OECD SIDSBENZOATESFOREWORDINTRODUCTIONBENZOATESCAS N°:65-85-0, 532-32-1, 582-25-2, 100-51-6

UNEP PUBLICATIONS

1OECD SIDSBENZOATESSIDS Initial Assessment Reportfor13th SIAM(Bern, 7th - 9th November 2001)

Chemical Name:

Benzoates: Benzoic acid, Sodium benzoate,
Potassium benzoate, Benzyl alcohol

CAS No:65-85-0, 532-32-1, 582-25-2, 100-51-6

Sponsor Country:

The Netherlands

National SIDS Contact Point in Sponsor Country: Mr. Dick Sijm

HISTORY:
In 2001 ICCA asked The Netherlands to be the sponsor country for the benzoates
no testing (X )testing( )COMMENTS:
The Benzoates were already discussed in other frameworks such as the WHO. Therefore theoriginal data were not again evaluated. The conclusions of other frameworks are discussed in the
SIAR. This SIAR can be considered as a state of the art report on benzoates.
Deadline for circulation:
Date of Circulation:(To all National SIDS Contact Points and the OECD Secretariat)

2

UNEP PUBLICATIONSOECD SIDSBENZOATESSIDS INITIAL ASSESSMENT PROFILE
Benzoates Category

CAS No.

65-85-0532-32-1

582-25-2

100-51-6

Chemical Name

Benzoic acid

Sodium benzoate

Potassium benzoate

Benzyl alcohol

C OOH

C O O - Na +C O O- K +

C H2

OH

Structural Formula

RECOMMENDATIONS
The chemicals are currently of low priority for further work.

SUMMARY CONCLUSIONS OF THE SIAR
Benzyl alcohol, benzoic acid and its sodium and potassium salt can be considered as a single category
regarding human health, as they are all rapidly metabolised and excreted via a common pathway
within 24hrs. Systemic toxic effects of similar nature (e.g. liver, kidney) were observed. Howeverwith benzoic acid and its salts at higher doses than with benzyl alcohol. For environmental effects thecategory is less clear, however all are readily biodegradable, non-bioaccumulative and acute toxicity
values are similar. For human health all exposure routes are possible, despite benzoic acid and its
salts being solids and benzyl alcohol being a liquid. For workers it will mainly be by inhalation andby skin, whereas for consumers it will mainly be by oral and dermal routes.
Human Health
The compounds exhibit low acute toxicity as for the oral and dermal route. The LD50 values are >2000 mg/kg bw except for benzyl alcohol which needs to be considered as harmful by the oral route inview of an oral LD50 of 1610 mg/kg bw. The 4 hrs inhalation exposure of benzyl alcohol or benzoic
acid at 4 and 12 mg/l as aerosol/dust respectively gave no mortality, showing low acute toxicity byinhalation for these compounds.
Benzoic acid and benzyl alcohol are slightly irritating to the skin, while sodium benzoate was not skinirritating. No data are available for potassium benzoate but it is also expected not to be skin irritating.
Benzoic acid and benzyl alcohol are irritating to the eye and sodium benzoate was only slightly
irritating to the eye. No data are available for potassium benzoate but it is expected also to be only
slightly irritating to the eye.
The available studies for benzoic acid gave no indication for a sensitizing effect in animals, however
occasionally very low positive reactions were recorded with humans (dermatological patients) inpatch tests. The same occurs for sodium benzoate. It has been suggested that the very low positive
reactions are non-immunologic contact urticaria. Benzyl alcohol gave positive and negative results in
UNEP PUBLICATIONS

3

OECD SIDSBENZOATES

animals. Benzyl alcohol also demonstrated a maximum incidence of sensitization of only 1% inhuman patch testing. Over several decades no sensitization with these compounds has been seenamong workers.
For benzoic acid repeated dose oral toxicity studies give a NOAEL of 800 mg/kg/day. For the salts
values > 1000 mg/kg/day are obtained. At higher doses increased mortality, reduced weight gain,
liver and kidney effects were observed.
For benzyl alcohol the long-term studies indicate a NOAEL > 400 mg/kg bw/d for rats and > 200
mg/kg bw/d for mice. At higher doses effects on bodyweights, lesions in the brains, thymus, skeletal
muscle and kidney were observed. It should be taken into account that administration in these studies
was by gavage route, at which saturation of metabolic pathways is likely to occur.
It can be concluded that benzoic acid and its salts exhibit very low repeated dose toxicity. Benzyl
alcohol exhibits low repeated dose toxicity.
All chemicals showed no mutagenic activity in in vitro Ames tests. Various results were obtainedwith other in vitro genotoxicity assays. Sodium benzoate and benzyl alcohol showed no genotoxicity
in vivo. While some mixed and/or equivocal in vitro chromosomal/chromatid responses have been
observed, no genotoxicity was observed in the in vivo cytogenetic, micronucleus, or other assays. The
weight of the evidence of the in vitro and in vivo genotoxicity data indicates that these chemicals are
not mutagenic or clastogenic. They also are not carcinogenic in long-term carcinogenicity studies.
In a 4-generation study with benzoic acid no effects on reproduction were seen (NOAEL ≥ 750
mg/kg). No compound related effects on reproductive organs (gross and histopatology examination)
could be found in the (sub) chronic studies in rats and mice with benzyl acetate, benzyl alcohol,
benzaldehyde, sodium benzoate and supports a non-reprotoxic potential of these compounds. In
addition, data from reprotoxicity studies on benzyl acetate (NOAEL >2000 mg/kg bw/d; rats andmice) and benzaldehyde (tested only up to 5 mg/kg bw; rats) support the non-reprotoxicity of benzyl
alcohol and benzoic acid and its salts.
In rats for sodium benzoate dosed via food during the entire gestation developmental effects occurred
only in the presence of marked maternal toxicity (reduced food intake and decreased body weight)(NOAEL = 1400 mg/kg bw). For hamster (NOEL: 300 mg/kg bw), rabbit (NOEL: 250 mg/kg bw) andmice (CD-1 mice, NOEL: 175 mg/kg bw) no higher doses (all by gavage) were tested and no maternal
toxicity was observed. For benzyl alcohol: NOAEL= 550 mg/kg bw (gavage; CD-1 mice). LOAEL =750 mg/kg bw (gavage mice). In this study maternal toxicity was observed e.g. increased mortality,
reduced body weight and clinical toxicology. Benzyl acetate: NOEL = 500 mg/kg bw (gavage rats).
No maternal toxicity was observed.
Environment
From the data (fish, daphnia, algae, bacteria) it is obvious that neutralization of the pH greatly reduces(up to one order of magnitude) the acute toxicity of benzoic acid. This is also supported by the lower
toxicity observed with sodium benzoate. Under environmental relevant conditions therefore the acutetoxicity of benzoic acid, sodium benzoate and potassium benzoate for all four trophic levels is > 100
mg/l. Under environmental relevant conditions the acute toxicity of benzyl alcohol for fish, daphnia
and bacteria is > 100 mg/l. For algae, an EC 50 3hrs of 95 mg/l is reported. Under environmental
relevant conditions, benzoic acid and its salts have very low acute toxicity, whereas benzyl alcohol has
low to moderate acute toxicity.

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UNEP PUBLICATIONSOECD SIDSBENZOATES

Exposure
Worldwide production capacity of benzoic acid is estimated at 700 kt per year. The major outlet(75%) for benzoic acid is as a chemical intermediate in the production of phenol, which in turn ismainly used to produce caprolactam. The next largest outlet is as a feedstock for sodium benzoate(10%) and chemical synthesis of plasticizers (5%).
Worldwide production capacity of sodium benzoate is estimated at 100 kt per year. The major outlet
for sodium benzoate is as preservative in food and beverages (60%). Second most important market iscooling liquids (10%). The main function of sodium benzoate in most applications is as preservative.
Worldwide production capacity of potassium benzoate is estimated at 7 kt per year. It is used as apreservative in nonalcoholic beverages.
Worldwide production capacity of benzyl alcohol is estimated at 50 kt. Major use for benzyl alcohol
is as curing agent in epoxy coatings (30%), where it becomes chemically bounded after reaction.
Other important uses include the use as a solvent in low concentrations in waterborne coatings (10%)
and use in paint strippers (10%) and chemical intermediate for synthesis for benzyl esters that areused in the flavor and fragrance industry (10%). The use in paint strippers is limited to uses inindustrial settings.
Benzyl alcohol, benzoic acid and its sodium and potassium salt are also used in pharmaceuticals,
cosmetics and/or food. Consumer exposure in these specific applications are controlled by the fact
that, for all these applications, specific regulatory frameworks (regional and/or national) withauthorization/approval procedures and specific advisory bodies exist (inter alia : the US FDA, WHO
JECFA, EU SCF, etc), including, on a regular basis, reevaluation of approvals, hazardous properties
and factual exposures. According to information from products registers, uses that are not specificallyregulated include uses of the substances in different kinds of products e.g. paints, varnishes solvents,
cleaning and washing agents, photochemicals and antifreeze agents.
Benzoic acid is a white solid, with a solubility in water of 2.9 g/l and with a vapour pressure of 0.0011
hPa at 20 °C. The log octanol/water partition coefficient was measured to 1.88; the Henry’s law
constant = 0.0046-0.022 Pa*m3/mol; and the pKa = 4.2. Sodium benzoate and potassium benzoate
are white solids, with solubility in water of 556 g/l and with a vapour pressure of <0.0011 hPa at
20 °C. The log octanol/water partition coefficient were measured to –2.269. Benzyl alcohol is acolorless liquid, with a solubility in water of 40 g/l and with a vapour pressure of 0.13 hPa at 20°C.
The log octanol/water partition coefficient was measured to 1.1.
The distribution modeling according to Mackay Level III indicates soil and water to be the favoredcompartments for the chemicals. However, physical chemical properties and use patterns indicate
water to be the main compartment for these substances. None are expected to hydrolyze. All are
readily biodegradable. None has bioaccumulative potential.

NATURE OF FURTHER WORK RECOMMENDED
Regarding all the information provided, the substances have low priority for further work.

UNEP PUBLICATIONS

5OECD SIDSBENZOATESSIDS Initial Assessme nt Report (SIAR)
1.

IDENTITY

Category name:Benzoates

Chemicals:Benzoic acid
Sodium benzoate
Potassium benzoate
BenzylalcoholCAS#:
65-85-0532-32-1
582-25-2
100-51-6

Molecular Weight122.12144.11160.21
108.4

Physico-chemical properties:
ChemicalAppearance

Melting
point

Boilingpoint@ 1013 hPa

Vapor
pressure(at 20ºC)

octanol /waterpartitioncoefficient(LogP)

Water
Solubility(at 20ºC)

Benzoic
acid

White solid

122.4ºC

249.2ºC

0.0011 hPa

1.88

2.9 g/lSodiumbenzoate

White solid

330.6ºC

464.9ºC< 0.001hPa-2.269556 g/lPotassium
benzoate *White solid

330.6ºC

464.9ºC< 0.001hPa-2.269556 g/lBenzylalcohol

Clear liquid-15ºC

205.3ºC

0.13 hPa

1.1

40 g/l*) No data for Potassium benzoate were available, but they are expected to be the same as for sodium benzoate.

Category Justification:
The proposed category of this ICCA HPV Benzoates submission consists of the following
chemicals:

COOH

CH2OH

Benzoic Acid
CAS# 65-85-0

Benzyl Alcohol
CAS# 100-51-6

6

UNEP PUBLICATIONSHenry’slaw
constant

pKa.0046 .022
Pa*m 3/mol

4.19

OECD SIDSBENZOATESCOO*NaCOO*K

Sodium Benzoate
CAS# 532-32-1

Potassium Benzoate
CAS# 582-25-2

The following chemicals (benzylacetate and benzaldehyde) are being used in this ICCA HPV
benzoates submission only for supportive data purposes. They are not as such included in thiscategory submission for reasons stated below:
CH2CO2CH3

CHO

Benzyl Acetate
CAS# 140-11-4

Benzaldehyde
CAS# 100-52-7

Sponsored in the US EPA HPV Programby the Flavor and Fragrance High Production
Volume Consortia (FFHPVC)

Completed SIDS/SIAR

The common metabolic pathway of all these substances, adapted from JECFA 1997 and theAmerican Conference of Governmental Industrial Hygienists Documentation of the Threshold
Limit Values and Biological Exposure Indices, is provided below (ACGIH, 1986):

R = Na, K, or H
CH2CO2CH3

benzyl acetate

CHO

CH2OH

benzyl alcohol

COOR*

benzaldehyde

< 20%
80%
CONHCH2COO

Hippuric Acid
(Urine)

UNEP PUBLICATIONSCO glucuronide

Benzoyl glucuronide(Urine)7

OECD SIDSBENZOATESThe sodium and potassium salts of benzoic acid are expected to immediately dissociate and form
benzoic acid in an aqueous environment.
The benzylacetate, benzylalcohol, benzaldehyde and benzoic acid and its sodium and potassium salt
were considered as a single category regarding human health by JECFA as they are all rapidly
metabolized and excreted via a common pathway within 24hrs (JECFA 1997).
Benzyl acetate, the first compound in the metabolic pathway diagram, is very rapidly hydrolyzed byesterases in several species including man to benzyl alcohol and acetic acid. The benzylalcohol isthen very rapidly metabolized as shown in the above diagram and only at very high dose (> 500
mg/kg/day by oral gavage route) some saturation of metabolic pathways occurs. This is among
others very well shown in studies on benzylacetate (see below; from JECFA 1997).
Male B6C3F1 mice and Fischer 344 rats treated either intravenously or orally with 14C-benzyl
acetate. The intravenous dose was equivalent to 10 mg/kg bw for mice and 5 mg/kg bw for rats. For
oral administration, benzyl acetate was dissolved in corn oil and administered at doses equivalent to10, 100, or 1000 mg/kg bw for mice and 5, 50, or 500 mg/kg bw for rats. The compound was
readily absorbed from the gastrointestinal tract of both species, and about 90% of the total dose wasrecovered as urinary metabolites after 24h. A small proportion (0.3-1.3%) of the total dose was
excreted in the faeces after both intravenous and oral administration. Elimination of benzyl acetate
as carbon dioxide or volatile substances was minimal after intravenous treatment and consequently
was not determined after oral treatment. Analysis of tissues of animals sacrificed 24 h after
intravenous or oral administration of labelled compound showed no 14C activity, indicating thatelimination of the label was virtually complete by this time. This clearance pattern indicates thatbenzyl acetate is readily absorbed and excreted after oral administration. The relative amounts ofbenzyl acetate absorbed, metabolized, and excreted were unaffected by the size or number of doses
administered. Repeated treatment of rats with benzyl acetate at 500 mg/kg bw per day for 14 days,
followed by a single dose of labelled compound did not change the clearance pattern. More than
90% of the radiolabel in the urine was present as hippuric acid, with minor amounts as benzyl
alcohol and benzylmercapturic acid (up to 4%); no unchanged benzyl acetate was found, and thelevels of benzoyl glucuronide were not measured.
There was no evidence to suggest saturation or reduction of metabolic capacity in either species
over the dose range tested. At much higher dosing the proportion of the dose present as benzoyl
glucuronide increased with dose, indicating a limited capacity for glycine conjugation only at
extreme high dose levels.
These studies clearly show, that the compound is rapidly absorbed from the gastrointestinal tract ofrats and mice, and about 90% of the total dose is recovered as urinary metabolites after 24h. Morethan 90% of the radio-label in the urine is present as hippuric acid, with minor amounts as benzyl
alcohol and benzylmercapturic acid (up to 4%); no unchanged benzyl acetate was found. Only atvery high doses, saturation of these pathways will occur.
This clearly shows the rapid pathway of hydrolysis to benzyl alcohol and subsequent oxidation tobenzaldehyde to benzoic acid and subsequent conjugation to the hippuric acid.
All supports a very rapid absorption, distribution, biotransformation, and excretion of thesesubstances by the common pathway given above.
Repeated dose toxicity studies (information in this SIAR) reveal only sytemic toxic effects (e.g.
liver, kidney) of similar nature, at high dose.
For environmental effects the category is less clear, however all are readily biodegradable, nonbioaccumulative and acute toxicity values for water organisms under environmental relevant
conditions are similar.
For human health all exposure routes are possible, despite benzoic acid and its salts being solids
and benzylalcohol being a liquid. For workers exposure will mainly be by inhalation and by skin,whereas for consumers it will mainly be oral and dermal.
8
UNEP PUBLICATIONSOECD SIDS
2.

BENZOATES

GENERAL INFORMATION ON EXPOSURE

Production and use:
Benzoic Acid
Worldwide production capacity is estimated at 700 kt per year. Average operating rate is at max
80% resulting in a production of 560 kt benzoic acid per year. The major outlet (75%) for benzoic
acid is in the production of phenol, which in turn is mainly used to produce caprolactam. The next
biggest outlet is as a feedstock for sodium benzoate (10%) and chemical synthesis of plasticizers(5%). Benzoic acid is therefore mainly (>80%) used as a chemical intermediate for synthesis ofother chemicals, as well as for the production of sodium salt (10%). So it has mainly a controlled
use in industrial settings.
Sodium Benzoate
Worldwide production capacity is estimated at 100 kt per year. Average operating rate is at max
75% resulting in a production of 75 kt sodium benzoate per year. The major outlet for sodium
benzoate is as a preservative in food and beverages (60%). Second most important market iscooling liquids (10%). The main function of sodium benzoate in most applications is as apreservative.
Potassium Benzoate:
Worldwide production capacity is estimated at 7 kt per year. It is used as a preservative innonalcoholic beverages.
Benzyl AlcoholWorldwide production capacity is estimated at 50 kt per year. Average operating rate is at max 80%
resulting in a production of 40 kt benzyl alcohol per year. The major use for benzyl alcohol is as acuring agent in epoxy coatings (30%), where it becomes chemically bound after reaction. Other
important uses are as a solvent in low concentrations in waterborne coatings (10%), and use in paintstrippers (10%) and as chemical intermediate for synthesis of benzyl esters that are used in the
Flavor and Fragrance industry (10%). The use in paint strippers is limited to uses in industrial
settings.
Benzylalcohol, benzoic acid and its sodium and potassium salt have been used for decades inpharmaceuticals, cosmetics and/or food as preservatives and flavoring/fragrance agents
Information in Product registers:
According to information in Product Registers the substances are used in different kinds of products
e.g. paints, varnishes, solvents, cleaning and washing agents, photochemicals and antifreeze agents.
Release into the environment during production and use :In DSM Geleen The Netherlands, during production, about 650 kg/year of benzylalcohol are
emitted into the atmosphere (< 0.01 % of production volume). Based on the amount benzylalcohol
discharged to the DSM WWTP, it can be calculated that the influent concentration of the WWTP is
at about 1 ug/l. Because of its ready biodegradability and the existing dilution of effluent to thereceiving water, the concentration in the receiving water will be < 0.01 ug/l.
In DSM Rotterdam The Netherlands, during production sodium benzoate is emitted to air at < 0.01
% of the production volume. For benzoic acid this is < 0.001 %.

UNEP PUBLICATIONS

9OECD SIDS
2.1

BENZOATES

Environmental Exposure and Fate

Distribution modelling using Mackay Level III (the EPA default: equal releases (10,000 kg/hr) andequal distribution to all compartments was used) indicates water (34.8-50%) and soil (48.4-64.2%)
to be the main compartment for all four chemicals. None are expected to volatilize to theatmosphere (< 1.51%), nor to adsorb to sediment (< 0.09 %) (Meylan & Howard, 1999).
However physical chemical properties and use patterns indicate water to be the main compartment
for these substances.
Distribution (%) according to Fugacity Level III
ChemicalBenzoicacid
Sodiumbenzoate
Potassium
benzoate
Benzylalcohol

CAS#

Air

Water

Soil

Sediment

65-85-0

0.911

34.8

64.2

0.093

532-32-1

1.45e-007

45.3

54.6

0.0755582-25-2

1.61 e-007

45.3

54.6

0.0755100-51-6

1.51

50.0

48.4

0.0923

Based on structure and organic chemistry rules (e.g. bonding in organic molecules, activationenergy, reactivity, transformations, addition, substitution, elimination) no hydrolysis is expected at
pH ranges of 4 - 11.
The calculated photodegradation for benzyl alcohol and the benzoates are 50% after 1.3 to 3 days
(Meylan and Howard, 1999), and the measured photodegradation for benzoic acid is 90% after 140
minutes (Matthews, 1990).
Biodegradation and Bioaccumulation
All four chemicals are readily biodegradable (> 90% after 28 days) both aerobically (MITI, 1992;
Zahn & Wellens, 1980; Salanitro et al., 1988) and anaerobically (Battersby & Wilson, 1989;
Horowitz et al., 1982).
(Benzoic acid is used as positive control in OECD Guideline for ready biodegradability testing).
From the results of numerous removal experiments the main elimination pathway for the chemicals
is biotic mineralization.
The octanol/water partition coefficient of all compounds indicates a low potential forbioaccumulation. This is also supported by the rapid biotransformation and/or excretion of thesecompounds in urine in mammals.
2.2

Human Exposure

For human health all exposure routes are possible, despite benzoic acid and its salts being solids
and benzyl alcohol being a liquid. For workers exposure will mainly be by inhalation and by skin,whereas for consumers it will mainly be oral and dermal

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UNEP PUBLICATIONSOECD SIDSBENZOATES

Consumer exposure:
Benzoic acid, benzylalcohol, sodium benzoate and potassium benzoate are widely used in food,cosmetic and pharmaceutical applications as preservatives and flavoring/fragrance agents. Benzoic
acid and benzylalcohol are naturally occurring (Merck Index, 1996). Consumer exposure in these
specific applications are controlled by specific regulatory frameworks (regional and/or national)
with authorization/approval procedures and specific advisory bodies (among others US FDA, WHO
JECFA, EU SCF, etc). A re-evaluation of approvals, hazardous properties and factual exposures(among others compliance to the ADI) inclusive, are performed on a regular basis. According to
information in Product Registers the substances are used in different kinds of products e.g. paints,
varnishes, solvents, cleaning and washing agents, photo chemicals and antifreeze agents.
Benzoic acid and sodium benzoate are under re-evaluation at the EU Scientific Committee forFood. From preliminary information (June 2001) re-approval is expected for these substances. The
Joint FAO/WHO Expert Committee on Food Additives (JEFCA) has established a group
Acceptable Daily Intake (ADI) for benzoic acid and its salts and benzyl alcohol, benzyl acetate andbenzaldehyde of 5 mg benzoic acid equivalent/kg bodyweight. This group ADI is based on the
structural similarity and common metabolic fate of these chemicals (WHO, 1997).
Worker exposure:
Companies have provisionally advised exposure limits for benzoic acid and its salts as well as forbenzyl alcohol. Also the US WEEL (Workplace Environmental Exposure Limit) Committee of the
AIHA has set limits for benzyl alcohol at a value of 10-ppm (44 mg/m3) 8hr TWA.
In the several past decades of production, no cases of health complaints (sensitisation inclusive)
have occurred.
Also from companies that use the substances no health complaints (sensitisation inclusive) haveever been reported.

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OECD SIDS
3.

BENZOATESHUMAN HEALTH

3.1 Effects on Human HealthIn general:••••

Benzoate from potassium benzoate and sodium benzoate will change from the ionized form
to the undissociated benzoic acid molecule under physiological conditions.
Benzyl acetate, benzyl alcohol and benzaldehyde are all metabolized to benzoic acid and itis therefore reasonable to assume that the results of studies on members of the group will
apply to the others.
All benzyl compounds are rapidly absorbed, and rapidly and completely excreted in theurine. The main transformation of benzoic acid is the formation of hippuric acid.
It is considered also that data gaps for one substance can be adequately addressed by theexisting data for the other compounds.

Only the results of the critical studies are given, but for most endpoints additional studies exist (seefull IUCLID documents), that support the results in the critical studies.

3.1.1 Acute Oral Toxicity
Three of the four compounds were tested according to Guideline methods. All demonstrated very
low or low toxicity, especially the benzoate salts. Only benzyl alcohol has a LD50 slightly lessthan 2000mg/kg bw and should therefore be considered as harmful. Although the studies on
potassium benzoate were not Guideline studies, these were accepted because the results showed low
toxicity, similar to the sodium salt.

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UNEP PUBLICATIONSOECD SIDSBENZOATES

ChemicalSpeciesProtocolBenzoicacidrat

Directive
84/449/EEC

LD50 =2565 mg/kg

IRDC#163-282, 1974

mouse

OPPTS
870.1100

LD50 =2250 mg/kg

BRL#9348, 1979

rat

Directive
84/449/EEC

LD50 =3140 mg/kg

Loeser, 1977-A; Deuel et al.,
1954

rat

other

LD50 =4070 mg/kg

Smyth & Carpenter, 1948

rat

Directive
84/449/EEC

LD50 =1610 mg/kg

Loeser, 1978

rat

other

LD50 =2080 mg/kg

Graham & Kuizenga, 1945;
Opdyke, 1973

mouse

other

LD50 =1580 mg/kg

Jenner, 1964; Opdyke, 1973

rat

other

LD50 = >10,000 mg/kg

Kravets-Bekker & Ivanova, 1970

mouse

LD50 = >10,000 mg/kg

Kravets-Bekker & Ivanova, 1970

guinea pig

LD50 = >10,000 mg/kg

Kravets-Bekker & Ivanova, 1970

Sodiumbenzoate

Benzylalcohol

Potassium
benzoate

ResultReference

3.1.2 Acute Dermal Toxicity
Two of the compounds were tested for acute dermal toxicity. Both demonstrated low toxicity.
ChemicalSpeciesProtocolResultBenzoicacidrabbitEPA OTS
798.1100

LD50= > 2000 mg/kg

IRDC#163-282, 1974;
Opdyke, 1973

Benzylalcohol

RabbitOther

LD 50 = 2000 mg/kg

NPIRI,1974

guineapig

Other

LD 50 = < 5 ml/kg

Jones, 1967; Opdyke, 1973

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Reference13

OECD SIDSBENZOATES

3.1.3 Acute Inhalation Toxicity
Two of the compounds were tested for acute inhalation toxicity according to Guideline procedures;
both demonstrating very low toxicity.
ChemicalSpeciesProtocolResultBenzoicacidrat

EPA OTS
798.1150

LC50 = >12.2 mg/l/4h.
No mortality at 12.2
mg/l as dust.

IRDC#163-282, 1974

BenzylalcoholratOECD Guideline 403 and
GLP

LC 50 = > 4.178 mg/l/4h.
No mortality at 4.178
mg/l as aerosol

Bayer AG, 1990

Reference

In conclusion: The compounds exhibit low acute toxicity, except benzylalcohol that has an oral
LD50 slightly less than 2000 mg/kg bw and should therefore be considered as harmful by the oralroute.

3.1.4 Skin Irritation
Three of the compounds were tested for skin irritation according to Guideline procedures; thepotassium salt should be similar to the sodium salt, therefore being non-irritating.
ChemicalSpecies

Benzoicacid

RabbitSodiumbenzoate

Benzylalcohol

ProtocolResultReference

EPA OTS 798.4470

not irritating

IRDC # 163-282

rabbitDirective 84/449/EEC

slightly irritating

RCC N OTOX - study
no. 0847/1083, 1988.

RabbitOECD Guide-line 404

not irritating

RCC NOTOX - study
no. 014658

rabbitDirective 84/449/EEC

not irritating

Loeser, E., 1977-B

rabbitOECD Guide-line 404

not irritating

Bayer AG data, Report
No. 19232, 1990

rabbitOtherslightly irritating

Smyth, H. F. et al.,1951; reported in US
NTP: TR 343, 1989.

3.1.5 Eye Irritation
Three of the compounds were tested for eye irritation according to Guideline procedures; thepotassium salt should be similar to the sodium salt, therefore being non- to slightly irritating.

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UNEP PUBLICATIONSOECD SIDSBENZOATES

ChemicalSpecies

Benzoicacid

RabbitDirective
84/449/EEC

highly irritating

RCC NOTOX - study no.
0847/1084, 1988

rabbitEPA OTS
798.4500

severely irritating

IRDC #163-282

RabbitDirective
84/449/EEC

not irritating

Loeser, E., 1977-B

rabbitOECD Guide-line
405slightly irritating

RCC NOTOX - study no.
014669, 1988

RabbitOECD Guide-line
405

moderately
irritating

Bayer AG data, Report No.
19232, 1990

rabbitOther: limited data

highly irritating

Smyth, H. F. et al., 1951;
reported in US NTP: TR
343, 1989

Sodiumbenzoate

Benzylalcohol

ProtocolResultReference

In conclusion: Benzoic acid and benzylalcohol are slightly irritating to the skin, while sodium andpotassium benzoate are not skin irritating. Benzoic acid and benzyl alcohol are irritating to eyes,and sodium and potassium benzoate are only slightly irritating to eyes
3.1.6 Sensitization
The available studies for benzoic acid gave no indication for a sensitizing effect in animals,
however some weak positive reactions were recorded with the human patch test. Benzyl alcohol
was non-sensitizing in the Draize and Guinea Pig Maximization Tests, but a positive sensitizer in
the Freund’s Complete Adjuvant Test and the guinea pig Open Cutaneous Test and demonstrated amaximum incidence of sensitization of 1% in clinical human patch testing. A clinicaldermatological study showed positive patch test reactions in 0.2% of the patients treated with 5%
sodium benzoate in petrolatum. It has been suggested that this very low potential of sodium
benzoate to elicit a non-immunologic contact urticaria may be due to the formation of benzoic acidat skin contact.

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ChemicalSpecies

Benzoic
acid

guineapig

Draizenot sensitizing

BRL #9347, 1979

guineapig

Guinea pig
maximizationtest

not sensitizing

Gad, 1986

human

Patch test

occasional
positive result

Rademaker & Forsyth, 1989;
Forsbeck & Skog, 1977

Human

Patch test

5 of 2045 patients
positive

Brasch, J. et al., 1993

human

Patch test

nonimmunologic
contact urticaria

Nethercott, J.R.,1984

guineapig

Draize Test

not sensitizing

Klecak, G. et al., 1977

guineapig

Guinea pig
maximizationtest

not sensitizing

Klecak, G. et al., 1977

guineapig

Freund's
completeadjuvant test

sensitizing

Klecak, G. et al., 1977

guineapig

Openepicutaneous test

sensitizing

Klecak, G. et al., 1977

human

Patch-Testsensitizing

Malten, K. E. et al.,1984;
Mitchell, J. C. et al., 1982;
Nethercott, J. R., 1982

Sodiumbenzoate

Benzylalcohol

ProtocolResultReference

In conclusion: No firm conclusion on the sensitizing potential of benzyl alcohol can be made dueto the varied results with the various tests. Both benzoic acid and sodium benzoate were nonsensitizing in animal test but showed a very low incidence in humans (patients) tested by the patch
test.
CICAD conclusion on benzoic acid and sodium benzoate was: “However, both substances are
known to cause non-immunologic immediate contact reactions. This effect is scarce in healthy
subjects, while in patients with frequent urticaria or asthma, symptoms or exacerbation of thesymptoms were observed”.
3.1.7 Repeat Dose Toxicity
Several short term repeated dose toxicity studies are available (see IUCLID documents) on
compounds of the group (as well as benzaldehyde and benzyl acetate) and support the outcome and
No Observed Adverse Effect Level (NOAEL) of the longer term studies given below.
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In a 4-generation study 20 rats/sex/group were dosed continuously by diet with 375 or 750
mg/kg/day benzoic acid. In all 4 generations no influence on growth (weight, weight gain and foodefficiency (measured by protein efficiency)) and organ weights was found. The animals of the 3rd
generation were killed and examined histopathologically after 16 weeks (after lactation of thepups). No histo-pathological findings were found. In the paper, no information is given on theorgans investigated, however the robustness of the total study, the reputation of the investigators, aswell as the reputation of the Professor who did the histopathologic investigation, a high scientificquality has to be assumed even though the studies were performed many years ago. From otherparameters it can be assumed that as a minimum the brains, heart, liver, kidney, testis and spleen
were examined.
Feeding of 375 mg/kg/day led to prolongation of survival compared to controls
NOAEL > 750 mg/kg/day(Kieckebusch & Lang, 1960)
Due to missing hematological and clinical chemistry investigations in all studies only a preliminary
NO(A)EL of about 800 mg/kg can be derived for rats which is based on the studies from
Kieckbusch & Lang (1960), Kreis et al. (1967) and Bio-Fax (1973) (Details to be found in the
IUCLID).
A 21 day dermal study with male/female New Zealand white rabbits dosed with 100, 500, or 2500
mg/kg bw benzoic acid 5 days/week showed no compound related effects in behavior, body weightorgan weights, clinical laboratory tests or survival. Very slight dermal irritation was noted for 1/8
rabbits at the 2500 mg/kg level.
NOAEL = 2500 mg/kg/day(IRDC# 163-675, 1981)
Four groups of 10 CD rats/sex/group were exposed to 0, 25, 250 or 1200 mg benzoic acid dust
aerosol/m3 (analytical concentration; MMAD 4.7 µm) for 6 hours/day and 5 days/week over 4
weeks. At ≥ 25 mg/m3 an increased incidence of interstitial cell infiltrate and interstitial fibrosis in
the lungs in treated animals compared with controls was seen. However, there was no clear dosedependency. A concentration of ≥ 250 mg/m3 resulted in upper respiratory tract irritation anddecreased absolute kidney weights in females. In the highest-dose group one rat/sex died and the
body weight gain was decreased in males and females. Other effects included a decrease in platelets(males/females), absolute/relative liver weights (males) and trachea/lung weights (females).
LOAEC (local effect) = 25 mg/m3 (However no clear dose-response was observed).
NOAEC (systemic) = 25 mg/m 3(IRDC# 163-676,1981)
In a 10-day study, rats received sodium benzoate in feed. At the lowest tested concentration of1358 mg/kg changes in serum chlolesterol levels occurred in females. At doses of 1568 mg/kg andabove changes in further serum parameters and an increased relative liver weight were described.
Histopathological changes of the liver, increased relative kidney weights and disorders of thecentral nervous system were seen after dosing via diet with ≈ 1800 mg/kg.(Fujitani, 1993)
A 90-day study with male/female Sherman rats given 640, 1280, 3145, or 6290 mg/kg/day USP
sodium benzo ate continuously in feed showed no adverse effects at < 3145 mg/kg bw. There wasincreased mortality (4/8 died); reduced weight gain; increased weight of livers and kidneys;
pathological lesions (not specified) in livers and kidneys at 6290 mg/kg bw.
NOAEL = 3145 mg/kg bw/day(Deuel, 1954)
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For mice the NO(A)EL of sodium benzoate is higher. According to a 35 day study (by drinking
water) no effects were observed at 3000 mg/kg bw. At this dose level also in a chronic study no
toxic effects were found in histopathological examinations (see 3.1.9 paragraph 2, Toth, 1984)(Toth, 1984).
A 13-week study with male/female F344/N rats given 50, 100, 200, 400, or 800 mg/kg/day benzyl
alcohol by gavage showed staggering, respiratory difficulty, and lethargy in rats of the high dosegroup. Hemorrhages occurred around the mouth and nose, and there were histologic lesions in thebrain, thymus, skeletal muscle, and kidney. There were reductions in relative weight gain in malerats dosed with 800 mg/kg and in female rats dosed with 200 mg/kg or more. No notable changes inbw gain or compound-related histopathologic lesions were observed in rats from the lower dosegroups.
In the 2-y study(see 3.1.9 paragraph 3), however, no notable changes were found on bw or bw gain
at 200 or 400 mg/kg/d. The NOAEL in this 2-y rat study was 400 mg/kg/day, the highest dosetested.
NOAEL = 400 mg/kg/day (based on investigated parameters and taking into account the bw resultsof the 2-y study)(US NTP Technical Report No. TR 343, 1989)
A 13-week study with male/female B6C3F1 mice given 50, 100, 200, 400, or 800 mg/kg/day
benzyl alcohol by gavage showed staggering in mice dosed with 800 mg/kg, after dosing during
the first 2 weeks of the study. Staggering after dosing occurred during the first 2 w of the study inmice dosed with 800 mg/kg. There were reductions in relative weight gain in male mice dosed with
400 or 800 mg/kg, and in female mice dosed with 200 mg/kg or more. No notable changes in bw
gain or compound-related histopathologic lesions were observed in mice from the lower dosegroups.
In the 2-y study (see 3.1.9 paragraph 4), however no notable changes were found on bw or bw gain
at 200 mg/kg/d. The NOAEL in this 2-y mice study was 200 mg/kg/day the highest dose tested.
NOAEL = 200 mg/kg/day (based on reduction of relative weight gain only and taking into accountthe bw results of the 2-y study).
(US NTP Technical Report No. TR 343, 1989)
It should be noted: these studies were done by gavage (leading to greater toxicity due to the “bolus
effect”.) The administration of the benzyl compounds by gavage are likely to reveal changes atlower doses compared to studies where the substances are applied in the diet, leading to a
distribution in the body over time.
In conclusion: For benzoic acid repeated dose (long-term inclusive) oral toxicity gives a NOAEL
of 800 mg/kg/day. For the salts values > 1000 mg/kg/day are obtained. At higher doses increased
mortality, reduced weight gain, liver and kidney effects were observed. For benzyl alcohol taking
into account also the results of the long-term studies indicate a NOAEL > 400 mg/kg bw/d for rats
and > 200 mg/kg bw/d for mice, however it should be taken into account that in these studies
administration was by gavage, at which bolus dosing occurs and saturation of metabolic pathways
is likely to occur. At high doses, effects on bodyweights, lesions in the brains, thymus, skeletal
muscle and kidney were observed.
It can be concluded that benzoic acid and its salts exhibit very low repeated dose toxicity. Benzyl
alcohol exhibits low repeated dose toxicity.

