it should be kept in mind that these citrateconcentrations do not only derive from manmade citric acid but that citric acid isextremely widespread in nature respectively widely distributed in plants and animal
tissues and fluids and that every single eukaryote organism produces citric acid andexcretes part of it to the environment.

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OECD SIDS

CITRIC ACID

Estimation of the indirect photolysis using a photochemical hydroxyl radical reaction
constant of 7.02 x 10 -12 cm 3/mol sec and assuming a hydroxyl radical concentration 0.5 x
10 6 OH/cm3 would result in an atmospheric half life of 2.3 days (Meylan and Howard,
Epiwin, SRC).

2.3

Consumer and Occupational Exposure

Industrial releases of citric acid may occur from the sites of production and through use inindustrial processes. Consumers are directly exposed to citric acid or its salts in diluted
concentrations in many applications from soft drinks and processed food to common
household cleaners, detergents, washing powders etc.; there are no acceptable daily intake
levels. Occupational expos ure may occur during manufacturing and processing of citricacid; there are no recommended occupational exposure levels.

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3.

CITRIC ACID

HUMAN HEALTH HAZARDSIn human (as well as in animal and plant) physiology, citric acid is a very common
intermediate in one of the central biochemical cycles, the Krebs or tricarboxylic acidcycle, which takes place in every cell. It completes the breakdown of pyruvate formed
from glucose through glycolysis, thereby liberating carbon dioxide and a further fourhydrogen atoms which are picked up by electron transport molecules. Thus, in man
approximately 2 kg of citric acid are formed and metabolised every day. This
physiological pathway is very well developed and capable of processing very highamounts of citric acid as long as it occurs in low concentrations. Part of the circulating(mainly metabolic but also ingested) citric acid is excreted in urine, with 24-hour urinereference values between 1.5 and 3.68 mmol, corresponding to 0.29– 0.71 g citric acidexcreted per person per day.

3.1

Acute toxicity

Citric acid has a low acute toxicity by oral application in both rat (LD50 = 3,000– 12,000
mg/kg, 3 different values) and mouse (LD 50 = 5,400 mg/kg). General effects comprised
physiological disturbances (acidosis and calcium deficiency), while “high” doses caused
nervous system effects as well as severe damage to the stomach mucosa.
By subcutaneous application, LD50 values of 5,500 mg/kg in rats and 2,700 mg/kg in mice
were reported.
Injection of citric acid by various routes in rats, mice and rabbits (no doses stated) caused
nervous system, lung, spleen and liver effects that were in part attributed to acidosis andcalcium deficiency.
Ingestion of a single dose of 25 g of citric acid by a woman (corresponding to approx. 417
mg/kg) caused vomiting and nearly dying in one reported case. Volunteers given oral
doses of potassium or magnesium citrate corresponding to approx. 4.7 g of citric acid did
not suffer any overt gastrointestinal effects.
Injection of large volumes of citrated blood during transfusion may lead to hypocalcaemia
and changes in blood composition with concomitant nausea, muscle weakness, breathingdifficulties and even cardiac arrest.
No animal studies are available for acute dermal and acute inhalation toxicity.

3.2

Irritation and sensitisation

3.2.1 Irritation to the skin
Local effects of citric acid to the skin (rabbit) are repor ted as slightly irritating in two
studies and as not irritaing in a third study using a 30% aqueous solution.
The application of a 50% citric acid solution to the tongue of dogs for 5 minutes resulted
in severe ulceration and tissue damage.

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CITRIC ACID

3.2.2 Irritation to the eye
Two nonstandard studies on eye irritation using presumably neat citric acid applied for 24hours respectively a 2% aqueous solution for 30 minutes found severe and permanent
injury to rabbit eyes. In a recent study the application of 0.1 ml of a 30% solution of citricacid to one eye for one second resulted in a well-defined to moderate conjunctival
irritation which disappeared in two of the three treated rabbits within 14 days;
additionally, a short-lasting superficial lesion of the conjunctiv al epithelium was noted,
but no macroscopical alteration of the cornea.
In an acute eye irritation/corrosion test in rabbits according to OECD 405 citric acid washighly irritating.
3.2.3 Irritation to the respiratory tract
Citric acid (concentration and application not stated) caused brochoconstriction in dogs
with nonspecific airway hyperreactivity.
Coughing is reported for guinea pigs exposed for 30 minutes to atmospheric citric acidconcentrations of 81 mg/m 3 (aerosolised 6% solution). Coughing was also pro duced inguinea pigs exposed to 75 mg citric acid/ml as an aerosol for 3 minutes.
Coughing was also caused by instillation of 1 ml of an approx. 5.2% solution to the lower
trachea in lambs, but not by instillation to the mid-trachea or laryngeal area.
According to current criteria, pure citric acid and aqueous solutions must be judged as
irritant to the eyes but not to the skin.
3.2.4 Experience with human exposure
An irritant skin dermatitis attributed to citric acid has been reported amongst waiters andbakers. While presumably aqueous solutions (2% in one case, not stated in the other) may
produce pain or “sting”, patch testing of 60 eczema patients with 2.5% citric acid in
petrolatum did not produce any irritant or allergic reactions; thus, the reaction appears toreflect mainly the acid effect of the substance, which in unbuffered 2% to 2.5% aqueous
solution results in a pH of approximately 2.
Severe eye damage was described in a patient who was splashed in the eye with asaturated solution of citric acid. Mouth ulcers may be provoked by citric acid andinhalation of citric acid aerosols may induce coughing and bronchoconstriction.
Symptoms of possible sensitisation were described in a man after the ingestion of foods
containing citric acid; challenge by direct application of citric acid crystals to insidesurface of his mouth produced sores, as did some other organic acids, but potassium
citrate crystals and magnesium citrate solution did not. In another case, urticaria andmouth ulcers were reported followin g exposure to citric acid, with no further details
given.
A standard textbook implies that citric acid might be a skin sensitizer by recommending
patch tests with aqueous solutions to detect sensitised individuals. However, patch testingof 60 eczema patients with 2.5% citric acid in petrolatum did not produce any irritant orallergic reactions. Genuine sensitisation to citric acid seems to be a rare phenomenon.

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3.3
3.3.1

CITRIC ACID

Repeated dose toxicity
Animal data

Groups of 10 male and 10 female rats were given 2 g to 16 g/kg/d orally by gavage during
5 days. A NOEL of 4000 mg/kg/d and an LD 50 of 5600 mg/kg/d were determined.
Groups of 10 male rats being fed up to 4.8% citric acid in feed (corresponding to approx.
4.67 g/kg/d) for 6 weeks showed slight growth reduction and, in the highest-dose group,
mild blood and urine parameter changes and slight degeneration of the thymus gland andspleen.
In 9 rats being fed 2% citric acid (approx. 0.13 g/kg/d) no effect on food consumption or
body weight was noted nor were the absorption and urinary excretion of calcium andmagnesium affected, however, urinary zinc excretion was found to be temporarily
elevated.
In male mice being fed 5% citric acid (approx. 7.5 g/kg/d; in the range of published acute
LD 50 ) for an unspecified time, decreased growth and lower survival times (11–13 vs. 16–
17 months in controls) were reported.
In guinea pigs fed 1–5% citric acid (approx. 0.4– 2 g/kg/d) for 60 days, a reduced packed
cell volume in the blood was the only effect noted.
No adverse effects were seen in both rabbits and dogs fed approx. 1.5 resp. 1.4 g/kg/d for
150 resp. 120 days.
Body weight gain was unaffected in young pigs fed a cadmium-enriched diet containing
5% citric acid (approx. 4 g/kg/d), but elevated cadmium in the liver and kidneys anddecreased zinc levels in muscle were found.
A 2-year chronic oral study in rats being given 5% or 3% citric acid in feed (approx. 2
resp. 1.2 g/kg/d) found slightly decreased growth in the higher dosage group but no tissue
abnormalities in the major organs. From the lower dosage a NOAEL of 1200 mg/kg/d
results. Similarly, NOAELs of 1500 mg/kg/d (rabbit) and of 1400 mg/kg/d (dog) havebeen determined.
No adverse effects, with the possible exception of slight changes of tooth structure, were
found when two successive generations of rats were fed 1.2% citric acid (approx. 600
mg/kg/d; duration not stated, probably about one year).
3.3.2 Human data
Repeated exposure of up to 15 g/d of potassium and sodium citrate as medications did notcause any reported marked side effects, but minor gastrointestinal disturbances (diarrhoea,
indigestion, nausea, “burning”) were experienced by 22 out of 81 patients taking
potassium citrate in water and 7 out of 75 taking solid potassium citrate (doses not statedin both gr oups) for the treatment of renal calculi.
Ingestion of potassium citrate solutions, an unknown but large volume on possibly morethat on occasion in one case and 200–400 ml over 5–7 days in two other cases, caused
abnormal heart rhythms, which were assessed as probably due to elevated potassium levels
rather than to citrate.

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CITRIC ACID

Daily ingestion of 6 g of sodium citrate in 10% aqueous solution over 4 days in 10 men
affected the blood acid- base balance, with the urine becoming more alkaline and sodium
excretion being increasing while magnesium and potassium excretion was decreased.
In general, citric acid is a strong chelating agent, the dietary uptake of which may
interfere with biological availability, absorption and excretion of metals. Further, loss ofsuperficial enamel and erosion of teeth as well as local irritation result from frequent
ingestion of citric acid in beverages including natural fruit juices; citric acid fumes werereported to apparently affect the teeth of exposed workers.
The average daily intake of citric acid from natural sources in the diet and food additives
was estimated at about 40 mg/kg for women, 130 mg/kg for infants and 400 mg/kg forindividuals on slimming diets; maximum daily intake is reported to reach levels of 500
mg/kg. No formal ADI (acceptable daily intake) level has been specified for citric acidand its common salts by the Joint FAO/WHO Expert Committee on Food Additives nor by
the EC Scientific Committee for Food.

3.4

Mutagenicity

In several in vitro and in vivo tests citric acid was not mutagenic. The substance was not
mutagenic either in bacterial tests with Salmonella typhimurium (Ames test, 2 studies) and
Escherichia coli, with and without metabolic activation. Citric acid was shown to reduce
the activity of a recognised chemical mutagen in S. typhimurium. No clear indication ofmutagenicity was reported from studies with S. typhimurium or the yeast Saccharomyces
cerevisiae living in the body cavity of an unspecified laboratory animal nor in S.
cerevisiae cell cultures with or without metabolic activation. Neither was chromosomal
damage caused by citric acid in human and hamster cell cultures.
A dominant lethal assay with male rats being treated with up to 3 g/kg/d for 5 days was
negative; no chromosomal damage occurred in the bone marrow cell of these male rats.

3.5

Reproduction and developmental toxicity

In a two-generation 90 days study with male and female rats fed 1.2 % citric acid noadverse effect on reproductive parameters nor any teratogenicity of dietary citric acid wasseen. There were no indications of teratogenic or other adverse effects in three shorter term reproductive studies in rats with dietary dosage of either 5 % citric acid (approx.
2.5 g/kg/d) previous, during and after mating (NOEL = 2500 mg/kg/d), or 295 mg/kg/d(route unspecified) during days 6–15 of pregnancy.
Similar findings of no effects were reported for two reproductive and teratogenicity
studies in mice receiving either 5 % citric acid (approx. 7.5 g/kg/d; in the range of
published acute LD 50 ) previous, during and after mating (NOEL = 7500 mg/kg/d) or
241 mg/kg/d during days 6–15 of pregnancy.
Further, there were no indications of teratogenicity or other adverse effects in female
hamsters receiving 272 mg citric acid/kg (presumably daily) during days 6–10 ofpregnancy nor in female rabbits receiving up to 425 mg/kg/d during days 6–18 (NOEL =425 mg/kg/d).

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3.6

CITRIC ACID

Carcinogenicity

In a study with only 20 male rats receiving op to 5% citric acid in the feed (approx. 2
g/kg/d) for 2 years no evidence of carcinogenicity was reported.
In a further study with rats fed 1.7% sodium citrate (approx. 0.74 g/kg/d) for 8 weeks noincrease in DNA synthesis, a measure of cell proliferation, in the bladder epithelium wasfound.
In contrast, several nonstandar d studies report an increased incidence of tumours in rats
treated with known carcinogens and receiving citric acid or citrate (between 1.4 and 2.6 g
citric acid equivalents/kg/d for 20–45 weeks) at the same time. In at least one of thestudies with sodium citrate in feed and the carcinogen given in drinking water theobserved tumorigenic effect was not attributed to the citrate anion but to the sodium cation
causing increased water (and thereby carcinogen) intake; in this and another study, citricacid was judged not to have a tumour-promoting effect, respectively not to be a potent
tumour promoter.

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4.