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3.1.8 Genetic Toxicity
3.1.8.1 Genetic Toxicity in vitro
Benzoic acid was not mutagenic in Ames tests with and without metabolic activation (EGG# 580192-1-78, 1978). The Sister Chromatid Exchange assay with human lymphocytes was negative - nometabolic activation was used (Jansson, 1988; Tohda, 1980). A Chromosome Aberration study
with CHL cells was ambiguous - no metabolic activation was used (Ishidate, et al., 1984). A
recombination assay with Bacillus subtilus H17 and M45 was positive (reported with minimal
documentation in an abstract, Nonaka, 1989).
Sodium benzoate was not mutagenic in Ames tests with and without metabolic activation (Ishidate,
et al., 1984). A cytogenetic assay using anaphase preparations of cultured human embryonic lungcells was negative - no metabolic activation was used (FDA PB 245453, 1974). An Escherichia
coli reverse mutation assay was negative with and without metabolic activation (Prival, 1991). A
cytogenetic assay using CHL cells was positive without metabolic activation (Ishidate, et al., 1984;
Ishidate & Odashima, 1977). Sister Chromatid Exchange assays using Chinese hamster cells orhuman lymphocytes were positive without metabolic activation (Abe & Saski, 1977; Xing &Zhang, 1990). A recombination assay with Bacillus subtilus H17 and M45 was positive (reportedwith minimal documentation in an abstract, Nonaka, 1989).
Potassium benzoate tested positive in a recombination assay using Bacillus subtilus H17 and M45,
with and without metabolic activation (Ishizaki & Ueno, 1989).
Benzyl alcohol was not mutagenic in Ames tests with and without metabolic activation (US NTPTechnical Report No. TR 343, 1989). Escherichia coli reverse mutation assay was negative withand without metabolic activation (Leifer et al., 1981). A cytogenetic assay using CHO cells was
negative without metabolic activation and positive with metabolic activation (Anderson et al., 1990;
Zeiger et al., 1990). A Sister Chromatid Exchange assay using CHO cells was ambiguous with andwithout metabolic activation (US NTP Technical Report No. TR 343, 1989). A recombination
assay with Bacillus subtilus H17 and M45 was positive (reported with minimal documentation,
Kuroda et al., 1984).

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Summary of (non-Ames) in vitro results:
Species (test system)
End-point

Results
without
withmetabolic metabolic
activation activation

Remarks

Benzoic acid

Human lymphoblastoid
cells (transformed by
Epstein-Barr virus)
Bacillus subtilis H17,
M45

Sister chromatid
exchange

Chinese hamster cells(CHL)

Chromosome
aberration

NegativeNT

Recombination assay?

NT

Anaphase preparation

NegativeNT

Reverse mutation
assay
Recombination assay

Negative

Negative

Chromosome
aberration
Sister chromatid
exchange
Sister chromatid
exchange

Positive

NT

Positive?

NT

PositiveNT

tested positive(no further information
available, only
summary given)
result given as
negative in: Ishidate etal. (1984)

Sodium benzoate

Human embryonic lung
cells
E.coli WP2Bacillus subtilis H17,
M45

Chinese hamster cells(CHL)
Chinese hamster cells(DON)
Human lymphocytes

tested positive(no further information
available, only
summary given)slight increase without
dosage effectPotassium benzoate

Bacillus subtilis H17,
M45

Recombination assay

tested positive(limited data)

Benzyl alcohol

E.coliChinese hamster cells(CHO)
Chinese hamster cells(CHO)
Bacillus subtilis H17,
M45
? = ambiguous
NT = not tested

Reverse mutation
assay
Cytogenetic assay

Negative

Negative

Negative

Positive

Sister chromatid
Exchange
Recombination assay?

?
tested positive(limited data)

In conclusion: Studies of these chemicals in the Ames point mutation assay do not show evidenceof mutagenicity.
However, some have been reported to be positive in the less commonly used Bacillus subtilus
recombination assay. In a number of cases adverse effects on the chromosome could be noticed,
however also negative and/or equivocal results were reported.
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However many higher-level in vivo tests (clastogenicity inclusive) were negative (see 3.1.8.2).
3.1.8.2 Genetic Toxicity in vivo
General remark: Since the sodium salt of benzoic acid instantaneously dissociates to the benzoic
acid, the studies with sodium benzoate are also representative for benzoic acid and potassium
benzoate.
A cytogenic assay in male rats given single or multiple gavage doses of 50, 500, or 5,000 mg/kg
sodium benzoate showed no significant increase in chromosomal aberrations in the bone marrow.
(FDA PB 245453, 1974)
A dominant lethal assay using male rats given single or multiple gavage doses of 50, 500, or 5,000
mg/kg sodium benzoate was non-mutagenic.
(FDA PB 245453, 1974)
Remark: IPCS CICAD 26 (2000) mentioned this dominant lethal assay as a positive result,however evaluation of the raw data in the original report (by experts of the industry consortium anda recent independent review by Prof. R. Kroes) gives no support for this. In addition the authors of
the study clearly conclude negative. FDA also evaluated this study as negative. In addition sodium
benzoate doesn’t contain a structural alert for genotoxicity.
A host mediated assay using male rats given multiple gavage doses of 50, 500, or 5,000 mg/kg
sodium benzoate showed no elevation of mutant frequencies in Salmonella typhimurium G46; noelevation of mutant frequencies in Salmonella typhimurium TA 1530; no increase in recombinantfrequencies in Saccharomyces cerevesiae D3.
(FDA PB 245453, 1974)
A host mediated assay using male rats given a single gavage dose of 50, 500, or 5,000 mg/kg
sodium benzoate showed an elevation of mutant frequencies in Salmonella typhimurium TA 1530
in the intermediate dose level; the other doses were negative.
(FDA PB 245453, 1974)
A Mouse Micronucleus assay using 50, 100, 200 mg/kg benzyl alcohol by i.p. injection was
negative at all doses tested.
(Hayashi et al., 1988)
A Replicative DNA Synthesis assay using male Fischer 344 rats given a single dose of 0, 300 or
600 mg/kg bw benzyl alcohol by gavage was negative at all doses tested.
(Uno et al., 1994) ;A Replicative DNA Synthesis assay using male B6C3F1 male mice given a single dose of 0, 400 or
800 mg/kg bw benzyl alcohol by gavage was negative at all doses tested.
(Miyagawa et al., 1995)
A Drosophila melanogaster SRL assay with benzylalcohol 5000 ppm (feed) and 8000 ppm(injection) was negative (Foureman, et al., 1994)
Summary of genetic toxicity in vivo results:

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End-point

Results

male Sprague Dawleyratsmale ICR mice

Cytogenetic Assay(bone marrow)
Host-Mediated Assay(tester strains Salmonella
typhimurium TA 1530,
G 46 and Saccharomyces
cerevisiae D3)

Negativemale random bred rats

Dominant Lethal Assay

Negative

Mouse Micronucleus
Assay
Replicative DNA
Synthesis
Replicative DNA
Synthesis
SLR assay

Negative

Species (test system)

Remarks

Sodium benzoate

Negative

elevated mutant
frequency with
TA 1530 in theintermediate single
gavage dosing only(clear negative after
multiple gavage
dosing)Benzyl alcohol

male micemale Fischer 344 rats
male B6C3F1
Drosophila melanogaster

Negative
Negative
Negative

In addition data from in-vivo genotoxicity studies on benzyl acetate and benzaldehyde (JECFA
report, 1997) are supportive evidence for the non-genotoxicity of benzyl alcohol and benzoic acidand its salts.

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Summary genetic toxicity in vivo results:
End-point
Species (testDosesystem)Benzaldehyde
Drosophila
Sex-linked
150 ppm (feed),melanogasterrecessive lethal
2500 ppm
mutation(injection)
Benzyl acetate
Drosophila
Sex-linked
300 ppm (feed),melanogasterrecessive lethal
20,000 ppm
mutation(injection)
Mouse boneChromosomal
325-1700
marrow cells
aberration
mg/kg bw ( i.p.)

Results

Remarks

Negative

Woodruff et al.
(1985);US NTP (1990)

Negative

US National
Toxicology Program(1993)US National
Toxicology Program(1993)US National
Toxicology Program(1993)US National
Toxicology Program(1993)US National
Toxicology Program(1993)

Negative

Mouse bonemarrow cells

Micronucleus
formation

312-1250
mg/kg bw ( i.p.)

Negative

Mouse
peripheral
blood
Mouse bonemarrow cells

Micronucleus
formation

3130-50 000
ppm in diet

Negative

Sisterchromatid
exchange325-1700
mg/kg bw ( i.p.)

Negative

In conclusion: The compounds exhibit no genotoxicity in several in-vivo assays evaluating
different endpoints.
3.1.9 Carcinogenicity
In a 2-year carcinogenicity study, groups of 50 male and 52 female Fischer 344 rats, four to five
weeks old, received diets containing 1% (500 mg/kg bw per day) or 2% (1000 mg/kg bw per day)sodium benzoate for 18-24 months. Controls, consisting of 25 male and 43 female rats, received
basal diet. Food intake was adequately controlled to avoid an excess; tap water was available adlibitum. Survival was very poor in all groups, due to intercurrent sialodacryoadenitis andmycoplasma infections. All surviving animals were sacrificed between 18 and 25 months, all were
autopsied, and various tissues were examined histopathologically. No adverse clinical signs directly
attributable to treatment were observed, and only negligible differences in average body weight andmortality rate were seen between the treated and control groups. Although a variety of tumors
occurred among treated and control rats of each sex, they were of similar type and incidence.
(Sodemoto & Enomoto, 1980)
Poor survival in all groups, due to infections, limits the usefulness of this study.
A lifelong study using male/female Swiss Albino mice given 2% sodium benzoate continuously indrinking water showed no carcinogenic effect.
In the main study, a 2% solution of sodium benzoate (purity, 99%) was administered in the drinking
water to groups of 50 male and 50 female five-week-old mice for their lifetime. Groups of 100
males and 100 females were used as untreated controls. Both treated and control animals were'carefully checked'; their body weights were measured weekly, and gross pathological changes wererecorded. The animals were either allowed to die or were sacrificed when moribund. Complete
necropsies were performed on all animals, and the liver, spleen, kidneys, bladder, thyroid, heart,pancreas, testes, ovaries, brain, nasal turbinates, at least four lobes of the lungs, and organs with
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gross pathological changes were examined histologically. The average daily intake of sodium
benzoate was 124.0 mg for males and 119.2 mg for females on the basis of daily water consumptionof 6.2 and 5.9 ml, respectively. The dose of sodium benzoate was equivalent to 6200 mg/kg bw per
day for males and 5960 mg/kg bw per day for females. Treatment had no effect on survival or theincidence of tumors.
(Toth, 1984).
This study is sufficiently reliable due to the number of animals and detailed histopathologicalexaminations.
In a 2-year carcinogenicity study, benzyl alcohol was administered in corn oil by gavage to groupsof 50 Fischer 344/N rats of each sex at a dose of 0, 200, or 400 mg/kg bw per day on five days aweek for 103 weeks The rats were observed twice daily, and body weights were recorded weekly
for the first 12 weeks and once a month thereafter. Gross necropsy was performed on all animals
and 49 tissues and organs, including brain, kidney, pancreas, and skeletal muscle, from all female
rats and from male rats in the vehicle control and high-dose groups and those in the other groups
that died before 22 months or which had gross lesions were examined histologically. The mean
body weights of treated and control animals were comparable throughout the study. No compoundrelated clinical signs were observed, although a sialodacryoadenitis viral infection was widespreadamong the study animals in the third month. The survival of treated females was significantly
lower than that of vehicle controls: 70% of controls, 34% of low-dose females, and 34% of highdose females; this was due to a much higher incidence of accidental deaths related to the gavage
process. Survival among the male rats was comparable in all groups: 56% of controls, 54% at the
low dose, and 48% at the high dose.
Cataracts and retinal atrophy were observed at increased incidences in rats at the high dose. The
authors attributed this effect to the proximity of this group of animals to fluorescent light for mostof the study. An increased incidence of hyperplasia of the forestomach epithelium was seen (notstatistically significant) in male rats: control, 0/48; low dose, 0/19; high dose, 4/50. Hemorrhage
and foreign material in the respiratory tract seen in treated rats that died before the end of the study
were suggested by the authors to have been the result of either direct deposition of material into thelung during gavage 'accidents' or the anaesthetic properties of benzyl alcohol resulting in reflux ofgavage material and aspiration into the lungs. No pancreatic acinar-cell adenomas were reported,and no other effects of treatment were seen at gross necropsy or histopathological examination.
(US National Toxicology Program, 1989)
In a 2-year carcinogenicity study , benzyl alcohol (purity, 99%) was given to groups of 50 B6C3F1
mice of each sex, eight to nine weeks of age, at a dose of 0, 100, or 200 mg/kg bw per day in corn
oil by gavage on five days a week for 103 weeks. The doses were selected on the basis of thosefound to induce neurotoxic effects (lethargy and staggering) in short-term studies. The mice wereobserved twice daily, and their body weights were recorded weekly for the first 12 weeks and oncea month thereafter. Gross necropsy was performed on all animals, and 50 tissues and organs,including brain, liver, kidney, and stomach, from all vehicle controls, animals at the high dose, andanimals at the other doses that died before 22 months or had gross lesions were examinedhistologically.
The mean body weights of treated and control mice were comparable throughout the study. The
survival of control females was significantly lower than that of animals at the high dose after week
74, but no other differences in survival were seen: 68% of control, 66% of low-dose, and 70% of
high-dose males; and 50% of control, 62% of low-dose, and 72% of high-dose females. No
significant treatment- related effects were noted at gross necropsy or histopathological examination.
(US National Toxicology Program, 1989).
In conclusion: The compounds exhibit no carcinogenicity.
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3.1.10 Toxicity to Reproduction
In a 4-generation study 20 rats/sex/group were dosed continuously by diet with 375 or 750
mg/kg/day benzoic acid. In all 4 generations, no effects on fertility (“Fortpflanzung”) and lactation(“Aufzugt der Jungen”) were found. In addition a so-called “Alters Paarung” after 48 weeks gave
no influence on start of menopauze.
NOAEL (Parental) > 750 mg/kg/day
NOAEL (F1 Offspring) > 750 mg/kg/day
NOAEL (F2 Offspring) > 750 mg/kg/day(Kieckebusch & Lang, 1960)
In addition data from reprotoxicty studies on benzyl acetate and benzaldehyde (JECFA report 1997)
give supportive evidence for the non-reprotoxicity of benzyl alcohol and benzoic acid and its salts.
The potential reproductive toxicity of benzyl acetate was assessed by examining spermmorphology, vaginal cytology, and the weights of male reproductive organs at the end of the 13week feeding study (US National Toxicology Program, 1993) in mice. Dietary levels of 3130-50000 ppm benzyl acetate ( > 3000 mg/kg bw/d) had no effect on the weights of the epididymis,
cauda epididymis, or testis or on sperm motility or density or the percent of abnormal sperm. The
mean length of the estrous cycle of mice at the high dose was significantly greater than that of thecontrol group. This effect was associated with a significant decrease in body weight.
(Morrissey et al., 1988)
The potential reproductive toxicity of benzyl acetate was assessed by examining spermmorphology, vaginal cytology, and the weights of male reproductive organs at the end of the 13week feeding study in rats. Dietary levels of 3130-50 000 ppm benzyl acetate (> 2000 mg/kg bw/d)
had no effect on the weights of the epididymis, cauda epididymis, or testis, on sperm motility, or on
the density or percent of abnormal sperm.
(US National Toxicology Program, 1993)
A single study was conducted to examine the potential reproductive toxicity of benzaldehyde , andthe report was available as a translation from Romanian. A group of 10 rats of breeding age were
given 2 mg benzaldehyde in oil (type not specified) by gavage every other day for 32 weeks,
equivalent to about 5 mg/kg bw per day. Ten controls were used. Two pregnancies in each rat, one
at 75 days and one at 180 days, were studied. The end-points examined included the number ofpregnant females, number of offspring born, pup body weight at days 7 and 21 post partum, andpup viability.
At the end of treatment, the body weights of control and treated rats were similar: 265 g and 260 g,
respectively. It was reported that fewer females in the group given benzaldehyde than in thecontrol group became pregnant; however, no data or statistical analyses were presented. The
authors concluded that treatment did not significantly modify any of the parameters studied. No
further details were available.
The NOAEL was about 5 mg/kg bw per day.
(Sporn et al., 1967)
In addition no compound related effects on reproductive organs (gross and histopatology
examination) could be found in the (sub) chronic studies in rats and mice with benzyl acetate,
benzyl alcohol, benzaldehyde, sodium benzoate and supports a non-reprotoxic potential of thesecompounds (see studies in sections on repeated dose toxicity and carcinogenicity).
In conclusion: According to IPCS CICAD 26 (2000) (only evaluating benzoic acid and sodium
benzoate), no clear statement on the reproductive effects can be given on basis of the Kieckebusch& Lang (1960) and Toth (1984) studies only. However, critical evaluation of the original paper of
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the Kieckebusch & Lang study gives confidence of an adequately performed study although it was
performed many years ago. In addition, reprotoxicity studies on benzaldehyde and benzylacetate
and the fact that no compound related effects on reproductive organs were found in the (sub)chronic
studies with all the compounds supports the lack of reproductive potential. Therefore the available
consistent data on compounds in this group (data on benzyl acetate and benzaldehyde inclusive)taken as a whole are sufficient to demonstrate the lack of reprotoxic potential.
3.1.11 Developmental Toxicity
Pregnant Wistar rats were treated on day 9 of gestation with one dose of 510 mg/kg benzoic acid incarboxymethylcellulose. Animals were sacrificed on Day 20 of gestation and the uterus observed insitu for implantation and resorption sites. Live fetuses were removed, examined for grossmalformations, weighed, and prepared for histopathological examination. Treatment with benzoic
acid resulted in no dead or resorbed implants and 3 % abnormal survivors, rates comparable to thecontrol animals.
NOAEL Maternal toxicity:
510 mg/kg bw
NOAEL Teratogenicity:
510 mg/kg bw(Kimmel et al., 1971)
A 4-generation study with female rats dosed with 375 or 750 mg/kg/day benzoic acid during
pregnancy and lactation showed no effects on the dams or on the growth and development of theoffspring.
NOAEL Maternal toxicity:> 750 mg/kg/day
NOAEL Teratogenicity:> 750 mg/kg/day(Kieckebusch & Lang, 1960)
Studies on the developmental toxicity of sodium benzoate administered by gavage to multiple
species (rat, mice, rabbit, hamster) were conducted by Food and Drug Research Labs, Inc. (1972):
A study using pregnant Wistar rats, dosed with 1.75, 8, 38 or 175 mg/kg sodium benzoate bygavage on Days 6-15 of gestation showed no effect on nidation or on maternal or fetal survival; thenumber of abnormalities of soft and skeletal tissues did not differ from controls.
NOAEL Maternal toxicity:
175 mg/kg bw
NOAEL Teratogenicity:
175 mg/kg bw(FDA PB# 221777, 1972)
A study using pregnant CD-1 mice, dosed with 1.75, 8, 38 or 175 mg/kg sodium benzoate bygavage on Days 6-15 of gestation showed no effect on nidation or on maternal or fetal survival; thenumber of abnormalities of soft and skeletal tissues did not differ from controls.
NOAEL Maternal toxicity:
175 mg/kg bw
NOAEL Teratogenicity:
175 mg/kg bw(FDA PB# 221777, 1972)
A study using pregnant Dutch-belted rabbits, dosed with 2.5, 12, 54 or 250 mg/kg sodium
benzoate by gavage on Days 6-18 of gestation showed no effect on nidation or on maternal or fetal
survival; the number of abnormalities of soft and skeletal tissues did not differ from controls.
NOAEL Maternal toxicity:
250 mg/kg bw
NOAEL Teratogenicity:
250 mg/kg bw(FDA PB# 221777, 1972)

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A study using pregnant Golden hamsters, dosed with 3, 14, 65 or 300 mg/kg sodium benzoate bygavage on Days 6-10 of gestation showed no effect on nidation or on maternal or fetal survival; thenumber of abnormalities of soft and skeletal tissues did not differ from number in controls.
NOAEL Maternal toxicity:
300 mg/kg bw
NOAEL Teratogenicity:
300 mg/kg bw(FDA PB# 221777, 1972)
A study using pregnant Wistar rats, dosed with 700, 1400, 2800, 5600 mg/kg sodium benzoate in
the diet during the entire gestation showed no statistical difference in organ and bone abnormalities
of fetuses between experimental groups and controls; growth of treated offsprings was similar tocontrols in rats dosed with 1400 mg/kg/day; reduced food intake and decreased body weight of thepregnant rats especially in the 5600 mg/kg group; 100% perinatal death rate; organ abnormalities offetuses involved eye, brain and kidneys, in addition abnormalities of the skeletal system were foundin rats dosed with >2800 mg/kg/day. The authors concluded that the effects on the dams andfetuses at the 2800 and 5600 levels were due to reduced maternal feed intake in these groups,
leading to malnutrition,
NOAEL Maternal toxicity:
1400 mg/kg bw
NOAEL Teratogenicity:
1400 mg/kg bw(Onodera et al., 1978)
Fifty female mice were given benzyl alcohol at 550 mg/kg bw per day by gavage on days 6-15 ofgestation; a further 50 mice received the corn oil vehicle. All dams were allowed to deliver
naturally, and pups and dams were observed until day 3 post partum, when the experiment was
terminated. Body weight, clinical observations, and mortality were recorded daily throughout
treatment and up to day 3 post partum. Mortality was not significantly increased in animals given
benzyl alcohol over that in the control group. One treated mouse showing
languid behaviour, laboured breathing, and a rough coat died, but no other deaths or clinical signs
were reported. Maternal body weight and body-weight gain during treatment and up to day 3 post
partum were virtually identical for treated and control animals. All other parameters examined,
including gestation index, average number of live pups per litter, and postnatal survival and pup
body weight on days 0 and 3 post partum, were not significantly different from the control values.
The authors concluded that, at the predicted LD10, benzyl alcohol had no significant effects on thedevelopment of CD-1 mice.
NOAEL = 550 mg/kg bw per day(York et al., 1986; JECFA, 1997).
Benzyl alcohol dissolved in distilled water was administered by gavage at a dose of 750 mg/kg bw
per day to 50 CD-1 mice on days 7-14 of gestation; evidence of copulation was considered the firstday of gestation. A control group of 50 animals received distilled water only. All animals wereallowed to deliver their litters and nurse their pups for three days, at which time necropsies were
performed. Maternal body-weight gain and mortality, mating, gestation, numbers of live and deadpups per litter, total litter weight on days 1 and 2 post partum, litter weight change between days 1
and 3 post partum, and pup survival on days 1 and 3 post partum were recorded. During thetreatment period, 18 deaths were reported, all of which were attributed to treatment; a further death
was reported on day 15 of gestation, the day after treatment was terminated. Clinical signs of
toxicity, including hunched posture, tremors, inactivity, prostration, hypothermia, ataxia, dyspnoea,
swollen or cyanotic abdomen, and piloerection, were reported in up to 20 mice during treatment.
Piloerection was also reported in some animals up to day 3 post partum, but no other clinical signs
were seen after the period of administration. No differences were observed in the mating or
gestation indices, the total number of resorptions, the mean length of gestation, or the number oflive pups per litter between treated and control groups. Maternal body weight, measured on days 4
and 7 of gestation, was not significantly different from control values; however, statistically
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significant reductions were reported on day 18 of gestation (P < 0.001) and on day 3 post partum (P< 0.05). Maternal body-weight gain during days 7-18 of gestation was significantly lower than thatof controls (P < 0.001). Significant reductions in pup body weight were reported, including a lower
mean pup weight per litter on days 1 (P < 0.01) and 3 post partum (P < 0.001), a mean litter weightchange between day 1 and day 3 post partum (P < 0.05), and a mean pup weight change between
days 1 and 3 post partum (P < 0.001). No differences in pup survival were observed by day 3 post
partum. The authors concluded that benzyl alcohol may be a reproductive hazard, apparently on thebasis of the reductions in pup body weights, an effect that was observed in conjunction withmaternal toxicity evidenced by increased mortality, reduced body weights, and clinical toxicity
during the period of administration. As effects were seen on the dams and fetuses at the only doseused in this study, there was no NOAEL.
LOAEL = 750 mg/kg bw per day(US National Institute of Occupational Safety and Health, 1983; Hardin et al., 1987).
In a developmental toxicity study in rats, benzyl acetate given by gavage did not show teratogenic
effects and on the basis of fetotoxic effects a NOEL of 500 mg/kg/day could be established.
(Ishiguro et al., 1993)
Many of these studies were done by gavage (leading to greater toxicity due to the “bolus effect”). In
these studies NOEL of >= 500 mg/kg were found.
Thus, studies on reproductive and/or developmental toxicology performed by the administration of
the benzyl compounds by gavage are likely to reveal changes at lower doses compared to studies
where the substances are applied in the diet, leading to a distribution in the body over time,
In conclusion: The compounds exhibit no developmental toxicity and a NOEL of 500 mg/kg/day
can be established for developmental effects for this group of substances

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4

HAZARDS TO THE ENVIRONMENT

4.1

Aquatic Effects

The studies used as the basis for the following data did not always state whether effect values werebased on nominal or measured concentrations. However, because of the good water solubility, theirinsignificant volatility and low adsorption potential, all nominal concentrations of the test
substances are expected to correspond to effective concentrations even in tests with open systems
and longer exposure durations.
Acute toxicity to fish
ChemicalBenzoic
acid

Species
Lepomismacrochirus

Protocol
EPA-660/3-75009

Salmo
gairdneri

EPA-660/3-75009
other

Sodiumbenzoate

Leuciscus
idus
Pimephales
promelas

Benzylalcohol

Pimephales
promelasPimephales
promelas
Leuciscus
idus

Benzylalcohol

ResultLC50 (96 h) =44.6 mg/l
LC0 = 180 mg/l (pHcontrol)
LC50 (96 h) =47.3 mg/l

Reference
UCES#11506-03-85, 1979

LC50 (48 h) =460 mg/l
(pH 7 –8)
LC50 (96 h) =484 mg/l
(pH 7.4, flow -through,measured concentrations)

Juhnke & Luedemann,
1978
Geiger et al., 1985

LC50 (96 h) > 100 mg/l

Ewell et al 1986

EPA OPP 72-1

LC50 (96 h) =460 mg/l

DIN 38412 Teil
15
Specific acutespill testing (*)

LC50 (48 h) =646 mg/l

Mattson, V.R. et al., EPA600 /3-76-097, PB262897, 1976
Knie et al., 1983

EPA OPP 72-1

LC50 (96 h) 10 and 15
mg/l

Buzzel et al 1968
UCES#11506-03-84, 1979

Dawson et al 1975/1977

No data for potassium benzoate were identified, but it should be similar to sodium benzoate.
(*) REMARK: For benzylalcohol two valuable guideline studies gave acute toxicity values > 100
mg/l.
Dawson et al, however reported acute toxicity values 10 – 15 mg/l. Their static tests however weredirected to simulate acute spill circumstances. The test substances were pipetted or poured
undiluted directly into the aquaria with fish.
So without preparing defined concentrations according to guideline. No analytical monitoring wasdone. Aeration was not used during the first 24 hrs thus allowing chemicals to act in an
uninterrupted state at the onset of the test period.
For environmental relevant conditions and for derivation of a PNECaqua a benzylalcohol acutetoxicity (LC50 96 hrs) to fish of > 100 mg/l should therefore be used.

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Acute toxicity to aquatic invertebrates
ChemicalBenzoicacid

Sodiumbenzoate
Benzylalcohol

SpeciesDaphniamagna

Protocol
EPA-660/375-009

Result
EC 50 (48 h) => 100
mg/l (pH 8.4)

Reference
UCES#11506-03-80, 1979other

EC 50 (24 h) = 500 mg/l
(with neutralization)

Bringmann, & Kuehn, 1982

other

EC 50 is 102 mg/l
(without neutralization)
EC 50 (48 h) => 100
mg/l
EC 50 (24 h) =400 mg/l

Bringmann, & Kuehn, 1982

EC 50 (48 h) = 360 mg/l

Bringmann & Kuehn, 1959

Daphniamagna
Daphnia
magna

other

Daphnia
magna

other

DIN 38412
Teil 11

Ewell et al., 1986
Knie et al., 1983

No data for potassium benzoate were identified, but it should be similar to sodium benzoate.

Acute toxicity to aquatic plants (algae)
ChemicalBenzoicacid

Sodiumbenzoate
Benzylalcohol

Species
Scenedesmus
quadricauda

Protocolother

ResultEC50 (3 h) = 75 mg/l

Reference
Stratton & Corke, 1982

Scenedesmus
quadricauda

cellmutiplication
inhibition test;
staticInhibition starts at 1630
mg/l (96 hr)(pH = 7)

Bringmann & Kuehn, 1977

Chlorellapyrenoidosa

otherEC50 (3 h) = 60 mg/l

Stratton & Corke, 1982

Anabaena
variabilis
Green algae

other
ECOSAR

EC50 (14d) = >10 mg/l
EC50 (96 h) = 478 mg/l

Stratton & Corke, 1982

Chlorellapyrenoidosa

otherEC50 (3 h) = 95 mg/l

Stratton & Corke, 1982

Haematococc
us pluvialis

otherEC50 (4 h) = 2600 mg/l

Knie et al., 1983

Scenedesmus
quadricauda

cellmutiplication
inhibition test

Inhibition starts at 640
mg/l (96 h)

Bringmann & Kuehn 1959

Remark: The studies are no guideline studies, but despite this shortcoming they indicate a moderate
to low acute toxicity. The Scenedesmus study of Stratton and Cork was not used because theendpoint is about the inhibition of the photosynthesis and not growth (rate). The blue green algae
were left out because they are not directly used for the effect assessment for the aquatic
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environment and the endpoint was inhibition of the photosynthesis and not growth (rate). No datafor potassium benzoate were identified, but it should be similar to sodium benzoate.

Acute toxicity to micro-organisms (bacteria)
ChemicalBenzoic
acid

Species
activated sludge

ProtocolOECD 209(respiration
inhibition)
StaticResultEC50 (3 h) > 1000 mg/l
(pH 7.5)

Reference
Klecka et al., 1985

EC50 (30 min) = 16.85
mg/l

Kaiser, 1987

Pseudomonas
putidaAchromobacterliquefaciens

StaticCicad 2000

other: static

Inhibition starts at 480 mg/l
(16 h) (pH neutral)
EC50 (24 h) = > 3000 mg/l

Micrococcus
flavusEscherichia coli

other: static

EC50 (24 h)= >500 mg/l

Nikkilae, 1955

cellmultiplication
inhibition test

EC0 (48 h) = 1000 mg/l

Bringmann & Kuhn,
1959

Pseudomonas
putidacell
multiplication
inhibition test

EC10 (16-18 h) = 658 mg/l

Knie et al., 1983

Photobacterium
phosphoreum

Sodiumbenzoate

Benzylalcohol

Nikkilae, 1955

No data for potassium benzoate were identified, but it should be similar to sodium benzoate.
In conclusion:
From the data (fish, daphnia, algae, bacteria) it is obvious that neutralization of the pH greatly
reduces (up to one order of magnitude) the acute toxicity of benzoic acid. This is also supported by
the lower toxicity observed with the sodium benzoate. Under environmental relevant conditions
therefore the acute toxicity of benzoic acid, sodium benzoate and potassium benzoate for all four
trophic levels is > 100 mg/l.
Under environmental relevant conditions the acute toxicity of benzylalcohol for fish, daphnia andbacteria is > 100mg/l. For algae an acute EC 50 3hrs of 95 mg/l
Therefore it can be concluded that under environmental relevant conditions, benzoic acid and its
salts have very low acute toxicity, whereas benzylalcohol has low to moderate acute toxicity
4.2

Terrestrial Effects

There were no available studies on terrestrial organisms.
IPCS CICAD 26 (2000) concluded for benzoic acid and sodium benzoate: No information on toxic
effects of benzoic acid and sodium benzoate on plants, earthworms or other terrestial organisms oron ecosystems were identified. Only antimicrobial properties were identified preventing bacterial or
fungal growth. Based on these data they conclude a low toxicity potential of benzoic acid andsodium benzoate in the terrestrial environment.
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5.

CONCLUSIONS AND RECOMMENDATIONS

5.1

Conclusions

Benzylalcohol, benzoic acid and its sodium and potassium salt can be considered as a single
category regarding human health, as they are all rapidly metabolised and excreted via a common
pathway within 24hrs.
Systemic toxic effects of similar nature (e.g liver, kidney) were observed. However, with benzoic
acid and its salts at higher doses than with benzylalcohol. For environmental effects the category isless clear, however all are readily biodegradable, non-bioaccumulative and acute toxicity values are
similar.
For human health all exposure routes are possible, despite benzoic acid and its salts being solids
and benzylalcohol being a liquid. For workers exposure will mainly be by inhalation and by skin,whereas for consumers it will mainly be by oral and dermal route.
Human Health:
The compounds exhibit low acute toxicity as for the oral and dermal route. The LD50 values are >2000 mg/kg bw except for benzylalcohol which needs to be considered as harmful by oral route inview of an oral LD50 of 1610 mg/kg bw. The 4 hrs inhalation exposure of benzylalcohol or
benzoic acid at 4 and 12 mg/l as aerosol/dust respectively gave no mortality, showing low acutetoxicity by inhalation for these compounds.
Benzoic acid and benzyl alcohol are slightly irritating to the skin, while sodium benzoate was notskin irritating. No data are available for potassium benzoate but it is also expected not to be skinirritating. Benzoic acid and benzyl alcohol are irritating to the eye and sodium benzoate was only
slightly irritating to the eye. No data are available for potassium benzoate but it is expected also to
be only slightly irritating to the eye.
The available studies for benzoic acid gave no indication for a sensitizing effect in animals,
however occasionally very low positive reactions were recorded with humans (dermatologicalpatients) in patch tests. The same occurs for sodium benzoate. It has been suggested that the very
low positive reactions are a non-immunologic contact urticaria. Benzyl alcohol gave positive andnegative results in animals. Benzyl alcohol also demonstrated a maximum incidence of sensitizationof only 1% in human patch testing. Over several decades no sensitization with these compounds has
been seen among workers.
For benzoic acid repeated dose oral toxicity studies give a NOAEL of 800 mg/kg/day. For the salts
values > 1000 mg/kg/day are obtained. At higher doses increased mortality, reduced weight gain,
liver and kidney effects were observed.
For benzyl alcohol the long-term studies indicate a NOAEL > 400 mg/kg bw/d for rats and > 200
mg/kg bw/d for mice. At higher doses effects on bodyweights, lesions in the brains, thymus,
skeletal muscle and kidney were observed. It should be taken into account that administration inthese studies was by gavage route, at which saturation of metabolic pathways is likely to occur.
It can be concluded that benzoic acid and its salts exhibit very low repeated dose toxicity.
Benzylalcohol exhibits low repeated dose toxicity.
All chemicals showed no mutagenic activity in in vitro Ames tests. Various results were obtainedwith other in vitro genotoxicity assays.
Sodium benzoate and benzyl alcohol showed no genotoxicty in vivo.
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While some mixed and/or equivocal in vitro chromasomal/chromatid responses have been
observed, no genotoxicity was observed in the in vivo cytogenetic, micronucleus, or other assays.
The weight of the evidence of the in vitro and in vivo genotoxicity data indicates that thesechemicals are not mutagenic or clastogenic. They also are not carcinogenic in long-term
carcinogenicity studies. In addition data from in-vivo genotoxicity studies on benzyl acetate andbenzaldehyde (JECFA report, 1997) support the non-genotoxicity of benzylalcohol and benzoic
acid and its salts.
Carcinogencity studies (2-year) with sodium benzoate and benzyl alcohol showed no evidence of
carcinogenic activity.
In a 4-generation study with benzoic acid no effects on reproduction were seen (NOAEL ≥ 750
mg/kg). No compound related effects on reproductive organs (gross and histopatology examination)
could be found in the (sub) chronic studies in rats and mice with benzyl acetate, benzyl alcohol,
benzaldehyde, sodium benzoate and supports a non-reprotoxic potential of these compounds. In
addition, data from reprotoxicity studies on benzyl acetate (NOAEL >2000 mg/kg bw/d; rats andmice) and benzaldehyde (tested only up to 5 mg/kg bw; rats) support the non-reprotoxicity ofbenzyl alcohol and benzoic acid and its salts.
In rats for sodium benzoate dosed via food during the entire gestation developmental effects
occurred only in the presence of marked maternal toxicity (reduced food intake and decreased bodyweight) (NOAEL = 1400 mg/kg bw ).. For hamster (NOEL : 300 mg/kg bw), rabbit (NOEL :250
mg/kg bw) and mice (CD-1 mice, NOEL : 175 mg/kg bw) no higher doses (all by gavage) were
tested and no maternal toxicity was observed For benzyl alcohol: NOAEL= 550 mg/kg bw(gavage; CD-1 mice). LOAEL = 750 mg/kg bw (gavage mice). In this study maternal toxicity wasobserved e.g. increased mortality, reduced body weight and clinical toxicology. Benzyl acetate:
NOEL = 500 mg/kg bw (gavage rats). No maternal toxicity was observed.
Environment:
From the data (fish, daphnia, algae, bacteria) it is obvious that neutralization of the pH greatly
reduces (up to one order of magnitude) the acute toxicity of benzoic acid. This is also supported by
the lower toxicity observed with sodium benzoate. Under environmental relevant conditions
therefore the acute toxicity of benzoic acid, sodium benzoate and potassium benzoate for all four
trophic levels is > 100 mg/l.
Under environmental relevant conditions the acute toxicity of benzylalcohol for fish, daphnia andbacteria is > 100mg/l. For algae an acute EC 50 3hrs of 95 mg/l is reported.
Therefore it can be concluded that under environmental relevant conditions benzoic acid and its
salts have very low acute toxicity, whereas benzylalcohol has low to moderate acute toxicity.
Exposure:
Worldwide production capacity of benzoic acid is estimated at 700 kt per year. The major outlet(75%) for benzoic acid is as a chemical intermediate in the production of phenol, which in turn ismainly used to produce caprolactam. The next largest outlet is as a feedstock for sodium benzoate(10%) and chemical synthesis of plasticizers (5%).
Worldwide production capacity of sodium benzoate is estimated at 100 kt per year. The major
outlet for sodium benzoate is as preservative in food and beverages (60%). Second most important
market is cooling liquids (10%). The main function of sodium benzoate in most applications is aspreservative.

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OECD SIDSBENZOATESWorldwide production capacity of potassiumbenzoate is estimated at 7 kt per year. It is used as apreservative in nonalcoholic beverages.
Worldwide production capacity of benzyl alcohol is estimated at 50 kt. Major use forbenzylalcohol is as curing agent in epoxy coatings (30%), where it becomes chemically bound afterreaction. Other important uses include the use as a solvent in low concentrations in waterborne
coatings (10%) and use in paint strippers (10%) and chemical intermediate for synthesis for benzyl
esters that are used in the flavor and fragrance industry (10%). The use in paint strippers is limited
to uses in industrial settings.
Benzylalcohol, benzoic acid and its sodium and potassium salt are also used in pharmaceuticals,
cosmetics and/or food. Consumer exposure in these specific applications are controlled by the factthat for all these applications specific regulatory frameworks (regional and/or national) withauthorization/approval procedures and specific advisory bodies exist (among others US FDA, WHO
JECFA, EU SCF, etc), with on regular basis reevaluation of approvals, hazardous properties andfactual exposures inclusive. According to information from products registers uses that are notspecifically regulated includes uses of the substances in different kinds of products e.g. paints ,varnishes solvents, cleaning and washing agents, photochemicals and antifreeze agents.
Benzoic acid is a white solid, with solubility in water of 2.9 g/l and with a vapor pressure of 0.0011
hPa at 20 °C. The octanol/water partition coefficient was measured to 1.88; the Henry’s law
constant = 0.0046-0.022 Pa*m3/mol; and the pKa = 4.2.
Sodium benzoate and potassium benzoate are white solids, with solubility in water of 556 g/l andwith a vapor pressure of <0.0011 hPa at 20 °C. The octanol/water partition coefficient were
measured to –2.269.
Benzyl alcohol is a colorless liquid, with solubility in water of 40 g/l and with a vapor pressure of
0.13 hPa at 20 °C. The octanol/water partition coefficient was measured to 1.1.
The distribution modeling according to Mackay Level III indicates soil and water to be the favoredcompartments for the chemicals. None are expected to hydrolyze. All are classified as readily
biodegradable. None has bioaccumulative potential.

5.2

Recommendations

Several of the toxicological studies on benzyl alcohol and benzoic acid and its salts were carried out
some years ago and do not always fulfill for 100% present-day guidelines. However, well-known
research groups and/or test laboratories ran the studies according to scientific standards and or
accepted protocols at that time. They did appear to be acceptable studies for evaluation.
Also, all were peer-reviewed and published in high quality scientific literature. Most of them havebeen reviewed and accepted by other fora like FDA, JECFA, and IPCS as acceptable studies.
In addition, there is good consistency in the individual data for a substance in the group as well as
between members of the group (benzyl acetate and benzaldehyde data inclusive). Therefore, taken
as a whole, the available studies give a robust database for hazard assessment and hazard evaluationof these compounds and further studies are not indicated. The JECFA Committee (1997) concluded
that the data reviewed for compounds in this group were sufficient to demonstrate lack ofteratogenic, reproductive or carcinogenic potential. Consequently, the Committee concluded thatfurther studies were not required.
Taking into account the rapid biodegradability, the low bioaccumulation potential, the low tomoderate toxicity to most aquatic species, and the rapid metabolism of these substances, thesesubstances will pose a minimal risk to the aquatic environment.
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Taking into account the rapid metabolism and excretion, the non-bioaccumulation, the low toxicity
after acute and repeated exposures, the non-reprotoxicity, the non-genotoxicity and the noncarcinogenicity, the low irritating and non- to very low sensitizing properties of these substances, aswell as the controlled (industrial settings) and /or regulated (pharma, cosmetics and /or food) uses,
these substances will pose a minimal risk to humans (workers and consumers).
Therefore these substances have low priority for further work.

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6.

BENZOATESREFERENCES

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Knie, J. et al., Deutsche Gewaesserkundl. Mitt. 27 (3): 77-79 (1983)
Kravets-Bekker A.A. & Ivanova O.P. (1970). Faktory Vnesh. Sredy Ikh Znachenie Zdorov'ya
Naseleniya No.2, 125: in BIBRA Toxicity Profiles, BIBRA International, Great Britain.
Kuroda, K. et al.: Mutat. Res. 130: 369 (1984)
Leifer Z. et al., Mutat. Res. 87: 211-297 (1981)
Loeser, E., Bayer AG data, Akute orale Toxizitaet (1977-A)
Loeser, E., Bayer AG data, Untersuchungen zur Haut- und Schleimhautvertraeglichkeit (1977-B)
Loeser, E.: Bayer AG data, short report, (3. 11. 1978)
Malten, K. E. et al.: Contact Dermatitis 11, 1-10 (1984)
Matthews, R.W., Water Res. 24: 653-660 (1990)
Mattson, V.R. et al., EPA-600/3-76-097. P B-262 897. (Oct. 1976)
Merck Index – An Encyclopedia of Chemicals, Drugs and Biologicals. 12th ed. pps. 183, 189,
1471. (1996)
Meylan W. and Howard P. EPIWin Modeling Program. Syracuse Research Corporation.
Environmental Science Center, 6225 Running Ridge Road, North Syracuse, NY 13212-2510(1999)
Mitchell, J. C. et al.: Contact Dermatitis 8, 336-337 (1982)
MITI, Biodegradation and Bioaccumulation Data of Existing Chemicals Based on the CSCL Japan,
Compiled under the Supervision of Chemical Products Safety Division, Basic Industries Bureau,
Ed. by CITI, Published by Japan Chemical Industry Ecology-Toxicology & Information Center(October,1992)
Miyagawa M. et al., Mutat. Res. 343: 157-183 (1995)
Morrissey, R.E., Schwetz, B.A., Lamb, J.C., Ross, M.D., Teague, J.L. & Morris, R.W. (1988)
Evaluation of rodent sperm, vaginal cytology, and reproductive organ weight data from National
Toxicology Program 13-week studies. Fundam. Appl. Toxicol., 11, 343-358
Nethercott, J. R.: Contact Dermatitis 8, 389-395 (1982)
Nethercott, J.R. et al., J. Occ. Med. 26, 734-736 (1984)
Nikkilae, O.E., Fette, Seifen, Anstrichmittel 57, 494-98 (1955)
Nonaka, M., Environ. Mol. Mutagen. 14: 143 (1989)
NPIRI: Raw Mater. Data Handb. Vol. 1: 6 (1974)
Onodera, H. et al., Eisei Shikenjo Hokoku 96: 47-55 (1978)
38
UNEP PUBLICATIONSOECD SIDSBENZOATES

Opdyke, D. L. J.: Monograph on Fragrance Raw Materials. Fd. Cosmet. Toxicol.
11: 1011-1013 (1973)
Prival, M.J. et al., Mutat. Res. 260: 321-329 (1991)
Rademaker, M. & Forsyth, A., Contact Dermatitis 20, 104-107 (1989)
RCC NOTOX, Primary skin irritation/corrosion study of benzoic acid in the rabbit (study no.
0847/1083). RCC NOTOX B.V., DD's-Hertogenbosch (1988)
RCC NOTOX, Eye irritation/corrosion study of benzoic acid in the rabbit (study no. 0847/1084).
RCC NOTOX B.V., D's-Hertogenbosch (1988)
RCC NOTOX, Primary skin irritation/corrosion study with natrium benzoate in rabbits (study no.
014658). RCC NOTOX B.V., 's-Hertogenbosch
RCC NOTOX, Acute eye irritation/corrosion study with natrium benzoate in rabbits (study no.
014669). RCC NOTOX B.V., 's-Hertogenbosch
Salanitro, J.P. et al., Water Sci. Technol. 20: 125-130 (1988)
Smyth, H.F., Jr. & Carpenter, C.P., J. Ind. Hyg. Toxicol. 30: 63-68 (1948)
Smyth, H. F. et al.: Arch. Ind. Hyg. Occup. Med. 4, 119-120 (1951)
Sporn, A. et al. Igiena, 16:23-24 (1967)
Sodemoto, Y. & Enomoto, M., J. Environ. Pathol. Toxicol. 4:87-95 (1980)
Stratton, G.W. & Corke, C.T., Environ. Pollut. 29: 71-80 (1982)
Tohda, H. et al., Cancer Res. 40: 4775-4780 (1980)
Toth, B., Fundam. Appl. Toxicol. 4: 494-496 (1984)
UCES#11506-03-80 (Unpublished study). The acute toxicity of benzoic acid (technical grade) tothe water flea, Daphnia magna Straus. (1979)
UCES#11506-03-84 (Unpublished study). The acute toxicity of benzoic acid to the Rainbow trout,
Salmo gairdneri. Richardson. (1979)
UCES#11506-03-85 (Unpublished study). The acute toxicity of benzoic Acid (technical grade) tothe Bluegill sunfish, Lepomis macrochirus Rafinesque. (1979)
Uno Y. et al., Mutat. Res. 320: 189-205 (1994)
US National Institute of Occupational Safety and Health. (1983)
US NTP. National Toxicology Program: Technical Report No. TR 343 (1989)
US NTP. National Toxicology Program (1990)
UNEP PUBLICATIONS

39

OECD SIDSBENZOATESUS NTP. National Toxicology Program Toxicology and carcinogenesis studies of benzyl acetate in
F344 rats and B6C3F1 mice (feedstudies).
US NTP-TR-431; NIH Publication No. 92-3162. (1993)
WHO. World Health Organization. Technical Report Series 868. Evaluation of Certain Food
Additives and Contaminants. Forty-sixth report of the Joint FAO/WHO Expert Committee on Food
Additives (JECFA). Geneva. (1997)
Woodruff, R.C., et al. Chemical mutagenesis testing in drosophila V, results of 53 codedcompounds tested for US NTP, Environmental Mutagenesis, 7, 677-702. (1985).
Xing, W. & Zhang, Z., Mutat. Res. 241: 109-113 (1990)
York, R.G. et al., Teratology 37, 503-504 (1988)
Zahn, R. & Wellens, H., Z. Wasser Abwasser Forsch. 13: 1-7 (1980)
Zeiger, E. et al., Environ. Mutagen. Molec. Mutagen. 16 (Suppl. 18): 1-14 (1990)

40

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATIONBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

I U C L I D D a t a S e t

Existing Chemical
CAS No.
EINECS NameEC No.
TSCA Name
Molecular Formula

ID: 65-85-0
65-85-0
benzoic acid200-618-2
Benzoic acid
C7H6O2

Producer Related Part
Company:
Creation date:

Bayer Corporation
21-OCT-1999

Substance Related Part
Company:
Bayer Corporation
Creation date:21-OCT-1999
Memo:

Bayer Corporation

Printing date:
Revision date:
Date of last Update:

14-FEB-2002

Number of Pages:

82

14-FEB-2002

Chapter (profile):
Chapter: 1, 2, 3, 4, 5, 6, 7, 8, 10
Reliability (profile): Reliability: without reliability, 1, 2,
3, 4
Flags (profile):
Flags:
without flag, confidential, nonconfidential, WGK(DE), TA-Luft (DE),Material Safety Dataset, Risk Assessment,
Directive 67/548/EEC, SIDSUNEP PUBLICATIONS

41

OECD SIDS
1. GENERAL INFORMATIONBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

1.0.1 Applicant and Company Information
Type:
Name:
Street:Town:
Country:
14-AUG-2001

lead organisation
American Chemistry Council (formerly Chemical
Manufacturers Association, HPV Benzoates Panel
1300 Wilson Boulevard
22209 Arlington, VA
United States

Type:
Name:
Country:
14AUG-2001

cooperating company
ATOFINA Chemicals, Inc.
United States

Type:
Name:
Country:
14-AUG-2001

cooperating company
Bayer Corporation
United States

Type:
Name:
Country:
13-DEC-2000

cooperating company
DSM Special Products
Netherlands

Type:
Name:
Country:
14-AUG-2001

cooperating company
Noveon, Inc.
United States

Type:
Name:
Country:

cooperating company
Velsicol Chemical Corporation
United States

21-MAY-2001
Type:
Name:
16-JAN-2001

lead organisation
American Chemistry Council, Benzoates Panel

1.0.2 Location of Production Site, Importer or Formulator
1.0.3 Identity of Recipients
1.0.4 Details on Category/Template

42

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATIONBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

1.1.0 Substance Identification
1.1.1 General Substance Information
1.1.2 Spectra

1.2 Synonyms and Tradenames

1.3 Impurities

1.4 Additives

1.5 Total Quantity

1.6.1 Labelling
1.6.2 Classification
1.6.3 Packaging

1.7 Use Pattern
1.7.1 Detailed Use Pattern
1.7.2 Methods of Manufacture

1.8 Regulatory Measures
1.8.1 Occupational Exposure Limit Values
1.8.2 Acceptable Residues Levels
1.8.3 Water Pollution
1.8.4 Major Accident Hazards
1.8.5 Air Pollution
1.8.6 Listings e.g. Chemical Inventories

UNEP PUBLICATIONS

43OECD SIDS
1. GENERAL INFORMATIONBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

1.9.1 Degradation/Transformation Products
1.9.2 Components

1.10 Source of Exposure

1.11 Additional Remarks

1.12 Last Literature Search
Type of Search:
Date of Search:

Internal and External
07-SEP-1999

Remark:Only HPV endpoints: TOXLINE data base andinternal studies.

14-AUG-2001

1.13 Reviews

44

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATABENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

2.1 Melting Point
Value:= 122.4 degree C

Method:Test substance:other: measured
other TS: benzoic acid; purity not noted

Reliability:(2) valid with restrictions
Data from Handbook or collection of data
Critical study for SIDS endpoint(1) (2)

Flag:
14-AUG-2001
Value:
15-JAN-2001= 122 degree C

Value:
15-JAN-2001= 121.7 degree C

(3)

(4)

2.2 Boiling Point
Value:= 249.2 degree C at 1013 hPa

Method:Test substance:other: measured
other TS: benzoic acid; purity not noted

Reliability:
Flag:
14-AUG-2001(2) valid with restrictions
Data from Handbook or collection of data
Critical study for SIDS endpoint(1) (5)

Value:= 250 degree C at 1013 hPa

Reliability:
15-JAN-2001(2) valid with restrictions

Value:= 249 degree C at 1013 hPa(2)15-JAN-2001(4)

2.3 Density
Type:
Value:

density= 1.2659 at 15 degree C

Method:other:UNEP PUBLICATIONS

45

OECD SIDS
2. PHYSICO-CHEMICAL DATA

Reliability:
Flag:
14-AUG-2001

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(2) valid with restrictions
Data from Handbookor collection of data
Critical study for SIDS endpoint
(1)

Type:
Value:
15-JAN-2001

density= 1.321 g/cm³ at 20 degree C(6)

2.3.1 Granulometry

2.4 Vapour Pressure
Value:= .0011 hPa at 20 degree C

Method:other (measured): Handbook Value

Reliability:(2) valid with restrictions
Data from Handbook or collection of data
Critical study for SIDS endpoint

Flag:
14-AUG-2001(7)

Value:= .0053 hPa at 20 degree C

Flag:
15-JAN-2001

Critical study for SIDS endpoint(8)

2.5 Partition Coefficientlog Pow:= 1.88

Method:other (measured): centrifugal distribution
chromatography
1988

Year:
Reliability:(2) valid with restrictions
Meets generally accepted scientific method andis described in sufficient detailFlag:
14-AUG-2001

Critical study for SIDS endpoint

log Pow:= 1.9

Method:Year:other (calculated):
1991

46

(9)

UNEP PUBLICATIONSCLOGP-3.63 (1991)

OECD SIDS
2. PHYSICO-CHEMICAL DATA

Reliability:
Flag:
26-JAN-2001

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(10)

log Pow:= 1.93

Method:other (measured): gemessen, Schuettelmethode,spektralphotometrischeKonzentrationsbestimmung(11)
1.81 - 1.88

15-JAN-2001
log Pow:
Method:14-AUG-2001

other (measured): gemessen, Schuettelmethode,spektralphotometrischeKonzentrationsbestimmung(12)2.6.1 Solubility in different media
Solubility in:
Value:

Water= 2.931 g/l at 20 degree C

Method:Test substance:other: similar to OECD Guideline 105
other TS: Research grade benzoic acid (Merck)

Method:Flag:
14-FEB-2002

According to Pal, A., Maity, S.K., & Lahiri,
S.C. J. Indian Chem. Soc. (1983) 60:475.
pH-Value: no data
2.45 g/l at 15 degree C (0.0210 mol/l at 288K)
2.93 g/l at 20 degree C (0.0240 mol/l at 293K)
3.47 g/l at 25 degree C (0.0284 mol/l at 298K)(2) valid with restrictions
Meets generally accepted scientific standards,
Well documented and acceptable for assessment
Critical study for SIDS endpoint(13)

Solubility in:
Value:

Water= 2.91 g/l at 20 degree C

Remark:14-FEB-2002

pH-value: no data

Remark:Result:Reliability:(14)

2.6.2 Surface Tension

2.7 Flash Point
Value:= 121 degree C
UNEP PUBLICATIONS

47

OECD SIDS
2. PHYSICO-CHEMICAL DATA

Method:other: no data

Remark:15-JAN-2001

nicht angegeben

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(2)

2.8 Auto Flammability
Value:= 574 degree C at 1013 hPa

Method:Year:
GLP:
15-JAN-2001

other
1990
no
(15)

2.9 Flammability
Remark:14-AUG-2001

Not applicable.

2.10 Explosive Properties
Remark:Dust explosions possible. LEL 0.95 % and UEL
8.2 %14-AUG-2001

2.11 Oxidizing Properties
Remark:14-AUG-2001

Not applicable.

2.12 Dissociation Constant

2.13 Viscosity

2.14 Additional Remarks
Remark:Flag:
14-AUG-2001
48

Henry-constant (Pa * m3/mol):
0.0046 - 0.022 (calculated as quotient ofvapour pressure and water solubility at 20
degree C)
Critical study for SIDS endpoint

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATA

Remark:Flag:

Dissociation-constant (25 degree C): pka =4.1951
Critical study for SIDS endpoint

14-AUG-2001
Remark:Flag:
14-AUG-2001
Remark:14-AUG-2001
Remark:BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(16)
Dissociation-constant (20 degree C): pKa =4.21
Critical study for SIDS endpoint(17)
Dissociation-constant pKa (25 degree C): 3.994.205 (various methods; summarized values)(18)

14-AUG-2001

Begin of sublimation at ca. 100 degree C.
At ca. 150 degree C formation of anhydride, at
ca. 370 degree C decarboxylation.
Volatile with steam.
(2)

Remark:14-AUG-2001

pH-value: 3,1 at 1 g/l water(roomtemperature)(19)

Remark:14-AUG-2001

pH-value: 2.8(saturated solution, 25 degree C)(2)

UNEP PUBLICATIONS

49

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

3.1.1 PhotodegradationType:other:mineralization in aqueous TiO2
Light source:other:20W NEC blacklight blue flourescent tube
Light spect.:<= 350 nm
Conc. of subst.: 50 mg/l at 40 degree C
INDIRECT PHOTOLYSIS
Sensitizer:
other: aqueous TiO2
Conc. of sens.: 40 mg/l
Degradation:
90 % after 140 minute(s)Method:Year:
GLP:
Test substance:othermeasured):mineralization in aqueous TiO2
1990
no dataother TS: benzoic acid, purity not noted

Remark:Photochemical dissociation of benzoic acid by
Irradiation with UV light if fixed on solid
carriers:-90 % mineralization in aqueous
TiO2- suspension after 2-3 h of irradiation
with sunlight on 1 m2 water
surface(concentration 50 mg/l related to test
substance)
This endpoint has been studied several times
by several other investigators/groups and all
support the result of the study mentioned
above.
(2) valid with restrictions
Meets generally accepted scientific standards,
Well documented and acceptable for assessment
Critical study for SIDS endpoint(20)

Reliability:

Flag:
14-FEB-2002

Type:other: calculated
Light source:
Sun light
Conc. of subst.: at 25 degree C
INDIRECT PHOTOLYSIS
Sensitizer:
OH
Conc. of sens.: 1560000 molecule/cm³
Rate constant: ca. .000000000001242 cm³/(molecule * sec)
Degradation:
50 % after 8.6 day(s)Method:Year:
Test substance:

50

other (calculated): AOPWin version 1.89
1999
other TS: molecular structure

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Reliability:
Flag:
14-AUG-2001
Remark:(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(21)
UV-Spectrum lambda max (nm):227.5 (Methanol; lg epsilon: 4.27)
222 (Methanol/KOH; lg epsilon: 4.07)

15-JAN-2001
Remark:15-JAN-2001
Remark:15-JAN-2001
Remark:15-JAN-2001

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(22)photochemical dissociation of benzoic acid by
UV-irradiation if fixed on solid carriers(SiO2):-10.2 % mineralization after 17 hirradiation with light(lambda > 290 nm)(no data
concerning concentration)(23)
photochemical dissociation of benzoic acid by
Irradiation with UV light if fixed on solid
carriers:- 67 % mineralization in aqueous ZnOsuspension after 24 h of irradiation withsunlight (concentration 100-200 mg/l
related to DOC)
(24)
Formation of a small amount of photochemical
aerosols after irradiation of some cristallsof benzoic acid with a deuterium lamp (180 <lamda < 400 nm) in a laboratory reactor.
(25)

3.1.2 Stability in Water
Result:Based on structure and organic chemistry rules(e.g. bonding in organic molecules, activationenergy, reactivity,transformations, addition,
substitution, elimination) no hydrolysis will
occur at pH ranges 4 - 11.

26-JAN-2001
3.1.3 Stability in Soil
Remark:14-AUG-2001

Not available.

UNEP PUBLICATIONS

51

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

3.2.1 Monitoring Data (Environment)
Remark:14-AUG-2001

Not available.

3.2.2 Field Studies

3.3.1 Transport between Environmental Compartments
Type:Media:
Method:adsorption
water - soil
other: see below

Method:14C-labeled benzoic acid (767MBq mmol-1) ofradiochemical purity greater than 98.5% was
prepared in 0.01 M calcium nitrate inconcentrations of 0.01, 0.1, 1.0, 10 mg/l.
The solutions were added to three types of
autoclaved, dry soils (2 g) and allowed toequilibrate on a mechanical shaker for 72 hrs
at 6C.
The soil types were sandy till, clayey till,
and melt water sand.
The suspension was allowed to settle and thesupernatant liquid tested for 14C activity.
Adsorption constants were determined.
No adsorption was observed for benzoic acid inmelt water sand and clayey till; very low
adsorption was observed in sandy till(K=0.23).
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment

Result:Reliability:

Flag:
14-AUG-2001

Critical study for SIDS endpoint

Type:
Media:

fugacity model level III
other: air - water - soil - sediment

Method:other: EPIWin Modeling Program

Remark:Modeling was performed using equal releases(10,000 kg/hr) and equal distribution to allcompartments.

52

(26)

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Result:
Air
Water
Soil
Sediment

Distribution(percent)
0.911
34.8
64.2
0.093

Half-Life
(hr)
207
360
360
1.44e+003

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
Emissions
Fugacity(kg/hr)(atm)
1000
2.3 e-011
1000
6.11e-013
1000
1.22e-011
04.73e-013

Persistence Time: 421 hr
Reaction Time:516 hrAdvection Time:
2.28e+003 hr
Percent Reacted: 81.5
Percent Advected(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint

Reliability:
Flag:
14-FEB-2002(21)

3.3.2 Distribution

3.4 Mode of Degradation in Actual Use
Remark:Benzoic acid is readily biodegradable, and in
production and use in chemical industry it isbiodegraded in a waste water treatment plant.
In many species, benzoic acid is rapidly
absorbed, conjugated with glycine and excreted
as hippuric acid.