CITRIC ACID

HAZARDS TO THE ENVIRONMENT

Citric acid was tested in many, although often nonstandard ecotoxicity tests that are
widely cited in standard works of literature and in reviewed databases. Table 3 lists theresults of aquatic tests.
Table 3: Ecotoxicity of citric acid.
SpeciesResults
Fish:
Carassius
LC 0 = 625 mg/l
auratus, goldfish
LC 100 = 894 mg/l
(freshwater)
Leuciscus
96-h LC50 = 440–
idus, golden orfe
760 mg/l(freshwater)
Lepomis96-h LC50 = 1,516 mg/l
macrochirus, bluegill (freshwater)
Crustaceans:
Daphnia magna
24-h EC0 = 1,206 mg/l
(freshwater)
24-h E C 50 = 1,535 mg/l
24-h E C 100 = 2,083 mg/l
24-h EC0 =73 mg/l24-h E C 50 =85 mg/l24-h E C 100 =98 mg/lDaphnia magna
EC 0 =
80 mg/l(freshwater)
EC 100 = 120 mg/l
Carcinus maenas(saltwater) (crab)
Algae:
Scenedesmus quadri c a u d a (freshwater
green algae)
Pavlova lutheri (saltwater chrysophytes)
Chaetoceros gracilis,
Navicularamosissima(saltwater diatoms)
Protozoa:
Entosiphon sulcatum(freshwater)
Tetramitus rostratus(freshwater)

48-h LC50 = 160 mg/l

Uronema parduczi(freshwater)
Tetraselmis
tetrathele (saltwater)

TLC = 622 mg/l

22

Notes
“long-time exposure in hard water”,
exposure period and method not stated“solution was not neutralised”,
method not statedmethod not statedneutralised

not neutralised“long-time exposure in soft water”,
exposure period and method notstatedmethod not stated

7-day TLC = 640 mg/l

toxic limit concentration,
method not stated

7-day TLC = 1–300 mg/l

toxic limit concentration,
method not statedtoxic limit concentration,
method not stated

7-day TLC = 1–300 mg/l

72-h EC0 = 485 mg/l

method not stated35-h TLC ≤ 108 mg/l

toxic limit concentration, exposure
period ambiguous,
method not statedtoxic limit concentration, exposure
period and method not statedtoxic limit concentration,
method not stated

7-day TLC = 1–300 mg/l

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CITRIC ACID

Bacteria (all freshwater):Microcystis
8-day EC 0 = 80 mg/l
aeruginosa
Nitrosomonas sp.
EC 0 = 100 mg/l
“37 Strains ofbacteria”
Pseudomonas putida
Arthrobacter globi formis, 10 strains

all strains positive
growth30-day E C 0 = 500 mg/l
16-h EC0 > 10,000 mg/l
good to excellent
degradation

cyanobacteria, method not statedno inhibition of nitrification,
exposure period and method notstatedmicrobes
isolated from acidic minewater, p H = 3, citric acid as solecarbon source, method not statedmethod not statedmicrobes isolated from soil, citricacid as sole C sour ce, mineral salts
added, exposure period and method

In freshwater, citric acid appears to be of low toxicity to aquatic acute test standard
organisms, fish, daphnia and algae, with consistent LC50 /EC 50 values of several hundred
milligrams per litre. Many more results refer to toxic limit concentrations or no effectconcentrations, from which no dependable EC 50 can be derived. In a “long-term” daphnia
test in “soft water”, which may be assumed not to buffer the acid effect of the test
substance , the EC 0 was found to be 80 mg/l and the EC100 was 120 mg/l, resulting in ageometric mean EC50 of 98 mg/l. Similarly, the lowest reported EC 0 in cyanobacteria was
80 mg/l.
Different strains of bacteria showed positive growth respectively good to excellent
degradation with citric acid as the sole carbon source and the same holds for sewage
sludge micro-organisms that thrive on citric acid.
The few marine species for which data are available seem to be somewhat more sensitive
to citric acid, although at 160 mg/l the only acute LC50 reported for a crab is over 100
mg/l, while for two algae and a protozoan the subacute toxic limit concentration is only
given as a wide range between 1 and 300 mg/l. Still, at least for the few tested organisms
citric acid does not seem to be highly or acutely toxic.
The toxicity of citric acid to other environmentally relevant species has not been
determined.

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5.

5.1

CITRIC ACIDCONCLUSIONS AND RECOMMENDATIONS

Conclusions

A large body of physicochemical, toxicological and environmenta lly relevant data exists
for citric acid, many of which are relatively old. While the quality of a single result often
may be hard or even impossible to assess, the sheer volume and high congruence of thedata result in a uniform picture all the same.
5.1.1 Human Health
Based on wide spectrum of data relating to experimental animals and on human experience
citric acid has a low acute toxicity; only one case of near fatal human intoxication was
found. In a repeated dose study with rats a NOAEL of 1200 mg/kg/d and a LOAEL of2000 mg/kg/d have been determined. The major subchronic and chronic toxic effects seemto be limited to changes in blood chemistry respectively metal absorption and excretion
kinetics, even at high doses. Citric acid is a powerful chelating agent and there is evidence
that dietary citric acid may reduce the biological avilability of iron and calcium. Tooth
erosion through dissolution of the enamel due to the acid effect in aqueous solution as
well as exposure to citric acid fumes has been reported as a possible adverse consequenceof long-term over-exposure to citric acid.
Based on several studies, citric acid is not suspected of being a carcinogen nor a
reprotoxic or teratogenic agent. Further, it is not mutagenic in vitro and in vivo . Judging
from the few reports on intolerance also the sensitising potential of citric acid is seen as
low.
Irritation, in particular of the eyes, but also the potential for irritation of the respiratory
pathways and the skin is the major, if not the only, genuine toxicological hazard presented
by citric acid. This conclusion is borne out by a series of reports relating to eye and skinirritation; further, it is also plausible with regard to the use pattern of citric acid, whichmust be characterised as ranging from closed to quasi-closed system in manufacturing andprocessing to wide -dispersive and concerning the whole population in its many final uses.
5.1.2 Environment
Due to its physicochemical characteristics citric acid is highly mobile in the environment
and will rapidly partition to the aquatic compartment; distribution to soil is of purely
temporary nature, while air or sediment constitute negligible sinks.
Based on several laboratory biodegradation tests (both ready and inherent), one fieldreport in lake water and a few monitoring data, citric acid is rapidly degraded in both
sewage works and surface waters. In spite of a genuine high-volume production that has
been going on for years, with wide dispersive use pattern, no increase in environmental
concentrations has been reported.
Citric acid is of low toxicity to freshwater fish, daphnia and algae; reported EC 50 values
range from just below 100 mg/l to several hundreds of milligrams per litre. LC 50 values
for fish range from 440 to 1516 mg/l. The one marine LC 50 published for a crab is 160
mg/l. Those tests that may qualify as subacute or possibly long-term show comparable
effect values. Similarly, citric acid has no obvious toxic potential against protozoans andmany species or strains of bacteria. No toxicity to activated sludge micro-organisms
24

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respectively inhibition
biodegradability tests.

CITRIC ACID
ofsubstratebiodegradationwasreportedinvariousBased on the available data, citric acid is not judged to be a substance that presents ahazard to the environment.

5.2

Recommendation

The chemical is currently of low priority for further work.

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CITRIC ACIDI U C L I D D a t a

S e tExisting Chemical
CAS No.
EINECS Name
EINECS No.
Molecular Weight
Molecular Formula

Substance ID: 77 -9 2- 9
77 -9 2-9
1,2, 3-Propanetricarboxylic acid, 2 -h y d r o x y2 0 1- 069 -1
192.12C6 H8 O7

Producer Related Part
Company:
Creation date:

F.Hoffmann- La Roche AG
22 -MAY- 00

Substance Related Part
Company:
F.Hoffmann- La Roche AG
Creation date:22 -MAY- 00
Printing date:
Revision date:
Date of last Update:18 -OCT- 01
24 -SEP- 01

Number of Pages:

63

Chapter (profile):
Chapter: 1, 2, 3, 4, 5, 7
Reliability (profile): Reliability: without reliability, 1, 2, 3, 4
Flags (profile):
Flags: without flag, confidential, non confidential,
WGK (DE), TA- Luft (DE), Material Safety Dataset, Risk
Assessment, Directive 67/548/EEC

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CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

1. General Information
1.0.1 OECD and Company Information
Type:
Name:

sponsor country
Switzerland

07 -MAY- 01
Type:
Name:
Partner:
Town:
Country:lead organisation
Swiss Agency for Environment, Forests and Landscape
Dr Urs Stämpfli
Date:3003 Bern
Switzerland

08 -MAY- 01
Type:
Name:
Partner:Street:Town:
Country:
Phone:
Telefax:
Telex:

other: Sponsor Company
F.Hoffmann-La Roche Ltd
Pascal Iltis
Grenzacherst r a s s e
4070 Basel
Switzerland
0 6 1-6 8 8 ' 1 1 ' 1 1
0 6 1-6 9 1 ' 9 3 ' 9 1
962'292

Date:

08 -MAY- 01
Type:other: co -sponsors

Remark:

ADM (Republic of Ireland), Jungb unzlauer (Switzerland),Gadot(Israel)

03 -NOV- 00

1.0.2 Location of Production Site
Name of Plant:

European Citric Acid Manufacturers (ECAMA) Companies

Country:

Belgium, Republic of Ireland, United Kingdom, Austria,
IsraelCompanies: Roche, ADM, T&L/Stately, Jungbunzlauer, Gadot

Remark:17 -OCT- 00

1.0.3 Identity of Recipients
1.1 General Substance Information
Substance type:Physical status:
Purity:06 -DEC- 00

natural substance

Substance type:Physical status:
Purity:07 -DEC- 0 0organic> 99 % w/w(112)> 99 % w/w(29)

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CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

1. General Information
1.1.1 Spectra
1.2 Synonyms
2- Hydroxypropanetricarboxylic acid06 -DEC- 0 0(35)

beta -Hydroxytricarballylic acid06 -DEC- 0 0(22)

1.3 Impurities
C A S- No:
EINECS- N o :EI NECS- N a m e :Contents:
07 -DEC- 0 0
C A S- No:
EINECS- N o :EINECS- N a m e :Contents:
07 -DEC- 00
C A S- No:
EINECS- N o :EINECS- N a m e :Contents:
07 -DEC- 0 07732- 18 -5
2 3 1-791 -2
water< 1 % w/w
(29) (30)sulfate< .15 % w/w(29 ) (30)

oxalates< .035 % w/w(29) (30)C A S- No:
EINECS- N o :EINECS- N a m e :Contents:
07 -DEC- 0 0

7440- 70 -2
2 3 1-179 -5
calcium< .02 % w/w

C A S- No:
EINECS- N o :EINECS- N a m e :Contents:
07 -DEC- 0 07439- 89 -6
2 3 1-096 -4
iron< .005 % w/w

C A S- No:
EINECS- N o :EINECS- N a m e :Contents:
07 -DEC- 00(29) (30)( 2 9) ( 3 0 )chloride< .005 % w/w(29) (30)

1.4 Additives
C A S- No:
EINECS- N o :EINECS- N a m e :28

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

1. General Information
Remark:06 -DEC- 00

No additives are being used(30)

1.5 Quantity
Production during the last 12 months: yes
Quantity produced :100 000 - 500 000 tonnes in 2000
Country:
European Union, Eastern Europe and Israel
25 -JUL- 00
Prod uction during
Quantity produced
Country:
Remark:20 -SEP- 00

the last 12 months: yes:500 000 - 1 000 000 tonnes in 2000
Worldwideindustry estimate

1.6.1 Labelling
Labelling:
Symbols:
R- Phrases:
S- Phrases:
06 -DEC- 00

Xi(36) Irritating to eyes
(24/25) Avoid contact with skin and eyes
(35)

1.6.2 Classification
Classification:
Class of danger:
R- Phrases:
06 -DEC- 00

as in Directive 67/548/EEC
irritating(36) Irritating to eyes
(35)

1.7 Use Pattern
Type:
Category:
04 -SEP- 00

industrial
other: wide dispersive use

Type:Category:
04 -SEP- 00

industrial
other: soft drinks and beverage industry, approx. 50%

Type:
Category:
04 -SEP- 00

industrial
other: food industry, approx. 20%

Type:
Category:
04 -SEP- 00

industrial
other: pharmaceutical industry, approx. 10%

Type:
Category:

industrial
other: various industries (softening agent, cleaning
agent,corrosive agent, synergist in antioxidant
mixtures)

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CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

1. General Information
06 -DEC- 0 0
Type:Category:( 2 5 ) (96)industrial
other: detergent industry (complex forming agent inwashing powders and detergents)

04 -SEP- 00

1.7.1 Technology Production/Use
Remark:Uses in Consumer Products: Processed food and beverages(solid/liquid); Pharmaceutical preparations, mainly
effervescent tablets (solid); Household cleaners(liquid)

22 -MAY- 00

1.8 Occupational Exposure Limit Values
Type of limit:
Limit value:
Remark:06 -DEC- 00
Type of limit:
Limit value:
Remark:06 -DEC- 00
Type of limit:
Limit value:
Remark:06 -DEC- 00

MAC (NL)
no data available(48)
MAK (DE)no data available(48)
MEL (UK)no data available(48)

1.9 Source of Exposure
Memo:

Exposure to concentrated solid substance or solutions ismost likely during manufacturing, packaging andindustrial use.

04 -SEP- 00

1.10.1 Recommendations/Precautionary Measures
Type:

Handling

Remark:For industrial h andling use eye protection with tightly
fitting goggles, skin protection with acid-proof gloves
and full protective working clothes.

03 -NOV- 00

1.10.2 Emergency Measures
Remark:30

I n c a s e o f e y e c o n t a c t , r i n s e eyes for at least 10 minutes
keeping eyelids forcibly open. For skin contact, takeoff affected clothing and wash skin with water and soap

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

1. General Information

only. In case of accidental ingestion drink a lot ofwater. If itching, soreness or irritation develops
consult a doctor.
04 -SEP- 00

1.11 Packaging
Memo:

Polyethylene -lined approved strong paper bags or fibre
Drum for dry substance; food -approved plastic orstainless steel drums or tanks for aqueous solutions.

20 -SEP- 00

1.12 Possib. of Rendering Subst. HarmlessType ofdestruction:

Incineration

04 -SEP- 00

1.13 Statements Concerning Waste
Memo:

Incinerate solids. Biological wastewater treatment
for solutions.