23-OCT-1995

3.5 Biodegradation
Type:
Inoculum:
Concentration:

Degradation:
Method:Year:
GLP:
Test substance:

aerobic
activated sludge, industrial, non-adapted1000 mg/l related to COD (Chemical Oxygen
Demand)508 mg/l related to Test substance> 90 % after 2 day(s)OECD Guide-line 302 B "Inherent
biodegradability: Modified
Zahn-Wellens Test"
1981
no dataother TS: reagent grade benzoic acid

UNEP PUBLICATIONS

53

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Reliability:
Flag:
14-FEB-2002

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(1) valid without restriction
Guideline study
Critical study for SIDS endpoint
(27)

Type:
Inoculum:
Concentration:
Contact time:
Degradation:

anaerobic
anaerobic sludge
73 mg/l related to Test substance
28 day(s)96 - 100 % after 7 day(s)Method:GLP:Test substance:other: see below
no dataother TS: commercial grade benzoic acid,purity > 95%

Method:

A 10% anaerobic sludge inoculum wastransferred to 160 ml serum bottles previously
amended with 50 ppm Carbon (related to test
substance) using strict anaerobic techniques.
Methane production from test bottles vs.
controls monitored weekly for 4 weeks or until
net production occurred.
At that time, the bottles were amended again
with the same substrate and methane production
monitored to confirm the observation.
All data were obtained from duplicate bottles.
Methane was measured using a flame ionization
detector on a Perkin-Elmer Model 900 GC
equipped with a 3-m Tenax-G.C. column
96 % mineralisation (CH4-Production) in 1 weekwith sludge from Jackson, MI waste-treatment
plant 100 % mineralisation (CH4-Production) in
2 weeks with sludge from Adrian, MI wastetreatment plan
The test bottles were incubated at 35 degree C
in the dark.
Substrates were kept under an atmosphere of
90% N2 and 10% H2

Remark:Test condition:

Reliability:

Flag:
14-AUG-2001(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint
(28)

Type:

anaerobic

54

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Concentration:

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Contact time:
Degradation:

50 µg/l related to DOC (Dissolved Organic
Carbon)2 month> 75 % after 2 month

Method:GLP:Test substance:other: see below
no dataother TS: benzoic acid, purity not noted

Method:Sludge samples collected from primary andSecondary anaerobic digesters were diluted to
10% and incubated anaerobically with 50 ug
Carbon per ml (related to test substance).
All compounds were tested in triplicate. Gas
production was measured by gas chromatography
and by a pressure transducer. Biodegradation
was determined by net increase in gas pressure
in bottles amended with test chemicals over
non-amended controls.
Degradation is expressed as percentage ofTheoretical Methane production based on the
stoichiometry of degradation.
The test bottles were incubated at 35 degree C
in the dark.
Substrates were kept under atmospheres of 10%
CO2 and 90% N2.
(2) valid with restrictions
Meets generally accepted scientific standards,
Well documented and acceptable for assessment
Critical study for SIDS endpoint(29)
aerobic
activated sludge, industrial
86.9 % after 5 day(s)Result:

Test condition:

Reliability:

Flag:
14-AUG-2001
Type:
Inoculum:
Degradation:
Test substance:other TS: benzoic acid-1-14C (0.026mC/mg)
obtained from NewEngland Nuclear Corporation,
Boston, Massachusetts.

Method:Radio-respirometric study using radio-labeledchemicals by activated sludge and in a complex
photographic processing effluent using
acclimated industrial sludge.
Concentration of test substance was 0.1 or
0.2ml of radioactive substrate(27,000-400,000dpm). Samples were incubated in the dark at
ambient temperature.

UNEP PUBLICATIONS

55

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Result:BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

30-JAN-2001

14CO2 recovery without effluent = 68.2% after
5 days 14CO2 recovery in presence of effluent= 86.9% after 5 days
(30)

Inoculum:
Concentration:
Degradation:

activated sludge, domestic
10 mg/l related to Test substance
74 % after 5 day(s)Method:other: BOD test; 20 degree C; pH 7.0; minimal
mediumRemark:Degradation after 20 d: 78 %t 1/2 for TOC: 1 d
BOD: 2 dno lag phase

14-FEB-2002(31)

Inoculum:
Concentration:

activated sludge, non-adapted
100 mg/l related to Test substance

Method:other: Respirometer, 20 degree C; pH 7

Remark:phase
14-FEB-2002

Degradation after 65-80 h: 61-69 %; 5-20 h lag

Inoculum:
Concentration:
Degradation:

activated sludge, domestic
500 mg/l related to Test substanceafter 6 day(s)Method:other: Warburg-Respirometer, 20 degree C

Remark:Measured O2-consumption (graphicallydetermined; considering endogenous
respiration): ca. 525-750 mg/l
= ca. 1050-1500 mg O2/g substance (ThOD 1967
mg O2/g substance)(32)

15-JAN-2001(33)

Inoculum:
Concentration:

activated sludge, non-adapted
500 mg/l related to Test substance

Method:other: Warburg-Respirometer; 20 degree C

Remark:Measured O2-consumption (graphically determined;

56

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

15-JAN-2001
Inoculum:
Concentration:

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Considering endogenous respiration): after 1 d
ca. 410 mg/l = ca. 820 mg O2/g substance (ThOD
1967 mg O2/g substance).
Benzoic acid had an initial toxic effect on
two of three samples of activated sludge fromdifferent communal purification plants, after
24 hours degradation started in these samples,
too.
(34)

Degradation:

activated sludge, adapted
200 mg/l related to COD (Chemical Oxygen
Demand)99 % after 5 day(s)Method:other: aerobic degradation, 20 degree C

Remark:14-FEB-2002

Concentration related to 101.7 mg substance/l
20 days adaption, degradation 88.5 mg COD/g.h(35)

Inoculum:
Concentration:
Degradation:

activated sludge, domestic
16 mg/l related to Test substance
100 % after 1 day(s)Method:other: aerobic degradation, static, 30 degree
C; pH 7.3

Remark:Substance specific analysis

14-FEB-2002(36)

Inoculum:
Concentration:
Degradation:

activated sludge, domestic.059 mg/l related to Test substance
99.5 % after 7 day(s)Method:other: aerobic degradation; 29 degree C;
measurement of radioactivity(C14 labelled at
the carboxygroup)(CO2-formation)

Remark:15-JAN-2001

Test with trace concentrations

Inoculum:
Concentration:
Degradation:

activated sludge, industrial
150 mg/l related to Test substance
86 % after 1 day(s)(37)

UNEP PUBLICATIONS

57

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Method:other: aerobic degradation; semi-continuous;
25-30 degree C; pH 7; parameter: TOC

Remark:15-JAN-2001

1 day acclimation

Inoculum:
Concentration:

activated sludge, domestic, adapted1000 mg/l related to COD (Chemical Oxygen
Demand)97 % after .2 day(s)Degradation:(38)

Method:other: aerobic degradation; static; test
temperature 30 degree C ; pH 7.2

Remark:Concentration equivalent to 508 mg substance/l
20 days adaptation with glucose as additional
C-source(39)

14-FEB-2002
Inoculum:
Concentration:
Degradation:other bacteria: obligatory anaerobic species
from sludge of the first purification step
300 mg/l related to Test substance
91 % after 18 day(s)Method:other: anaerobic degradation, enrichment
culture; 35 degree C; parameter: gas
production

Remark:8 days lag phase
Degradation after 18 d: 91 +- 7.8 %14-FEB-2002(40)

Inoculum:
Concentration:
Degradation:other bacteria: anaerobic sludge, domestic
50 mg/l related to Test substanceafter 21 day(s)Method:other: anaerobic degradation, static, 35
degree C, adding of test substance in solid
form; parameter: gas production

Remark:14-FEB-2002

Degradation: 110.5 %Inoculum:other bacteria: anaerobic sludge, domestic,
washed50 mg/l related to Test substanceConcentration:

58

(41)

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Degradation:

89.5 % after 35 day(s)Method:other: anaerobic degradation, static, 35
degree C, adding of test substance in solid
form; parameter: gas production

15-JAN-2001
Inoculum:
Concentration:
Degradation:
Method:(41)
other bacteria: anaerobic laboratory sludge,
adapted24 mg/l related to Test substance86 - 93 % after 23 day(s)other: anaerobic degradation, static,
parameter:gas production, 37degree C

15-JAN-2001
Inoculum:(42)

Concentration:other bacteria: activated sludge,
domestic/industrial sewage.8 mg/l related to Test substance

Degradation:> 71.5 % after 5 day(s)Method:other: closed bottle-test

15-JAN-2001(19)

Inoculum:
Concentration:
Degradation:

activated sludge, domestic
700 mg/l related to Test substance
76 % after 5 day(s)Method:other: respirometric determination of BOD; 20
degree C

15-JAN-2001(43)

3.6 BOD5, COD or BOD5/COD Ratio
Method:Year:
Method:Remark:14-AUG-2001

BOD5/COD ratio is 0.72, indicating readily
biodegradation.
(15)

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OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

3.7 Bioaccumulation
BCF:

3.16

Method:Year:
Test substance:other: BCF Program (v2.13)
1999
other TS: molecular structure

Result:Reliability:

Estimated Log BCF = 0.500 (BCF = 3.162)(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint

Flag:
14-AUG-2001
Remark:(21)
Based on the log P and the fact that many
species absorb benzoic acid rapidly andrapidly metabolize it to hippuric acid that is
excreted in urine, no bioaccumulation isindicated.

15-JAN-2001

3.8 Additional Remarks
Remark:Soil sorption coefficient Kd at 50 ug/l
Loamy sand : 0.4 m depth:Sand: 18.9 m depth:

23-OCT-1995
Remark:

1.92
0.62
(44)

Biomagnification factors (modell ecosystem)(0.01-0.1 ppm; radiolabelled):
Gambusia affinis (mosquito fish)
21
Daphnia magna
1772
Oedogonium cardiacum (green algae)
102
Culex quinquifasciatus (midge, larvae) 138
Physa (snail)2786
Duration of test: 48 h
Fishes were added after 24 h; nodifferentiation between bioaccumulationand magnification.
There is no evidence whether a plateau wasachieved; the depuration rate is unknown.

23-OCT-1995

60

(45)

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Remark:23-OCT-1995

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Bioconcentration factor:
Selenastrum capricornutum (green algae) 7.6(46)

Remark:Bioconcentration factors:
Leuciscus idus (golden orfe)< 10(fresh weight) (3 d)
Chlorella fusca (green algae)< 10(fresh weight) (1 d)activated sludge
1300 (dry weight)(5 d)There is no evidence whether a plateau was achieved;
the depuration rate is unknown.
23-OCT-1995(23)

Remark:Bioconcentration factor (calculated):
Oncorhynchus mykiss (rainbow trout, muscle) 14

23-OCT-1995
Remark:23-OCT-1995
Remark:23-OCT-1995
Remark:14-AUG-2001
Remark:(47)
Degradation in soil:
Half life in soil: 35 d
(Determination of mineralization byradioactive labelling)(loamy sand/sand, independent of depth 3-18 m)(44)
Degradation in soil:
Inoculum: soil microorganisms ("septic tanktile fields")
Method: anaerobic degradation, static;
parameter: 14 CO2;
20 degree C
Concentration: 1 mg/kg related to soil
Half life: 18.2 h(48)
Degradation in sea water:
Inoculum: sea water
Method: Determination of BOD
Concentration: 2 mg/l related to test
substance
Degradation after 5 d: 74.9 %No further information about test conditions(49)
Degradation in sea water:
Inoculum: sea water (New York, USA)

UNEP PUBLICATIONS

61

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

14-AUG-2001
Remark:BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Method: aerobic degradation, static; 29 degree
C; measurement of radioactivity of the 14Clabelled substance(at carboxyl group)
Concentration: 0.059 mg/l related to test
substance
Degradation after 7 d: 98.7 %Determination with trace concentrations(50)
Degradation in marine ecosystems:
Benzoic acid can be degraded by different
marine yeasts (9 of 12 tested species:
Saccharomyces rosei, S. italicus,
S. chevaliero, Cryptococcus laurentii,
C. luteolus, C. neoformans, Rhodotorulus
rubra, R. glutinis, Hansenulaanomala). No
information about test conditions.

23-OCT-1995
Remark:(50)
Elimination in rainwater:
Inoculum: rainwater
Methode: aerobic degradation; 22 degree C
Concentration: 0.001 mg/l related to test

substance
Degradation after 7 d: 22-40 %Degradation after 45 d: 100 %23-OCT-1995
Remark:23-OCT-1995
Remark:62(51)
Inoculum: Basische Parabraunerde (ueber
p-Hydroxybenzoesaeure isoliertes Inokulum)
Method: aerobic degradation, static, room
temperature
Concentration: 20 mg test substance/kg soil
Degradation after 3 d: 40 %Degradation after 7 d: 44 %Degradation after 70 d: 63 %related to the release of labelled CO2 in %applied radioactivity (labelled benzene ring)(52)
Inoculum: soil microorganisms (loamy sand)
Method: aerobic degradation, static, 30 degree
C, pH = 7.3
Concentration: 16 mg/l related to test
substance
Degradation after 1 d: 100 %substance specific analysis

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

23-OCT-1995
Remark:(36)
Inoculum: soil microorganisms (sandy soil in
18.3 m depth)
Method: aerobic degradation, static,
24 degree C
Concentration: 0.05 mg/kg related to test
substance
Degradation after 15 d: 40 %Half life: 35 d (graphically determined)

14-AUG-2001
Remark:BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(44)Inoculum: soil microorganisms (loam)
Method: aerobic degradation, static,
25 degree C
Concentration: 25 mg/l related to test
substance
Degradation after 1 d: 100 %The cleavage of the benzene ring was detectedby UV adsorption.

14-AUG-2001(53)

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OECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

AQUATIC ORGANISMS
4.1 Acute/Prolonged Toxicity to Fish
Type:
Species:
Exposure period:
Unit:
NOEC:
LC50:

staticLepomis macrochirus
96 hour(s)
mg/l
10
44.6

Method:other: Test conducted according to EPA-660/375-009 except that replicate concentrations
were not used.
1975
no dataother TS: technical grade benzoic acid

Year:
GLP:
Test substance:
Remark:Result:(Fish, fresh water)
Analytical monitoring: no

Flag:
14-FEB-2002

Higher LC50s were seen with other species.
24 hr LC50 = >56.0 mg/l; 48 hr LC50 = 46.0
mg/l; 72 hr LC50
= 46.0 mg/l
Purified, deionized ater reconstituted to Phof 7.49, total hardness of 44 mg/l CaCO3,
total alkalinity of 31 mg/l CaCO3.
(2) valid with restrictions
Guideline study with acceptable restrictions
Critical study for SIDS endpoint
(54)

Type:
Species:
Exposure period:
Unit:
NOEC:
LC50:

staticSalmo gairdneri
96 hour(s)
mg/l
10
47.3

Year:
GLP:
Test substance:

1979
no dataother TS: technical grade benzoic acid

Method:Test conducted according to EPA-660/3-75-009
except that replicate concentrations were notused.
24 hr LC50 = 47.3 mg/l; 48 hr LC50 = 47.3
mg/l; 72 hr LC50 = 47.3 mg/l

Test condition:

Reliability:

Result:64(Fish, estuary, fresh water)

UNEP PUBLICATIONS

Analytical monitoring: noOECD SIDS
4. ECOTOXICITY

Test condition:

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Flag:
14-AUG-2001

Purified, deionized water reconstituted to pHof 7.44, total hardness of 36 mg/l CaCO3,
total alkalinity of 27 mg/l CaCO3.
(2) valid with restrictions Guideline study
with acceptable restrictions
Critical study for SIDS endpoint
(55)

Type:
Species:
Exposure period:
Unit:
LC0:
LC50:
LC100:

staticLeuciscus idus
48 hour(s)
mg/l
400
460
600

Method:other: Fish test acc. to Deutsche
Einheitsverfahren zur
Wasser-,Abwasser- und Schlammuntersuchung L15
1976
no dataother TS: benzoic acid, purity not noted

Reliability:

Year:
GLP:
Test substance:
Remark:Reliability:(Fish, fresh water)
Analytical monitoring: no data

Flag:
14-AUG-2001

pH 7 - 8(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint
(56)

Type:
Species:
Exposure period:
Unit:
LC0:

staticLepomis macrochirus
96 hour(s)
mg/l
180

Method:other: aerated; 19.5-20.5 degree C; pH control(Fish, fresh water)
Analytical monitoring:

15-JAN-2001(31)

Species:
Unit:
LC100:

Carassius auratus
mg/l
200

Method:other: no data

(Fish, fresh water)
Analytical monitoring:

UNEP PUBLICATIONS

65OECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Remark:15-JAN-2001

exposure period: 7-96 hSpecies:
Exposure period:
Unit:
LC100:

Lepomis humilis
1 hour(s)mg/l
550 - 570

Method:other: no data

(57)
(Fish, fresh water)
Analytical monitoring:

15-JAN-2001(57)

4.2 Acute Toxicity to Aquatic Invertebrates
Species:
Exposure period:
Unit:
EC0:
EC50:
EC100:

Daphnia magna
24 hour(s)
mg/l
260
500
1000

Method:other: Immobilization test at 20 degree C; pH
8.0
1982
no dataother TS: benzoic acid, purity not noted

Year:
GLP:
Test substance:
Remark:(Crustacea)
Analytical monitoring: no data

standardized culture
without neutralization

Flag:
14-AUG-2001

EC0 :77 mg/l
EC50 :
102 mg/l
EC100:
136 mg/l(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint
(58)

Type:

staticSpecies:
Exposure period:
Unit:
NOEC:
EC50:

Daphnia magna
48 hour(s)
mg/l
100
> 100

Reliability:

66(Crustacea)
Analytical monitoring: no

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Method:Year:
GLP:
Test substance:other: EPA-660/3-75-009
1979
no dataother TS: technical grade benzoic acid

Test condition:

The water was vigorously aerated anddetermined by analysis to have pH of 8.45,
total hardness of 250 mg/l CaCO3,
total alkalinity of 141 mg/l CaCO3.
(2) valid with restrictions
Guideline study
Critical study for SIDS endpoint

Reliability:
Flag:
14-FEB-2002(59)

Species:
Exposure period:
Unit:
EC0:
EC50:

Daphnia magna
24 hour(s)
mg/l
540
1540

(Crustacea)

Method:other: Immobilization test(neutralization);20-22 degree C;
pH 7.6 - 7.7

Remark:06-JUN-2001

wild population

Species:
Exposure period:
Unit:
EC50:

Daphnia magna
24 hour(s)
mg/l
300

Method:other: Immobilization test acc. to Bringmann &Kuehn

Analytical monitoring:(60)(Crustacea)
Analytical monitoring:

15-JAN-2001(61)

4.3 Toxicity to Aquatic Plants e.g. Algae
Species:
Endpoint:
Exposure period:
Unit:
EC50:

Scenedesmus quadricauda (Algae)
other: Inhibition of photosynthesis
3 hour(s)mg/lAnalytical monitoring: no data
75

Method:other: see below

UNEP PUBLICATIONS

67OECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Year:
GLP:
Test substance:

1982
no dataother TS: >95% pure, purchased from Aldrich
Chemical Co. Milwaukee, Wisconsin, USA

Method:Flag:
14-FEB-2002

Photosynthesis was assayed by following theuptake of(14C)O2 from NaH(14C)O2.
Plastic culture flasks contained 9.9ml cellsuspension (containing 1.0 E+5 algalcells/ml),
0.1ml radioisotope, and 0.1ml of test
chemical. The flasks were incubated for 3
hours and photosynthetic activity assayed.
Five replicates of five concentrations,
ranging from 0 to 100 mg/ml, were used.
Per cent inhibition was calculated relative tophotosynthetic activity in the controls. EC50
values were determined by probit (Finney DJ.
1971. Probit Analysis, 3rd ed).
Analyses for significant differences (p=0.05)
were performed using Dunnett's test (Winer
BJ.1971. Stat. Prin. in Exp. Design, 2nd ed).
20 degree C; 12 h light/dark-cycle; lightintensity 7000 lux(2) valid with restrictions
Meets generally accepted scientific standards,
Well documented and acceptable for assessment
Critical study for SIDS endpoint(62)

Species:
Exposure period:
Unit:
TGK :

Scenedesmus quadricauda (Algae)
8 day(s)mg/lAnalytical monitoring:
1630

Method:other: static, inhibition of cell
multiplication; 27 degree C; pH 7

Reliability:

Flag:
14-AUG-2001(2) valid with restrictions
Meets generally accepted scientific standards,
Well documented and acceptable for assessment
Critical study for SIDS endpoint(63)

Species:
Endpoint:
Exposure period:
Unit:

Scenedesmus quadricauda (Algae)
growth rate
14 day(s)mg/lAnalytical monitoring:

Test condition:
Reliability:

68

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

EC50:

> 10

Test substance:other TS: >95% pure, purchased from Aldrich
Chemical Co. Milwaukee, Wisconsin, USA

Method:Flag:
14-AUG-2001

Growth was assessed by measuring theabsorbance of cultures with time using a
Bausch and Lomb Spectronic 20
spectrophotometer.
The wavelength employed (420 nm) was
determined by the method of Sorokin C. (1973.
Handbook of Phycological Methods).
Sidearm flasks containing 94.9ml of medium and
0.1 ml of test chemical were inoculated with 5
ml of an active culture (containing 6.5 E+4cyanobacterial and 1.0 E+5 algal cells per ml)
and incubated for 12 - 14 days.
Five replicates of five concentrations of test
chemical, ranging from 0 to 10 mg/ml, wereused. Optical densities of treatedcultures were determined daily and per centinhibition was calculated relative to thecontrols.
Growth rates were determined by Sorokin C(1973) and EC50 values were determined byprobit (Finney DJ. 1971. Probit Analysis, 3 rded).
20 degree C; 12 h light/dark-cycle; lightintensity 7000 lux(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(62)

Species:
Endpoint:
Exposure period:
Unit:
EC50:

Chlorella pyrenoidosa (Algae)
other: inhibition of photosynthesis
3 hour(s)mg/lAnalytical monitoring: no data
60

Method:Year:
GLP:
Test substance:other: see below
1982
no dataother TS: >95% pure, purchased from Aldrich
Chemical Co. Milwaukee, Wisconsin, USA

Test condition:
Reliability:

UNEP PUBLICATIONS

69

OECD SIDS
4. ECOTOXICITY

Method:BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Flag:
14-AUG-2001

Photosynthesis was assayed by following theuptake of (14C)O2 from NaH(14C)O2.
Plastic culture flasks contained 9.9ml
cell suspension (containing 1.0 E+5 algal
cells/ml), 0.1ml radioisotope, and 0.1ml oftest chemical. The flasks were incubated for
3 hours and photosynthetic activity assayed.
Five replicates of five concentrations,
ranging from 0 to 100 mg/ml, were used.
Per cent inhibition was calculated relative tophotosynthetic activity in the controls. EC50
values were determined by probit (Finney DJ.
1971. Probit Analysis, 3rd ed).
Analyses for significant differences (p=0.05)
were performed using Dunnett's test (Winer BJ.
1971. Stat. Prin. in Exp. Design, 2nd ed).
20 degree C; 12 h light/dark-cycle; lightintensity 7000 lux(2) valid with restrictions
Meets generally accepted scientific standards,
Well documented and acceptable for assessment
Critical study for SIDS endpoint(62)

Species:
Endpoint:
Exposure period:
Unit:
EC50:

Chlorella pyrenoidosa
growth rate
14 day(s)
mg/l
> 10

Test substance:other TS: >95% pure, purchased from Aldrich
Chemical Co. Milwaukee, Wisconsin, USA

Method:Growth was assessed by measuring theabsorbance of cultures with time using a
Bausch and Lomb Spectronic 20
spectrophotometer.
The wavelength employed(420 nm) wasdeterminedby the method of Sorokin C. (1973. Handbook of
Phycological Methods).
Sidearm flasks containing 94.9ml of medium and
0.1 ml of test chemical were inoculated with 5
ml of an active culture (containing 6.5 E+4cyanobacterial and 1.0 E+5 algal cells per ml)
and incubated for 12 - 14 days.

Test condition:
Reliability:

70

UNEP PUBLICATIONS(Algae)Analytical monitoring:OECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Flag:
14-AUG-2001

Five replicates of five concentrations of test
chemical, ranging from 0 to 10 mg/ml, wereused. Optical densities of treated cultures
were determined daily and per cent inhibition
was calculated relative to the controls.
Growth rates were determined by Sorokin C(1973) and EC50 values were determined byprobit (Finney DJ.1971. Probit Analysis, 3rded).
20 degree C; 12 h light/dark-cycle; lightintensity 7000 lux(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(62)

Species:
Endpoint:
Exposure period:
Unit:
EC50:

Anabaena variabilis (Algae)
growth rate
14 day(s)mg/lAnalytical monitoring: no data
> 10

Method:GLP:Test substance:other: see below
no dataother TS: >95% pure, purchased from Aldrich
Chemical Co. Milwaukee, Wisconsin, USA

Method:Growth was assessed by measuring th absorbanceof cultures with time using a Bausch and Lomb
Spectronic 20 spectrophotometer.
The wavelength employed (420nm) was determinedby the method of Sorokin C. (1973. Handbookof Phycological Methods).
Sidearm flasks containing 94.9ml of medium and
0.1 ml of test chemical were inoculated with 5
ml of an active culture (containing 6.5 E+4cyanobacterial and 1.0 E+5 algal cells
per ml) and incubated for 12 - 14 days.
Five replicates of five concentrations of test
chemical, ranging from 0 to 10 mg/ml, wereused. Optical densities of treated cultures
were determined daily and per cent inhibition
was calculated relative to the controls.

Test condition:
Reliability:

UNEP PUBLICATIONS

71

OECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Growth rates were determined by Sorokin C(1973) and EC50 values were determined by probit(Finney DJ. 1971. Probit Analysis, 3rd ed).
Test condition: 20 degree C; 12 h light/dark-cycle; lightintensity 7000 lux
Reliability:(2) valid with restrictions
Meets generally accepted scientific standards,
Well documented and acceptable for assessment
Flag:
Critical study for SIDS endpoint
14-AUG-2001(62)
Species:
Endpoint:
Exposure period:
Unit:
EC50:

Anabaena cylindrica (Algae)
other: inhibition of photosynthesis
3 hour(s)mg/lAnalytical monitoring:60

Test substance:other TS: >95% pure, purchased from Aldrich
Chemical Co. Milwaukee, Wisconsin, USA

Method:Photosynthesis was assayed by following theuptake of (14C)O2 from NaH(14C)O2.
Plastic culture flasks contained 9.9ml
cell suspension (containing 1.0 E+5 algal
cells/ml), 0.1ml radioisotope, and 0.1ml oftest chemical. The flasks were incubated for
3 hours and photosynthetic activity assayed.
Five replicates of five concentrations,
ranging from 0 to 100 mg/ml, were used.
Per cent inhibition was calculated relative tophotosynthetic activity in the controls.EC50
values were determined by probit (Finney DJ.
1971. Probit Analysis, 3rd ed).
Analyses for significant differences(p=0.05) were performed using Dunnett's test
(Winer BJ.1971. Stat. Prin. in Exp. Design,
2nd ed).
20 degree C; 12 h light/dark-cycle; lightintensity 7000 lux(2) valid with restrictions(62)

Test condition:
Reliability:
23-MAY-2001
Species:
Exposure period:

72

Microcystis aeruginosa
cyanobacteria)
8 day(s)UNEP PUBLICATIONS(Algae, blue,

OECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Unit:
TGK :

mg/l
55

Analytical monitoring:

Method:other: inhibition of cell multiplication at 27
degree C; pH 7

15-JAN-2001(64)

Species:
Endpoint:
Exposure period:
Unit:
EC50:

Anabaena inaequalis (Algae)
growth rate
14 day(s)mg/lAnalytical monitoring:
9

Test substance:other TS: >95% pure, purchased from Aldrich
Chemical Co. Milwaukee, Wisconsin, USA

Method:Reliability:
13-DEC-2000

Growth was assessed by measuring theabsorbance of cultures with time using a
Bausch and Lomb Spectronic 20
spectrophotometer.
The wavelength employed (600 nm) was
determined by the method of Sorokin C. (1973.
Handbook of Phycological Methods).
Sidearm flasks containing 94.9ml of medium and
0.1 ml of test chemical were inoculated with 5
ml of an active culture (containing 6.5 E+4cyanobacterial and 1.0 E+5 algal cells per ml)
and incubated for 12 - 14 days.
Five replicates of five concentrations of test
chemical, ranging from 0 to 10 mg/ml, wereused. Optical densities of treated cultures were
determined daily and per cent inhibition was
calculated relative to the controls.
Growth rates were determined by Sorokin C(1973) and EC50 values were determined byprobit (Finney DJ. 1971. Probit Analysis,
3rd ed).
20 degree C; 12 h light/dark-cycle; lightintensity 7000 lux(2) valid with restrictions(62)

Species:
Endpoint:
Exposure period:
Unit:

Anabaena cylindrica
growth rate
14 day(s)mg/lTest condition:

UNEP PUBLICATIONS(Algae)Analytical monitoring:73OECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

EC50:

> 10

Test substance:other TS: >95% pure, purchased from Aldrich
Chemical Co. Milwaukee, Wisconsin, USA

Method:Reliability:
06-SEP-2000

Growth was assessed by measuring theabsorbance of cultures with time using a
Bausch and Lomb Spectronic 20
spectrophotometer. The wavelength employed(600 nm) was determined by the method ofSorokin C. (1973. Handbook of
Phycological Methods).
Sidearm flasks containing 94.9ml of medium and
0.1 ml of test chemical were inoculated with 5 mlof an active culture (containing 6.5 E+4cyanobacterial and 1.0 E+5 algal cells per ml)
and incubated for 12 - 14 days. Five replicatesof five concentrations of test chemical, ranging
from 0 to 10 mg/ml, were used. Optical densitiesof treated cultures were determined daily and percent inhibition was calculated relative to thecontrols. Growth rates were determined by
Sorokin C (1973) and EC50 values were determinedby probit (Finney DJ. 1971. Probit Analysis,
3rd ed).
20 degree C; 12 h light/dark-cycle; lightintensity 7000 lux(2) valid with restrictions(62)

Species:
Endpoint:
Exposure period:
Unit:
EC50:

Anabaena inaequalis (Algae)
other: Inhibition of photosynthesis
3 hour(s)mg/lAnalytical monitoring:5

Test substance:other TS: >95% pure, purchased from Aldrich
Chemical Co. Milwaukee, Wisconsin, USA

Method:Photosynthesis was assayed by following theuptake of (14C)O2 from NaH(14C)O2.
Plastic culture flasks contained 9.9ml
cell suspension (containing 1.0 E+5 algal
cells/ml), 0.1ml radioisotope, and 0.1ml oftest chemical. The flasks were incubated for
3 hours and photosynthetic activity assayed.

Test condition:

74

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Reliability:
14-AUG-2001

Five replicates of five concentrations,ranging
from 0 to 100 mg/ml, were used.
Per cent inhibition was calculated relative tophotosynthetic activity in the controls.EC50
values were determined by probit (Finney DJ.
1971. Probit Analysis, 3rd ed).
Analyses for significant differences (p=0.05)
were performed using Dunnett's test (Winer BJ.
1971. Stat. Prin. in Exp. Design, 2nd ed).
20 degree C; 12 h light/dark-cycle; lightintensity 7000 lux(2) valid with restrictions(62)

Species:
Endpoint:
Exposure period:
Unit:
EC50:

Anabaena variabilis (Algae)
other: Inhibition of photosynthesis
3 hour(s)mg/lAnalytical monitoring:
55

Method:other: inhibition of photosynthesis;
20 degree C; 12 h light/dark-cycle; lightintensity 7000 lux
other TS: >95% pure, purchased from Aldrich
Chemical Co. Milwaukee, Wisconsin, USA

Test condition:

Test substance:

Method:Test condition:
Reliability:

Photosynthesis was assayed by following theuptake of (14C)O2 from NaH(14C)O2.
Plastic culture flasks contained 9.9ml
cell suspension (containing 1.0 E+5 algal
cells/ml), 0.1ml radioisotope, and 0.1ml oftest chemical. The flasks wereincubated for 3 hours and photosynthetic
activity assayed.
Five replicates of five concentrations,
ranging from 0 to 100 mg/ml, were used.
Per cent inhibition was calculated relative tophotosynthetic activity in the controls.EC50
values were determined by probit (Finney DJ.
1971. Probit Analysis, 3rd ed).
Analyses for significant differences (p=0.05)
were performed using Dunnett's test (Winer BJ.
1971. Stat. Prin. in Exp. Design, 2nd ed).
20 degree C; 12 h light/dark-cycle; lightintensity 7000 lux(2) valid with restrictions

UNEP PUBLICATIONS

75

OECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

14-AUG-2001(62)

4.4 Toxicity to Microorganisms e.g. Bacteria
Species:
Exposure period:
Unit:
EC50:

activated sludge
3 hour(s)mg/l> 1000

Method:OECD Guide-line 209 "Activated Sludge,
Respiration Inhibition Test"
1984
other TS: benzoic acid; purity not notedYear:
Test substance:
Remark:Reliability:
Flag:
14-AUG-2001

Analytical monitoring:pH 7,5(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(62)

Species:
Exposure period:
Unit:
EC50:

Photobacterium phosphoreum (Bacteria)
30 minute(s)mg/lAnalytical monitoring:
16.85

Method:Test substance:other: static at 15 degree C; Microtox-Testother TS: benzoic acid; purity not noted

Reliability:

Flag:
14-AUG-2001(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(66)

Species:
Exposure period:
Unit:
TGK :

Pseudomonas putida (Bacteria)
16 hour(s)mg/lAnalytical monitoring:
480

Method:Test substance:other: static; 25 degree C; pH 7
other TS: benzoic acid; purity not noted

Reliability:(2) valid with restrictions
Meets generally accepted scientific standards,
Well documented and acceptable for assessment
Critical study for SIDS endpoint

Flag:

76

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

14-AUG-2001(63)

Species:
Exposure period:
Unit:
EC0:

Pseudomonas fluorescens (Bacteria)
24 hour(s)mg/lAnalytical monitoring:
1000

Method:other: Bestimmung der biologischen
Schadwirkung toxischer Abwaessergegen
Bakterien. DEV, L 8 (1968) modifiziert

14-AUG-2001(19)

Species:
Exposure period:

other bacteria: Pseudomonas Stamm Berlin
1 hour(s)

Unit:
EC10:

mg/l
50

Method:other: Oxygen consumption test acc. to Robra,
GWF-Wasser/Abwasser 117,80-86 (1976)

Analytical monitoring:

14-AUG-2001
Species:
Exposure period:
Unit:
Tlm :
Method:(61)
other bacteria: population of microorganisms
from communal sewage
24 hour(s)mg/lAnalytical monitoring:500
other: static, inhibition of cell
multiplication; 37 degree C; pH 6.9

14-AUG-2001(31)

4.5 Chronic Toxicity to Aquatic Organisms
4.5.1 Chronic Toxicity to Fish
Remark:14-AUG-2001

No data available.

4.5.2 Chronic Toxicity to Aquatic Invertebrates
Remark:14-AUG-2001

No data available.

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OECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

TERRESTRIAL ORGANISMS

4.6.1 Toxicity to Sediment Dwelling Organisms
4.6.2 Toxicity to Terrestrial Plants
Remark:14-AUG-2001

No data available.

4.6.3 Toxicity to Soil Dwelling Organisms
Remark:14-AUG-2001

No data available.

4.6.4 Toxicity to other Non-Mamm. Terrestrial Species
Remark:14-AUG-2001

No data available.

4.7 Biological Effects Monitoring
Remark:14-AUG-2001

No data available.

4.8 Biotransformation and Kinetics
Remark:14-AUG-2001

No data available.

4.9 Additional Remarks

Remark:23-OCT-1995
Remark:Toxicity to protozoa:
TT (Chilomonas paramaecium): 48 h EC5 356 mg/l
(cell multiplication) pH 6,9(67)
Toxicity to protozoa:
Entosiphon sulcatum 72 h(cell multiplication)

23-OCT-1995
Remark:78

EC5: 218 mg/l
(68)

Toxicity to protozoa:
Uronema parduczi 20 h(cell multiplication)
UNEP PUBLICATIONS

TT: 31 mg/l, pH 6.9

OECD SIDS
4. ECOTOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

23-OCT-1995(69)

Remark:Toxicity to yeast:6 w MIC (pH 3.5; 25 degree C
adapted non-adapted-Saccharomyces cerevisiae St 1297
170 mg/l
100 mg/l-Kluveromyces fragilis
173
125-Kloeckera apiculata
188
125-Hansenula anomala
223
140-Candida crusei
440300-Saccharomycodes ludwigii
650
300-Schizosaccharomyces pombe
567
325-Zygosaccharomyces bailii
1250
600
23-OCT-1995(70)
Remark:Toxicity to fungi:
Fusarium oxysporum:
Test concentration: 610 mg/l
Growth inhibition at
pH 4.0 : 83.5 %pH 4.8 : 74.6 %pH 5.6 : 57.9 %pH 6.4 : 39.5 %pH 7.2 : 23.7 %23-OCT-1995
Remark:(71)
Antimicrobial effects (pH 6):
minimal microbizide
Conc. (MMC)-Aspergillus niger-Candida albicans-Escherichia coli
-Klebsiella pneumoniae-Penicillium notatum-Pseudomonas aeruginosa-Pseudomonas cepacia-Pseudomonas fluorescens-Staphylococcus aureus
23-OCT-1995

1000 mg/l
1200
160
160
1000
160
160
160
20

UNEP PUBLICATIONS

minimal inhib.
conc. (MIC)(serial dilution
test)
500-1000 mg/l
500-1000
100-200
100-200
500-1000
200-500
200-500
50-100(72)

79

OECD SIDS
5. TOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

5.0 Toxicokinetics, Metabolism and Distribution

5.1 Acute Toxicity
5.1.1 Acute Oral Toxicity
Type:Species:Sex:
No. of Animals:
Vehicle:Value:

LD50
ratmale/female
50
other: corn oil
2565 mg/kg bw

Method:Directive 84/449/EEC, B.1 "Acute toxicity(oral)"no dataother TS: technical grade benzoic acid

GLP:
Test substance:
Method:Result:80

25 male and 25 female Spartan rats weighing 200
to 250 grams were used for this study.
The test compound was suspended in corn oil andadministered orally at the following dosage
levels: 500, 1250, 1984, 3150, and 5000 mg/kg.
Five rats of each sex were used at each dosage
level.
Volumes of 10 ml/kg bw were administered at all
dosage levels.
All rats were observed for mortality continuously
during the first 4 hours after dosing, at 24hours and once daily thereafter for a total of 14days. Body weights were recorded initially andat 14 days.
All surviving rats, males and females, exhibited
normal body weight gains during the 14 day
observation period.The acute oral LD50 of
benzoic acid in male albino rats was calculated
to be 2742 mg/kg (2279-3299 mg/kg).
The acute oral LD50 of benzoic acid in female
albino rats was calculated to be 2360 mg/kg(2042-2726 mg/kg).
A combined acute oral LD50 for benzoic acid inmale and female albino rats was calculated to be
2565 mg/kg (2292-2870 mg/kg).

UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
LD50 calculations were done according to WR
Thompson. 1947.Bact. Rev. 11:115-145.

Reliability:
Flag:

Dose level (mg/kg)
Mortality
500
0/5
1250
0/5
1984
0/5
3150
4/5
5000
5/5
(1) valid without restriction
Guideline study
Critical study for SIDS endpoint

14-FEB-2002

(73)

Type:
Species:Sex:
No. of Animals:
Vehicle:Value:

LD50
mouse
male/female
60
other: Tween 80 (1.5%)2250 mg/kg bw

Method:Year:
GLP:
Test substance:

EPA OPPTS 870.1100
1979
no dataother TS: Commercial Grade benzoic acid
(Velsicol lot #52829055)

Reliability:(1) valid without restriction
Guideline study
Critical study for SIDS endpoint

Flag:
14-FEB-2002
Type:
Species:Value:

(74)
LD50
rat
= 1700 mg/kg bw

26-JAN-2001
Type:
Species:Value:

(75)
LD50
rat
= 3040 mg/kg bw

26-JAN-2001(4)

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81

OECD SIDS
5. TOXICITY

Type:
Species:Value:BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
LD50
rat= 2530 mg/kg bw

26-JAN-2001
Type:
Species:Value:

(76)
LD50
mouse
= 1940 mg/kg bw

26-JAN-2001
Type:
Species:Value:

(77)
LD50
mouse
= 2370 mg/kg bw

26-JAN-2001(78)

5.1.2 Acute Inhalation Toxicity
Type:Species:Sex:
No. of Animals:
Exposure time:
Value:

LC50
rat
male/female10
4 hour(s)> 12.2 mg/l

Method:Year:
GLP:
Test substance:

EPA OTS 798.1150
1974
no dataother TS: technical grade benzoic acid

Method:Ten rats (4 units of 2 or 3 rats/unit to prevent
piling) were placed in a sealed 59.1 liter glasschamber and exposed to a dynamic atmosphere
containing the dust of the test material.
A Wright Dust Feeder controlled addition of
The test substance; airflow regulated by aflowmeter. The rats were observed continuously
during the 4-hour exposure, and for a periodof 14 days following exposure.

Result:All of the rats survived the 4-hour exposureand the 14-day observation period.
Signs during the exposure period included
occasional increased motor activity and slighterythema. At the conclusion of exposure, 1 rat
exhibited salivation.

82

UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Flag:
14-FEB-2002

At 24 hours and through the 14-day observation
period, all rats appeared normal and exhibited
normal body weight gains.
(1) valid without restriction
Guideline study
Critical study for SIDS endpoint
(73)

Type:
Species:
Exposure time:
Value:

LC50
rat
1 hour(s)> .026 mg/l

Remark:exposure to vapor
generalized inactivity, lacrimation at 0.026
mg/l/1h, no mortality(4)

Reliability:

15-JAN-2001

5.1.3 Acute Dermal Toxicity
Type:Species:Sex:
No. of Animals:
Vehicle:Value:

LD50
rabbitmale/female
4other: neat
> 2000 mg/kg bw

Method:Year:
GLP:
Test substance:

EPA OTS 798.1100
1974
no dataother TS: technical grade benzoic acid

Method:The test compound was applied once only to a
shaved area of the back of each rabbit at adose of 2000 mg/kg bw.
The skin of 1 male and 1 female was abraded witha scalpel blade prior to test application.
The area was wrapped with a gauze bandage andoccluded with plastic wrap.
The bandages were removed and the backs washed24 hours after application.
The rabbits were observed for a period of 14
days.

Reliability:(1) valid without restriction
Guideline study
Critical study for SIDS endpoint

Flag:
14-FEB-2002
Type:

(73)
LD50
UNEP PUBLICATIONS

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OECD SIDS
5. TOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Species:Value:

rabbit> 10000 mg/kg bw

Remark:15-JAN-2001

mortality: 0/5

Type:Species:Value:

LD50
rabbit> 5000 mg/kg bw

Remark:15-JAN-2001

mortality: no information

(4)

(79)

5.1.4 Acute Toxicity, other Routes
Type:Species:Route of admin.:Value:

LD50
mouse
i.p.
= 1460 mg/kg bw

23-MAR-2001(80)

5.2 Corrosiveness and Irritation
5.2.1 Skin Irritation
Species:
Concentration:
Exposure:
Exposure Time:
No. of Animals:
PDII:
Result:EC classificat.:rabbitundiluted
Semiocclusive
4 hour(s)60
not irritating
not irritating

Method:GLP:Test substance:

EPA OTS 798.4470
no dataother TS: benzoic acid, technical flakes

Remark:Flag:
14-AUG-2001

Primary Skin Irritation and Corrosive Hazard(Title 49, Transportation, Chapter 1)(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(73)

Species:
Concentration:
Exposure:

rabbitundiluted
Semiocclusive

Reliability:

84

UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Exposure Time:
No. of Animals:
PDII:
Result:EC classificat.:4 hour(s)3.5slightly irritating
not irritating

Method:Directive 84/449/EEC, B.4 "Acute toxicity(skin irritation)"yesother TS: benzoic acid, purity not noted

GLP:
Test substance:
Method:Flag:
14-AUG-2001

The flank site of 3 albino rabbits was exposed
to 0.5 g of the test substance moistened with
0.25 ml Milli-RO water for 4 hours using semiocclusive dressings.
The primary skin irritation index amounted to
0.5; based on these results, the test
substance should be considered as minimallyirritating to the skin; According to Annex VI
of EEC Council Directive 67/548/EEC (amended
by Directive 83/467/EEC), the test substanceneed not be labelled as a skin irritant.
(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(81)

Species:

rabbit

Method:other: see remarks

Remark:23-MAR-2001

irritation score: 1.66/8.00 single applicationof 500 mg dry powder (no further information),
response scored at 24 h and 72 h
(4)

Species:

rabbitConcentration:
Exposure Time:undiluted
24 hour(s)No. of Animals:
Result:2
not irritating

Method:Test substance:other:
other TS: benzoic acid, purity not noted

Method:2 animals; application of 500 mg/animal at the
inner side of the ear for 24 h
(82)

Result:Reliability:

13-MAR-2001

UNEP PUBLICATIONS

85

OECD SIDS
5. TOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Species:human

Method:other: see remarks

Remark:23-MAR-2001

Chamber-Scarification-Test
threshold irritating concentration:
1) normal skin: 30 % in ethanol
2) scarified skin: 7.5 % in ethanol: moderate
irritations;application of 15 % in ethanol leads tomarked irritation with erosions(83) (84)Species:humanRemark:23-MAR-2001

intermittent exposure, total dose applied: 22
mg, duration of exposure: 3 days
irritation classified as moderate(85)

Species:human

Method:other: see remarks

Remark:23-MAR-2001

16 mM benzoic acid (in petrolatum) produced an
Erythematous reaction in 12 of 13 healthy
volunteers on the cheek and in 6 subjects on
the forehead, neck and upper back.
8 mM and 4 mM benzoic acid produced only areaction on cheek.open application method(86)

Species:human

Method:other: see remarks

Remark:23-MAR-2001

benzoic acid (in 50 % aqueous isopropanol) wasapplied to the medial cheek of adultvolunteers; a 2 % solution led to wheals(11/11), a 0.04 % solution to erythema (11/11)
and pruritus (4/11)(87)

Species:human

Method:other: see remarks

86

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Remark:23-MAR-2001

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
non-immunologic immediate contact reactions
30-45 min after application skin-test with 10
ul doses of 50, 100, 250, 500 or 1000 mM
benzoic acid in various vehicles (emollient
cream, petrolatum, 2-propyl alcohol/watermixture (1:1), abs. ethyl alcohol, synthetic
lanolin substitute), openly applied on theback of 11 healthy subjects and 3 patientswith psoriasis, eczema, and rosacea resp. for
15 min(88)

5.2.2 Eye Irritation
Species:
rabbitConcentration:
undiluted
Dose:
.1 ml
Exposure Time:
1 hour(s)Comment:rinsed after (see exposure time)
No. of Animals:
8
Result:corrosive
EC classificat.: risk of serious damage to eyes
Method:GLP:Test substance:

EPA OTS 798.4500
no dataother TS: benzoic acid, technical flakes

Remark:Flag:
14-AUG-2001

Group I, consisting of 5 rabbits, were exposedto the test compound for 5 minutes; 3 rabbits
in Group II were exposed to the test substancefor 24 hours.
Following the exposure period, the treatedeyes were washed with a gentle continuous
stream of water for 2 minutes.
Eye Irritation Test in Albino Rabbits (21 CFR,
Part 191)
Both Group I (5 minute exposure) and Group II(24 hrs exposure) - an extremely irritating
and corrosive substance.
(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(73)

Species:
Concentration:
Dose:
Result:EC classificat.:rabbitundiluted
77 other: mg
highly irritating
irritating

Result:Reliability:

UNEP PUBLICATIONS

87

OECD SIDS
5. TOXICITY

Method:GLP:Test substance:
Remark:BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
Directive 84/449/EEC, B.5 "Acute toxicity(eye irritation)"yesother TS: benzoic acid, purity not noted

Flag:
14-AUG-2001

Based on Draize score of 35 the test substanceshould be classified as severely irritating
according to the scheme of Kay & Calandra;
according to Annex VI of EEC Council Directive
67/548/EEC (amended by Directive 83/467/EEC),
the test substance should be labelled as aneye irritant. instillation of approx. 77 mg in
the eye(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(89)

Species:

rabbit

Method:other: see remarks

Remark:irritation score: 65.0/110

Reliability:

single application of 100 mg dry powder,
responses scored at 24, 48 or 72 h
23-MAR-2001(4)

Species:Result:rabbitslightly irritating

Method:other: OECD Guideline 405

23-MAR-2001(90)

Species:Result:rabbitmoderately irritating

Method:other: see remark

Remark:2 animals; instillation of 50 mg/animal into
The conjunctical sac(82)23-MAR-2001

5.3 Sensitization
Type:
Draize Test
Species:guinea pig
Concentration 1st:Induction 500 undiluted occlusive epicutaneous
88

UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

2nd:Challenge 500 undiluted occlusive epicutaneous
No. of Animals:
10
Result:not sensitizing
Classification:
not sensitizing
Method:Year:
GLP:
Test substance:

EPA OPP 81-6
1959
yesother TS: benzoic acid, purity not noted

Result:During induction and challenge, the grand meanfor erythema and edema at 24 and 48 hours was 0.
Based on this study, it was concluded that
Benzoic acid is neither an irritant nor asensitizer when applied to guinea pigs.
(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(91)

Reliability:
Flag:
14-AUG-2001
Type:
Species:
Concentration 1st:
2nd:
3rd:
Result:Classification:

Guinea pig maximization test
guinea pig
Induction
10 % intracutaneous
Induction
20 % semiocclusive
Challenge
20 % semiocclusive
not sensitizing
not sensitizing

Method:GLP:Test substance:

OECD Guide-line 406 "Skin Sensitization"
no dataother TS: benzoic acid, purity not noted

Remark:test concentrations: intradermal injection
10 %, topical induction 20 %, challenge 20 %(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(92)

Reliability:
Flag:
14-AUG-2001
Type:
Species:Result:Buehler Testguinea pig
not sensitizing

Test substance:other TS: benzoic acid; purity not noted

Remark:14-AUG-2001

test concentrations: induction 20 %, challenge
20 %
(92)

Type:

Mouse local lymphnode assay
UNEP PUBLICATIONS

89

OECD SIDS
5. TOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Species:Result:mouse
not sensitizing

Test substance:other TS: benzoic acid; purity not noted

Remark:14-AUG-2001

test concentrations: 5, 10 or 20 %Type:
Species:Result:Mouse ear swelling test
mouse
not sensitizing

Test substance:other TS: benzoic acid; purity not noted

Remark:14-AUG-2001

test concentrations: induction 20 %, challenge
20 %
(92)

Type:
Species:Result:other: see remarks
guinea pig
sensitizing

Method:other: ear swelling test

Remark:14-AUG-2001

groups of five guinea pigs were challenged byapplying various concentrations of benzoic
acid to both sides of the earlobe.
The thickness of the ear was measured atvarious time intervals. Benzoic acid was
positive (concentration-dependent effect).
(94)

Type:
Species:other: see remarks
human

Method:Test substance:other: patch-testother TS: benzoic acid; purity not noted

Remark:3 workers of a pharmaceutical plant withtransient urticaria after exposure to sodium
benzoate and 3 previously unexposed healthy
control subjects were tested.
All subjects reacted to benzoic acid at 0.25 %in aqueous solution under occlusion. 1 worker
and 2 controls reacted to sodium benzoate at
0.5 % in saline under occlusion, but none
reacted to sodium benzoate at 0.5 % in aqueous
solution. All 3 workers reacted in a closed patch
test to benzoic acid at 5 % in petrolatum.

90

(93)

UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

14-AUG-2001

The time course of the responses to benzoic acidand sodium benzoate was similar in controls andworkers.
The potential of sodium benzoate to elicite
Nonimmunologic contact urticaria may be due tothe formation of benzoic acid at skin contact.
(95)

Type:
Species:other: see remarks
human

Method:other: patch-test

Remark:14-AUG-2001

3/5 patients with chronic urticaria developed
positive skin reactions in a patch test withbenzoic acid (5 % in petrolatum).
(96)

Type:
Species:other: see remarks
human

Method:Test substance:other: patch-testother TS: benzoic acid; purity not noted

Remark:14-AUG-2001

In a patch test with benzoic acid (5 % in
petrolatum), 108/113 patients showed noreaction and 5/113 patients showed a 1+
reaction.
Benzoic acid was not classified as asensitizer.
(97)

Type:

other: see remarks

Species:human

Method:other: patch-test

Remark:In a study of cosmetic intolerance withpatients tested for possible contact
dermatitis, 34 (0.7 %) of all patients and1 (0.6 %) patient with pure allergy tocosmetics reacted positive.

14-AUG-2001
Type:
Species:(98)
other: see remark
human
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Method:Test substance:
Remark:14-AUG-2001

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
other: patch-testother TS: benzoic acid; purity not noted
a baker developed dermatitis from flours whichcontained traces of benzoic acid;patch tests
showed contact type eczematous hypersensitivity
to benzoic acid (6 % in petrolatum).
(99)

Type:
Species:other: see remark
human

Method:Test substance:other: patch-testother TS: benzoic acid; purity not noted

Remark:14-AUG-2001

40 children (under 12 years old) were tested
for contact urticaria against food additives.
14 of them reacted positive to benzoic acid(no further information).
(3) invalid
Documentation insufficient for assessment
(100)

Type:
Species:other: see remarks
human

Method:other: skin-prick-test

Remark:14-AUG-2001

23 out of 91 subjects suffering from chronicor recurrent urticaria were tested in a skintest: 10/23 positive subjects (at least one
histamine equivalent skin test reaction)
reacted to benzoic acid (5 % in petrolatum).
(101)

Type:
Species:other: see remarks
human

Method:other: oral provocation test

Remark:a chemical worker suffered from allergic
reactions of increasing intensity while being
constantly exposed to benzoic acid duringwork. After oral exposure to sodium benzoate(500 mg) he suffered a severe anaphylactic
shock.
He showed similar but milder reaction after
consuming food containing benzoic acid.
(102)

Reliability:

14-AUG-2001
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Type:Species:other: see remarks
human

Method:other: oral provocation test

Remark:only one out of 7 subjects with a positive
skin test for benzoic acid showed a positive
response (itching, wealing) after repeatedoral exposure

14-AUG-2001

(101)

Type:
Species:other: see remarks
human

Method:other: oral provocation test

Remark:14-AUG-2001

to patients suffering from asthma benzoic acidwas given orally (no details reported);
approx. 50 % of the subjects showed asthmatic
hypersensitivity, rhinitis and urticaria.
(103)

Type:
Species:other: see remarks
human

Method:other: patch-test

Remark:7 patients with recurrent episodes of erythemamultiforme were found to be sensitive tobenzoic acid. Advice on avoidance of benzoic
acid resulted in resolution of attacks
in 4 patients (3 patients were not able toadhere to an exclusion diet).
(104)

14-AUG-2001

5.4 Repeated Dose Toxicity
Type:
Chronic
Species:rat
Sex: male/female
Strain:no data
Route of administration: oral feed
Exposure period:
generation 1 and 2: lifelong,
generation 3: 16 weeks,
generation 4: until breeding
Frequency of treatment: continuously in diet
Post exposure period:noDoses:
0.5 or 1 % in diet (approx. 375 or 750
mg/kg/day)
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Control Group:
NOAEL:BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
yes
750 mg/kg bw

Year:
GLP:
Test substance:1960
noother TS: benzoic acid, purity not noted

Method:A robust protocol according to standards at
That time was used. Taking into account the
reputation of the investigators a high quality
has to be assumed.
40 rats/group; initial body weight: 40-50 g
The mean compound consumption was calculated
according to Lehman, A.J., Assoc. Food Drug
Off. Q. Bull. 18, 66 (1954).
In all 4 generations no influence on growth(weight, weight gain and food efficiency(measured by protein efficiency))and organ
weights was found. In all 4 generations, noeffects on fertility ("Forzplanzung")andlactation ("Aufzugt der Jungen")was found. The
animals of the 3rd generation were killed andexamined histopathological after 16 weeks(after lactation of the pups.)No histopathological findings were found. In thepaper no information is given on the organs
investigated, however due to the robustness ofthe total study, the reputation of theinvestigators, as well as the reputationof the Professor who did the histopathologic
investigation, a high quality has to be
assumed. From other parameters it
can be assumed that as a minimum the brains,
heart, liver, kidney, testis and were
examined.
Feeding of 0.5 % led to prolongation ofsurvival compared to controls. In addition a
so-called "Alters Paarung" after 48 weeks gave
no influence on start of menopause.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(105)

Remark:Result:Reliability:

Flag:
14-FEB-2002

Type:
Sub-chronic
Species:rat
Strain:no data
Route of administration: oral feed
Exposure period:
28 days
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Sex: maleOECD SIDS
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SUBSTANCES ID: 65-85-0

Frequency of treatment:
Post exposure period:
Doses:

continuously in dietnoControl Group:
NOAEL:

760, 3800 or 7600 ppm (approx. 65, 324.1 or
647.5 mg/kg/day)
yes
647.5 mg/kg bw

Method:GLP:Test substance:otherno dataother TS: benzoic acid; purity not noted

Remark:10 rats/group; initial body weight: 120 gmean feed consumption: 85.5; 85.3 or
85.2 g/kg/d
no deaths or signs of intoxication duringexperiment, no significant gross pathologicallesions at autopsy(2) valid with restrictions
Meets generally accepted scientific standards,
Well documented and acceptable for assessment
Critical study for SIDS endpoint(4)

Result:Reliability:

Flag:
14-FEB-2002

Species:
rabbitSex: male/female
Strain:New Zealand white
Route of administration: dermal
Exposure period:
21 daysFrequency of treatment: 5 days/week for 3 weeks
Doses:
100, 500, 2500 mg/kg bw
Control Group:
yes, concurrent vehicle
NOAEL:

2500 mg/kg bw

GLP:
Test substance:yesother TS: benzoic acid, purity not noted

Method:Four male and four female rabbits were used ineach treatment group and in the control group.
The skin of one-half of the animals wasabraded and the others left intact.
Benzoic acid was applied 5 days a week for 3
weeks at dosage levels of 100, 500, 2500 mg/kg
bw.
The rabbits were observed daily for signs ofdermal irritation and changes in generalbehavior and appearance. Individual bodyweights were recorded weekly. Hematologic andbiochemical studies were conducted once in thepretest period and again
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Result:Reliability:

Flag:
14-AUG-2001

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
at 21 days of the study. Gross andhistopathology was performed on liver,kidneys, thyroid/parathyroid, heart,
lung, ovaries, testes, adrenals as well as
most gastrointestinal tract and neurologicalorgans.
Very slight dermal irritation was noted for
one rabbit at the 2500 mg/kg dosage level.
No compound-related effects were seen ingeneral behavior and appearance, body weight,
clinical laboratory tests, organ weights, or
survival.
(1) valid without restriction
Meets generally accepted scientific method andis described in sufficient detail
Critical study for SIDS endpoint
(106)

Type:
Sub-chronic
Species:rat
Sex: male/female
Strain:Sprague-Dawley
Route of administration: inhalation
Exposure period:
4 weeks
Frequency of treatment: 6 h/d; 5 d/w
Post exposure period:
none
Doses:
0, 25, 250, 1200 mg/m3
Control Group:
yes
NOAEL:
25 mg/m³
LOAEL:
250 mg/m³
Year:
GLP:
Test substance:

1981
yes
other TS: technical grade benzoic acid

Method:Four groups of rats (10 animals/sex/group)
were exposed to a dust aerosol of benzoic acidat concentrations of 0, 25, 250, 1200 mg/m3,
6 hrs/day, 5 days/week, 4 consecutive weeks.
The animals were observed twice daily,
pharmacotoxic signs observed weekly, and theirbody weights recorded prior to exposure andweekly thereafter.
Animals found in a moribund condition were sacrificed. After 4
weeks of exposure, all surviving animals were
necropsied and biochemical, hematologic, organ
weights and histopathlogic evaluations wereconducted.

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Result:No compound-related gross lesions were seen in
any animal from any dose group.
Compound-related microscopic lesions,consisting of an increase of inflammatory cell
infiltrate and an increase in the incidence,
intensity, and extent of interstitial fibrosis
in lungs of rats from all dose groups (but notdose related), were observed.
1200 mg/3: 1 animal/sex died; decreased bodyweight; decrease in platelets; decreased
absolute and relative weights of liver (m) andtrachea/lung (f); no significant difference inbiochemical parameters.
>/= 250 mg/m3: upper respiratory tract
irritation, decreased absolute and relative
weights of kidney (f).
0 - 250 mg/m3: No deaths; no effects on weight
gain; no significant effects on organ weights,
biochemical or hematologic parameters.
Test condition:
The concentration was generated as a dust
aerosol with an IRAD dust generator.
The test material (white flakes) was ground in
an Oster blender to produce a more respirable
particle. Actual exposure concentration wasdetermined by gravimetric techniques.
Particle size distribution was determinedusing Andersen 8 stage cascade impactor.
Average particle size was 4.7um.
Reliability:(1) valid without restriction
Meets generally accepted scientific method andis described in sufficient detail
Flag:
Critical study for SIDS endpoint
14-FEB-2002(107)
Species:mouse
Sex: male/female
Strain:other: cross bred white mice
Route of administration: gavage
Exposure period:
12 weeks
Frequency of treatment: once daily
Post exposure period:noDoses:
80 mg/kg/day
Control Group:yes
Test substance:other TS: analytical grade benzoic acid

Method:50 mice/sex (initial body weight: 8-10 g)
received benzoic acid by oral intubation.
Observations for general condition, behavior,survival, food consumption, and weight gain
were recorded daily.
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Result:Reliability:
Flag:
14-AUG-2001

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
reduced weight gain without reduced foodintake; mortality rate at week 10: 32 % inmales and females(3) invalid
No histopathology or clinical chemistry
Critical study for SIDS endpoint(108)

Species:rat
Sex: male
Strain:WistarRoute of administration: oral feed
Exposure period:
5 daysFrequency of treatment: continuously in diet
Post exposure period:
19 or 30 days
Doses:
3 % in diet (approx. 2250 mg/kg/day)Control Group:yesRemark:Result:Flag:
14-AUG-2001

15 rats; initial body weight: 60 g
the mean compound consumption was calculated
according to Lehman, A.J., Assoc. Food Drug
Off. Q. Bull. 18, 66 (1954)
growth retardation; histologicallydemonstrable brain damage (necrosis ofparenchymal cells of the stratum granulosum of
the fascia dentata and the cortex of thelobus piriformis) still present after 35 days
Critical study for SIDS endpoint(109)

Species:rat
Sex: male/female
Strain:WistarRoute of administration: oral feed
Exposure period:
72 weeks
Frequency of treatment: continuously in diet
Post exposure period:
no data
Doses:
1.5 % in diet (approx. 1125 mg/kg/day)Control Group:yesRemark:Result:14-AUG-2001

98

20 m + 30 f (dosed group), 13 m + 12 f
(control); initial body weight: 50-60 g
the mean compound consumption was calculated
according to Lehman, A.J., Assoc. Food Drug
Off. Q. Bull. 18, 66 (1954)
reduced food intake, growth retardation,
increased mortality rate (15/50 vs. 3/25 in
the control)(110)

UNEP PUBLICATIONSOECD SIDS
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SUBSTANCES ID: 65-85-0

Species:rat
Sex: male
Strain:WistarRoute of administration: oral feed
Exposure period:
7 - 35 days
Frequency of treatment: continuously in diet
Post exposure period:noDoses:
1.1 % in diet (approx. 825 mg/kg/day)Control Group:yesRemark:Result:15-JAN-2001

5-10 rats/groupthe mean compound consumption was calculated
according to Lehman, A.J., Assoc. Food Drug
Off. Q. Bull. 18, 66 (1954)
reduced food intake, growth retardation, no
pathological findings(109)

Species:rat
Sex: male
Strain:WistarRoute of administration: oral feed
Exposure period:
5 daysFrequency of treatment: continuously in diet
Post exposure period:noDoses:
3 % in diet (approx. 2250 mg/kg/day)Control Group:yesRemark:Result:15-JAN-2001

5-10 rats/group; initial body weight: approx.
60 g the mean compound consumption was
calculated according to Lehman, A.J., Assoc.
Food Drug Off. Q. Bull. 18, 66 (1954)
after 4-5 days disorders of central nervous
system:excitation, ataxia, tonoclonic
convulsions; after 3-5 days brain damage wasdemonstrable histologically (necrosis ofparenchymal cells of the stratum granulosum of
the fascia dentata and the cortex of the lobus
piriformis)(109)

Species:rat
Sex: male/female
Strain:WistarRoute of administration: oral unspecified
Exposure period:
72 weeks
Frequency of treatment: once daily
Post exposure period:noDoses:
40 mg benzoic acid/kg/day and 80 mg
sodium bisulphite/kg/day
Control Group:
yes
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Test substance:other TS: analytical grade

Remark:50 rats/sex; initial body weight: 100-120 g;
test
reduced weight gain, kidney function and thereaction on stress factors were altered (nofurther information); the erythrocyte
sedimentation rate was increased(108)

Result:14-AUG-2001

Species:rat
Strain:WistarRoute of administration: oral unspecified
Exposure period:
72 weeks
Frequency of treatment: once daily
Post exposure period:
no data
Doses:
40 mg/kg/day
Control Group:yesRemark:Result:15-JAN-2001

Sex: male/female

10 rats/sex; initial body weight: 100-120 g;
test substance: analytical grade
the rats developed some tolerance to a single
add. application of 4000 mg sodium benzoate/kg
given terminally, the mortality rate was 25 %(108)

Species:mouse
Strain:no data
Route of administration: gavage
Exposure period:
12 weeks

Sex: male/female

Frequency of treatment:
Post exposure period:

once dailynoDoses:

80 mg benzoic acid/kg/day and 160 mg
sodium bisulphite/kg/day
yesControl Group:

Remark:Result:15-JAN-2001

100 mice/group; initial body weight: 8-10 g;test substance: analytical grade
reduced weight gain without reduced foodintake; mortality rate at week 10: 70 % inmales and 62 % in females(108)

Species:mouse
Strain:no data
Route of administration: oral unspecified
Exposure period:
68 weeks
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Sex: male/female

OECD SIDS
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SUBSTANCES ID: 65-85-0

Frequency of treatment:
Post exposure period:
Doses:
Control Group:
Remark:Result:15-JAN-2001(108)

once daily
no data
40 mg/kg/day
yes

25 mice/sex (initial body weight 10-15 g) or
25 mice/sex (initial body weight 16-20 g) were
tested; test substance: analytical grade
no effects were reported(108)

Species:mouse
Sex: male/female
Strain:no data
Route of administration: oral unspecified
Exposure period:
68 weeks
Frequency of treatment: once daily
Post exposure period:
no data
Doses:
40 mg benzoic acid/kg/day and 80 mg
sodiumbisulphite/kg/day
Control Group:yesRemark:25 mice/sex (initial body weight 10-15 g) or
25 mice/sex (initial body weight 16-20 g) were
tested; test substance: analytical grade

Result:reduced weight gain without reduced foodintake; mortality rate at week 32: 56-65 % inmales and 45-72 % in females

15-JAN-2001(108)

Species:cat
Strain:no data
Route of administration: oral feed
Exposure period:
15 daysFrequency of treatment: continuously in diet
Post exposure period:
no data
Doses:
100 or 200 mg/kg/day
Control Group:yesRemark:Result:15-JAN-2001
Species:
Strain:Sex: male

4 cats/group were tested; initial body weight:
1.7-2.27 kg
no effects were observed
(111)
cat
no data
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SUBSTANCES ID: 65-85-0

Route of administration: oral feed
Exposure period:
3-4 daysFrequency of treatment: continuously in diet
Post exposure period:
no data
Doses:
0.5 % in diet (approx. 300-420 mg/kg/day)Control Group:yesRemark:Result:15-JAN-2001

4 cats were tested; initial body weight:
1.42-2.0 kg
convulsions, hyperaesthesia, apprehension,
swollen hepatocytes with infiltrations ofmacrophages and fibroblasts, swollen kidney
tubules, no pathological findings in brain andspinal cord; mortality: 2/4(111)

Species:cat
Strain:no data
Route of administration: oral feed
Exposure period:
23 daysFrequency of treatment: continuously in diet
Post exposure period:
no data
Doses:

0.25 % in diet (approx. 130-160
mg/kg/day)yesControl Group:
Remark:Result:15-JAN-2001

Sex: male

4 cats were tested; initial body weight: 3.24.0 kg
no effects were observed(111)

5.5 Genetic Toxicity 'in Vitro'
Type:
System of testing:Concentration:
Metabolic activation:
Result:Salmonella typhimurium reverse mutation
assay
TA 98, TA100, TA 1535, TA1537, TA1538
0, 20, 100, 500, 1000, 2000ug/platewith and without
negative

Method:Year:
GLP:
Test substance:

OECD Guide-line 471
1983
no dataother TS: technical grade benzoic acid

Reliability:(1) valid without restriction
Guideline study

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Flag:
14-FEB-2002

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
Critical study for SIDS endpoint
(112)

Type:
other: Sister chromatid exchange
System of testing:human lymphocytes
Concentration:
0 to 2.0 mM
Cytotoxic Concentration: no data
Metabolic activation:
without
Result:negative
Method:Year:
Test substance:other: similar to OECD Guide-line 479
1986other TS: benzoic acid, purity = 99%(estimated by NMR)

Reliability:(2) valid with restrictions
Comparable to Guideline study with acceptable
restrictions
Critical study for SIDS endpoint

Flag:
14-AUG-2001

(113)

Type:
System of testing:other: Sister chromatid exchange
human lymphoblastoid cells transformed by
Epstein- Barr virus (NL2, NL3, NL4)

Concentration:
0.001, 0.003, 0.01, 0.03 M
Cytotoxic Concentration: 0.03 M
Metabolic activation:
without
Result:negative
Method:Year:
Test substance:

OECD Guide-line 479
1986other TS: benzoic acid purchased from Kanto
Chemical Co.,Tokyo, Japan

Test condition:
Reliability:

Test done only without metabolic activation.
(2) valid with restrictions
Guideline study with acceptable restrictions
Critical study for SIDS endpoint
(114)

Flag:
14-AUG-2001
Type:
System of testing:Concentration:
Metabolic activation:
Result:
Test substance:other: Chromosomal aberration test
Chinese hamster fibroblast cell line
(CHL)
up to 10 mg/plate
without
ambiguous

other TS: benzoic acid, >99% pure
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Method:BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Reliability:

The study was carried out using a Chinese
Hamster fibroblast cell line (CHL) which were
exposed to the test substance at one of threedose levels for 24 and 48 hr.
No metabolic activation systems were applied.
Chromosome preparations were made following
treatment with Colcemid. A hundred well-spread
metaphases were observed per plate and theincidence of polyploid cells and cells withchromosome aberrations was recorded.
At 48 hr, there was an incidence of 1%
polyploid cells and 8% cells with structuralaberration (incidence between 5-9.9% isconsidered equivocal).
(2) valid with restrictions

Flag:
14-FEB-2002

Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(115)

Result:Type:

Bacillus subtilis recombination assay

System of testing:
Metabolic activation:
Result:Bacillus subtilis H17, M45
no datapositive

Test substance:

no data

Method:An overnight culture of B. subtilis, H17 andM45, was mixed with test solutions andincubated for 30 minutes at 37 degree C.
After treatment viable cells were counted andthe ratio of 50% survival concentrations were
calculated.
Result:Benzoic acid showed DNA damaging potential
although it had been negative in the Ames
test.
Reliability:(4) not assignableinsufficient documentation (abstract only)
Flag:
Critical study for SIDS endpoint
06-JUN-2001
(116)
Type:
other: Salmonella microsome assay
System of testing:S. typhimurium TA 98, TA 100, TA 1535,
TA 1536, TA 1537, TA 1538
Metabolic activation:with and without
Result:negative
Remark:12-JAN-2001
104

insufficient documentation(117)
UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

Type:
System of testing:
Metabolic activation:
Result:12-JAN-2001
Type:
System of testing:
Metabolic activation:
Result:other: Salmonella microsome assay
S. typhimurium TA 97, TA 98, TA 100,
TA 1535, TA 1537
with and without
negative(118)
other: Salmonella microsome assay
S. typhimurium TA 98, TA 100, TA 1535,
TA 1537
with and without
negative

11-JAN-2001

(119)

Type:
System of testing:
Metabolic activation:
Result:other: Mitotic recombination
Saccharomyces cerevisiae D3
with and without
negative

Remark:11-JAN-2001
Type:
System of testing:insufficient documentation

Metabolic activation:
Result:(117)
other: Chromosomal aberration test
Chinese hamster fibroblast cell line
(CHL)
without
ambiguous

11-JAN-2001

(120)

Type:
System of testing:
Metabolic activation:
Result:other: umu test
S. typhimurium TA 1535/pSK1002
with and without
negative

11-JAN-2001(121)

5.6 Genetic Toxicity 'in Vivo'
Remark:See IUCLID data set on sodium benzoate(CAS# 532-32-1).
Data on sodium benzoate reveal no in vivo
genotoxicity.
Therefore no in vivo genotoxicity study for
benzoic acid is indicated.