04 -SEP- 00

1.14.1 Water Pollution
1.14.2 Major Accident Hazards
1.14.3 Air Pollution
1.15 Additional RemarksMemo:
05 -DEC- 00

The substance can be incinerated in an appropriate
installation with flue gas scrubbing(35)

1.16 Last Literature Search
Date of Search:

20 -S E P- 00

03 -NOV- 00

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CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

1. General Information
1.17 Reviews
Memo:
04 -SEP- 00

HEDSET Datas e t 1 9 9 3

Memo:Fed. Am. Soc. Exp. Biology (1977): evaluation of thehealth aspects of citric acid, sodium citrate, ammonium
citrate, triethyl citrate, isopropyl citrate and stearyl
citrate as food ingredients.
(36)

03 -NOV- 00
Memo:

(48)

BIBRA Toxicity profile (1993): Citric acid and its
common salts

03 -NOV- 00(7)1.18 Listings e.g. Chemical Inventories
Type:
Additional Info:

EINECS
201 069 1

04 -SEP- 00
Additional Info:

RTECS accession no. GE 7350000

21 -SEP- 00

32

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

2. Physico-chemical Data
2.1 Melting Point
Value:
Reliability:
08 -MAY- 01= 152 - 159 degree C(4) not assignable

Value:
Decomposition:
Sublimation:
Re liability:
08 -MAY- 01

ca. 153 degree Cnono(4) not assignable

(85)

(19)

2.2 Boiling Point
Value:
Decomposition:
Remark:Reliability:
08 -MAY- 01
Value:
Decomposition:
Remark:Reliability:
08 -MAY- 01

yes
No boiling point due to substance decomposition above
175 deg ree C(4) not assignable
(96)

yes
No boiling point due to substance decomposition(4) not assignable(19)

2.3 Density
Type:
Value:
Reliability:
08 -MAY- 01

relative density= 1.665 at 20 degree C(4) not assignable

Type:
Value:
Method:Reliability:
21 -SEP- 00

bulk density
ca. 500 - 950 kg/m3 at 20 degree C
other: DIN 53912(2) valid with restrictions

(19)

(48)

2.3.1 Granulometry
2.4 Vapour Pressure
Value:
Remark:24 -SEP- 01

No studies located

Value:
Method:Result:24 -SEP- 01

QSAR estimation
7.3 x 10E -7 Pa(94)

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33

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

2. Physico-chemical Data
2.5 Partition Co efficientlog Pow:
Method:Year:
Reliability:
08 -MAY- 01= -1.72 at 20 degree C(4) not assignable(116)

2.6.1 Water Solubility
Value:
Reliabi l i t y :08 -MAY- 01

ca. 592 g/l at 20 degree C(4) not assignable

Value:
Reliability:
08 -MAY- 01

ca. 643 g/l at 30 degree C(4) not assignable

Value:
Reliability:
05 -DEC- 00

ca. 576 g/l at 20 degree C(2) valid with restrictions

Value:
Test condition:
Reliability:
08 -MAY- 01

ca. 771 g/l
Water at room temperature(2) valid with restrictions

Value:
Test condition:
Reliability:
21 -SEP- 00= 1330 g/l"cold" water(4) not assignable

pH:
Test substance:
Reliability:
08 -MAY- 01= 2.2 at .1 other: N (normal)
Citric acid monohydrate(4) not assignable

pH:
Test substance:
Reliability:
21 -SEP- 00

c a . 1 . 8 a t 5 o t h e r : w% and 25 degree C
Citric acid(2) valid with restrictions

pKa:
Remark:Reliability:
08 -MAY- 01
pKa:
Remark:Reliability:
08 -MAY- 01

3.13 at 25 degree C
pKa(1)( 4 ) n ot assignable

pKa:
Remark:Reliability:
08 -MAY- 01

34

(77)

(77)

(48)

(28)

(116)

(85)

(48)

(77)
4.76 at 25 degree C
pKa(2)(4) not assignable(77)
6.4 at 25 degree C
pKa(3)(4) not assignable(77)

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

2. Physico-chemical Data
2.6.2 Surface Tension
2.7 Flash Point
2.8 Auto Flammability
Value:
Test substance:
Reliability:
08 -MAY- 01= 1010 degree C
Citric acid powder(4) not assignable(113)

2.9 Flammability
Result:
GLP:
Remark:Reliability:
08 -MAY- 01

non flammableno"Fire potential slight when heated"(4) not assignable(99)

2.10 Explosive Properties
Result:
Method:GLP:
Remark:Reliability:
06 -DEC- 00
Result:Remark:Reliability:
06 -DEC- 00

other: dust explosion
other: Modified Hartmann Tubeno
Dust explosible at a concentration of 500 mg/l air,substance swirled up using a defined jet of pressurised
air, ignition source electrical spark. In same test
series dust ignition (but not explosion, based on theenergy liberated) was found starting at concentrationsof 200 mg/l air.
(1) valid without restriction(98)
not explosive
Minimum ignition energy of citric acid (particle size
range 3 to 150 mcm) was between 1300 mJ (no ignition)and 4000 mJ (ignition )(2) valid with restrictions(48)

2.11 Oxidizing Properties
Result:Remark:no oxidizing properties
No studies located, but not expected from stru cture tohave oxidizing properties

08 -MAY- 01

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35

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

2. Physico-chemical Data
2.12 Additional Remarks
Memo:
Method:08 -MAY- 01

Henry's Law Constant: KH<=2.3*10E- 7 Pa*m3/mol
QSAR estimation assuming a water solubility of >= 600 mg/l
(95)

Memo:
Reliability:
08 -MAY- 01

Viscosity = 6.5 cP (50% aqueous solution) at 25 degree C(4) not assignable
(20)

36

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

3. Environmental Fate and Pathways
3.1.1 Photodegradation
Type:
Method:Year:
Test substance:
Remark:25 -MAY- 00

GLP:
no data available

3.1.2 Stability in Water
Type:
t1/2 pH 1 :Method:Year:
Test substance:
Remark:Result:
Test condition:
Test substance:
Reliability:
21 -MAY- 01

abiotic= 72.9 year
other: chemical analysis, half -life calculated
G L P : noabiotic degradation due to the reaction with OH
radicals, based on literature value for OH radical
concentration in water of 1*10E- 1 7 m o l / ldegradation rate constant: 0.30*10E8 l/mol*s
room temperature
aqueous solution(4) not assignable(4)

3.1.3 Stability in Soil
Type:
Concentration:
Cation exch.
capac.
Microbial
biomass:
Method:Year:
Test substance:
Result:Reliability:
08 -MAY- 01

other: biotic degradation in soil Radiolabel :no dataother: not statedother: not statedother: not stated
1977
G L P : noother TS: "citrate""Substantial disappearance of citrate from soil isreported to occur in seven days"(4) not assignable(80)

3.2 Monitoring Data (Environment)
Type ofmeasurement:
Medium:Result:Reliability:
24 -SEP- 01
Type ofmeasurement:
Medium:Result:Reliability:

background concentration
surface water
0.025 -0.145 mg/l, Atlan tic coast seawater(4) not assignable(89)

surface water< 0.04- 0.2 mg/l, river water(4) not assignable

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37

OECD SIDS
3. Environmental Fate and Pathways

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

24 -SEP- 01
Type ofmeasurement:
Medium:Result:Reliability:
24 -SEP- 01(1) (23)

other: raw sewage
Raw sewage contains up to 10 mg/l of citrate(4) not assignable(80)

3.3.1 Transport between Environmental Compartments
Type:Media:
Method:Year:
Remark:25 -MAY- 00

No studies located

3.3.2 Distrib ution
Media:
Method:Year:
Method:Remark:Result:21 -MAY- 01
Media:
Method:Year:
Method:Remark:Result:21 -MAY- 01

other: air-s e d i m e n t-s o i l- water

Level III, Fugacity-based Environmental Equilibrum
Partitioning Model v.2.20
System default values for the environmental paramete rs
were not changed. Water solubility 576,000 mg/l, vapour
pressure 1Pa and logPow - 1.72 were used for the
calculation; 33% emission each to air, soil and water.
55.76% to water, 44.20% to soil, 0.02% to sediment and
0.02% to air(72)
other: air-s e d i m e n t-s o i l- water

Level I, EQC Model v.1.0
System default values for the environmental parameters
were not changed. Water solubility 576,000 mg/l, vapour
pressure 1 Pa and logPow -1.72 were used for the
calculation.
99.99% to water, <0.01% to soil, <0.01% to sediment and<0.01% to air(72)

3.4 Mode of Degradation in Actual Use
Result:38

Citric acid is found in all eukaryote cells, forming anintermediate in the Krebs cycle. It is synthesised but
subsequently broken down in the course of this very
basic biochemical cycle.
Citric acid is easily biodegradable by sewage treatment
bacteria. It is expected to be biodegradable by common
soil and sediment bacteria.
Citric acid is easily oxidised by a variety of oxidising

UNEP PUBLICATIONSOECD SIDS
3. Environmental Fate and Pathways

24 -SEP- 01

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

agents, eg, peroxides or hypochlorites. The usual
oxidation products are acetonedicarboxylic acid (CAS5 4 2-0 5- 2), oxalic acid (CAS 6153 -5 6-6), carbon dioxide(CAS 124- 38- 9 ) a n d w a ter (CAS 7732 -18 -5 )(17) (48) (116)

3.5 Biodegradation
Type:
Inoculum:
Result:
Method:aerobic
other: non-adapted
readily biodegradable
Directive 84/449/EEC, C.5
Sturm test"

Year:
Test substance:
Remark:Result:G L P : noother TS: Not statedMedium: sewage treatment
Readily biodegradable.
97% (duration not stated), based on CO2 evolution
100% (duration not stated), based on DOC removal(2) valid with restrictions(41)

Reliability:
21 -MAY- 01
Type:Inoculum:
Degradation:
Kinetic:
Method:Year:
Test substance:
Remark:Result:Organic
Reliability:
21 -MAY- 01
Type:Inoculum:
Degradation:
Kinetic:
Method:Year:
Test substance:
Remark:Result:Reliability:
08 -MAY- 01"Biotic degradation - modified

aerobic
activated sludge, non -a d a p t e d= 85 % after 1 day
1 day= 85 %
Directive 87/302/EEC, part C, p. 99 "Biodegradation:
Zahn- Wellens test"
G L P : noother TS: Not statedMedium: sewage treatment
inherently biodegradable, related to DOC (Dissolved
Carbon)(2) v alid with restrictions(41)
aerobic
activated sludge, non -a d a p t e d= 98 % after 7 day
7 day= 98 %
Directive 87/302/EEC, part C, p. 99 "Biodegradation:
Zahn- Wellens test"
G L P : noother TS: purity > 99%
Medium: sewage treatment
inherently biodegradable, related to DOC (Dissolved
Organic
Carbon)(2) valid with restrictions(28)

UNEP PUBLICATIONS

39

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

3. Environmental Fate and Pathways
3.6 BOD5, COD or BOD5/COD Ratio
B O D 5
Method:Directive 84/449/EEC, C.8
Oxygen Demand"= 526 mgO2/l

BOD5:"Biodegradation: Biochemical

C O D
COD:
R A T I O

= 728 mg/g substanceB O D 5 / C O D

BOD5/COD:= .72

Reli ability:
21 -SEP- 00(2) valid with restrictions

Method:other: Coupled Units Test

Result:Reliability:
21 -MAY- 01

93% of COD removed(2) valid with restrictions

Method:Result:Reliability:
21 -MAY- 01

Closed Bottle Test
Ratio BOD30/COD = 90% of COD(2) valid with restrictions

Remark:Result:Reliability:
08 -MAY- 01

Data collated from three publications
Ratio BOD5/ThOD = 58% to 61%(4) not assignable

Remark:Sewage treatment, initial concentration 720 mg/l, BOD
determination
Activated sludge after 20d: 98% of ThOD
(2) valid with restrictions(71)
Sewage treatment, BOD determination
Activated sludge after 24h: 13% of ThOD
(2) valid with restrictions(74)

Result:Reliability:
06 -DEC- 00
Remark:Result:Reliability:
06 -DEC- 00

(48)

(41)

(41)

(116)

3.7 Bioaccumulation
Species:
Exposure period:
Concentration:
BCF:
Elimination:
Method:Year:
Test substance:
Remark:40

other: Fish

= .01
no
other
G L P : no
Estimate: logBCF (wet wt, fish)=0.85*logPow - 0.70

UNEP PUBLICATIONSOECD SIDS
3. Environmental Fate and Pathways

Reliability:
07 -DEC- 00

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9[for logPow < 6.0] = -2 . 1 6Type of test: calculated(2) valid with restrictions(115)

3.8 Additional Remarks
Memo:Remark:08 -MAY- 01
Memo:Remark:Result:Reliability:
21 -MAY- 01

Indirect photolysis
Estimation of the indirect photolysis using aphotochemical hydroxyl radical reaction constant of
7.02*10E- 12 cm3/mol.sec and assuming a hydroxyl radical
concentration 0.5*10E6 OH/cm3 would result in an
atmospheric half life of 2.3 days (Meylan and Howard,
Epiwin, SRC).
(79)
Other Information
Initial concentrations 6.5*10E -7 M citric acid, 0.01 M
FeCl3
In a parallel citric acid recovery tests by ironcoprecipitation, only half to one third of citric acidrecover ed from distilled water was recovered from Lake
Mendota water at pH values above 8.5, showing
appreciable abiotic or biotic degradation under natural
conditions(2) valid with restri ctions(109)

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41

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

4. Ecotoxicity
AQUATIC ORGANISMS
4.1 Acute/Prolonged Toxicity to Fish
Type:
Species:
Exposure period:
Unit:
LC50:
Method:Year:
Test substance:
Remark:Re l i a b i l i t y :05 -DEC- 00
Type:
Species:
Exposure period:
Unit:
LC50:
Method:Year:
Test substance:
Reliability:
05 -DEC- 00
Type:
Species:
Exposure period:
Unit:
LC0:
LC100:
Method:Year:
Test substance:
Remark:effect.
Reliability:
21 -MAY- 0 1

staticLeuciscus idus (Fish, fresh water)
96 hour(s)mg/lAnalytical monitoring:
440 - 760
other: not stated
GLP: no"Solution was not neutralised"(2) valid with restrictions(58)
staticLepomis macrochirus
96 hour(s)mg/l= 1516other: not stated(Fish, fresh water)
Analytical monitoring:

GLP: no(2) valid with restrictions(104)
other: not stated
Carassius auratus(Fish, fresh water)

mg/l
= 625
= 894
other: not statedAnalytical monitoring:

GLP: noExposure period: "Long- time exposure in hard water".
"Hard water" buffers the acidity respectively the acid(2) valid with restrictions(27)

4.2 Acute Toxicity to Aquatic Invertebrates
Species:
Exposure period:
Unit:
EC0:
EC100:
Method:Year:
Test substance:
Remark:Reliability:

42

Daphnia magna(Crustacea)

mg/l
= 80
= 120
other: not statedAnalytical monitoring:

GLP: noExposure period: "Long- time exposure in soft water".
"Soft water", does not buffer the acidity respectively
the acid effect.
(2) valid with restrictions

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

4. Ecotoxicity
08 -MAY- 0 1
Species:
Exposure period:
Unit:
EC0:
EC50:
EC100:
Method:Year:
Test substance:
Test condition:
Reliability:
21 -MAY- 01
Species:
Exposure period:
Unit:
EC0:
EC50:
EC100:
Method:Year:
Test substance:
Test condition:
Reliability:
21 -MAY- 01
Species:
Exposure period:
Unit:
LC50 :
Method:Year:
Test substance:
Reliability:
21 -MAY- 01(1)
Daphnia magna (Crustacea)
24 hour(s)mg/lAnalytical monitoring:= 1206= 1535= 2083other: not stated
1982
GLP: no data
neutralised(4) not assignable(13)
Daphnia magna (Crustacea)
24 hour(s)mg/lAnalytical monitoring:
= 73
= 85
= 98
other : not stated
1982
GLP: no data
not neutralised(4) not assignable(13)
other aquatic crustacea: Carcinus maenas (crab)
48 hour(s)mg/lAnalytical monitoring:= 160
other: not stated
GLP: no(2) valid with restrictions(93)