14-FEB-2002

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5.7 Carcinogenicity
Remark:Flag:
14-FEB-2002

See IUCLID data set on sodium benzoate(CAS# 532-32-1).
Data on sodium benzoate reveal no in vivo
genotoxicity.
Therefore no in vivo genotoxicity study for
benzoic acid isindicated.
Critical study for SIDS endpoint

5.8.1 Toxicity to Fertility
Type:Species:Sex:other: 4 generation study
ratmale/female

Strain:Route of administration:

no dataother: oral feed (first 8 weeks
paired feed technique; afterwards ad
libitum)
generation 1 and 2: lifelong;
generation 3: 16 weeks;
generation 4: until breeding
continuously in diet
0.5 or 1 % in diet (approx. 375 or
750 mg/kg/day)yes>= 750 mg/kg bw>= 750 mg/kg bw>= 750 mg/kg bw

Exposure Period:

Frequency of treatment:
Doses:
Control Group:
NOAEL Parental:
NOAEL F1 Offspring:
NOAEL F2 Offspring:
Year:
GLP:
Test substance:1960
noother TS: benzoic acid, purity not noted

Method:A robust protocol, according to standards atthat time, was used. Taking into account the
reputation of the investigators a high quality
has to be assumed.
40 (20 M = 20 F) rats/group; initial bodyweight:40-50 g.
The mean compound consumption was calculated
according to Lehman, A.J., Assoc. Food Drug
Off. Q. Bull. 18, 66 (1954).
In all 4 generations no influence on growth(weight, weight gain and food efficiency(measured by protein efficiency))and organ

Remark:Result:106

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5. TOXICITY

Reliability:

Flag:
14-AUG-2001

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
weights was found.
In all 4 generations, no effects on fertility("Forzplanzung")and lactation ("Aufzugt derJungen")was found. The animals of the 3rd
generation were sacrificed and examinedhistopathologically after 16 weeks (after
lactation of the pups.) No remarkable histopathological findings were found.
In the paper no information is given on theorgans investigated, however the robustness ofthe total study, the reputation of theinvestigators, as well as the reputationof the Professor who did the histopathologic
investigation, a high quality has to be assumed.
From other parameters it can be assumed that asa minimum the brains, heart, liver, kidney,testis and were examined.
Feeding of 0.5 % led to prolongation ofsurvival compared to controls. In addition a socalled "Alters Paarung" after 48 weeks gave noinfluence on start of menopause.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(105)

5.8.2 Developmental Toxicity/Teratogenicity
Species:femaleStrain:Route of administration:
Exposure period:
Frequency of treatment:
Duration of test:
Doses:
Control Group:
NOAEL Maternal Toxity:
NOAEL Teratogenicity:

rat

Sex:

Wistargavagesingle application
at day 9 of gestation
20 days
510 mg/kg
no510 mg/kg bw
510 mg/kg bw

Method:GLP:Test substance:other: Kimmel et al. (1971)
no dataother TS: benzoic acid, purity not noted

Method:Pregnant Wistar rats were treated on day 9 ofgestation with one dose of benzoic acid incarboxymethylcellulose. Animals were sacrificed
on day 20 of gestation and the uterus observed in
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situ for implantation and resorption sites. Livefetuses were removed, examined for grossmalformations, weighed, and prepared forhistological examination. Skeletal examination
was carried out under low magnification.

Remark:Result:Reliability:

Flag:
14-AUG-2001

Group I was dosed with 510 mg/kg.
Group II was dosed with 510 mg/kg; then 2 hlater: 250 or 500 mg/kg acetylsalicylic acid
Treatment with benzoic acid alone resulted in
no dead or resorbed implants and 3 % abnormal
survivors, rates comparable to the control
animals.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(122)

Species:
Strain:Route of administration:
Exposure period:
Frequency of treatment:
Duration of test:
Doses:
Control Group:
NOAEL Maternal Toxicity:
NOAEL Teratogenicity:
Year:

rat
Sex: male/female
no dataother: oral feed (first 8
weekspaired feed technique;generation 1 and 2: lifelong;
generation 3: 16 weeks;
continuously in dietlifelong
0.5 or 1 % in diet (approx. 375 or
750 mg/kg/day)yes>= 750 mg/kg bw
750 mg/kg bw

1960

Test substance:other TS: benzoic acid, purity not noted

Method:A robust protocol, according to standards atthat time, was used. Taking into account the
reputation of the investigators a high quality
has to be assumed.
The mean compound consumption was calculated
according to Lehman, A.J., Assoc. Food Drug
Off. Q. Bull. 18, 66 (1954).
The study demonstrated no effects on the dams
or on the growth and development of theoffspring.
(2) valid with restrictions
Meets generally accepted scientific standards,

Remark:Result:Reliability:
108

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Flag:
14-FEB-2002

Remark:BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
well documented and acceptable for assessment
Critical study for SIDS endpoint(105)

See IUCLID data set on sodium benzoate(CAS# 532-32-1).
Data on sodium benzoate reveal no in vivo
genotoxicity.
Therefore no in vivo genotoxicity study for
benzoic acid is indicated.

14-FEB-2002
5.8.3 Toxicity to Reproduction, Other Studies

5.9 Specific Investigations

5.10 Exposure Experience
Remark:23-OCT-1995
Remark:23-OCT-1995
Remark:23-OCT-1995
Remark:23-OCT-1995
Remark:Single oral doses of 1-1.5 g resulted indyspepsia, Nausea and vomiting.
(123)
A systemic inhibitory effect of UV light(UVA and UVB) on non-immunologic immediatecontact reactions to benzoic acid was foundin healthy volunteers.
(124)
Effects of infra-red and laser irradiation
were studied on non-immunologic immediatecontact reactions to benzoic acid.
The strength of the contact urticaria wasincreased.
(125)
Daily oral doses of benzoic acid of < 0.5 g
or sometimes up to 4 g/d did not induce
adverse effects in man.
(126)
Metabolism in humans:
Percutaneous absorption of 14C-labelled
benzoic acid (4 ug/cm2; area: 2.5 cm2) was
lower in aged subjects (> 65 years) than inyoung (18-40 years): cumulative doseabsorbed within 7 days was 19.5 vs. 36.2 %.
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23-OCT-1995

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
The diminished surface lipid content of oldskin implies a diminished dissolution
medium.
(127)

5.11 Additional Remarks
Type:

Metabolism

Remark:15-JAN-2001

The transdermal absorption of benzoic acid wasstudied in excised human skin and compared toabsorption in living man. In equivalent time,
the total absorption (% of applied dose) was
42.6 % (in vivo) or 44.9 % (in vitro).
(128)

Type:

Metabolism

Remark:23-OCT-1995

The percutaneous absorption and the excretionof benzoic acid were tested in female weanlingyorkshire swine (approx.20 kg) after topicaland intravenous administration.
After i.v. injection of 200 ug (10 uCi)/pig
84.5 % of 14C-activity were excreted with urine
and 4.6 % in faeces within 6 days; theradiolabel recovery in carcass was 0.1 %.
After topical application of the same dose theradiolabel recovery within 6 days (% of applieddose) was in urine 20 %, faeces 2.9 %,carcass 0.8 %, border 40.2 %, dosed skin 12.2 %and adjacent skin 9.1 %.
(129)

Type:

Metabolism

Remark:A concentration of 4 ug/cmE+2 of 14C-labelled
benzoic acid was applied to the shaved backs
of guinea pigs. The percutaneous absorption
was determined from urinary and fecal
excretion. Absorption of benzoic acid was
similar to published human absorption data (nofurther information).
The percutaneous absorption of 14C-labelled
benzoic acid was studied in the Mexican
hairless dog and compared to human data. Total
absorption and maximum absorption rates
were greater in humans than in hairless dogs.
Surface counting experiments showed that
benzoic acid persisted on the dog skin far

110

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SUBSTANCES ID: 65-85-0

23-OCT-1995

longer than on human skin (no further
information). The percutaneous absorption ofincreasing topical doses of benzoic acid wasdetermined in the Rhesus monkey and humans(dosage: 4, 40, 2000 ug/cmE+2;
dose absorbed: monkey 59.2 %, 3.6 %, 17.4 %;human 42.6 %, 25.7 %, 14.4 %).
In vivo percutaneous absorption was similar,
also the dose-response curve was similar in
the two species (no further information).
(130)

Type:

Metabolism

Remark:Damaging the skin (tape stripping, irritation,
delipidization) increased absorption of
benzoic acid dissolved in acetone (200 ug/ml,
50 uCi; topical application: 4 ug/cm2) inhairless guinea pigs:
71.1/73.4/94.1 % vs. 34.2 % absorbed in thegroup with intact skin.
(131)
Metabolism

23-OCT-1995
Type:
Remark:The effect of topical application of benzoic
acid on the in vivo percutaneous absorption wastested in 4 rhesus monkeys.
Daily applications of 4 ug/cmE+2 were given for
14 days, the 1st and the 8th application used
14C-labelled test substance.
To quantify absorption, urine was collected andassayed for radioactivity.
The penetration results are expressed as thepercentage of the applied dose absorbed,
i.e. (% of topical dose eliminated in urine / %of i.v. dose eliminated in urine)*100. After
1st dose 85 % and after 8th dose 89 % were
found. No significant change in percutaneousabsorption from that following the initial dose
was observed following the 8th dose of amultidose regimen.

23-OCT-1995

(132)

Type:

Metabolism

Remark:In vitro, the permeation of benzoic acid wasmeasured across isolated stratum corneum,
stratum corneum and epidermis, and splitthickness skin. The stratum corneum was shown
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SUBSTANCES ID: 65-85-0

23-OCT-1995

to be the rate limiting barrier and the flux
was proportional to the concentration of theundissociated compound.
(133)

Type:

Metabolism

Remark:The percutaneous absorption and metabolism of
benzoic acid was determined through hairless
guinea pig skin in vitro.
The absorption within 48 h was greater throughnonviable skin (60.1 % of applied dose) than
through viable skin(49.5%). 6.9 % of absorbed
dose (2 ug/cm2) were conjugated with glycine
to form hippuric acid.

23-OCT-1995

(134)

Type:

Metabolism

Remark:After s.c. administration of radiolabelled
benzoic acid to maternal rats it was found,that the acidic compound penetrated theplacental barrier readily. The fetal t1/2
values were in general lower than those forthe corresponding maternal tissues. The fetal
blood-brain barrier was penetrated more
readily than the adult one for the tested
compound.

14-AUG-2001
Remark:(135)
After a single i.p. injection of 410 umol 14Clabelled benzoic acid/kg to female Wistar rats
90 % of the applied 14C-activity was excreted
in urine and 1.3 % in bile within 3 hours,
mainly as hippuric acid. After 24 hours theexcretion was approx. 100 %.

23-OCT-1995
Remark:112(136)
Benzoic acid is detoxicated by some mammalian
species mainly by conjugation with glycine toform hippuric acid. There is a marked species
difference in the efficiency of the process.
After an oral dose of 50 mg 14C-benzoic acid most
species excreted 50-100 % of radioactivity in theurine within 24 hours. In the turtle and gecko
excretion was slower (39 % in 3 days).
UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
In herbivorous and omnivorous species (rhesus,
squirell and capuchin monkeys, pig, rabbit,
rat, mouse, guinea pig, hamster, lemming, gerbil)
benzoic acid was excreted in the urine almost
entirely as hippuric acid, though 10-20 % of thetotal 14C-activity appeared as free benzoic acidin pigs and squirell monkeys within 24 hours,
possibly as a result of the decomposition of
benzoyl glucuronide. In the 2 men given 1 mg
benzoic acid/kg, almost all the urinary
metabolite was hippuric acid, with 97 % of
the radioactivity excreted within 4 hours andvirtually 100 % within 12 hours.
In the carnivorous animals tested (dog, cat,ferret) the main metabolite was hippuric acid,with the dog and ferret excreting also somebenzoyl glucuronide. In the hedgehog, aninsectivore, a similar excretion occurred.
The Indian fruit bat (Pteroptus gigantus)
excreted 70-80 % of benzoic acid as the
glucuronide and the remainder as freeacid within 24 hours. The pigeon excreted mainly
hippuric acid and in the chick, turtle and gecko
the major metabolite was ornithuric acid. Whenthe dose of benzoic acid in the ferret was raised
to 200 and 400 mg/kg, the proportion excreted as
glucuronide was markedly increased. During themetabolism of benzoic acid, the relative amountof conjugation with glycine and with glucuronic
acid varies from species to species and may
depend to some extend upon the magnitude of thedose.

14-AUG-2001
Remark:(137)
In many species, benzoic acid is rapidly
absorbed, conjugated with glycine and excreted
as hippuric acid.
There appears to be no accumulation of benzoic
acid at low doses, but one limiting factor in
the biosynthesis of hippuric acid is theavailability of glycine: once the glycine poolis exhausted (after application of highdoses), an additional metabolite, benzoyl
glucuro- nide, is excreted in the urine ofsome species (no further information
available).

14-AUG-2001(138)
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Remark:BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

5 days after i.p. injection of 1 ml (4 ug)
labeled benzoic acid in saline to female
hairless guinea pigs, 92.1 % of theadministered dose was excreted in urine.

14-AUG-2001
Remark:(131)
In most animals, the conversion of benzoic
acid to hippuric acid has been found to occur
in kidney, with conversion possible in theliver when kidney malfunction exists. The
monkey metabolized benzoic acid only in theliver (no further information available).

14-AUG-2001
Remark:14-AUG-2001
Remark:(139)
After a single i.v. injection of 2.0 to 2.2 mg
13C-labelled benzoic acid/kg to male Wistar
rats 85 - 99 % of the applied 13C-activity was
excreted as hippuric acid in urine within 120
minutes after application.
(140)
In an in vitro study, the nitrosation of
methylurea to form N-nitrosomethylurea by
benzoic acid at a concentration of 10, 50 or
100 mM was not reduced (101, 108 or 102-110 %compared to control).

14-AUG-2001
Remark:(141)
Regional differences in percutaneousabsorption of benzoic acid were tested invitro (face, abdomen, back, forearm,tigh, lower leg, dorsal food, dorsal hand,palm and sole).
A trend of increasing permeability fromtruncal to acral sites was observed(exception: palmar/plantar skin).

23-OCT-1995
Remark:114(142)
Benzoic acid was positive in the microsomal
degranulation assay, if microsomes wereprepared at low 'g' force (10000).

UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
In the test with rough endoplasmatic reticulum
prepared at high 'g' forces (>= 105000) it was
negative. The degranulation assay tests theability of a chemical to dissociate polysomes
and ribosomes from the endoplasmatic
reticulum.

14-AUG-2001
Remark:(143)
Benzoic acid (purity 99,9 %; 2 % solution inphosphate buffered saline) was administeredi.v. (jugular catheter) to two male F 344 rats
at approx. 2 mg/l for a total dose of 108 mg.
The substance caused no neuroexcitation.

14-AUG-2001
Remark:14-AUG-2001
Remark:14-AUG-2001(144)
The application of benzoic acid (1 % in diet[approx. 450-890 mg/kg/d]) for 1 day to 4 malecats (initial body weight: 1.06- 1.70 kg)
resulted in convulsions, aggression,
hyperaesthesia, swollen hepatic cells withcentrilobular vacuolation, infiltration of
inflammatory cells, and marked distension of
the kidney glomeruli. No pathologicalfindings in brain and spinal cord.
Mortality: 1/4
control group: yes(111)
Other: In a screening with COMPACT (computeroptimized molecular parametric analysis ofchemical toxicity) benzoic acid was predicted
as a potential substrate for cytochrome P450
IIE.
(145)

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6. ANALYT.METH.FOR DETECTION AND IDENTIFICATIONDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
6.1 Analytical Methods

6.2 Detection and Identification

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7. EFF AGAINST TARGET ORG.AND INTENDED USESBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

7.1 Function

7.2 Effects on Organisms to be Controlled

7.3 Organisms to be Protected

7.4 User

7.5 Resistance

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8. MEAS. NEC. TO PROT. MAN, ANIMALS, ENVIRONMENTDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0
8.1 Methods Handling and Storing

8.2 Fire Guidance

8.3 Emergency Measures

8.4 Possib. of Rendering Subst. Harmless

8.5 Waste Management

8.6 Side-effects Detection

8.7 Substance Registered as Dangerous for Ground Water

8.8 Reactivity Towards Container Material

118

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9. REFERENCES

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(1) CRC Handbook of Chemistry and Physics. 1999. David R.
Lide,ed. CRC Press, New York. p 3-69, #2475.
(2) Maki, T. & Suzuki, Y., Ullmann's encyclopedia ofindustrial chemistry, Vol. A3, VCH Verlagsgesellschaft
mbH, Weinheim, 555-569 (1985)(3) Neumueller, O.-A., Roempps Chemie-Lexikon, 8.
neubearbeitete und erweiterte Auflage, Franckh'sche
Verlagshandlung, Stuttgart, S. 400 u. 2728 (1987)(4) Bio-Fax, Benzoic acid, Industrial Bio-Test Laboratories,
Inc., Northbrook, Ill., Data Sheet No. 28-4/73 (1973)(5) Windholz, M. et al., The Merck Index. An encyclopedia ofchemicals, drugs, and biologicals, 10th ed. Sodium
Benzoate, Merck & Co., Inc., Rayway, N.J., U.S.A., 1230
(1983)(6) Auer Technikum, Ausgabe 12, Auergesellschaft GmbH,
Berlin,123-127 (1974)(7) Jordan, T.E., Vapor pressure of organic compounds,
Interscience Publishers Inc., New York, 124-130, 136(1954)(8) Stull, D.R., Ind. Eng. Chem. 39, 517-540 (1947)(9) Berthod, A. et al., J. Liq. Chromatogr. 11, 1441-1456(1988)(10) Leo, Hansch: A. Leo, CLOGP-3.63 (1991) Daylight,
ChemicalInformation Systems, Inc. Irvine, CA, USA(11) Kramer, C.-R. & Henze, U., Z. Physiol. Chem. 271, 503-513(1990)(12) Fujita, T. et al., J. Am. Chem. Soc. 86, 5175-5180 (1964)(13) Pal, A. & Lahiri, S.C., Indian J. Chem., Sect. A 28,
276-279 (1989)(14) Safety Data Sheet Bayer AG of 18.06.93(15) DSM data.

UNEP PUBLICATIONS

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BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(16) Niazi, M.S.K. et al., J. Solution Chem. 19, 623-638(1990)(17) Briegleb, G. & Bieber, A., Z. Elektrochem. 55, 250-259(1951)(18) Serjeant, E.P. & Dempsey, B., IUPAC Chemical data series
23, Ionisation constants of organic acids in aqueous
solution, Pergamon Press, Oxford, 262-265 (1979)(19) Bayer AG data
(20) Matthews, R.W., Water Res. 24, 653-660 (1990)(21) Meylan W. and Howard P. 1999. EPIWin Modeling Program.
Syracuse Research Corporation. Environmental Science
Center, 6225 Running Ridge Road, North Syracuse, NY
13212-2510(22) Sadtler (1966), Sadtler Research Laboratories Inc.,
Benzoic acid(23) Freitag, D. et al., Chemosphere 14, 1589-1616 (1985)(24) Kinney, I.C. & Ivanuski, V.R., Photolysis mechanisms forpollution abatement, U.S. Department of the Interior,
Cincinnati, Ohio (1969)(25) Sekya, T et. al., Colloid. Polym. Sci. 266, 1037-1041(1988)(26) Lokke H.
(1984)

Water, Air, and Soil Pollution. 22: 373-387.

(27) Zahn, R. & Wellens, H., Z. Wasser Abwasser Forsch. 13,1-7(1980)(28) Horowitz, A. et al., Dev. Ind. Microbiol. 23, 435-444(1982)(29) Shelton D.R. and Tiedje J.M.
47(4):850-857. (1984)

Appl. Environ. Microbio.

(30) Belly R.T. and Goodhue C.T. Proceedings of theInternational Biodegradation Symposium. 3:1103-1107(1976)

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BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(31) Buzzell, J.C., Jr. et al., Behavior of organic chemicals
in the aquatic environment, Part II - Behavior in dilute
systems, Manufacturing Chemists Association, Washington,
D.C. (1968)(32) Urano, K. & Kato, Z., J. Hazard. Mater. 13, 147-159(1986)(33) Lutin, P.A. et al., Purdue Univ. Eng. Bull. Ext. Series
118, 131-145 (1965)(34) Marion, C.V. & Malaney, G.W., Proc. 18th Ind. Waste
Conf., Eng. Bull. Purdue Univ., Eng. Ext. Ser., 297-308(1964)(35) Pitter, P., Water Res. 10, 231-235 (1976)(36) Haller, H.D., J. Water Pollut. Control Fed. 50, 2771-2777(1978)(37) Rubin, H.E. et al., Appl. Environ. Microbiol. 43, 11331138 (1982)(38) Matsui, S. et al., Water Sci. Technol. 20, 201-210 (1988)(39) Lund, F.A. & Rodriguez, D.S., J. Gen. Appl. Microbiol.
30, 53-61 (1984)(40) Healy, J.B., Jr. & Young, L.Y., Appl. Environ. Microbiol.
38, 84-89 (1979)(41) Birch, R.R. et al., Chemosphere 19, 1527-1550 (1989)(42) Nottingham, P.M. & Hungate, R.E., J. Bacteriol. 98,
1170-1172 (1969)(43) Jaroszynski, T. & Gomolka, E., Environ. Prot. Eng. 5,375-386 (1979)(44) Federle, T.W., Can. J. Microbiol. 34, 1037-1042 (1988)(45) Lu, P.-Y. & Metcalf, R.L., Environ. Health Perspect. 10,
269-284 (1975)(46) Mailhot, H., Environ. Sci. Technol. 21, 1009-1013 (1987)

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SUBSTANCES ID: 65-85-0(47) Branson, D.R., In: Cairns, J., Jr., et al. (eds.)
Estimating the hazard of chemical substances to aquatic
life, American Society for Testing and Materials, 55-70(1978)(48) Ward, T.E., Environ. Toxicol. Chem. 4, 727-737 (1985)(49) Takemoto, S. et al., Jpn. J. Water Poll. Res. 4, 80-90(1981)(50) Patel, K.S. & Desai, S.B., Chem. Era 15, 8-9 (1979)(51) Kawamura, K. & Kaplan, I.R., Wat. Res. 24, 1419-1423(1990)(52) Haider, K. et al., Arch. Microbiol. 96, 183-200 (1974)(53) Alexander, M. & Lustigman, B.K., J. Agric. Food Chem. 14,
410-413 (1966)(54) Unpublished study (UCES#11506-03-85). The acute toxicity
of benzoic acidc(technical grade)to the Bluegillsunfish,
Lepomis macrochirus Rafinesque. (1979)(55) Unpublished study (UCES#11506-03-84). The acute toxicity
of benzoic acid to the Rainbow trout, Salmo gairdneri
Richardson. (1979)(56) Juhnke, I. & Luedemann, D., Z. Wasser Abwasser Forsch.
11, 161-164 (1978)(57) Ellis, M.M., Bull. Bur. Fish 48, 365-437 (1937)(58) Bringmann, G. & Kuehn, R., Z. Wasser Abwasser Forsch. 15:
1-6 (1982)(59) Unpublished study (UCES#11506-03-80). The acute toxicity
of benzoic acid (technical grade) to the water flea,
Daphnia magna Straus. (1979)(60) Bringmann, G. & Kuehn, R., Z. Wasser Abwasser Forsch. 10,
161-166 (1977)(61) Niemitz, W. et al., Wasser 8/72, Wasser 19/72,
Abschlussbericht Forschungsvorhaben, Wasser-, Boden- undLufthygiene des Bundesgesundheitsamtes, Berlin (1972)

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SUBSTANCES ID: 65-85-0(62) Stratton, G.W. & Corke, C.T., Environ. Pollut. 29, 71-80(1982)(63) Bringmann, G. & Kuehn, R., Z. Wasser Abwasser Forsch. 10,
87-98 (1977)(64) Bringmann, G. & Kuehn, R., Vom Wasser 50, 45-60 (1978)(65) Klecka, G.M. et al., Chemosphere 14, 1239-1251 (1985)(66) Kaiser, K.L.E. et al., In: Kaiser, K.L.E. (ed.) QSAR inenvironmental toxicology II, D. Reidel Publishing
Company, 153-168 (1987)(67) Bringmann, G. et al., Z. Wasser Abwasser Forsch. 13,
170-173 (1980)(68) Bringmann, G. & Kuehn, R., Water Res. 14, 231-241 (1980)(69) Bringmann, G. & Kuehn, R., Z. Wasser Abwasser Forsch. 13,
26-31 (1980)(70) Warth, A.D., Appl. Environ. Microbiol. 54, 2091-2095(1988)(71) Soni, G.L. & Bhatia, I.S., Indian J. Agric. Sci. 50,
772-777 (1980)(72) Wallhaeusser, K.H., Praxis der Sterilisation,Desinfektion- Konservierung, Keimidentifizierung - Betriebshygiene,
3. Aufl., Thieme Verlag, Stuttgart, 399-400 (1984)(73) Unpublished study (IRDC#163-282). Acute Toxicity Studies
in Rats and Rabbits. (1974)(74) Unpublished study (BRL#9348). Acute oral toxicity in miceadministered benzoic acid. (1979)(75) Fassett, D.W., in: Patty, F.A. (ed.) Industrial hygiene
and toxicology, 2nd rev. ed., Vol. II. Interscience
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Henschler, D. (ed.) Toxikologisch-arbeitsmedizinische
Begruendung von MAK-Werten, Benzoesaeure. VCH
VerlagsGmbH, Weinheim (1985)

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SUBSTANCES ID: 65-85-0(76) Marhold, J.V., Personal communication to the editor of
RTECS, VUOS 539-18, Cincinnati (1977); cited in: Henschler,
D. (ed.) Toxikologisch-arbeitsmedizinische Begruendung von
MAK-Werten, Benzoesaeure. VCH VerlagsGmbH, Weinheim (1985)(77) Abe, S. et al., Iyakuhin Kenkyu 15, 359-370 (1984)(78) McCormick, G.C. & Speaker, T.J., Toxicol. Appl.
Pharmacol. 25, 478 (1973); cited in: Henschler, D. (ed.)
Toxikologisch-arbeitsmedizinische Begruendung von
MAK-Werten, Benzoesaeure. VCH VerlagsGmbH, Weinheim(1985)(79) Moreno, O.M., Report to RIFM (1977); cited in: Opdyke,
D.L.J., Food Cosmet. Toxicol. 17, 715-722 (1979)(80) Caujolle, F. & Meynier, D., Compt. Rend. Hebdo. Des
Seances de l'Academie des Sciences 246, 851-852 (1958)(81) RCC NOTOX, Primary skin irritation/corrosion study ofbenzoic acid in the rabbit (study no. 0847/1083). RCC
NOTOX B.V., DD's-Hertogenbosch (1988)(82) Bayer AG, Untersuchung zur Haut- undSchleimhautvertraeglichkeit. Bayer AG, Wuppertal (1978)(83) Frosch, P.J. & Kligman, A.M., cited in: Drill, V.A. &Lazar, P. (ed.) Cutaneous Toxicity. Academic Press Inc.,New York, 127-154 (1977)(84) Frosch, P.J. & Kligman, A.M., Contact Dermatitis 2, 314324 (1976)(85) Sax, N.I., Dangerous properties of industrial materials,
6 th ed.. Van Nostrand Reinhold Co., New York (1984)(86) Larmi, E. et al., Contact Dermatitis 20, 38-40 (1989)(87) Kligman, A.M., Dermatol. Clin. 8, 57-60 (1990)(88) Ylipieti, S. & Lahti, A., Contact Dermatitis 21, 105-106(1989)(89) RCC NOTOX, Eye irritation/corrosion study of benzoic acidin the rabbit (study no. 0847/1084). RCC NOTOX B.V.,
DD's-Hertogenbosch (1988)

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BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(90) Suberg, H., Bayer AG data, Benzoesaeure DAB 8, Pruefung
auf primaer reizende/aetzende Wirkung am Kaninchenauge(1986)(91) Unpublished study (BRL #9347). Dermal sensitization study
in Guinea pigs with benzoic acid. (1979).
(92) Gad, S.C. et al., Toxicol. Appl. Pharmacol. 84, 93-114(1986)(93) Gerberick, G.F. et al., Fundament. Appl. Toxicol., 19,438-445 (1992)(94) Lahti, A. & Maibach, H.I., Toxicol. Appl. Pharmacol. 76,
219-224 (1984)(95) Nethercott, J.R. et al., J. Occ. Med. 26, 734-736 (1984)(96) Forsbeck, M. & Skog, E., Contact Dermatitis 3, 201-205(1977)(97) Baer, R.L. et al., Arch. Derm. 71, 19-23 (1955)(98) Broeckx, W. et al., Contact Dermatitis 16, 189-194 (1987)(99) Baird, K.A. & Saint John, N.B., J. Allergy 16, 195-198(1945)(100) Rademaker, M. & Forsyth, A., Contact Dermatitis 20, 104107(1989)(101) Malanin, G. & Kalimo, K., Clin. Exp. Allergy 19, 539-543(1989)(102) Pevny, I. et al., Dermatosen 29, 123-130 (1981)(103) Rosenhall, L. & Zetterstroem, O., Tubercle (Edinb.) 56,
168(1975); cited in: Henschler, D., Toxikologischarbeitsmedizinische Begruendung von MAK-Werten (1985)(104) Lewis, M.A.O. et al., Br. Dent. J. 166, 371-373 (1989)(105) Kieckebusch, W. & Lang, K., Arzneim.-Forsch. 10, 10011003 (1960)(106) Unpublished study (IRDC #163-675). 21-Day Dermal Toxicity
Study in Rabbits. (1981)