4.3 Toxicity to Aquatic Plants e.g. Algae
Species:E n d p oint:
Exposure period:
Unit:
EC0:
Method:Year:
Test substance:
Reliability:
21 -MAY- 01

Scenedesmus quadricauda
7 day
mg/l
= 640
other: not stated(Algae)Analytical monitoring:

GLP: no(2 ) valid with restrictions(12)

Species:other algae: Pavlova lutheri (saltwater chrysophytes)
Endpoint:
Exposure period:
7 day
Unit:
mg/l
Analytical monitoring:
T L C:= 1 - 300

UNEP PUBLICATIONS

43OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

4. Ecotoxicity
Method:Year:
Test substance:
Reliability:
24 -SEP- 01
Species:
Endpoint:
Exposure period:
Unit:
TLC :
Method:Year:
Test substance:
Reliability:
24 -SEP- 01

other: not stated
GLP: no data
(4) not assignable(84)
other algae: Chaetoceros gracilis, Navicula ramosissima(saltwater diatoms)
7 day
mg/l
= 1 - 300
other: not statedAnalytical monitoring:

GLP: no data
(4) not assignable(84)

4.4 Toxicity t o Microorganisms e.g. Bacteria
Type:Species:
Exposure period:
Unit:
EC0:
Method:Year:
Test substance:
Reliability:
08 -MAY- 01
Type:Species:
Exposure period:
Unit:
NOEC :
Method:Year:
Test substance:
Remark:Reliability:
08 -MAY- 01
Type:Species:
Exposure period:
Unit:
EC0:
Method:Year:
Test substance:
Reliability:
21 -MAY- 0 1
Type:Species:44

aquatic
Microcystis aeruginosa (Bacteria)
8 day
mg/l
Analytical monitoring:= 80
other: not state d
GLP: no(2) valid with restrictions(10 )aquatic
Nitroso monas sp.
mg/l
= 100
other: not stated(Bacteria)
Analytical monitoring:

GLP: noNo inhibition on NH3 oxidation(2) valid with restrictions(49)
aquatic
Pseudomonas putida
1 6 h o ur ( s )mg/l> 10000
other: not stated(Bacteria)
Analytical monitoring:

GLP: n o(2) valid with restrictions(12)aquatic
other bacteria: 37 strains of bacteria

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

4. Ecotoxicity
Exposure period:
Unit:
EC0:
Method:Year:
Test substance:
Remark:Result:Reliability:
08 -MAY- 01
Type:Species:
Exposure period:
Unit:
EC0:
Method:Year:
Test substance:
Reliability:
21 -MAY- 01
Type:
S p ec i e s :Exposure period:
Unit:
Method:Year:
Test substance:
Remark:Result:Reliability:
21 -MAY- 01
Type:Species:
Exposure period:
Unit:
TLC :
Method:Year:
Test substance:
Reliability:
24 -SEP- 01
Type:Species:
Exposure period:
Unit:
TLC :
Method:Year:
Test substance:

30 daymg/l= 500
other: not statedAnalytical monitoring:

GLP: noConcentration: 500 mg/l, pH=3.0; Microbes from acidic
mine water (Central Pennsylvania), isolated fromenrichment cultures, test substance as C source instatic culture
positive growth on all strains(2) valid with restrictions(121)
other: not statedEntosiphon sulcatum
72 hour(s)
mg/l
= 485
ot her: not stated(Protozoa)
Analytical monitoring:

GLP: no(2) valid with restrictions(12)other: not statedother bacteria: Arthrobacter globiformis, 10 strains
5 day
Analytical monitoring:other: not stated
GLP: noMicrobes isolated from soil, test substance as sole C
source, mineral salts added
good to excellent degradation with all strains(2) valid with restrictions(56)
other: not statedother protozoa: Tetraselmis tetrathele (saltwater)
7 day
mg/l
Analytical monitoring := 1 - 300
other: not stated
GLP: no data
(4) not assignable(84)
other: not statedother protozoa: Tetramitus rostratus (freshwater )35 hour(s)mg/lAnalytical monitoring:<= 108other: not s t a t e d
GLP: no data

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45

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

4. Ecotoxicity
Reliability:
24 -SEP- 01(4) not assignable

Type:
Species:
Exposure period:
Unit:
TLC :
Method:Year:
Test substance :Reliability:
21 -MAY- 01

other: not stated
Uronema parduzci (Protozoa)

(55)

mg/l
= 622
other: not statedAnalytical monitoring:

GLP: no data
(4) not assignable(11)

4.5 Chronic Toxicity to Aquatic Organisms
4.5.1 Chronic Toxicity to Fish
Species:
Endpoint:
Exposure period:
Unit:
Method:Year:
Test substance:
Remark:Analytical monitoring:
GLP:
No studies located, with the possible exception of the
one recorded under 4.1

14 -JUL- 00

4.5.2 Chronic Toxicity to Aquatic Invertebrates
Species:
Endpoint:
Exposure period:
Unit:
Method:Year:
Test substance:
Remark:Analytical monitoring:
GLP:
No studies located with the possible exception of the
one recorded chapter 4.2

21 -SEP- 00

46

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

4. Ecotoxicity
TERRESTRIAL ORGANISMS
4.6.1 Toxicity to Soil Dwelling Organisms
Type:
Species:
Endpoint:
Exposur e period:
Unit:
Method:Year:
Test substance:
Remark:14 -JUL- 00

GLP:
No studies located

4.6.2 Toxicity to Terrestrial Plants
Species:
Endpoint:
Expos. period:
Unit:
Method:Year:
Test substance:
Remark:08 -MAY- 0 1

GLP:
All plants produce citric acid as an intermediate of theKrebs cycle.
No studies located.
(24) (96)4.6.3 Toxicity to other Non-Mamm. Terrestrial Species
Species:
Endpoint:
Expos. period:
Unit:
Method:Year:
Test substance:
Remark:03 -NOV- 00

GLP:
No studies located

4.7 Biological Effects Monitoring
Remark:Based on the low n -octanol/water partition coefficienton one hand and based on the fact that citric acid as anintermediate in the Krebs cycle (see 4.8) is transformed
into other substances in every body cell of eukaryotes
on a daily basis, no biomagnification is given.
No studies located.

05 -DEC- 00

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47

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

4. Ecotoxicity
4.8 Biotransformation and Kinetics
Type:
Result:08 -MAY- 01

Citric acid is an intermediate in the citric acid or
Krebs cycle, also known as the tricarboxylic acid cycle,
which takes place in every eukaryote cell and which
breaks down glucose through glycolysis(17)

4.9 Additional Remarks
Memo:
Result:21 -MAY- 0 1(a)Citric acid is "extremely widesprad in nature"

Memo:
Result:(b)
Citric acid is "widely distributed in plants and animal
tissues and fluids"(77)

08 -MAY- 01
Memo:
Result:08 -MAY- 01

48

(37)

(c)
I n m a n , d u r i n g 2 4 h a p p r o x y m a t e l y 2 0 0 0 g o f c itric acidare formed and further metabolised as intermediates in
the citric acid cycle in adults(96)

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
5.1 Acute Toxicity
5.1.1 Acute O ral Toxicity
Type:Species:Sex:
Number of
Animals:
Vehicle:Value:
Method:Year:
Test substance:
Remark:Reliability:
08 -MAY- 01
Type:Species:Sex:
Number of
Animals:
Vehicle:Value:
Method:Year:
Test substance:
Remark:Reliability:
21 -MAY- 0 1
Type:Species:Sex:
Number of
Animals:
Vehicle:Value:
Method:Year:
Test substance:
Reliability:
06 -DEC- 0 0
Type:Species:Sex:
Number of
Animals:

LD50
mouse
male/female10= 5400 mg/kg bw
1981

G L P : no

5 male and 5 female mice in each treatment group wereadministered 3000 mg/kg, 4243 mg/kg, 6000 mg/kg, 8485
mg/kg or 12000 mg/kg of citric acid by gavage. The test
substance was dissolved in pure water at suchconcentrations that in every group 20 ml/kg were given.
Controls were administered 0.4 ml tap water by gavage.
(2) valid with restrictions(32)
other: lethal dose
rabbit= 7000 mg/kg bw
G L P : noP r obably lowest Lethal dose(4) not assignable
(119)
LD50
rat

= 3000 mg/kg bw
other: not stated
G L P : no(2) valid with restrictions
(88)
LD50
ra t

Vehicle:Value:= 12000 mg/kg bw

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49

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Method:Year:
Test substance:
Reliability:
16 -MAY- 01
Type:Species:Sex:
Number of
Animals:
Vehicle:Value:
Method:Year:
Test substance :Reliability:
16 -MAY- 01

other: not stated
G L P : no(2) valid with restrictions
(125)
LD50
rat

= 5000 mg/kg bw
other: not stated
G L P : no(2) valid with restrictions(125)

5.1.2 Acute Inhalation Toxicity
Type:Species:Sex:
Number of
Animals:
Vehicle:Exposure time:
Value:
Method:Year:
Test substance:
Remark:17 -JUL- 00

GLP:
No studies located

5.1.3 Acute Dermal Toxicity
Type:Species:Sex:
Number of
Animals:
Vehicle:Value:
Method:Year:
Test substance:R e m a rk:
17 -JUL- 00

GLP:
No studies located

5.1.4 Acute Toxicity, other Routes
Type:Species:
Sex:

50

LD50
rat

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Number of
Animals:
Vehicle:Route of admin.:Value:
Method:Year:
Test substance:
Reliability:
16 - MAY- 01
Type:Species:Sex:
Number of
Animals:
Vehicle:Route of admin.:Value:
Method:Year:
Test substance:
Reliability:
16 - MAY- 01

s.c.
= 5500 mg/kg bw
Other
G L P : no(2) valid with restrictions
(125)
LD50
mouse

s.c.
= 2700 mg/kg bw
Other
G L P : no(2) valid with restrictions(125)

5.2 Corrosiveness and Irritation
5.2.1 Skin Irritation
Species:
Concentration:
Exposure:
Exposure Time:
Number of
Animals:
PDII:
Result:EC classificat.:
Method:Year:
Test substance:
Re mark:
16 - MAY- 0 1
Species:
Concentration:

human

GLP:
An irritant skin dermatitis attributed to citric acidhas been reported amongst waiters and bakers.
(38)
human

Exposure:
Expo sure Time:
Number of
Animals:
PDII:
Result:EC classificat.:

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51

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Method:Year:
Test substance:
Remark:08 -MAY- 01
Species:
Concentration:
Exposure:
Exposure Time:
Number of
Animals:
PDII:
Result:EC classificat.:
Method:Year:
Test substance:R e mark:
08 -MAY- 01
Species:
Concentration:
Exposure:
Exposure Time:
Number of
Animals:
PDII:
Result:EC classificat.:
Method:Year:
Test substance:
Remark:GLP:
In solution, the acid may produce pain if applied toabraded skin.
(46)
human

GLP:
A 0.3 N solution (approximatively 2%) can "sting" intact
skin, this appears unrelated to irritant potential.
(65)
human

GLP:

Reliability:
08 -MAY- 01

Patch testing of 60 eczema patients with 2.5 % citricacid in petrolatum (probably 24 h covered contact) did
not produce any irritant reactions.
(4) not assignable(83)

Species:
Concentration:other: rabbit, New Zealand White, > 3 kg bw
other: 30% aqueous solution

Exposure:
Exposure Time:
Number of
Animals:
PDII:
Result:EC classificat.:
Method:Year:
Test substance:

Occlusive52

3
not irritating
not irritating
Draize Test
G L P : no

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Remark:Reliability:
08 -MAY- 01

Species:
Concentration:
Exposure:
Exposure Time:
Number of
Animals:
PDII:
Result:EC classificat.:
Method:Year:
Test su b s t a n c e :Remark:Reliability:
21 -MAY- 0 1
Species:
Concentration:
Exposure:
Exposure Time:
Number of
An i m a l s :PDII:
Result:EC classificat.:
Method:Year:
Test substance:
Remark:Reliability:
21 -MAY- 01

Dose=0.5ml (corresponding to 0.15 g in aqueous solution)
during 4 h under occlusive patch; subsequent
observations at 4 h, 24 h and 48 h. Effects rep orted asnil (no erythema/eschar, no oedema) for intact skin,effects reported as "slight to well defined" in one
instance for abraded skin. Overall Primary Irritation
Index (avera ge of all observations) = 0.84, hence inthis test the substance is not a primary skiirritant.
(1) valid without restriction(33)

ra bbit24 hour(s)slightly irritating
irritatingother: not stated
G L P : no data
Dose=500 mg/24 h; Effects reported as "mild"(4) not assignable(75)
rabbitslightly irritating
not irritating
OECD Guide-line 404"Acute Dermal Irritation/Corrosion"
G L P : no data

"A verage result of 24, 48 and 72 hours: erythemascore=0.33, oedema score=0"(4) not assignable(63)

5.2.2 Eye Irritation
Species:
Concentration:
Dose:
Exposure Time:
Comment:
Number of
Animals:
Result:other: rabbi t, New Zealand White, > 2 kg bw
other: 10% and 30% aqueous solution3
not irritating

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53

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
EC classificat.:
Method:Year:
Test substance:
Remark:Reliability:
07 -DEC- 00
Species:
Concentration:
Dose:
Exposure Time:
Comment:
Number of
Animals:
Result:EC classificat.:
Method:Year:
Test substance:
Remark:Reliability:
21 -MAY- 01
Species:
Concentration:
Dose:
Exposure Time:
Comment:
Number of
Anima l s :Result:EC classificat.:
Method:Year:
Test substance:
Remark:54

not irritating
Draize Test
G L P : no
Dose=0.1 ml (corresponding to 0.01 g resp. 0.03 g inaqueous solution) is placed into the lower conjunctival
sac of one eye held closed for one second; subsequent
observation period was14 days. Effects of the 10%
solution reported as moderate to weak conjunctival
irritation disappearing within one
week, without further effects on the cornea. Overall
Primary Eye Irritation Index (Draize score, average of
all observations) = 9.3 for the 10% solution, resulting
in a classification of "minimally irritating". Effectsof the 30% solution reported as well -defined to moderate
conjunctival irritation which disappeard in two of thethree rabbits within 14 days; additionally, a shortlasting superficial lesion of the conjunctivalepithelium was noted; no macroscopical alterationof the cornea was observed. Overall Primary Eye
Irritation Index (Draize score, average of allobservati ons)=16.0 for the 30% solution, resulting in aclassification of "mildly to moderately irritating"(1) valid without restriction
(34)
human