UNEP PUBLICATIONS

125OECD SIDS
9. REFERENCES

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(107) Unpublished study (IRDC#163-676). 4-week subacuteinhalation toxicity study of benzoic acid in rats with
amendment. (1981)(108) Shtenberg, A.J. & Ignat'ev, A.D., Food. Cosmet.
Toxicol. 8, 369-380 (1970)(109) Kreis, H. et al., Food Cosmet. Toxicol. 5, 505-511 (1967)(110) Marquardt, P., Arzneim.-Forsch. 10, 1033 (1960)(111) Bedford, P.G.C. & Clarke, E.G.C., Vet. Rec. 90, 53-58(1972)(112) Unpublished study (EGG#580-192-1-78).
Salmonella/Mammalian-microsome plate incorporation
mutagenesis assay of benzoic acid 99.5%. (1978)(113) Jansson, T. et al., Mutat. Res. 206, 17-24 (1988)(114) Tohda, H. et al., Cancer Res. 40, 4775-4780 (1980)(115) Ishidate M., Sofuni T., Yoshikawa K., Hayashi M., et al.
1984. Primary mutagenicity screening of food additives
currently used in Japan. Fd Chem. Toxic. 22(8):623-636.
(116) Nonaka, M., Environ. Mol. Mutagen. 14: 143 (1989)(117) Cotruvo, J.A. et al., Ann. N. Y. Acad. Sci. 298, 124-140(1977)(118) Zeiger, E. et al., Environ. Mol. Mutagen. 11, Suppl. 12,
1-158 (1988)(119) McCann, J. et al., Proc. Nat. Acad. Sci. U.S.A. 72,
5135-5139 (1975)(120) Ishidate, M., Jr. et al., Food Chem. Toxicol. 22, 623-636(1984)(121) Nakamura, S. et al., Mutat. Res. 192, 239-246 (1987)(122) Kimmel, C.A. et al., Teratology 4, 15-24 (1971)

126

UNEP PUBLICATIONSOECD SIDS
9. REFERENCES

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(123) Wiley, H.W., US Dept. Agr. Bur. Chem. Bull. No. 88,
p. 1043 (1908); cited in: Henschler, D. (ed.)
Toxikologisch-arbeitsmedizinische Begruendung von
MAK-Werten, Benzoesaeure. VCH VerlagsGmbH, Weinheim(1985)(124) Larmi, E., Acta Derm. Venereol. 69, 296-301 (1989)(125) Larmi, E. et al., Derm. Beruf Umwelt 37, 210-214 (1989)(126) Remsen, J., US Dept. Agr. Rep. No. 88 (1909); cited in:
Henschler, D. (ed.) Toxikologisch-arbeitsmedizinische
Begruendung von MAK-Werten, Benzoesaeure. VCH
VerlagsGmbH, Weinheim (1985)(127) Roskos, K.V. et al., J. Pharmacokinet. Biopharm. 17,
617-630 (1989)(128) Franz, T.J., J. Invest. Derm. 64, 190-195 (1975)(129) Carver, M.P. & Riviere, J.E., Fundam. Appl. Toxicol. 13,
714-722 (1989)(130) Maibach, H.I. & Wester, R.C., J. Am. Coll. Toxicol. 8,
803-813 (1989)(131) Moon, K.C. et al., Dermatologica 180, 8-12 (1990)(132) Bucks, D.A.W et al., Food Chem. Toxicol. 28, 129-132(1990)(133) Parry, G.E. et al., Pharm. Res. (N.Y.) 7, 230-236 (1990)(134) Nathan, D. et al., Pharm. Res. (N.Y.) 7, 1147-1151 (1990)(135) Maickel, R.P. & Snodgrass, W.R.,Toxicol. Appl. Pharmacol.
26, 218-230 (1973)(136) Hirom, P.C. et al., Xenobiotica 6, 55-64 (1976)(137) Bridges, J.W. et al., Food Cosmet. Toxicol. 9, 907-908(1971)UNEP PUBLICATIONS

127

OECD SIDS
9. REFERENCES

BENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0(138) Select Committee on GRAS Substances. Evaluation of thehealth aspects of benzoic acid and sodium benzoate as
food ingredients. US Food and Drug Administration Report.
NTIS Report No. PB-223837 (1973); cited in: Opdyke,
D.L.J., Food Cosmet. Toxicol. 17, 715-722 (1979)(139) Wan, S.H. & Riegelman, S., J. Pharm. Sci. 61, 1278-1284(1972); cited in: Opdyke, D.L.J., Food Cosmet. Toxicol.
17, 715-722 (1979)(140) Akira, K. et al., Anal. Biochem. 210, 86-90 (1993)(141) Yamamoto, M. et al., Food Addit. Contam. 5, 289-298(1988)(142) Lantz, D.M. et al., Clin. Res. 37, 756A (1989)(143) Gupta, M.M. & Dani, H.M., Toxicol. Lett. 30, 167-172(1986)(144) Mattsson, J.L. et al., Neurotoxicol. Teratol. 11, 71-75(1989)(145) Parke, D.V. & Lewis, D.F.V., Food Addit. Contam. 9, 561577 (1992)

128

UNEP PUBLICATIONSOECD SIDS
10. SUMMARY AND EVALUATIONBENZOATESDATE: 14-FEB.-2002
SUBSTANCES ID: 65-85-0

10.1 End Point Summary

10.2 Hazard Summary

10.3 Risk Assessment

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129

OECD SIDSBENZOATESI U C L I D D a t a S e t( SODIUM BENZOATE: CAS N°: 532-32-1)

Existing Chemical
CAS No.
EINECS Name
EINECS No.
TSCA Name
Molecular Formula

ID: 532-32-1
532-32-1
sodium benzoate
208-534-8
Benzoic acid, sodium salt
C7H6O2.Na

Producer Related Part
Company:
Creation date:

Bayer Corporation
21-OCT-1999

Substance Related Part
Company:
Bayer Corporation
Creation date:21-OCT-1999
Memo:

Bayer Corporation

Printing date:
Revision date:
Date of last Update:

10-AUG-2001

Number of Pages:

68

10-AUG-2001

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

130

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATIONBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

1.0.1 OECD and Company Information
Type:
Name:

Street:Town:
Country:lead organisation
American Chemistry Council (formerly Chemical
Manufacturers Association), Benzoates HPV
Panel
1300 Wilson Boulevard
22209 Arlington, VA
United States

09-AUG-2001
Type:
Name:
Country:

cooperating company
ATOFINA Chemicals, Inc.
United States

09-AUG-2001
Type:
Name:
Country:

cooperating company
Bayer Corporation
United States

09-AUG-2001
Type:
Name:
Country:

cooperating company
DSM Fine Chemicals
Netherlands

03-JAN-2001
Type:
Name:
Country:

cooperating company
Noveon, Inc.
United States

09-AUG-2001
Type:
Name:
Country:

cooperating company
Velsicol Chemical Corporation
United States

26-MAY-2000
1.0.2 Location of Production Site
1.0.3 Identity of Recipients

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131OECD SIDS
1. GENERAL INFORMATIONBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

1.1 General Substance Information
1.1.0 Details on Template
1.1.1 Spectra

1.2 Synonyms

1.3 Impurities

1.4 Additives

1.5 Quantity

1.6.1 Labelling
1.6.2 Classification

1.7 Use Pattern
1.7.1 Technology Production/Use

1.8 Occupational Exposure Limit Values

1.9 Source of Exposure

1.10.1 Recommendations/Precautionary Measures
1.10.2 Emergency Measures

1.11 Packaging

1.12 Possib. of Rendering Subst. Harmless

1.13 Statements Concerning Waste
132

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATIONBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

1.14.1 Water Pollution
1.14.2 Major Accident Hazards
Legislation:
Substance listed:
10-JUL-2000
1.14.3 Air Pollution
Classified by:Labelled by:
Number:Class of danger:
10-JUL-2000

1.15 Additional Remarks

1.16 Last Literature Search
Type of Search:
Date of Search:

Internal and External
07-SEP-1999

Remark:Only HPV endpoints: TOXLINE data base andinternal studies.

09-AUG-2001

1.17 Reviews

1.18 Listings e.g. Chemical Inventories

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OECD SIDS
2. PHYSICO DATA CHEMICALBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

2.1 Melting Point
Value:
Method:Remark:Reliability:
Flag:
09-AUG-2001
Value:
Method:Year:
Testsubstance:
Reliability:
Flag:
09-AUG-2001
Value:
Method:Remark:26-JAN-2001> 300 degree C
other: measured
Carbonisation at temperature > 500 degree C(2) valid with restrictions
Data from Handbook or collection of data
Critical study for SIDS endpoint(1) (2)330.6 degree C
other: (calculated) MPBPWIN (v1.31) Program;
Adapted Joback Method
1999
other TS: molecular structure(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(3)
410 - 430 degree C
other
DSM datasheet.

2.2 Boiling Point
Value:
Method:Year:
Testsubstance:
Reliability:
Flag:
09-AUG-2001

464.9 degree C
other: (calculated) MPBPWIN (v1.31) Program ;Adapted Stein and Brown Method
1999
other TS: molecular structure(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(3)

2.3 Density
Type:
Value:
Flag:
26-JAN-2001

134

relative density= 1.44 g/cm3
Critical study for SIDS endpoint(4) (5)

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO DATA CHEMICAL

Type:
Value:
Remark:Source:BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

bulk density
650 kg/m3
thickened
DSM Special Products B.V. GeleenECB –Existing Chemicals Ispra (VA)

26-MAY-2000
Type:
Value:
Remark:Source:(6)bulk density
350 kg/m3
not thickened
DSM Special Products B.V. GeleenECB –Existing Chemicals Ispra (VA)

26-MAY-2000(6)

2.3.1 Granulometry

2.4 Vapour Pressure
Value:
Method:Year:
Testsubstance:
Result:Reliability:
Flag:
09-AUG-2001.00000000489 hPa at 25 degree C
other (calculated): MPBPWIN (v1.31) Program;
Modified Grain Method
1999
other TS: molecular structure
3.67E-009 mm Hg; 4.89E-09 hPa(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(3)

2.5 Partition Coefficientlog Pow:
Method:Year:
Testsubstance:
Reliability:
Flag:
09-AUG-2001
log Pow:
Method:Year:
Testsubstance:-2.269other (calculated): Log Kow(version 1.65
estimate)1999
other TS: molecular structure(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(7)= -2.13other (calculated): CLogP
other TS: molecular structure

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OECD SIDS
2. PHYSICO DATA CHEMICAL

Remark:Reliability:
Flag:
23-MAR-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

Calculated according to C. Hansch et al 1985.
(2) valid with restrictions
Critical study for SIDS endpoint

2.6.1 Water Solubility
Value:
Method:Remark:Reliability:
Flag:
09-AUG-2001

556 g/l at 20 degree C
other
pH-value: about 8.
(2) valid with restrictions
Data from Handbook or collection of data
Critical study for SIDS endpoint(8) (9)

Value:
pH:
26-JAN-2001

630 g/l at 20 degree C
7

Remark:concentrated solutions react neutral
diluted solutions react weakly alkaline (pH 8)(10)

26-JAN-2001(6) (6)2.6.2 Surface Tension

2.7 Flash Point
Value:
Type:
Method:Year:
Reliability:> 100 degree C
closed cup
other: DIN 51758(1) valid without restriction
Meets National standards method (AFNOR/DIN)

09-AUG-2001(6)

2.8 Auto Flammability

2.9 Flammability

2.10 Explosive Properties
Result:Remark:09-AUG-2001
136

Can form explosive mixtures with air.

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO DATA CHEMICALBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

2.11 Oxidizing Properties

2.12 Additional Remarks
Remark:23-OCT-1995
Remark:At a rel. humidity of > 50% the salt ishygroscopic and it dissolves at r. F.-values >
85 %
(10)
UV spectrum lambda max (nm):225 (water; lg epsilon: n.a.)23-OCT-1995
Remark:23-OCT-1995(11)
pH value ca. 7.5 at 10 g/l water(6)

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3. ENVIRONMENTAL FATE AND PATHWAYSBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

3.1.1 Photodegradation
Type:
air
Conc. of subst.: at 25 degree C
INDIRECT PHOTOLYSIS
Sensitizer:
OH
Conc. of sens.: 1560000 molecule/cm3
Rate constant: .0000000000017775 cm3/(molecule * sec)
Degradation:
50 % after 72.2 hour(s)Method:other (calculated): AOP Program (v1.89)
Year:
1999
GLP:
Test substance:other TS: molecular structure
Reliability:(2) valid with restrictions
Accepted calculation method
Flag:
Critical study for SIDS endpoint
09-AUG-2001
Type:
Method:Year:
Test substance:
Remark:(3)

GLP:
See IUCLID on benzoic acid (CAS# 65-85-0); thephotodegradation of the sodium salt should be
similar.

09-AUG-2001
3.1.2 Stability in Water
Type:
Method:Year:
Test substance:
Remark:Flag:
26-JAN-2001

GLP:
Based on structure and organic chemistry rules(e.g. bonding in organic molecules, activationenergy, reactivity, transformations, addition,
substitution, elimination) no hydrolysis will
occur at pH ranges 4 - 11.
Critical study for SIDS endpoint

3.1.3 Stability in Soil

138

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

3.2 Monitoring Data (Environment)
Type ofmeasurement:
Medium:Method:Concentration
Remark:See IUCLID on benzoic acid (CAS# 65-85-0); thedata on the sodium salt should be similar.

09-AUG-2001
3.3.1 Transport between Environmental Compartments
Type:fugacity model level III
Media:
other: air - water - soil - sediment
Air (Level I):
Water (Level I):
Soil (Level I):
Biota (L.II/III):
Soil (L.II/III):
Method:other: EPIWin Modeling Program
Year: 1999
Result:Distribution
Half-Life
Emissions
Fugacity(percent)(hr)(kg/hr)(atm)
Air
1.45e-007
144
1000
4.83e-019
Water
45.3
360
1000
1.38e-020
Soil
54.6
360
1000
6.16e-019
Sediment
0.07551.44e+003
01.15e-020
Persistence Time: 421 hr
Reaction Time:520 hrAdvection Time:
2.21e+003 hr
Percent Reacted: 80.9
Percent Advected: 19.1
(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint

Reliability:
Flag:
09-AUG-2001(12)

3.3.2 Distribution

3.4 Mode of Degradation in Actual Use
Remark:In many species benzoic acid sodium salt is
rapidly absorbed and rapidly metabolized namely
conjugated with glycine and excreted as hippuric
acid in the urine.
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139

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

The substance is readily biodegradable, and isbiodegraded within chemical industry via a waste
water treatment plant.
09-AUG-2001

3.5 Biodegradation
Type:
Inoculum:
Concentration:
Degradation:
Result:
Method:Modified Sturm
Year:
Test substance:
Remark:Test condition:
Reliability:
Flag:
09-AUG-2001
Type:
Inoculum:
Concentration:
Degradation:
Method:Year:
Test substance:

Method:140

aerobic
activated sludge, domestic
50 mg/l related to Test substanceca. 90 % after 7 dayreadily biodegradable
OECD Guide-line 301 B "Ready Biodegradability:
Test (CO2 evolution)"
1981
GLP: no data
other TS: sodium benzoate, purity not noted
Sodium benzoate is the recommended "readily
biodegradable reference substance" for OECD
Guideline studies.
This endpoint has been studied several times
by several other investigators/groups and all
support the result of the study mentioned
above.
25 degree C(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(13) (14)anaerobic
other bacteria: anaerobic sewage, domestic andindustrial
50 mg/l related to DOC (Dissolved Organic
Carbon)93 % 7.5 after 7 dayother: see below
GLP: no data
other TS: technical grade sodium benzoate
purchased from Aldrich Chemical Co. , UK
2-3 g sludge plus sodium benzoate(concentration equivalent to 50 mg
Carbon/liter or 85 mg substance/l).
Controls and tests done in triplicate.
Temperature = 35 degree C.
Measured gas production (CH4 + CO2).

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Remark:Result:Reliability:

Flag:
09-AUG-2001
Type:
Inoculum:
Concentration:
Degradation:
Result:Testsubstance:

Method:Modified Sturm
Year:
Test substance:
Method:Reliability:
03-JAN-2001
Type:
Inoculum:
Concentration:
Method:Year:
Test substance:
Remark:BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

retard lag 2 d
Degradation is expressed as percentage oftheoretical methane production based on the
stoichiometry of degradation.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(15)
aerobic
other: suspension from marine aquarium filters
10 mg/l related to DOC (Dissolved Organic
Carbon)> 97 % after 28 dayreadily biodegradable
2 day
20 %
4 day
45 %
6 day
55 %
8 day
70 %
20 day85 %OECD Guide-line 301 B "Ready Biodegradability:
Test (CO2 evolution)"
1981

Guideline adapted to use seawater as test
medium and inoculum(1) valid without restriction(16)
anaerobic
other bacteria: anaerobic sewage, domestic,
2 weeks preincubatedrelated to Test substanceother: anaerobic degradation, static,
35 degree C, parameter:gasproduction
GLP:
concentration: 50/60/90 mg/l
degradation : 47/49/28 d = 60.5/82.7/74 %26-JAN-2001
Type:
Inoculum:
Contact time:
Degradation:
Result:GLP:(17)aerobic
domestic sewage, non-adapted
28 day84 % after 14 day
readily biodegradable
UNEP PUBLICATIONS141

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Testsubstance:
Method:Year:
Test substance:
Reliability:
19-MAY-2000

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

14 day84 %28 day92 %Directive 84/449/EEC, C.7 "Biotic degradation- modified MITI test"
1982
GLP:
other TS: purchased from Sigma Chemicals(1) valid without restriction
(17)

Type:
Inoculum:aerobic
other: microorganisms already present inseawaterConcentration:
11.6 mg/l related to DOC (Dissolved Organic
Carbon)Contact time:
61 dayDegradation:
80.5 % after 20 day
Result:readily biodegradable
Testsubstance:
5 day
57.4 %
10 day72.8 %
30 day83.4 %
50 day91.7 %
61 day96.4 %
Method:OECD Guide-line 301 A (new version) "Ready
Biodegradability: DOC Die Away Test"
Year:
GLP:
Test substance:
no data
09-MAY-2000
(19)
Type:
Inoculum:
Degradation:
Result:
Method:Closed Bottle

aerobic
100 % after 28 dayreadily biodegradable
OECD Guide-line 301 D"Ready Biodegradability:

Test"
Year:
Test substance:
09-MAY-2000
Type:
Inoculum:
Concentration:
Degradation:
Method:GLP:no data(20)

activated sludge, non-adapted
100 mg/l related to Test substance
84 % after 10 day
Directive 84/449/EEC, C.7 "Biotic degradation- modified MITI test"

Year:
GLP:
Test substance:
142

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Remark:26-JAN-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

degradation after 10 d: 64 - 98 % (n=14)
after 28 d: 75 - 111 % (n=14)
0 d lag phase EG-Ringtest 1981-82
(21)

Type:
Inoculum:
Degradation:
88 % after 28
Testsubstance:
60 day95 %Method:OECD Guide-line 301 A (new version)
Biodegradability:
DOC Die Away Test"
Year:
GLP:
Test substance:
no data
09-MAY-2000
Type:
Inoculum:
Concentration:
Method:Year:
Test substance:
Remark:26-JAN-2001
Type:
Inoculum:
Concentration:
Degradation:
Method:Year:
Test substance:
Remark:Test condition:

Concentration:
Degradation:
Method:Year:
Test substance:(20)

other bacteria: purification plant outflow
mixed with a soil suspension
5 mg/l related to Test substanceother: Respirometer-Test (Closed Bottle Test)
GLP:
degradation after 30 d: 75 - 111 % ThSB
54-89 %: Medium without NH4 Cl
71-130%: Medium with NH4 Cl(22)other bacteria: anaerobic laboratory-sewage,
adapted300 mg/l related to Test substance
98 % after 4 dayother: anaerobic degradation, static
GLP:
parameter: gasproduction
35 degree, enrichment culture

26-JAN-2001
Type:
Inoculum:"Ready(23)

other bacteria: anaerobic sewage, domestic,
washed50 mg/l related to Test substance
49.8 % after 61 dayother: anaerobic degradation, static,
35 degree C, parameter:gasproduction
GLP:
UNEP PUBLICATIONS

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OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Remark:BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

concentration: 60/60 mg/l
degradation : 35/56 d = 95.3/96.5 %26-JAN-2001
Type:
Inoculum:
Concentration:
Degradation:
Method:Year:
Test substance:
26-JAN-2001
Type:
Inoculum:

Concentration:
Degradation:
Method:Year:
Test substance:
Remark:Test condition:
26-JAN-2001
Type:
Inoculum:
Concentration:
Degradation:
Method:Year:
Test substance:
26-JAN-2001(17)

other bacteria: methanogenic sewage laboratory
culture, benzoate-adapted
3000 mg/l related to Test substanceca. 99 % after 5 dayother: anaerobic degradation, static,
37 degree C, analytical control ofconcentration, pH 6.7-6.9
GLP:
(24)

other bacteria: anaerobic sewage from apurification plant of woodmanufactering
industry, benzoate-adapted
307 mg/l related to Test substanceca. 99 % after 2 dayother: anaerobic degradation, static,
analytical control of concentration
GLP:
Original data of concentration: 2.13 mM
37 degree C(24)other bacteria: anaerobic enrichment culture(fen), adapted
2306 mg/l related to Test substance
100 % after 4 dayother: anaerobic degradation, static,
parameter: gas production by GC, 39degree C,
pH 6.7GLP:(25)

3.6 BOD5, COD or BOD5/COD Ratio
Remark:09-AUG-2001
144

No data.

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

3.7 Bioaccumulation
Species:
Exposure period:
Concentration:
BCF:
Elimination:
Method:Year:
Test substance:
Remark:Result:Reliability:
Flag:
09-AUG-2001
Species:
Exposure period:
Concentration:
BCF:
Elimination:
Method:Year:
Test substance:
Remark:3.16
other: (calculated) BCF Program (v2.13)
1999
GLP:
other TS: molecular structure
Based on the log P and its rapid
metabolization and excretion in many species
no bioaccumulation is indicated.
Estimated Log BCF = 0.500 (BCF = 3.162)(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint
(3)

GLP:
Based on the log P and its rapid
metabolization and excretion in many species
no bioaccumulation is indicated.

09-AUG-2001

3.8 Additional Remarks
Remark:Aerobic degradation in sea water:
Inoculum: sea water; salinity 18,6 %,20 degree C
Method: Modified OECD Screening Test, OECD
Guideline 301 E adopted 12 May 81, EGRichtlinie 84/449/EWG, part C.3 im EGAmtsblatt L 251, ISO 7824 (1984)
Concentration:
20 mg/l DOC
degradation after 28d: 100 %degradation after 12d: 95 %23-OCT-1995(26)

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Remark:23-OCT-1995
Remark:23-OCT-1995
Remark:23-OCT-1995

146

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

Aerobic degradation in sea water:
Inoculum: sea water (38.7 o/oo), 20 degree C
Method: shake flask test - die away-test;
parameters: DOC initial concentration: 20 mg/l
related to Test substance; 11.6 mg DOC/l (1)40 mg/l resp. 23.2 mg/l related to DOC (2)degradation:after 5/20/61 d: 57.4/80.5/96.4 %;lag time: 4 d (1)after 5/20/61 d:30.8/72.8/98.0 %;lag time: 3 d (2)(27)
Anaerobic degradation in lake water:
Inokulum: sediment (eutrophic lake)
Method:anaerobic degradation, semistatic;
28 resp. 37 degree C; pH 7,4 - 7,6Concentration: 724 mg/l related to Test
substance
Degradation after 20 d: ca. 100 %Remark:50% (w/v) sediment in culture medium
started after 4 h (only in undiluted
sediment), complete transformation
to methane, detection of C14 sodium
benzoate (ring-labelled); adaption
to aliphatic fatty acids(28)
Anaerobic degradation in laboratory aquifer
column:
Method: continuous, room temperature, contentsof column:
30 % material of water-bearing soil
sediment/
70 % slate-debris
Concentration: 28.1 mg/l related to Test
substance
Degradation:> 95 %
Remark: Degradation after adaptation phase of
1 week to m-Xylol; 30 degree C; flow throughtime: 2.6 cm/h, length of column: 25 cm(29)

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITYBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

AQUATIC ORGANISMS

4.1 Acute/Prolonged Toxicity to Fish
Type:
Species:
Exposure period:
Unit:
NOEC:
EC50 :
Method:Year:
Test substance:
Method:Remark:Test condition:

Reliability:
Flag:
09-AUG-2001

flow throughPimephales promelas (Fish, fresh water)
96 hour(s)mg/lAnalytical monitoring: yes
> 245
484
EPA OPP 72-1
GLP: no data
other TS: sodium benzoate, 99+% purity
pH was adjusted to approximate that of Lake
Suprior water (pH 7.8) with NaOH or HCL.
Compound analyses were done by HPLC: all
exposure chambers at 0, 24, 48, 72 and 96 hr.
Fathead minnows used in this experiment were
cultured at US EPA Environmental ResearchLaboratory, Duluth, MN and University of
Wisconsin - Superior campus.
20 fish/concentration and control.
Behavior and toxic signs were noted at
4,24,48,72 and 96 hours and used to calculate
EC50.
Affected fish were hyperactive and lost
equilibrium prior to death. No effect data
were recorded. Individual lengths and weightsof the test fish were not recorded, however
the measured mean weight was 230 mg.
Alkalinity increased with increasing toxicant
concentration. This endpoint had been studied
by another investigator and reported results
similar to the study mentioned above.
temperature =23.9 degree C (+/-0.3); dissolved
oxygen = 7.0 mg/l; pH=7.37; hardness = 43.4
mg/l CaCO3;
alkalinity = 80.9mg/l CaCO3; tank volume = 7.3
liter; average measured concentrations 101,
163, 245, 400, 680 mg/l
(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(30) (31)UNEP PUBLICATIONS

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4. ECOTOXICITY

Type:
Species:
Exposure period:
Unit:
LC50:
Method:Year:
Test substance:
Method:Test condition:

Reliability:

09-AUG-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

staticPimephales promelas (Fish, fresh water)
96 hour(s)mg/lAnalytical monitoring: no> 100
other: see below
GLP: no data
other TS: sodium benzoate, reagent-grade
10 fish/dose were exposed to a solution of thetest substance for 96 hours (a total of sevenaquatic species were tested simultaneously).
Biological observations and determinations oftemperature, dissolved oxygen and pH were done
daily. Survival, condition,and behavior wererecorded.
The LC50 values were estimated by interpolation
Method (Stephan, CE, ASTM STP 634, FL Mayer & JL
Hamelink (eds.) pps 65-84).
20 degree C; pH 6.5-8.5; 16 hr light/day;size of minnows = 200-500 mg; food was withheld
for 24 hr prior to exposure; tests were done in
duplicate.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment(32)

4.2 Acute Toxicity to Aquatic Invertebrates
Type:
Species:
Exposure period:
Unit:
EC50:
Method:Year:
Test substance:
Method:148

staticDaphnia magna (Crustacea)
96 hour(s)mg/lAnalytical monitoring: no> 100
other: see below
GLP: no data
other TS: sodium benzoate, reagent grade
10 organisms/dose were exposed to a solutionof the test substance for 96 hours (a total ofseven aquatic species were tested
simultaneously).
Biological observations and determinations oftemperature, dissolved oxygen and pH were done
daily.

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITYBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

Survival, condition,and behavior were recorded.
The LC50 values were estimated by interpolation
method(Stephan, CE, ASTM STP 634, FL Mayer & JL
Hamelink (eds.) pps 65-84).
Remark:This endpoint had been studied by anotherinvestigator and reported results similar tothe study mentioned above.
Test condition: 20 degree C; pH 6.5-8.5; 16 hr light/day;
Daphnia were at first and second larval instar;food was withheld for 24 hr prior to exposure;tests were done in duplicate.
Reliability:(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Flag:
Critical study for SIDS endpoint
09-AUG-2001(33) (32)Type:
staticSpecies:Gammarus fasciatus (Crustacea)
Exposure period: 96 hour(s)
Unit:
mg/l
Analytical monitoring: no
EC50:
> 100
Method:other: see below
Year:
GLP: no data
Test substance:other TS: sodium benzoate, reagent grade
Method:10 organisms/dose were exposed to a solution of
the test substance for 96 hours (a total of sevenaquatic species were tested simultaneously).
Testing concentrations were 0.1, 1.0,
10, and 100 mg/l.
Biological observations and determinations oftemperature, dissolved oxygen and pH were done
daily.
Survival, condition,and behavior were recorded.
The LC50 values were estimated by interpolation
method (Stephan, CE, ASTM STP 634, FL Mayer & JL
Hamelink (eds.) pps 65-84).
Test condition:
20 degree C; pH 6.5-8.5; 16 hr light/day;Gammarus weighed approximately 7 mg at testing;food was withheld for 24 hr prior to exposure;tests were done in duplicate.
Reliability:(2) valid with restrictions
Meets generally accepted scientific standards,
Well documented and acceptable for assessment
Flag:
Critical study for SIDS endpoint
09-AUG-2001(32)

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4. ECOTOXICITY

Type:
Species:
Exposure period:
Unit:
EC50:
Method:Year:
Test substance:
Method:Test condition:

Reliability:

09-AUG-2001
Type:
Species:
Exposure period:
Unit:
EC50:
Method:Year:
Test substance:
Test condition:
09-AUG-2001
Type:
Species:
Exposure period:
Unit:
EC50:
Method:150

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

staticAsellus intermedius
96 hour(s)
mg/l
> 100
other: see below(Crustacea)
Analytical monitoring: no

GLP: no data
other TS: sodium benzoate, reagent grade
10 organisms/dose were exposed to a solution of
the test substance for 96 hours (a total of sevenaquatic species were tested simultaneously).
Testing concentrations were 0.1, 1.0,
10, and 100 mg/l.
Biological observations and determinations oftemperature, dissolved oxygen and pH were done
daily.
Survival, condition,and behavior were recorded.
The LC50 values were estimated by interpolation
Method (Stephan, CE, ASTM STP 634, FL Mayer & JL
Hamelink (eds.) pps 65-84).
20 degree C; pH 6.5-8.5; 16 hr light/day;organisms weighed approximately 12 mg at
testing; food was withheld for 24 hr prior to
exposure; tests were done in duplicate.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment.
(32)

Daphnia magna (Crustacea)
48 hour(s)mg/lAnalytical monitoring:< 650
other: no data
GLP:
25 degree C(34)
staticother aquatic mollusc: Helisoma trivolvis
96 hour(s)mg/lAnalytical monitoring: no> 100
other: see below

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITYYear:
Test substance:
Method:Test condition:

Reliability:

09-AUG-2001
Type:
Species:
Exposure period:
Unit:
EC50:
Method:Year:
Test substance:
Method:Test condition:

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
GLP: no data
other TS: sodium benzoate, reagent grade
10 organisms/dose were exposed to a solution of
the test substance for 96 hours (a total ofseven aquatic species were tested
simultaneously).
Testing concentrations were 0.1, 1.0,10, and 100
mg/l.
Biological observations and determinations oftemperature, dissolved oxygen and pH were done
daily.
Survival, condition,and behavior were recorded.
The LC50 values were estimated by interpolation
method(Stephan, CE, ASTM STP 634, FL Mayer & JL
Hamelink (eds.) pps 65-84).
20 degree C; pH 6.5-8.5; 16 hr light/day;organisms weighed approximately 180 mg at
testing; food was withheld for 24 hr prior to
exposure; tests were done in duplicate.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment.
(32)
staticother aquatic worm: Dugesia tigrina
96 hour(s)mg/lAnalytical monitoring: no> 100
other: see below
GLP: no data
other TS: sodium benzoate, reagent grade
10 organisms/dose were exposed to a solution of
the test substance for 96 hours (a total of sevenaquatic species were tested simultaneously).
Testing concentrations were 0.1, 1.0, 10, and 100
mg/l.
Biological observations and determinations oftemperature, dissolved oxygen and pH were done
daily.
Survival, condition,and behavior were recorded.
The LC50 values were estimated by interpolation
method (Stephan, CE, ASTM STP 634, FL Mayer & JL
Hamelink (eds.) pps 65-84).
20 degree C; pH 6.5-8.5; 16 hr light/day;organisms weighed approximately 6 mg at testing;food was withheld for 24 hr prior to exposure;tests were done in duplicate.
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OECD SIDS
4. ECOTOXICITYBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

Reliability:(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment.
(32)

09-AUG-2001
Type:
Species:
Exposure period:
Unit:
EC50:
Method:Year:
Test substance:
Method:Test condition:

Reliability:

09-AUG-2001

staticother aquatic worm: Lumbriculus variegatus
96 hour(s)mg/lAnalytical monitoring: no> 100
other: see below
GLP: no data
other TS: sodium benzoate, reagent grade
10 organisms/dose were exposed to a solution of
the test substance for 96 hours (a total of sevenaquatic species were tested simultaneously).
Testing concentrations were 0.1, 1.0, 10, and 100
mg/l.
Biological observations and determinations oftemperature, dissolved oxygen and pH were done
daily.
Survival, condition,and behavior were recorded.
The LC50 values were estimated by interpolation
Method (Stephan, CE, ASTM STP 634, FL Mayer & JL
Hamelink (eds.) pps 65-84).
20 degree C; pH 6.5-8.5; 16 hr light/day;organisms weighed approximately 6 mg at testing;food was withheld for 24 hr prior to exposure;tests were done in duplicate.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment(32)

4.3 Toxicity to Aquatic Plants e.g. Algae
Species:
Endpoint:
Exposure period:
Unit:
EC50:
Method:Year:other algae: green algae
96 hour(s)g/lAnalytical monitoring: no430
other: (calculated) ECOSAR Program (v0.99e)
1999
GLP: noTest substance:other TS: molecular structure
Result: ECOSAR Class: Neutral Organics
Organism: Green Algae
Predicted 96-hr EC50 = 4.3e+005 mg/l(> saturation)
152

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4. ECOTOXICITY

Reliability:
Flag:
10-AUG-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(12)

4.4 Toxicity to Microorganisms e.g. Bacteria
Type:Species:
Exposure period:
Unit:
EC50:
Method:Year:
Test substance:
Remark:Test substance:
Flag:
10-AUG-2001

other bacteria: Achromobacter liquefaciens
24 hour(s)mg/lAnalytical monitoring:>= 3000
other: static, 22 degree C, pH 7
GLP:
other TS
7 d-EC0 >= 3000 mg/l
sodium benzoate; purity not noted
Critical study for SIDS endpoint
(35)

Type:
Species:
Exposure period:
Unit:
EC50:
Method:Year:
Test substance:
Remark:Test substance:
Flag:
10-AUG-2001

other bacteria: Micrococcus flavus
24 hour(s)mg/lAnalytical monitoring:> 500
other: static, 22 degree C, pH 7
GLP:
other TS
7 d-EC0 >= 3000 mg/l
sodium benzoate; purity not noted
Critical study for SIDS endpoint
(35)

Type:
Species:
Exposure period:
Unit:
EC50:
Method:Year:
Test substance:
Remark:other bacteria: Sarcina flava
24 hour(s)mg/lAnalytical monitoring:< 100
other: static, 22 degree C, pH 7
GLP:
other TS
7 d-EC0 >= 3000 mg/l

Test substance:
Flag:
10-AUG-2001

sodium benzoate; purity not noted
Critical study for SIDS endpoint(35)

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4. ECOTOXICITY

Type:
Species:
Exposure period:
Unit:
EC50:
Method:Year:
Test substance:
Remark:10-AUG-2001
Type:
Species:
Exposure period:
Unit:
EC50:
Method:Year:
Test substance:
Remark:10-AUG-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

other bacteria: Micrococcus luteus
24 hour(s)mg/lAnalytical monitoring:500
other: static, 22 degree C, pH 7
GLP:
7 d-EC0 500 mg/l
(35)

other bacteria: Sarcina lutea
24 hour(s)mg/lAnalytical monitoring:< 100
other: static, 22 degree C, pH 7
GLP:
7 d-EC0 1000 mg/l
(35)

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 data. Based on the low acute toxicity andthe readily biodegradation no relevant chronic
toxicity is expected.