GLP:
Severe damage was reported in a patient who was splashedin the eye with a saturated solution of citric acid.
(4) not assignable(118)
rabbitirritating
irritatingother: not stated
G L P : no data
other TS: 0.5% aq. solution, 2% solution aq.
"Irrigation for 30 min with 0.5% to 2% solution causes
severe injury; the 0.5% solution causes permanent

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity

Reliability:
16 -MAY- 01
Species:
Concentration:
Dose:
Exposure Time:
Comment:
Number of
Animals:
Result:E C c l a s sificat.:
Method:Year:
Test substance:
Remark:Reliability:
16 -MAY- 01
Species:
Concentration:
Dose:
Exposure Time:
Comment:
Number of
Animals:
Result:EC classificat.:
Method:Year:
Test substance:
Remark:Reliability:
16 -MAY- 01

cloudiness of the cornea and the 2% solution causes
severe dense opacification"(4) not assignable(43)
rabbit750

other: ug/24 hhighly irritating
irritatingother: not stated
G L P : no data
Effect reported as "severe"(4) not assignable(75)
rabbithighly irritating
irritating
OECD Guide-line 405"Acute Eye Irritation/Corro sion"
G L P : no data

"Average results of 24, 48 and 72 hours: cornea score =
2.8, iris score = 0.0, conjunctiva score = 1.7"
(4) not assign able
(63)

5.3 Sensitization
Type:
Species:Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance :Remark:

human

GLP:
Mouth sores (canker sores), headache, asthma, nasal
blockage, general tiredness and itchiness were some ofthe symptoms reported by a man after the ingestion offoods containing citric acid. Application of crystals to
the inside surface of the mouth produced sores (as did
some other organic acids) but potassium citrate crystals

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55

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity

and magnesium citrate solution did not. Control subjects
did not react to mouth application of citric acid.
16 -MAY- 01
Type:Species:Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance:
Remark:16 -MAY- 01
Type:Species:Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance:
Remark:16 -MAY- 01
Type:Species:Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance:
Remark:21 -MAY- 01

(111)

human

GLP:
A standard text implies that citric acid might be a skinsensitizer by recommending 1% aqueous solutions for(24/48- h r c o v e r e d ) p a t c h- tests to detect the sensitizedstate.
(38)

human

GLP:
No allergic reactions were seen when 60 patients withhand eczema, all of whom were involved in handling food,were patch tested (covered contact, probably 24 hr) with
2.5% citric acid in petrolatum.
(83)

human

GLP:
Urticaria (a skin complaint) and mouth ulcers have been
noted following exposure to citric acid [no otherdetails were given].
(110)

5.4 Repeated Dose Toxicity
Species:
Strain:56

rat

Sex: male/female

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Route of admin.:
Exposure period:
Frequen c y o ftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:Result:femalesReliability:
16 -MAY- 01
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
peri o d :Doses:
Control Group:
Method:Year:
Test substance:
Remark:Reliability:
16 -MAY- 01
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:other: oral, gavage
5 daysOnce daily
10 days2000 mg/kg/day, 4000 mg/kg/day, 8000 mg/kg/day, 16000
mg/kg/day
no data specified
other: not stated
G L P : no
10 males and 10 females, avg weight = 150 g
NOEL = 4000 mg/kg
LD50 = 5600 +- 440 mg/kg/d, identical for males and( 1 ) valid without restriction
(31)
mouse

Sex: maleoral feed

G L P : no data
Decreased growth and lower survival times (11 -13 months
as opposed to 16 -17 months in the untreated controls)
were reported in male mice receiving 5% citric acid in
the diet (about 7.5 g/kg bw/day) for an unspecified
period.
(4) not assignable(124)
rabbitSex:

oral feed

G L P : no data
No adverse effects were seen in limited studies in 15
rabbits receiving 7.7% sodium citrate (equivalent to 5%
free citric acid) in the diet (about 1.5 g citricacid/kg bw/day) for 150 days.

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57

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Result:Reliability:
16 -MAY- 01

NOAEL = 1500 mg/kg/d(4) not assignable

Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:dog

Result:Reliability:
21 -MAY- 0 1
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:Reliability:
16 -MAY- 01
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:

58

(90)
Sex:

oral feed

G L P : no data
No adverse effects were seen in three d o g s f e d d a i l ydoses of 1.38 g citric acid/kg bw for up to 120 days.
NOAEL = 1400 mg/kg/d(4) not assignable(64)
guinea pig

Sex:oral feed

G L P : no data
A reduced packed cell volume in the blood was the only
effect noted in guinea- pigs receiving diets supplementswith 1- 5% citric acid (about 0.4 -2 g/kg bw/day) for a
maximum of 60 days. No tissue examinations were
undertaken. (The unsupplemented diets contained around
1.2% citric acid, so actual citric acid intakes weregreater than the quoted values).
(4) not assignable
(123)
pig

Sex:

oral feed

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Year:
Test substance:
Remark:Reliability:
21 -MAY- 01
Species:
Strain:Route of admin.:
Exposure pe riod:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:Reliability:
16 -MAY- 0 1
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:Cont rol Group:
Method:Year:
Test substance:
Remark:Reliability:
21 -MAY- 01
Species:
Strain:Route of admin.:
Exposure period:
Frequency of

G L P : no data
Body weight gain was unaffected in young pigs fed a
cadmium -enriched diet containing 5% citric acid(corresponding to about 4 kg/kg bw/day). Cadmium levels
were, however, elevated in the liver and kidneys and thezinc level was decreased in muscle in citricacid/cadmium treated pigs compared with pigs treatedwith cadmium only.
(4) not assignable
(100)
sheep

Sex:

other: ruminal cannula

G L P : no data
When six sheep were given 795 mg citric acid/kg bw/day
for 60 days via a ruminal cannula, no effects were seen
on feed intake, weight gain or mineral metabolism.
(4) not assignable(3)
rat

Sex: male/female

other: oral, dietary
90 weeks
Daily (feed)
Not stated
Feed containing 1.2% citric acidno data specified
other: not stated
G L P : no
Cited as "... no harmful effects on the growth of two
successive generations of rats over a 90 -week period. No
effect on reproduction, blood characteristics, pathology
or calcium was observed. Although a slight increase indental attrition was reported."( 2 ) v a l id with restrictions(8)
rat

Sex: maleother: oral, dietary
6 weeks

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59

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
treatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:Reliability:
21 -MAY- 0 1
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:Reliability:
21 -MAY- 01

Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:60

Feed containing 1.2, 2.4, 4.8% citric acid

G L P : noJapanese investigators have recorded slight growth
reduction in groups of 10 male rats fed 1.2, 2.4 or 4.8%
citric acid (apparently 1.15, 2.26 or 4.67 g/kg bw/d)for 6 weeks and, at the top dose, mild blood and urinechanges and slight degneration of the thymus gland andthe spleen.
(4) not assignable
(125)
rat

Sex:

other : oral dietary

Feed containing 2% citric acid

G L P : no data
Citric ac id had no effects on food consumption or bodyweight when fed at a dietary level of 2% (about 0.13
g/kg bw/d) to nine rats. The absorption and urinary
excretion of calcium and magnesium were unaffect ed,
although urinary zinc excretion was temporarily
elevated.
(4) not assignable
(103)

rat

Sex: maleother: oral dietary
2 years

Feed containing 5% and 3% citric acid

G L P : noIn 2 year studies with groups of 20 male rats, dietarylevels of 5% citric acid (about 2g/kg bw/d) or 3%
slightly decreased growth (food consumption was also
lower in the top -dose group), but no tissue

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity

Result:Reliability:
21 -MAY- 01
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:Reliability:
21 -MAY- 01

abnormalities were found on examination of the majororgans.
NOAEL = 1200 mg/kg/d(4) not assignable
(50)
rat

Sex:

other: oral dietary
1 yearFeed containing 1.2% citric acid

G L P : no
No adverse effects were reported (with the possible
exception of slight changes in tooth structure) when two
successive generations of rats were fed 1.2% citric acid(about 600 mg/kg bw/d) and 0.1% sodium citrate in thediet for apparently up to about 1 year (only a limited
range of tissues w as examined microspically).
(4) not assignable(8)

5.5 Genetic Toxicity 'in Vitro'
Type:
System oftesting:
Concentration:
Metabolicactivation:
Result:
Method:Year:
Test substance:
Remark:Reliability:
16 -MAY- 0 1
Type:
System oftesting:
Concentration:
Metabolicactivation:
Result:Bacterial reverse mutation assay
Species/stra in: Salmonella typhimurium TA 97, TA 98, TA
100, TA 104
Not statedwith and without
negative
OECD Guide-line 471"Genetic Toxicology: Salmonella
thyphimurium Reverse Mutation Assay"
G L P : no data
Activation system: Liver homogenate from rats pretreatedwith phenobarbital( 2 ) valid with restrictions(2)
Bacterial reverse mutation assay
Species/strain: Salmonella typhimurium TA 94, TA 98, TA
100, TA 1535, TA 1537
Up to 5 mg/platewith and without
negative

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61

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Method:Year:
Test substance:
Remark:Reliability:
21 -MAY- 01
Type:
System oftesting:
Concentration:
Metabolicactivation:
Result:
Method:Year:
Test substance:
Reliability:
16 -MAY- 01

OECD Guide-line 471"Genetic Toxicology: Salmonella
thyphimurium Reverse Mutation Assay"
G L P : no data
Activation system: Liver homogenate from rats preteatedwith polychlorinated biphenyl KC -400(2) valid with restrictions(54)
Bacterial reverse mutation assay
Escheria coli

negative
G L P : no data
(4) not assignable
(47)

Type:
System oftesting:
Concentration:
Metabolicactivation:
Result:
Method:Year:
Test substance:
Reliability:
21 -MAY- 01

Yeast gene mutation assay

Type:
System oftesting:

Yeast gene mutation assay

Concentration:
Metabolicactivation:
Result:
Method:Year:
Test substance:
Reliability:
21 -MAY- 01
Type:
System oftesting:
Concentration:
Metabolicactivation:
Result:62

Not stated> 3.5 g/kg
with and without
negativeother
G L P : no(4) not assignable(70)

Saccharomyces cerevisiaewith and without
negative
G L P : no(4) not assignable(69)
other: clastogenic assay
Fibroblast culture from chines e hamster (Cricetulus
griseus)
Up to 1mg/ml

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Method:Year:
Test substance:
Remark:Result:Reliability:
21 -MAY- 01

other: not stated
G L P : no data
No clastogen ic effects reported
Genotoxic effects: negative(2) valid with restrictions(54)

5.6 Genetic Toxicity 'in Vivo'
Type:
Species:
Strain:Route of admin.:
Exposure period:
Doses:
Result:
Method:Year:
Test substance:
Remark:Reliability:
21 -MAY- 0 1
Type:Species:
Strain:Route of admin.:
Exposure period:
Doses:
Result:
Method:Year:
Test substance:
Remark:Reliability:
21 -MAY- 01

Dominant lethal assay
rat

Sex: no data

unspecified

G L P : noNo mutagenic potentia l was detected in a dominant lethal
assay in rats in which doses of up to 3 g citric acid/kg
bw/day were administrated for 5 days. (A dominant lethal
effect is normally reflected by increased early foetal
death when treated males are mated with untreatedfemales).
(4) not assignable
(69)

rat

Sex: no data

unspecified

G L P : no
No chromosomal damage occurred in the bone marrow ofrats ingesting up to 3 g citric acid/kg bw/day for 5
days.
(4) not assignable(69)

5.7 Carcinogenicity
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.

rat

Sex: maleoral feed

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63

OECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
period:Doses:
Result:Control Group:
Method:Year:
Test substance:
Remark:Reliability:
21 -MAY- 01
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Result:Control Group:
Method:Year:
Test substance:
Remark:Reliability:
24 -SEP- 01
Species:
Strain:Route of admin.:
Exposure period:
Frequency o ftreatment:
Post. obs.
period:Doses:
Result:Control Group:
Method:64

G L P : noIn a limited study, no evidence of carcinogenicity wasreported in 20 male rats receiving up to 5% citric acidin the diet (about 2g/kg bw/day) for 2 years. (Modern
regulatory guidelines recommend that groups of 50
rodents of each sex are exposed to one of several doses
and that a comprehensive range of tissues is examined
microscopically).
(4) not assignable
(50)
rat

Sex: maleoral feed

G L P : no data
Male rats were fed citric acid or sodium citrate at
dietary levels providing about 2.6 g/kg bw/day (based on
their final body w eights) for 20 weeks and were
simultaneously given a known bladder carcinogen in theirdrinking water.
More carcinomas (malignant tumours) were induced inrats treated with carcinogen and sodium citrate than inthose treated with carcinogen alone, however, this was
attributed to the increased water intake (and hencecarcinogen intake) in this group. Citric acid did nothave a tumour promoting effect.
(2) valid with restrictions
(53)
rat

Sex:

oral feed

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Year:
Test substance:
Remark:Reliability:
16 -MAY- 01
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Result:Control Group:
Method:Year:
Test substance:
Remark:Reliability:
21 -MAY- 01
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Result:Control Group:
Method:Year:
Test substance:
Result:Reliability:
16 -MAY- 01
Species:
Strain:Route of admin.:E x posure period:
Frequency oftreatment:
Post. obs.

G L P : no data
No increase in DNA synthesis (a measure of cellproliferation) i n the bladder epithelium was found inrats fed 1.7% sodium citrate (about 0.74 g/kg bw/day)in the diet for 8 weeks.
(4) not assignable
(86)
rat

Sex: maleother: oral, stomach tube

G L P : noThree liver tumours developed in a group of 80 male rats
treated with a known carcinogen and receiving 470 mg
citric acid/kg bw three times daily by stomach tube forup to 45 weeks. (No control animals were apparently usedin this study, but clearly citric acid did not act as apotent tumour promoter).
(4) not assignable(6)
ratother: Albino Carworthoral feed
24 months

Sex: male

Daily
Not stated
2g/kg body weight/day
yes, concurrent no treatment
other
G L P : no
No differences between controls and experimental group(2) valid with restrictions
(50)
rat

Sex: maleoral feed

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Substance ID: 77-92-9

5. Toxicity
period:Doses:
Result:Control Group:
Method:Year:
Test substance:
Remark:Reliability:
16 -MAY- 0 1
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Result:Control Group:
Method:Year:
Test substance:
Remark:Reliability:
16 -MAY- 01

G L P : no data
Tumour yield increased when groups of 20 to 25 male rats
who had been treated with a known bladder carcinogen
were then given 5% sodium citrate in the diet (about 2.5
g/kg bw/day) for 32 weeks, then 5% sodium citrate in thediet for 4 weeks ( actual intake about 1.9 g/kg bw/day),followed by a 3- week period of treatment with uracil (toaccelerate tumour promotion), and then the sodium
citrate for a further 9 weeks.
The i ncidence of bladder papillomas (benign tumours) was
increased in rats treated with sodium citrate (andcarcinogen/uracil) compared with those treated with only
the carcinogen uracil. One of fifteen rats in the sodium
citrat- treated group developed a bladder carcinoma. No
papillomas or carcinomas developed in rats treated withsodium citrate and uracil but not carcinogen.
(4) not as s i g n a b l e
(117)
rat

Sex:

oral feed

G L P : no data
When the sodium citrate level was only 1.7% (actual
intake about 0.74 g/kg bw/day) no effects were seen on
the bladder tumour incidence in rats treated withcitrate (and carcinogen/uracil) compared with thosetreated with carcinogen and uracil only. However, if the
1.7% sodium citrate treatment was combined with theadministration of two other sodium salts (the ascorbate
and bicarbonate), the yield of papillomas and carcinomas
was increased in a synergist fashion.
( 4 ) n o t a s s i gnable(86)

5.8 Toxicity to Reproduction
Type:
Species:
Strain:

66

rat

Sex:

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CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity

Route of admin.:oral feed
Exposure Period:
Frequency oftreatment:
Du ration of test:
Doses:
Control Group:
Method:Year:
G L P : no
Test substance:
Remark:No effects on reproduction were reported in limited
studies in which rats were fed diets containing 1. 2%
citric acid (about 600 mg/kg bw/day) and 0.1% sodium
citrate for 29 weeks prior to mating and then foranother few months.
Reliability:(4) not assignable
21 -MAY- 01
(8)
Type:
Species:rat
Sex:
Strain:Route of admin.:unspecified
Exposure Period:
Frequency oftreatment:
Duration of test:
Doses:
Control Group:
Method:Year:
G L P : no
Test substance:
Remark:There were no indications of teratogenicity(malformations in the offspring) or other adverse
effects when female rats received up to 295 mg citricacid/kg bw/day on days 6 to 15 of pregnancy.
Reliability:(4) not assignable
21 -MAY- 01
(39)
Type:
Species:rat
Sex: female
Strain:Route of admin.:unspecified
Exposure Period:
Frequency oftreatment:
Duration of test:
Doses:
Control Group:
Method:Year:
G L P : no
Test substance:
Remark:No teratogenicity or other adverse effects w ere reported
when females received up to 241 mg citric acid/kg bw ondays 6 to 15 of pregnancy.
Reliability:(4) not assignable
21 -MAY- 01(39)

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CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity

Type:Species:mouse
Sex: female
Strain:Route of admin.:oral feed
Exposure Period:
Frequency oftreatment:
Duration of test:
Doses:
Control Group:
Method:Year:
G L P : no dataT e s t s u b s t a nc e :Remark:Litter size and survival of offspring up to weaning were
unaffected when female mice consumed 5% citric acid in
the diet (about 7.5 g/kg bw/day) previous to, during,and subseque nt to mating.
Result:NOEL = 7500 mg/kg/d
Reliability:(4) not assignable
16 -MAY- 01
(124)
Type:
Species:
rabbitSex: female
Strain:Route o f admin.:unspecified
Exposure Period:
Frequency oftreatment:
Duration of test:
Doses:
Control Group:
Method:Year:
G L P : no
Test substance:
Remark:There were no indications of teratogenicity or otheradverse effects when female rabbits were given up to 425
mg/kg bw on days 6 to 18 of pregnancy.
Reliability:(4) not assignable
21 -MAY- 0 1
(39)
Type:
Species:hamster
Sex: female
Strain:Route of admin.:unspecified
Exposure Period:
Frequency oftreatment:
Duration of test:
Doses:
Control Group:
Method:Year:
G L P : no
Test substance:
Remark:There were no indications of teratogenicity or otheradverse effects when female hamsters received up to 272
mg citric acid/kg (presumably da ily) on days 6 to 10 of

68

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Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Reliability:
21 -MAY- 0 1

pregnancy.
(4) not assignable
(39)

Type:
Two generation study
Species:rat
Sex : male/female
Strain:Route of admin.:other: oral, dietary
Exposure Period:
90 weeks
Frequency oftreatment:
Daily (feed)
Duration of test:
Doses:
Feed containing 1.2 w/w % citric acidControl Group:no data specified
Method:other: not stated
Year:
GLP: noTest substance:
Remark:Cited as "... no harmful effects on the growth of two
successive generations of rats over a 90 -week period. No
effect on reproduction, blood characteristics, pathology
or calcium was observed, although a slight increase indental attrition was reported."
Reliability:(2) valid with restrictions
07 -DEC- 00
(8)
Type:
Species:rat
Sex: female
Strain:Route of admin.:oral feed
Exposure Period:
Frequency oftreatment:
Duration of test:
Doses:
Control Group:
Method:Year:
G L P : no data
Test substance:
Remark:No effects on reproduction were reported in a study inwhich female rats ingested 5% citric acid (about 2.5
g/kg bw/day) previous to, du ring and subsequent tomating.
Result:NOEL = 2500 mg/kg/d
Reliability:(4) not assignable
21 -MAY- 01(124)

5.9 Developmental Toxicity/Teratogenicity
Spec ies:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Duration of test:

rat

Sex: female

other: not stated
Not stated
Daily
Days 6 to 15 of gestation

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CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Doses:
Control Group:
Method:Year:
Test substance:
Result:Reliability:
16 -MAY- 01> 241 mg/kg body weights per day
no data specified
other
G L P : no data
"No indication of adverse effects on nidation, maternalor foetal surviva l. The number of abnormalities did not
differ from control group."(4) not assignable(39)

Species:other: rats and miceSex: male/ female
Strain:Route of admin.:other: oral, diet
Exposure period:
Not statedFrequency oftreatment:
Not stated
Duration of test: N o t s t a t e dDoses:
Feed containing 5% citric acidControl Group:no data specified
Method:ot her: not statedYear:
G L P : no data
Test substance:
Remark:"5% Citric acid did not depress food intake but caused aloss in body weight gain and reduced survival time inmice, with a slightly greater influence on mature
animals." ... "No effect was detected on the litter sizeor survival up to weaning of young in mice or rats."
Reliability:(4) not assignable
16 -MAY- 01(124)

5.10 Other Relevant Information
Type:
Remark:Reliability:
21 -MAY- 01
Type:
Remark:Reliability:
21 -MAY- 01
Type:
Remark:70

other: General systemic effects, single exposure (nonhuman,injection)
Citric acid and its salts injected by various routes
into rats, mice and rabbits caused nervous system, lung,spleen and liver effects, some of which were attributed
to physiological disturbances (acidosis and calcium
deficie ncy).
(4) not assignable(44) (50) (125)other: General systemic effects, single exposure (nonhuman,injection)
Intravenous infusion of rats with sodium citratesolution (25 mM) was shown to increase calcium
excretion.
(4) not assignable(9)
other: General systemic effects, single exposure (nonhuman,injection)
No significant cardiovascular effects or effects on
blood composition were seen in six horses injected
i n travenously with 0.56 mg sodium citrate/kg bw.

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Reliability:
21 -MAY- 01(4) not assignableType:other: General systemic effects, single exposure (nonhuman, oral)
The effects of citric acid in mice and rats include
physiological disturbances (acidosis and calcium
deficiency).
(36)

Remark:16 -MAY- 0 1
Type:Remark:Reliability:
21 -MAY- 01
Type:
Remark:Reliability:
16 -MAY- 01
Type:
Remark:16 -MAY- 01
Type:
Remark:21 -MAY- 01
Type:
Remark:16 -MAY- 01
Type:
Remark:16 -MAY- 01(51)

other: General systemic effects, single exposure (nonhuman, oral)
Severe damage to the stomach lining and nervous systemeffects were reported in rats, mice and rabbits
receiving high doses of citric acid.
(4) not assignable(119) (125)other: General systemic effects, single exposure (nonhuman, oral)
The administration of 2ml/kg of a 500 mN citric acidsolution (64 mg/kg bw) to rats by stomach tube decreased
the volume of gastric juice secreted and the pepsin
activity, but increased the total gastric acid content
of the stomach.
(4) not assignable(81)
other: Toxicity consideration
Citric acid is a p owerful chelating agent and there isevidence that dietary citric acid may reduce thebiological availabilty of iron and calcium.
(97) (124)other: Toxicity consideration
Other studies suggest that dietary citric acid and its
salts may enhance calcium absorption and excretion andthe absorption of sodium.
(18) (21) (92) (102)other: Toxicity consideration
It has been shown in an in vitro system for thedevelopment of artificial caries, that the applicationof citr ic acid to teeth may make them more susceptible
to decay.
(73)
other: Toxicity consideration
No formal acceptable daily intake level h as been
specified by the joint FAO/WHO Expert Committee on Food
Additives since it was felt that citric acid and its
calcium, potassium and sodium salts did not constitute asignificant toxicological hazard to man when usedaccording to good manufacturing practice.
A similar view was expressed by the EC's ScientificCommittee for Food when it evaluated citrate.
(105) (120)UNEP PUBLICATIONS

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Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Type:
Remark:21 -MAY- 01
Type:
Remark:21 -MAY- 01
Type:
Remark:21 -MAY- 01
Type:
Remark:21 -MAY- 01
Type:
Remark:16 -MAY- 01
Type:
Remark:16 -MAY- 01
Type:
Remark:other: Toxicity consideration
Citric acid and its salts may increase the absorption
and retention of ingested metals such as aluminium, tin,
cadmium and lead.
(42) (57) (60) (62) (100) (107) (108) (114)other: Toxicity consideration
Bovine teeth immersed in a soft drink containing 2.6 g
citric acid/l were eroded within 2 hours.
(78)
other: Toxicity consideration
Severe ulceration and tissue damage occured in dogs
receiving tongue applications of 0.1ml of 50% citricacid solution (presumably aqueous) for 5 minutes.
(67)
other: Toxicity consideration
Bronchoconstriction was induced with citric acid (ofunspecified concentration) in dogs, which have non specific airway hyperactivity.
(68)
other : Toxicity consideration
When 14 guinea -pigs were exposed for 30 minutes toatmospheric citric acid concentrations of 31.1 or 81
mg/m3 (obtained by aerosolizing 4 or 6% solutionsr e spectively), only one cough was recorded at the lower
concentration, but significant coughing occured in the
top group.
(126)
other: Toxicity consideration
Coughing was produced in guinea- pigs exposed to 75 mg
citric acid/ml as an aerosol for 3 minutes.
Bronchoconstriction occured after 3-4 minutes.
(40)

21 -MAY- 01

other: Toxicity consideration
Coughing occured frequently when 1 ml of an aqueous
0.27 M (about 52 g/l; 5.2%) solution of citric acid was
instilled into the lower drachea (windpipe) of lambs, aneffect which was not apparently seen when the acid was
instilled into the mid- drachea or laryngeal area.
(52)

Type:
Remark:21 -MAY- 01

other: Toxicity consideration
Mouth ulcers may be provoked by citric acid (human).
(38)

Type:
R e mark:

16 -MAY- 01

other: Toxicity consideration
The lowest concentration of inhaled citric acid required
to produce involuntary coughing in 23 men ranged from
0.5 to 32 mg/ml.
(101)

Ty p e :other: Toxicity consideration

72

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CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

5. Toxicity
Remark:16 -MAY- 01
Type:
Remark:16 -MAY- 01

Citric acid (of unspecified concentration) induced
bronchoconstriction) in human asthmatics.
(68)
other: Toxicodynamics, Toxicokinetics
No studies located

5.11 Experience with Human Exposure
Remark:21 -MAY- 01
Remark:21 -MAY- 01
Remark:21 -MAY- 01
Remark:21 -MAY- 01
R e sult:

17 -MAY- 01
Remark:17 -MAY- 01
Remark:17 -MAY- 01
Remark:Systemic effects, single exposure (human, oral): a young
woman vomited and almost die d after ingesting a single
dose of 25g citric acid [about 417 mg/kg bw].
(82)
Systemic effects, single exposure (human, injection):transfusions of large volumes of citrated blood may
cause depletion of body calcium (hypocalcaemia) andeffects on blood composition which may be accompanied bynausea, exacerbation of muscle weakness, breathingdifficulties and even cardiac arrest.
(15) (16) (59) (106) (122)
General systemic effects, repeated exposure (human):minor gastrointestinal disturbances (diarrhoea,
indigestion, nausea and "burning") were experienced by
22 out of 81 patients taking potassium citrate in waterand seven out of 75 taking solid potassium citrate (doseunspecified in both cases) for the treatment of kidneystones.
(91)
Literature review: excretion of citric acid in 82 maleand female adults ranges from 1.5 to 3.68 mmol/d (total
range 0.4 -8.80 mmol/d) respectively from 290 to 707 mg/d
(total range 80- 1,690 mg/d).
(66)
Man's total daily consumption of citric acid fromnatural sources and from food additive sources may
exceed 500 mg/kg(124)
Citric acid ingested frequently or in large quantities
may cause tooth erosion and local irritation.
(76)
Fourteen volunteers given oral doses of up to 73.5 m Eq
(24.5 mmol) citrate as potassium -magnesium citrate,
tripotassium citrate or trimagnesium citrate during thecourse of a bioavailability study did not suffer any
ov ert gastrointestinal side effects.
(61)
General systemic effects, repeated exposure (human):potassium and sodium citrate (as the monohydrate and

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5. Toxicity

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

21 -MAY- 01

dihydrate respectively) have been used presumably
without marked side effects as medications in dose of up
to 15 g/day.
(76) (120)

Remark:21 -MAY- 01
Remark:21 -MAY- 01
Remark:21 -MAY- 01
Remark:21 -MAY- 01

74

Three patients who ingested potassium citrate solution(one took an unknown large volume, probably on more than
one occasion, two ingested 200 -400 ml over 5 -7 days)
suffered abnormal heart rhythms, probably due toexcessive potassium levels rather than to the citrateion.
(14) (26)T h e a c i d- base balance of the blood was affecte d in 10
men who ingested 60 ml of a solution containing 100 mg
sodium citrate/ml daily (i.e. about 0.86 mg/kg bw/d) for
4 days. Their urine became more alkaline and the amountof sodium excreted was increased while that of magnesium
and potassium was decreased.
(87)
Tooth erosion through dissolution of the enamel due tothe acid effect in aqueous solution has been reported(5)
Citric acid fumes apparently affected the teeth of
exposed workers.
(45)

UNEP PUBLICATIONSOECD SIDS

CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

6. References(1) A.N. Khomenco et al: Gidrokhim. Mater. 50: 96 -101, 1969
(2) Al -A n i , A l- Lamy: Mutat. Res. 206: 467, 1988
(3) Allen et al.: J. Anim. Sci. 68: 2496, 1990 (BIBR A toxicity
profile)(4) Anbar, Neta: A compilation of specific biomolecular rate
constant for the reactions of hydrated electrons, hydrogenatoms and hydroxyl radical with inorganic and organic
compounds in aqueous solution. Int. J. Appl. Radiat.
Isotopes 18: 493 -5 2 3 , 1 9 6 7(5) Asher & Read: Br. dent. J. 162: 384, 1987 (BIBRA toxicity
profile)(6) Behnke et al.: Ernährungsforschung 9 (2): 129, 1964 (BIBRA
toxicity profile)(7) BIBRA Toxicity profile: Citric acid and its common salts(TNO BIBRA Ltd., Carshalton, Surrey SM5 4DS, UK, 1993)(8) Bonting, Jansen: Voeding 17: 137, 1956
(9) Borensztein et al.: Miner. Electrolyte Metab. 15: 353, 1989
(BIBRA toxicity profile)(10) Bringmann, Kühn: Gwf Wasser/Abwasser 117(9), 1976(11) Bringmann, Kühn: Gwf Wasser/Abwasser 122 (7): 308, 1981(12) Bringmann, Kühn: Water Res. 14:231 -2 4 1 , 1 9 8 0(13) Bringmann, Kühn: Z.Wasser Abwasser Forsch. 15: 1 -6, 1982
(14) Browning & Channer: Br. med. J. 283: 1366, 1981 (BIBRA
toxicity profile)(15) Bunker et al.: J. Am. med. Ass. 157: 1361, 1955 (BIBRA
toxicity profile)(16) Charney & Salmond: ASAIO Trans. 36: M217, 1990 (BIBRA
toxicity profile)(17) Coleman, Dewar: Addison -Wesley Science Handbook.
Addison -Wesley, Don Mills (Ontario), 1997(18) Cowley et al.: Clin. Chem. 35: 23, 1988 (BIBRA toxicity
profile)(19) CRC Handbook of Chemistry and Physics, 73 rd ed. CRC Press,
Boca Raton, FL, 1992 -1993(20) CRC Handbook of Food Additives, 2nd ed. Chemical Rubber
Company, Cleveland OH, 1972

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CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

6. References(21) de Leacy et al.: Clin. Chem. 35: 1541, 1989 (BIBRA toxicity
profile)(22) DIMDI (Deutsches Institut für Medizinische Dokumen tation undInformation), Chemline- D a t a b a s e , 1 9 9 3(23) E.E. Shannon et al: Res. Rep. no. 61, Project 73 -3 -7 ,Canada, 1977(24) E.Strassburger: Lehrbuch der Botanik, 1975(25) ECAMA (European Citric Acid Manufacturers Association)(26) Elizabeth & Carter: Br. med. J. 295: 993, 1987 (BIBRA
toxicity profile)(27) Ellis: US Fisheries Bull. 22 (XLVIII): 365- 437, 1937(28) F. Hoffmann -La Roche Environmental Laboratories, unpublisheddata, 1983(29) F. Hoffmann -L a R oche Ltd, specifications of Citric Acid,
1987(30) F. Hoffmann -La Roche Ltd, unpublished Product Data Sheet,1999(31) F. Hoffmann -La Roche Ltd, unpublished report, 1976(32) F. Hoffmann -La Roche Ltd, unpublished report, 1981(33) F. Hoffmann -La Roche Ltd, unpublished report, 1984(a)(34) F. Hoffmann -La Roche Ltd, unpublished report, 1984(b)(35) F. Hoffmann -La Roche Safety Data Sheet, 25.02.2000(36) Fed. Am. Soc. Exp. Biology, Bethesda, MD, for FDA, Bureau of
F o o d s, 1977(37) Fenaroli's Handbook of Flavour Ingredients, vol. 2, 2nd ed.
Chemical Rubber Company, Cleveland OH, 1975(38) Fisher: Contact Dermatitis, 3rd edition, Lea & Febiger,
Philadelphia, p.420 (BIBRA toxicity profile)(39) Food & Drug Research Laboratories, Inc.: Teratologic
Evaluation of FDA 71 -54 Contract no. 71 -260, 1973 (BIBRA
toxicity profile)(40) Forsberg & Karlsson: Bull. Eur. Physiopathol. Respir. 23(Suppl. 10): 71S, 1986 (BIBRA toxicity profile)(41) Gericke, Fischer: A correlation study of biodegradability
determinations with various chemicals in various tests.
Ecotox. Environm. Safety 3: 159- 173, 1979

76

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Date: 18-Oct.01
Substance ID: 77-92-9

6. References(42) Gomez et al.: Toxicologist 11: 45, 1991 (BIBRA toxicity
prof ile)(43) Grant: Toxicology of the Eye, 3rd ed. Charles C.Thomas,
Springfield IL, 1986(44) Gruber & Halbeisen: J. Pharm. exp. Ther. 94: 65, 1948(45) Gupta: J. Soc. Occup. Med. 40: 149, 1990 (BIBRA toxicity
profile)(46) Harry: The Principles and Practice of Modern Cosmetics, Vol.
2 Leonard Hill (Books) Ltd, London (BIBRA toxicity profile)(47) Hayes et al.: Mutation Res. 130: 97, 1984 (BIBRA toxicity
profile)(48) HEDSET, Jungbunzlauer (for ECAMA), 1993
( 4 9) Hockenbury, Grady: JWPCF (Journal of the Water Pollution
Control Federation), May 1977(50) Horn et al.: J. agric. Fd Chem. 5(10): 759, 1957
(51) Hubbell et al.: Vet. Surg. 16: 245, 1987 (BIBRA toxicity
profile)(52) Hutchinson et al.: Pediat. Pulmonol. 3: 45, 1987 (BIBRA
toxicity profile)(53) Inoue et al.: Cancer Lett. 40: 265, 1988 (BIBRA toxicity
profile)(54) Ishidate et al.: Food Chem. Toxicol. 22: 623, 1984(55) Jaffe Toxicol. Ind. Health 11(5): 543, 19 95(56) Jensen: Studies on soil bacteria (Arthrobacter globiformis)
capable of decomposing the herbicide endothal. Acta Agric.
Scand. 14: 193-207(57) Jugo et al.: Toxic. Appl. Pharmac. 34: 259, 1975 (BIBRA
toxicity profile)(58) Juhnke, Lüdemann: Z Wasser Abwasserforsch. 11:161, 1978(59) Kelleher & Schulman: Am. J. Kidney Dis 9: 235, 1987 (BIBRA
toxicity profile)(60) Kirschbaum & Schoolwerth: Hum. Toxicol. 8: 45, 1989 (BIBRA
toxicity profile)(61) Koen ig et al.: J. Urol. 145: 330, 1991 (BIBRA toxicity
profile)UNEP PUBLICATIONS

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CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

6. References(62) Kojima et al.: Yakugaku Zasshi 98(4): 495, 1978 (BIBRA
toxicity profile)(63) Kowalski, RL; Hartnagel, RE: Toxicological Department, Miles
Inc., unpubl. report, 199 1(64) Krop & Gold: J. Am. pharm. Ass. Sci. Ed. 34: 86, 1946 (BIBRA
toxicity profile)(65) Laden: J. Soc. cosmet. Chem. 24: 385, 1973 (BIBRA toxicity
profile)(66) Lentner et al.: Ciba -Geigy Tables. Basel 1975(67) Lilly & Cutcher: J. biomed. Mater. Res. 6: 545, 1972 (BIBRA
toxicity profile)(68) Lindemann et al.: Fed. Amer. Soc. Exp. Biology J. 3: A 1227,
1989 (BIBRA toxicity profile)(69) Litton Bionetics Inc. Summary of mutagenicity screening
studies: host -mediated assay, cytogenetics, dominant lethal
assay, compound FDA 71- 54, citric acid (BIBRA toxicity
profile)(70) Litton Bionetics Inc; Contract no. FDA 71 -2 6 8 , 1 9 7 5(71) Ludzack, Ettinger: JWPCF (Journal of the Water Pollution
Control Federation), 32(12): 1173, 1960
(72) Mackay D, Di Guardo A, Paterson S, Cowan CE: Evaluating theenvironmental fate of a variety of chemicals using the EQC
model. Environ Toxicol Chem 15: 1627 -1637, 1996. EQC andlevel III software is available free at
http://www.trentu.ca/academic/aminss/envmodel/models.html(73) Makris & Kotsanos: Odontostomat. Proodos. 42: 53, 1988
(BIBRA toxicity profile)(74) Malaney, Gerhold: JWPCF (Journal of the Water Pollution
Control Federation), 41(2, part 2): R18 -R33, 1969(75) Marhold: Preheld Prumyslove Toxikologie; Organicky Latky.
Avicenum, Prague (CZ), p.658 (1986)(76) Martindale, 1989
(77) Merck Index, 11 th edition, 1989
(78) Meurman et al.: Scand. J. Dent. Res. 98: 120, 1990 (BIBRA
toxicity profile)(79) Meylan, Howard, Epiwin, SRC

78

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CITRIC ACID
Date: 18-Oct.01
Substance ID: 77-92-9

6. References(80) Miles Laboratories, Inc., Pfizer, Inc., and Proctor andGamble Co., 1977: The environmental safety of citrate.
Presentation to th e IJC task force on the ecological effects
of non- phosphate detergent builders.
(81) Mochizucki et al.: Nut. Rep. Int. 40: 585, 1989(82) Nazario: Ref. Inst. Adolfo Lutz 2: 141, 1952 (BIBRA toxicity
profile)(83) Niinimäki: Contact D ermatitis, 16: 11, 1987 (BIBRA toxicity
profile)(84) Ohgai, Matsui, Tsujinaka & Odanaka: Bull. Jpn. Soc. Sci.
Fish 59(4): 647, 1993(85) OHS Material Safety Data Sheet (10 September 1998), MDL
Information Systems, Nashville, Tenn., USA(86) Ono et al: Jap. J. Cancer Res. 83: 995, 1992 (BIBRA toxicity
profile)(87) Oster et al.: Clin. Chem. 35: 23, 1988 (BIBRA toxicity
profile)(88) Oyo Yakuri: Pharmacometrics 43: 561 (1992)(89) P. Creach: C.R. Acad. Sci . ( P a r i s ) 2 4 0 : 2 5 5 1- 2553, 1995(90) Packman et al.: Toxic. appl. Pharmaz. 5: 163, 1963 (BIBRA
toxicity profile)(91) Pak: Miner. Elect. Metab. 13: 257, 1987 (BIBRA toxicity
profile)(92) Patra et al.: J. Pediatr. Gastroenterol Nutr. 11: 385, 1990
(BIBRA toxicity profile)(93) Portmann & Wilson, Shellfish Information Leaflet No.22 (2nded), 1971(94) QSAR, Epiwin 3.05 Syracuse Research Co.
(95) QSAR, modified Grain method, Epiwin(96) Römpp Chemie- Lexikon, 9th ed. Georg Thieme, Stuttgart, 1989
(97) Rümenapf & Schwille Calcif. Tissue Int. 42: 326, 1988 (BIBRA
toxicity profile)(98) Safety Laboratory Test Report BS -2699, F. Hoffmann -La Roche
Ltd, Basel(99) Sax: Dangerous Properties of Industrial Materials. Van
Nostrand Reinhold, New York NY, 1975

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Date: 18-Oct.01
Substance ID: 77-92-9

6. References(100) Schenkel & Matthes In: Trace element analytical chemistry in
medicine and biology. Proceedings Int. Workshop, Vol. 5.
Edited by P. Braetter & P. Schramel, p.587, Walt e r d e
Gruyter & Co. Berlin, 1988 (BIBRA toxicity profile).
(101) Schreiber et al.: Am. Rev. Resp. Dis. 133: A216, 1986 (BIBRA
toxicity profile)(102) Schuette & Knowles Am. J. Clin. Nutr. 47: 884, 1988 (BIBRA
toxicity profile)( 103) Schwartz et al.: J. Nutr. 118: 183, 1988 (BIBRA toxicity
profile)(104) Schwartz, Davis: EPA -6 0 0 / 2- 74 -003, US EPA, Washington, 1973(105) Scientific Committee for Food. 25th Series. EUR 13416 EN,
1991 (BIBRA toxicity profile)(106) Silverstein et al.: Trans. Am. Soc. Artif. Int. Organs 35:
22, 1989 (BIBRA toxicity profile)(107) Slanina et al.: Clin. Chem. 32/3: 39, 1986 (BIBRA toxicity
profile)(108) Spickett et al.: Agents and actions 15: 3/4, 1984 (BIBRA
toxicity profile)(109) Sridharan, Lee: Environ. Sci. Technol. 6(12): 1031 -1 0 3 3 ,1972(110) Temime et al.: Revue fr. Diet. 69: 41, 1974 (BIBRA toxicity
profile)(111) Tuft & Ettelson: J.Allergy 27: 536, 1956 (BIBRA toxicity
p r o f il e )(112) Ullmann, Encyclopaedia of Technical Chemistry, 4th ed., 1975
(113) US Coast Guard, Dept of Transportation: Hazardous Chemical
Data, vol II. US Government Printing Office, Washington DC,
1984 -1985(114) Van der Voet et al.: Toxi c . Appl. Pharmac. 99: 90, 1989
(BIBRA toxicity profile)(115) Veith et al: J Fish Res Bd Can 26: 1040 -1048, 1976
(116) Verschueren: Handbook of Environmental Data on Organic
Chemicals; 3rd ed. Van Nostrand Reinhold, 1996
(117) Viana de Camargo et al.: Jap. J. Cancer Res. 83: 1220, 1991
(BIBRA toxicity profile)(118) Villard: Archs. Ophtal. 44: 21, 93, 167, 222 (BIBRA toxicity
profile)80

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Date: 18-Oct.01
Substance ID: 77-92-9

6. References(119) Weiss et al.: Ind. Engng. Chem. 15: 6, 1923 (BIBRA toxicity
profile)(120) WHO Food Additives Series No.5 and 733, 1974 and 1986 (BIBRA
toxicity profile)(121) Wichlacz, Unz: Acidophilic, heterotrophic bacteria of acidmine waters. Appl. Environm. Microbiol. 41: 1254 -1261, 1981(122) Wirguin et al.: Ann. Neurol. 27: 328, 1990 (BIBRA toxicity
profile)(123) Wright, Hughes: Fd Cosmet. Toxicol. 14: 561, 1976 (BIBRA
toxicity profile)(124) Wright, Hughes: Nutr. Rep. Int. 13: 563, 1976 (BIBRA
toxicity profile)(125) Yokotani et al.: J .Takeda Res. Lab. 30(1): 25, 1971 (BIBRA
toxicity profile)(126) Zelenak et al.: Fund. Appl. Toxic. 2: 177, 1982 (BIBRA
toxicity profile)

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Robust Study Summaries
Citric Acid (CAS No. 77–92–9)

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1) Melting Point
Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Method: not stated• GLP: no• Year: 1969
Results• Melting Point Value: 152–159 o CConclusions
Data Quality• Reliabilities: not assignable
References (Free Text)•OHS Material Safety Data Sheet (10 September 1998), MDL Information Systems,
Nashville, Tennessee, USA

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2) Boiling Point

Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Method: not stated• GLP: no• Year: 1989
Results• Value: –• Decomposition: yes• Remark: no boiling point due to substance decomposition above 175 o CConclusions• The boiling point could not be determined due to substance decomposition
Data Quality• Reliabilities: not assignable
References (Free Text)• Römpps Chemie-Lexikon, 9th ed. Georg Thieme, Stuttgart, 1989
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3) Vapour Pressure

Test Substance• Citric Acid (CAS: 77–92– 9)
Method• Method: QSAR estimation
Results• Value: 7.3 x 10 -7 Pa at 25 °C
Conclusions
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References (Free Text)• QSAR, Epiwin 3.05 Syracuse Research Co.
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4) Partition Coefficient

Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Method: not stated• GLP: no• Year: 1983
Results• Log Pow: –1.72• Temperature: 20 oC
Conclusions•–

Data Quality• Reliabilities: not assignable
References (Free Text)• Verschueren: Handbook of Environmental Data of Organic Chemicals, 3 rd ed. Van
Nostrand Reinold, New York, 1996
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5) Water Solubility: Solubilities and pKa Values

Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Method: not stated• GLP: no• Year: 1989
Results• Solubility value: 592,000 mg/l at 20 o C• Solubility value: 643,000 mg/l at 30 o C• p Ka1 = 3.13 at 25 o C• p Ka2 = 4.76 at 25 o C• p Ka3 = 6.4 at 25 oC
Conclusions• Freely soluble in water• Substance is partly present in ionised form at all environmentally relevant p H values.
Data Quality• Reliabilities: not assignable
References (Free Text)• The Merck Index, 11th edition, 1989
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5) Water Solubility: pH Value

Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Method: not stated• GLP: no• Year: 1998
Results• p H value: 2.2 at 0.1 N
Conclusions•–

Data Quality• Reliabilities: not assignable
References (Free Text)• OHS Material safety Data Sheet (10 September 1998), MDL I nformation Systems,
Nashville, Tennessee, USA
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CITRIC ACIDENVIRONMENTAL FATE AND PATHWAYS ELEMENTS
6) Photodegradation
Test Substance• Citric Acid (CAS: 77–92– 9)
Method• Method:• GLP:• Year:Results• No studies locatedConclusions•–

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7) Stability in water

Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Test type: abiotic degradation, no details stated• Method: chemical analysis, half-life calculated• GLP: no• Year: 1967
Results• t ½ at pH 1 = 72.9 years (calculated)• Degradation rate constant: 0.30 x 10 8 l/mol·s at room temperature in aqueous solution
Conclusions• Remarks: abiotic degradation due to the reaction with OH radicals, based on literature
value for OH radical concentration in water of 1 x 10-17 mol/l
Data Quality• Reliabilities: not assignable
References (Free Text)• Anbar, Neta: A compilation of specific biomolecular rate constant for the reactions ofhydrated electrons, hydrogen atoms and hydroxyl radical with inorganic and organic
compounds in aqueous solution. Int J Appl Radiat Isotopes 18: 493–523, 1967.
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8) Transport between Environmental Compartments (Fugacity)
Test Substance• Citric Acid (CAS: 77–92– 9)
Method• Method: Static environmental distribution model based on physicochemicalparameters: Level I, EQC Model v.1.0• Year: 1996
Results• Media: air, sediment, soil and water• Values: 99.99% to water, <0.01% to soil, <0.01% to sediment and <0.01% to air• Remarks: Default values for the environmental parameters were not changed. Water
solubility 592,000 mg/l, vapour pressure arbitrarily assigned 1 Pa and logPow –1.72
were used for the calculation.
Conclusions• Practically no partitioning to air, soil and sediment, substance distributes heavily towater.
Data Quality•–

References (Free Text)• Mackay D, Di Guardo A, Paterson S, Cowan CE: Evaluating the environmental fate ofa variety of chemicals using the EQC model. Environ Toxicol Chem 15: 1627–1637,
1996.
Other
• EQC software is available free at
http://www.trentu.ca/academic/aminss/envmodel/models.html

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9) Biodegradation

Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Method: Directive 84/449/EEC, C.5 „Biotic degradation – modified Sturm test“• Duration: not stated, probably 28 days (regular duration of test according to guideline)• GLP: no• Year: 1979
• Medium: water with activated sludge
Results• Values:

97%, based on CO2 evolution
100%, based on DOC removal

Conclusions• Readily biodegradable
Data Quality• Reliabilities: reliable with restrictions
References (Free Text)• Gericke, Fischer: A correlation study of biodegradability determinations with various
chemicals in various tests. Ecotox Environm Safety 3: 159– 173, 1979
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CITRIC ACIDECOTOXICITY ELEMENTS
10) Acute Toxicity to fish
Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Method: not stated• Type: static• GLP: no• Year: 1978
• Species: Leuciscus idus (golden orfe, freshwater)• Exposur e period: 96 hours
Results• Value: LC 50 = 440– 760 mg/l
• Remarks: solution was not neutralised
Conclusions• Low toxicity for fish
Data Quality• Reliabilities: reliable with restrictions
References (Free Text)• Juhnke, Lüdemann: Z Wasser Abwasserforsch. 11: 161, 1978
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11) Toxicity to aquatic plants

Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Method: not stated• GLP: no• Year: 1980
• Species: Scenedesmus quadricauda (Algae, freshwater)• Exposure period: 7 days
Results• Value: EC 0 = 640 mg/l
Conclusions• Low toxicity for algae
Data Quality• Reliabilities: reliable with restrictions
References (Free Text)• Bringmann, Kühn: Water Res 14: 231–241, 1980
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12) Acute toxicity to aquatic invertebrates

Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Method: not stated• GLP: no• Year: 1969
• Species: Daphnia magna (Crustacea)• Exposure period: “Long-time exposure period in soft water”.
Results• Values:

EC 0 = 80 mg/l
EC 100 = 120 mg/l

Conclusions• Geometric mean EC 50 = 98 mg/l
• „Soft water“ does not buffer the acidity respectively the acid effect of the test
substance.
• Low toxicity for daphnids
Data Quality• Reliabilities: reliable with restrictions
References (Free Text)• A.N. Khomenco et al: Gidrokhim. Mater 50: 96–101, 1969
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13) Acute toxicity
Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: > 99%
Method• Type: acute oral toxicity study• GLP: no• Year: 1981
• Species: mouse, SPF, albino, source on record• Sex: male + female• Number of animals: 5 males + 5 females per treatment respectively control group, 60
animals in total in main study.
• Housing: single sex groups in macrolon cages, with ad libitum access to water and
NAFAG 850 complete rodent maintenance diet feed, in a climate-controlled room withenvironmental parameters defined and on record• Route of administration: oral, gavage• Range -finding study: Performed with the following doses: 2,000 mg/kg, 2,828 mg/kg,
4,000 mg/kg, 5,657 mg/kg, 8,000 mg/kg and 10,000 mg/kg; 100% mortality after 24 h
in highest dose group, 50% at 8,000 mg/kg, 20% at 5,657 mg/kg and 0% in all lower
dose groups.
• Description main study: 5 male and 5 female mice in each treatment group wereadministered 3,000 mg/kg, 4,343 mg/kg, 6,000 mg/kg, 8,485 mg/kg or 12,000 mg/kg of
citric acid by gavage. The test substance was dissolved in food grade tap water at suchconcentrations that in every group 20 ml/kg, corresponding to approx. 0.4 ml per
animal, were given. Controls were administered 0.4 ml tap water by gavage. Clinicalsymptoms were observed 2 h and 24 h after administration. The survivors were
followed-up for 10 days after dosing, mortalities were recorded daily, then survivors
were sacrificed.
• L D 50 was calculated using probit analysis and rounded to the nearest 100 mg value.
Results• Value: LD 50 = 5400 mg/kg bw, 95% confidence interval = 4,500–6,400 mg/kg.
• All mortalities occurred in the first 24 h after administration.
Conclusions• Low toxicity to mic e.
Data Quality• Reliabilities: reliable with restriction
References (Free Text)• F. Hoffmann -La Roche Ltd, unpublished report, 1981
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14) Genetic toxicity in vivo (chromosomal aberrations)

Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Type: Dominant lethal assay• Species: rat• Sex: males (treated) and females (untreated)• Number of animals: not stated• Route of administration: oral
• Year: 1975
• GLP: no
Results• No reduced number of foetuses resp. newborn rats in treatment group• No chromosomal damage occurred in the bone marrow of rats ingesting up to 3 g citricacid/kg bw/day for 5 days.
Conclusions• Not mutagenic in the reported test
• No mutagenic potential was detected in a dominant lethal assay in rats in which dosesof up to 3 g citric acid/kg bw/day were administered for 5 days. A dominant lethal
effect is normally reflected by increased early foetal death when treated males are
mated with untreated females.
Data Quality• Reliabilities: not assignable
References (Free Text)• L itton Bionetics Inc 1975a, cited in: BIBRA Toxicity profile: citric acid and its
common salts (TNO BIBRA Ltd., Carshalton, Surrey SM5 4DS, UK, 1993).
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15) Genetic toxicity in vitro (gene mutations)

Test Substance• Citric Acid (CAS: 77–92– 9)• Purit y: not stated
Method• Method: OECD Guideline 471, „Genetic Toxicology: Salmonella thyphimurium
Reverse Mutation Assay“• Type: bacterial reverse mutation assay• Species/strains: Salmonella typhimurium TA 94, TA 98, TA 100, TA 1535, TA 1537
• Metabolic activation: with and without• Meatbolic activation system: liver homogenate from rats pretreated withpolychlorinated biphenyl KC-400• Concentration: up to 5 mg/plate• Year: 1984
• GLP: not stated
Results• Result: no increased incidence of revertant colonies, both with and without metabolic
activation
Conclusions• Not mutagenic in the reported test
Data Quality• Reliabilities: reliable with restrictions
References (Free Text)• Ishidate et al.: Food Chem. Toxicol 22: 623, 1984

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16) Repeated dose toxicity

T e s t Substance• Citric Acid (CAS: 77–92– 9)• Purity: > 99 %Method• Method: not stated• Year: 1976
• GLP: no• Species: rat• Strain: not stated• Sex: 10 males and 10 females, average weight = 150 g• Route of administration: oral, gavage• Doses: 2,000 mg/kg/day, 4,000 mg/kg/day, 8,000 mg/kg/day, 16,000 mg/kg/day,vehicle only (control group)• Vehicle: water, with test substance dissolved to attain the respective dose in the same
volume administered• Frequency of treatment: once daily• Exposure period: 5 days
• Post. obs. period: 10 days, animals were observed for clinical signs, after 10 days
survivors were sacrificed
Results• Results:

NOEL = 4000 mg/kg
LD 50 = 5600 ± 440 mg/kg/d, identical for males and females

Conclusions• Low toxicity on repeated oral administration
Data Quality• Reliabilities: reliable with restrictions
References (Free Text)• F. Hoffmann La Roche Ltd, unpublished report, 1976
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17) Reproductive toxicity

Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Method: not stated• Species: rat• Type: two generation study• Sex: male + female• Route of administration: oral, dietary• Frequency of treatment: daily (feed)• Exposure period: 90 weeks• Doses: feed containing 1.2% w/w citric acid, probably ad libitum• Endpoints: reproduction parameters, blood chemistry, gross pathology, no further
details given• Year: 1956
• GLP: no
Results• Results: cited as „ ... no harmful effects on the growth of two successive generations ofrats over a 90-week period. No effect on reproduction, blood characteristics, pathology
or calcium was observed, although a slight increase in dental attrition was reported.“Conclusions• No indication for reprotoxicity.
Data Quality• Reliabilities: not assignable
References (Free Text)• Bonting, Jansen: Voeding 17: 137, 1956; BIBRA Toxicity profile: citric acid and its
common salts (TNO BIBRA Ltd., Carshalton, Surrey SM5 4DS, UK, 1993).
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17) Reproductive toxicity

Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Method: not stated• Species: rat• Sex: female• Route of administration: oral, dietary• Doses: feed containing 5% w/w citric acid (about 2.5 g/ kg bw/day)• GLP: no
Results• No effects on reproduction.
• NOEL = 2500 mg/kg/d
Conclusions• No indication for reprotoxicity.
Data Quality• Reliabilities: not assig nable
References (Free Text)• Wright, Hughes: Nutr. Rep. Int. 13: 563, 1976; BIBRA Toxicity profile: citric acid andits common salts (TNO BIBRA Ltd., Carshalton, Surrey SM5 4DS, UK, 1993).
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18) Developmental Toxicity/Teratogenicity

Test Substance• Citric Acid (CAS: 77–92– 9)• Purity: not stated
Method• Method: not stated• Species: rat• Sex: males + females, numbers not stated• Route of administration: not stated, probably oral, feed
• Frequency of treatment: daily• Exposure period: days 6 to 15 of gestation• Doses: > 241 mg/kg bw/d
• Year: 1973
• GLP: no
Results• Results: „No indication of adverse effects on nidation, maternal or fetal survival. The
number of abnormalities did not differ from control group.“
Conclusions• No indication of maternal or foetal toxicity, no teratogenicity reported.
Data Quality• Reliabilities: not assignable
References (Free Text)• Food & Drug Research Laboratories, Inc.: Teratologic Evaluation of FDA 71-54
Contract no. 71-260, 1973
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