10-AUG-2001
4.5.2 Chronic Toxicity to Aquatic Invertebrates
Species:
Endpoint:
Exposure period:
Unit:
Method:Year:
Test substance:
Remark:10-AUG-2001
154

Analytical monitoring:
GLP:
No data.
UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITYBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

TERRESTRIAL ORGANISMS
4.6.1 Toxicity to Soil Dwelling Organisms
Type:
Species:
Endpoint:
Exposure period:
Unit:
Method:Year:
Test substance:
Remark:10-AUG-2001

GLP:
No data.

4.6.2 Toxicity to Terrestrial Plants
Species:
Endpoint:
Expos. period:
Unit:
Method:Year:
Test substance:
Remark:10-AUG-2001

GLP:
No data.

4.6.3 Toxicity to other Non-Mamm. Terrestrial Species
Species:
Endpoint:
Expos. period:
Unit:
Method:Year:
Test substance:
Remark:10-AUG-2001

GLP:
No data.

4.7 Biological Effects Monitoring
Remark:10-AUG-2001

No data.

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4. ECOTOXICITYBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

4.8 Biotransformation and Kinetics
Type:
Remark:Rapid absorbtion and metabolisation andexcretion. Conjugation with glycine andexcreted in urine as hippuric acid.

10-AUG-2001

4.9 Additional Remarks
Remark:23-OCT-1995
Remark:23-OCT-1995
Remark:23-OCT-1995
Remark:23-OCT-1995
Remark:pH 2.65
7

156

Carcinogenicity in fishes (Oryzias latipes):no tumor incidence up to concentration of
80000 mg/kg in food (ca. 8 g sodium benzoate
salt/kg fish and day); proliferation of tissue
in the bile-duct (observation period 24 weeks)
13/50 fishes died after an exposure period of
12-24 weeks(36)
Toxicity to fungi: MIC:
100 mg/l (Talaromyces flavus, 35 d, pH 3.5)
> 600 mg/l (Talaromyces flavus, 35 d, pH 5.4)
(37)
Toxicity to fungi: MIC (at room temperature):
100 mg/l (Byssochlamys fulva, 16 d, pH 3.5)
(38)
Toxicity to fungi: Depending on temperature(21, 30 oder 37 degree C) and concentration of
sodium benzoate (0, 200, 300, 400 oder 500mg/l) production of biomass by Byssochlamys
nivea was reduced in apple- and grapefruit
juice up to an exposure period of 105 days.
(39) (40)Toxicity to fungi:
no visible growth of:
Saccharomyces
Willia anomala
cerevisae
200 mg/l
120 mg/l
2000 mg/l
1000 mg/l
30000 mg/l
20000 mg/l
Method: n.a.
Test duration: n.a.

UNEP PUBLICATIONS

Penicillium
glaucum
600 mg/l
4000 mg/l
60000 mg/l

OECD SIDS
4. ECOTOXICITYBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

23-OCT-1995
Remark:23-OCT-1995(41)
Toxicity to yeast:
no visible growth of:
Saccharomyces ellipsoideus pH 3.5
500 mg/l
5.05000 mg/l
6.5 >25000 mg/l
Method: n.a.
Test duration: n.a.
(42)

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5. TOXICITYBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

5.1 Acute Toxicity
5.1.1 Acute Oral Toxicity
Type:Species:
Strain:Sex:
Number of
Animals:
Vehicle:Value:
Method:Year:
Test substance:
Method:Reliability:

Flag:
10-AUG-2001
Type:
Species:
Strain:Sex:
Number of
Animals:
Vehicle:Value:
Method:Year:
Test substance:
Method:LD50
rat
no datamale/female
5
water= 3450 mg/kg bw
other: see below
GLP: no data
other TS: USP Sodium benzoate, purchased fromMerck
5 animals/sex/group; animals did not fastprior to treatment; animals observed for 14
days.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint
(43)
LD50
rat
Shermanno data6
no data= 4070 mg/kg bw
other: see below

Flag:
10-AUG-2001

GLP: noother TS: sodium benzoate, purity not noted
Groups of 6 rats were given single oral doses
differing by a factor of 10. Animals wereobserved for morbidity and mortality.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint
(44)

Type:

LD50

Reliability:

158

UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

Species:
Strain:Sex:
Number of
Animals:
Vehicle:Value:
Method:rat

Year:
Test substance:
Reliability:

GLP: no data
other TS: sodium benzoate, purity not noted(1) valid without restriction
Guideline study
Critical study for SIDS endpoint
(45)

Flag:
10-AUG-2001
Type:
Species:
Strain:Sex:
Number of
Animals:
Vehicle:Value:
Method:Year:
Test substance:
Method:Reliability:
30-JAN-2001= 3140 mg/kg bw
Directive 84/449/EEC, B.1(oral)""Acute toxicity

LD50
rat
male/female70= 2100 mg/kg bw
GLP: no data
other TS: USP Sodium benzoate, purchased from
Merck
Animals fasted 18 h prior to treatment; dosed
by gavage; observed for 5 days.
(2) valid with restrictions(43)

5.1.2 Acute Inhalation Toxicity
Type:Species:
Strain:Sex:
Number of
Animals:
Vehicle:Exposure time:
Value:
Method:Year:
Test substance:

GLP:

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Remark:BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
See IUCLID dataset on benzoic acid
(CAS# 65-85-0); the loss of acidity due to thesodium salt should decrease toxicity.

10-AUG-2001
5.1.3 Acute Dermal Toxicity
Type:Species:
Strain:Sex:
Number of
Animals:
Vehicle:Value:
Method:Year:
Test substance:
Remark:GLP:
See IUCLID dataset on benzoic acid
(CAS# 65-85-0); the loss of acidity due to thesodium salt should decrease toxicity.

10-AUG-2001
5.1.4 Acute Toxicity, other Routes
Type:Species:
Strain:Sex:
Number of
Animals:
Vehicle:Route of admin.:Value:
Method:Year:
Test substance:
10-AUG-2001

LD50
rat

i.v.
= 1714 mg/kg bw
GLP:
(46)

5.2 Corrosiveness and Irritation
5.2.1 Skin Irritation
Species:
Concentration:

160

rabbitUNEP PUBLICATIONSOECD SIDS
5. TOXICITY

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

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

not irritating
OECD Guide-line 404 "Acute Dermal
Irritation/Corrosion"
1981
GLP: yesother TS: sodium benzoate; purity not noted(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint

10-AUG-2001

Species:
Concentration:
Exposure:
Exposure Time:
Number of
Animals:
PDII:
Result:EC classificat.:
Method:Year:
Test substance:
Remark:Flag:
10-AUG-2001
Species:
Concentration:
Exposure:
Exposure Time:
Number of
Animals:
PDII:
Result:EC classificat.:(47)

rabbitnot irritatingother: see remarks
GLP:other TS: sodium benzoate; purity not noted
application of dry powder (500 mg/animal) for
24 h; responses were scored at end oftreatment and after 48 h
Critical study for SIDS endpoint
(48)
rat

irritating

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Method:Year:
Test substance:
Remark:10-AUG-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
other: intradermal; see remark
GLP:other TS: sodium benzoate; purity not noted
sodium benzoate (dose 0.1 ml; 0, 10, 20 %saline solution) was tested for intradermal
irritation in male Wistar rats.
Radioactive indicator was used to quantify the
biological response (increase of permeabilityof blood capillaries).
At low concentrations (1 %) little irritation
and at higher levels (>= 3 %) significant
irritation was recorded. The degree of
irritation was dose-dependent.
(49)

5.2.2 Eye Irritation
Species:
Concentration:
Dose:
Exposure Time:
Comment:
Number of
Animals:
Result:EC classificat.:
Method:Year:
Test substance:
Remark:Reliability:
Flag:
10-AUG-2001
Species:
Concentration:
Dose:
Exposure Time:
Comment:
Number of
Animals:
Result:162

rabbitslightly irritating
OECD Guide-line 405 "Acute Eye
Irritation/Corrosion"
1987
GLP: yesother TS: sodium benzoate; purity not notedaccording to EEC Directive 84/449/EEC, Annex Vof the EEC Directive 67/548/EEC no labellingas eye irritantDraize score: 9.3(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(50)
rabbitnot irritating

UNEP PUBLICATIONSOECD SIDS
5. TOXICITYEC classificat.:
Method:Year:
Test substance:
Remark:Reliability:
Flag:
10-AUG-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

Directive 84/449/EEC, B.5
irritation)""Acute toxicity (eyeGLP:other TS: sodium benzoate; purity not noted
application of dry powder (50 mg/animal) for
24 h; responses were scored at 24 h, 48 h and
72 h; postexposure observation time: 7 d(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(48)

5.3 Sensitization
Type:
Species:Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance:
Remark:Flag:
10-AUG-2001
Type:
Species:Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance:
Remark:Patch-Testhumanother: patch-test
GLP:other TS: sodium benzoate; purity not noted
5 of 2045 patients of dermatological clinics
developed positive reactions to the treatment
with 5% sodium benzoate in petrolatum.
Critical study for SIDS endpoint(51)
Patch-Testhumanother: patch-test
GLP:other TS: sodium benzoate; purity not noted
3 workers of a pharmaceutical plant withtransient urticaria after exposition to sodium
benzoate and 3 previously unexposed healthy
control subjects were tested.

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5. TOXICITY

Flag:
10-AUG-2001
Type:
Species:
Concentration:
Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance:
Remark:Flag:
10-AUG-2001
Type:
Species:
Concentration:
Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance:

164

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
All subjects reacted to benzoic acid at 0.25 %in aqueous solution under occlusion. 1 worker
and 2 controls reacted to sodium benzoate at
0.5 % in saline under occlusion, but none
reacted to sodium benzoate at 0.5 % in aqueous
solution.
All 3 workers reacted in a closed patch test to
benzoic acid at 5 % in petrolatum. The timecourse of the responses to benzoic acid andsodium benzoate was similar in controls andworkers.
The potential of sodium benzoate to elicite
nonimmunologic contact urticaria may be due tothe formation of benzoic acid at skin contact.
Critical study for SIDS endpoint(52)
other: oral provocation testhuman
Challenge100
other: mgother: oral81
not sensitizing
not sensitizing
other
GLP: noother TS: sodium benzoate; purity not noted
Oral challenge test: double blind challenge;
81 persons who claimed to suffer from a foodrelated intolerance. No sensitisation found.
Critical study for SIDS endpoint(53) (54)
other
human
Challenge
Challenge

50
500

other: mgother: mgother: oral
other: oral

other: none
ambiguous
other: oral challenge
GLP: noother TS: sodium benzoate; purity not noted

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Remark:10-AUG-2001
Type:
Species:Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance:
Remark:10-AUG-2001
Type:
Species:Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance:
Remark:10-AUG-2001
Type:
Species:Number of
Animals:
Vehicle:BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
Various oral challenge tests; patients
suffering from asthma or rhinitis dosed with
50-500 mg benzoic acid sodium salt orally.
Result : 15/157; 11/531; 10/46 positive(55) (56)other: see remarks
humanother: double-blind oral challange test
GLP:
A patient with Melkersson-Rosenthal syndrome
reacted positive to sodium benzoate (50 mg).
no further information available(57)
other: see remarks
humanother: gastric challenge test
GLP:
in a double-blind placebo-controlled study 25
children with severe atopic dermatitis werechallenged with food and food additives, applied
by nasogastric tube. 3/6 patients challenged withsodium benzoate showed a response. Reactions
were excerbations of isolated skin symptoms inall 3 and additionally abdominal pain in
association with rash in one child.
(58)
other: see remarks
human

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5. TOXICITY

Result:Classification:
Method:Year:
Test substance:
Remark:10-AUG-2001
Type:
Species:Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance:
Remark:10-AUG-2001
Type:
Species:Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance:

166

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

other: oral challenge test
GLP:
in 21 patients (5-64 years old) with severe
atopic eczema oral challenge tests with foodadditives were performed.
4/19 patients reacted to sodium benzoate(10, 50, 100, 300 mg; administered in gelatine
capsules) with exacerbation of symptoms (flare
up of atopic eczema, anaphylactoid reactions,generalized pruritus).
(59)
other: see remarks
humanother: oral provocation test
GLP:a chemical worker suffered from allergic
reactions of increasing intensity while being
constantly exposed to benzoic acid duringwork. After oral exposure to sodium benzoate(500 mg) he suffered a severe anaphylactic
shock. He showed similar but milder reaction
after consuming food containing benzoic acid.
(60)
other: see remarks
humanother: oral provocation test
GLP:

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Remark:10-AUG-2001
Type:
Species:Number of
Animals:
Vehicle:Result:Classification:
Method:Year:
Test substance:
Remark:10-AUG-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
In a 19-year-old girl with no medical history
apart from atopic asthma during infancy, asevere anaphylaxis was observed after eating
food which mainly contained sodium benzoate as
food additive. The patient remained symptomfree during a sodium benzoate free diet.
In the oral provocation test (single oral
application of 20 mg sodium benzoate) a
localized urticaria (arms) and generalised
itching was observed. In a second oral
challenge (application of 160 mg sodium
benzoate), a higher tolerance level was noted.
(61)
other: see remarks
humanother: oral provocation test
GLP:
after a single oral application of 20 mg
sodium benzoate, 2/10 patients with asthma and2/7 patients with atopic dermatitis reacted
positive; observed were bronchial
obstruction/meteorism, nausea or dermatits
resp.
(62)

5.4 Repeated Dose Toxicity
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
NOAEL:

rat
Shermanoral feed
90 d

Sex: male/female

continuously in dietno1, 2, 4 or 8 % in diet (approx. 640-6290
mg/kg/day)yes3145 mg/kg bw

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5. TOXICITYLOAEL:
Method:Year:
Test substance:
Method:Result:Reliability:

Flag:
10-AUG-2001
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
NOAEL:
Method:Year:
Test substance:
Method:Remark:168

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
6290 mg/kg bw
other: see below
GLP: no data
other TS: USP sodium benzoate purchased from
Merck
Male rats (weighing 212 -430 grams) and female
rats (weighing 163 to 267 grams) were dosed bygavage after being fasted for 18 hours. Animals
were observed for 5 days (time interval chosenbecause all survivors were gaining weight and in"satisfactory nutritional condition").
<= 4 % in diet: no adverse effects;
8 % in diet: increased mortality (4/8 died);
reduced weight gain; increased weight of livers
and kidneys; pathological lesions(not specified)in livers and kidneys(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(43)
rat
Shermanoral feed
30 d

Sex: male/female

continuously in dietno data
16-1090 mg/kg/day
yes> 1090 mg/kg
other: see below
GLP: no data
other TS: sodium benzoate, purity not noted
Groups of 10 rats (5 males, 5 females) wereadministered doses of sodium benzoate by oral
feed for thirty days. Animals were observed forweight gain, appetite, morbidity and mortality.
Surviving animals were necropsied. Adrenal,
upper intestine, kidney, liver, and spleen were
examined.
10 rats/group
This endpoint has been studied several times by
several other investigators/groups and allreported results similar to the study mentioned
above.

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Result:Reliability:

Flag:
10-AUG-2001
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
NOAEL:LOAEL:
Method:Year:
Test substance:
Remark:Result:Reliability:

Flag:
10-AUG-2001
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
No adverse effects were observed.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(63) (44)mouseother: Albino Swiss
drinking water
35 days

Sex: male/female

continuously in drinking water
no data0.5; 1; 2; 4 or 8 % in drinking water
yes
2 %
4 %
other: Toth, B. (1984)
GLP: no data
other TS: sodium benzoate, purity not noted"By taking into account four parameters(survival rate, body weight, chemical
consumption, histological changes), the 2%
dose level was found suitable for the
lifelong treatment."
8 %: 4/4 males and 4/4 females died within 3
weeks; 4 %: 3/4 males and 3/4 females diedduring the treatment period and the bodyweight of surviving mice was substantiallyreduced.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(64)
ratother: F344/Ducrj
oral feed
10 d

Sex: male/female

continuously in dietno1.81; 2.09 or 2.4 % in diet (approx. 1358,
1568 or 1800 mg/kg/d)
yes
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OECD SIDS
5. TOXICITYLOAEL:
Method:Year:
Test substance:
Remark:Result:Reliability:

Flag:
10-AUG-2001
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
NOAEL:LOAEL:
Method:Year:
GLP: no data
Test substance:

Method:170

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
1358 mg/kg bw
GLP:other TS: sodium benzoate, purity not noted
The mean compound consumption was calculated
according to Lehman, Food Drug Off. Q. Bull.
18, 66 (1954).
At the lowest tested concentration of 1358
mg/kg changes in serum chlolesterol levels
occurred in females. At doses of 1568 mg/kg
and above changes in further serum parameters
and an increased relative liver weight were
described.
Histopathological changes of the liver,increased relative kidney weights anddisorders of the central nervous systemwere seen after dosing via diet with > 1800 mg.
1/6 male rat in the 2.4 %-group, who developed
increased sensitivity to stimuli andconvulsions, died.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment.
Critical study for SIDS endpoint
(65)
mouse
B6C3F1oral feed
10 d

Sex: male/female

continuously in dietno2.08; 2.5 or 3 % in diet (approx. 3012, 3750
or 4500 mg/kg/d)
yes
3750 mg/kg bw
4500 mg/kg bw
other: see below

other TS: sodium benzoate (specific grade)purchased from Wako Pure Chemical Ind., Osaka,Japan
Sodium benzoate, mixed with the powdered diet,was fed to groups of 12 mice (6 males, 6
females) for 10 days.
UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Remark:Result:Reliability:

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
Animals were observed for body weight gain andclinical signs 5 day/ week.
At the end of the experiment, surviving animals
were necropsied. Organ weights, clinicalchemistry and histological examinations were
performed.
The mean compound consumption was calculated
according to Lehman, Food Drug Off. Q. Bull. 18,
66 (1954).
All mice in the 3.0 %-group showed increased
sensitivity to stimuli and 1/5 male and 2/5
females showed convulsions; 2/5 females died;liver weights of males and females and kidneyweights of females were dose-dependently
increased; histopathologic examination showedenlarged hepatocytes, single cell necrosis andvacuolation of hepatocytes in all livers frommales; no histopathologic changes of the kidney
were described; serum cholesterol, lipid levels
and cholinesterase were increased in males.
(2) valid with restrictions
Meets generally accepted scientific standards,

well documented
Flag:
10-AUG-2001
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
NOAEL:
Method:Year:
Test substance:
Remark:Result:and acceptable for assessment
Critical study for SIDS endpoint(65)
rat
Fischer 344
oral feed
18-24 months

Sex: male/female

continuously in dietno1 or 2 % in dietyes
2 %other: OECD 451
GLP: no data
other TS: sodium benzoate, purity not noted
Mean compound consumption:
2 % in diet: m: 280 +- 9.8 mg/d
f: 202 +- 10.5 mg/d
No adverse clinical signs in treated rats; nodifferences in average body weight andmortality in comparison to controls.

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Reliability:

Flag:
10-AUG-2001
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
LOAEL:
Method:Year:
Test substance:
Method:Remark:BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(66)
rat
Shermanoral feed
28 dSex: male/female

continuously in diet2 or 5 % in diet (see remarks)
other: no data
2002 - 2357 mg/kg bw
other: see below
GLP: no data
other TS: sodium benzoate, food grade
Food grade sodium benzoate was incorporated into
the basal diet at concentrations of 2% and 5%.
The rats were weighed individually twice a week
and were inspected daily for signs of toxicity.
Food consumption for each group was recorded
weekly and the drug intake as mg/kg bw was
calculated using the average body weights foreach group. Fisher's T test for small samples
was used as a test for significant differences
between body weights for the various groups.
6 rats/group; initial body weight: 40-50 g;mean compound consumption:
2 % in diet: m: 2002 - 2357 mg/kg/day
f: 2171 - 2396 mg/kg/day
5 % in diet: m:
5686 mg/kg/day
f:7780 mg/kg/day

Result:2 %: slight depression of body weight gain
only in males
5 %: urine incontinence, convulsions, 100 %mortality after 2nd week

Reliability:(3) invalid
Significant methodological deficiencies

10-AUG-2001
Species:
Strain:Route of admin.:
Exposure period:
172

(67)
rat
Fischer 344
oral feed
42 d
UNEP PUBLICATIONS

Sex: male/female

OECD SIDS
5. TOXICITY

Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:

Method:Result:10-AUG-2001
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:Result:BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

continuously in dietno data0.5; 1; 2; 4 or 8 % in diet (approx. 375-6000
mg/kg/day)yesother: see below
GLP:
other TS: sodium benzoate, purity not noted;
supplied by National Institute of Hygienic
Sciences pellets in the basal diet
10 rats/group; initial body weight: 110-150 g;
the mean compound consumption was calculated
according to Lehman, Food Drug Off. Q. Bull.
18, 66 (1954); Animals were administered diets
containing various concentrations of sodium
benzoate for 6 weeks.
Survival rate, growth, food intake, behavior andgeneral status were observed during the feeding
period. Morphological examinations were carriedout.
2 % in diet (approx. 1500 mg/kg/day): maximum
tolerated dose;>= 4 % in diet (approx. >= 3000 mg/kg/day):mortality 10/11 or 10/10; atrophy of thespleen and lymph nodes at autopsy.
(66)
rat
no dataoral feed
until death (see below)

Sex: no data

continuously in dietno5 % in diet (approx. 3750 mg/kg/day)yes
GLP:other TS: benzoic acidthe mean compound consumption was calculated
according to Lehman, Food Drug Off. Q. Bull.
18, 66 (1954)
19/28 young rats (initial body weight:
62-70 g) died during the first 2 weeks; allothers died 1 week later; reduced food intake,diarrhea, intestinal haemorrhage and crusted
blood in the nose at autopsy.
UNEP PUBLICATIONS173

OECD SIDS
5. TOXICITYBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

10-AUG-2001
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:Result:10-AUG-2001
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:Result:10-AUG-2001
174

(68)
rat
no dataoral feed
no data

Sex: no data

continuously in dietno data
5 % in diet (approx. 3750 mg/kg/day)other: no data
GLP:
other TS: benzoic acidthe mean compound consumption was calculated
according to Lehman, Food Drug Off. Q. Bull.
18, 66 (1954)
4/5 adult rats (initial body weight:
221-232 g) died during 4-5 weeks; body weight
was reduced to 161 g(68)
rat
no dataoral feed
23 weeks

Sex: malecontinuously in dietno5 % in diet (approx. 3750 mg/kg/d)yes
GLP:other TS: sodium benzoate, purity not noted
Basic diet: low casein diet; the study wasdone to investigate the effect of several
xenobiotics on the growth retardation provokedin rats by sodium benzoate; the data presented
here are the results of the "long-term"
positive control group.
The mean compound consumption was calculated
according to Lehman, Food Drug Off. Q. Bull.
18, 66 (1954).
marked growth inhibition, occasionallyrestlessness, irritability, tremors(69)
UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Result:26-JAN-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
dogother: fox terrier
oral feed<= 250 days

Sex: male/female

once daily

0.1 - 7 g/animal/day
other: no data
GLP:
0.1 - < 7 g/animal/day: no toxic effect;
7 g/animal/day (approx. 1 g/kg/day): toxic
dose (ataxia, tonoclonic convulsions,vomiting, death)(70)

5.5 Genetic Toxicity 'in Vitro'
Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:

Remark:Reliability:
Flag:
10-AUG-2001
Type:
System oftesting:Ames test
Salmonella typhimurium TA 92, TA 94, TA 98,
TA 100, TA 1535, TA 1537
0-3 mg/platewith and without
negative
OECD Guide-line 471 "Genetic Toxicology:
Salmonella thyphimurium Reverse Mutation
Assay"
1983
GLP: no data
other TS: samples obtained from Japan Food
Additives Association; purity = 99% analysedat Ministry of Health and Welfare of Japan
This endpoint has been studied by several
other investigators/groups and all support theresult of the study mentioned above.
(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(71) (72)
Cytogenetic assay
cultured human embryonic lung cells
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OECD SIDS
5. TOXICITY

Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:
Remark:Reliability:

Flag:
10-AUG-2001
Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:

Reliability:

Flag:
10-AUG-2001
Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:
176

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
2.0, 20.0, 200.0 ug/ml

without
negative
other: anaphase preparations
GLP: no data
other TS: FDA 71-37 supplied by Food and Drug
Administration
This endpoint has been studied by several
other investigators/groups and all support theresult of the study mentioned above.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(73) (74)other: Chromosomal aberration test
Chinese hamster fibroblast cell line (CHL)
0 - 2 mg/plate

without
positive
other: similar to OECD Guideline 473
1983
GLP: no data
other TS: samples obtained from Japan Food
Additives Association; purity = 99% analysedat Ministry of Health and Welfare of Japan(2) valid with restrictions
Comparable to Guideline study with acceptable
restrictions
Critical study for SIDS endpoint(75) (72)other: E. coli reversion mutation assay
E. coli WP2
no datano datawith and without
negative
EPA OTS 798.5100
GLP: no data
other TS: sodium benzoate, purchased from
Baker; purity not noted
UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Reliability:
Flag:
10-AUG-2001
Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:

Method:Remark:Reliability:

Flag:
10-AUG-2001
Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:
Remark:BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(76)
other: Sister chromatid exchange
Chinese hamster cell line (Don)0.001 to 0.01 M / plate
no datawithout
ambiguous
other: see below
GLP: no data
other TS: sodium benzoate, supplied by
National Institute of Hygienic Sciences,
Japan; purity not noted
Sodium benzoate was dissolved in Hank's balanced
salt solution to desired concentrations. All
cultures were kept in complete darkness at
37 degree C for 26 hours (two cell cycles) and
0.25 ug colchicine/ml added for final 2 hours.
Cells were collected and stained by acridine
orange technique for fluorescence or modified
FPG (fluorecence plus Giemsa) for Giemsa.
The number of SCE per cell was determined on thebasis of 20-50 intact metaphases without grosschromosome aberrations.
slight increase in SCE/cell, but no dosage
effect(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(77)
other: Sister chromatid exchange
human lymphocytes

without
positive
GLP:
only one concentration (10E-2 M) tested
UNEP PUBLICATIONS

177OECD SIDS
5. TOXICITY

Reliability:
Flag:
10-AUG-2001
(78)
Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:
Remark:Reliability:
Flag:
10-AUG-2001
Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:
Method:Result:178

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1(3) invalid
Significant methodological deficiencies
Critical study for SIDS endpoint

other: Inhibition of DNA synthesis
Vicia faba root meristems

without
positive
GLP:
other observed effects:a. concentration-dependent decrease in mitotic
figures;b. concentration-dependent increase inanaphase bridges;c. premature chromosome condensation heading
to pycnotic nuclei; d. chromatin erosion ininterphase nuclei(3)invalid
Unsuitable test system
Critical study for SIDS endpoint(79)
Bacillus subtilis recombination assay
Bacillus subtilis H17, M45

no datapositive
GLP:
no data
An overnight culture of B. subtilis, H17 andM45, was mixed with test solutions and incubatedfor 30 minutes at 37 degree C. After treatment,
viable cells were counted and the ratio of 50%
survival concentrations were calculated.
Sodium benzoate showed DNA damaging potential
although it had been negative in the Ames test.

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Reliability:

Flag:
10-AUG-2001
Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:
10-AUG-2001
Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:
11-JAN-2001
Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:
01-SEP-2000
Type:
System oftesting:
Concentration:

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1(4) not assignable
Documentation insufficient for assessment;
abstract only
Critical study for SIDS endpoint(80)
Bacillus subtilis recombination assay
Bacillus subtilis H17, M45
6-20 mg/disk, in waterwith and without
ambiguous
GLP:(81)
Ames test

Salmonella typhimurium TA 98, TA 100, TA 1535,
TA 1537, TA 1538

with and without
negative
GLP:(76)
Ames test
Salmonella typhimurium, TA 98, TA100, TA1537

with and without
negative
GLP:(82)
other: Chromosomal aberration test
Chinese hamster cell line (Don)UNEP PUBLICATIONS179OECD SIDS
5. TOXICITY

Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:
11-JAN-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

without
positive
GLP:
(77)

Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:other: Chromosome aberration test

Result:
Method:Year:
Test substance:
Method:positive

01-SEP-2000
Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:
Remark:11-JAN-2001

Chinese hamster fibroblast cell line (CHL)

with

GLP:
other TS: purity not given
other: Ishidate M. and Odashima S. Mutation
Res. 48: 337-354(1977) and Matsuoka A. et al.
Mutation Res. 66: 277-290 (1979)(82)
other: Sister chromatid exchange
Vicia faba root tip cells

without
positive
GLP:
only one concentration (10E-2 M) tested(78)

5.6 Genetic Toxicity 'in Vivo'
Type:
Species:
Strain:Route of admin.:
Exposure period:
Doses:
Result:180

Cytogenetic assay
rat
no datagavagesingle application
50, 500 or 5000 mg/kg
negative
UNEP PUBLICATIONS

Sex: maleOECD SIDS
5. TOXICITY

Method:Year:
Test substance:

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
EPA OTS 798.5385

Flag:
10-AUG-2001

GLP: yesother TS: compound FDA 71-37, sodium benzoate,
as supplied by the Food and Drug
Administration
no detectable significant aberrations of thebone marrow metaphase chromosomes(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint
(74)

Type:
Species:

Cytogenetic assay
ratStrain:Route of admin.:
Exposure period:
Doses:
Result:
Method:Year:
Test substance:

no datagavageonce daily for 5 consecutive days
50, 500 or 5000 mg/kg
negative
EPA OPPTS 870.5385
GLP: yesother TS: compound FDA 71-37, sodium benzoate,
as supplied by the Food and Drug
Administration
no detectable significant aberrations of thebone marrow chromosomes(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(74)

Result:Reliability:

Result:Reliability:
Flag:
10-AUG-2001

Type:
Species:
Strain:Route of admin.:
Exposure period:
Doses:
Result:
Method:Year:
Test substance:

Reliability:
Flag:
10-AUG-2001

Dominant lethal assay
rat
no datagavagesingle application
50, 500 or 5000 mg/kg
negative
EPA OPPTS 870.5450

Sex: maleSex: male

GLP: yesother TS: compound FDA 71-37, sodium benzoate,
as supplied by the Food and Drug
Administration(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(74)
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SUBSTANCE ID: 532-32-1

Type:Species:
Strain:Route of admin.:
Exposure period:
Doses:
Result:
Method:Year:
Test substance:

Dominant lethal assay
rat
Sex: maleno datagavageonce daily for 5 consecutive days
50, 500 or 5000 mg/kg
negative
EPA OPPTS 870.5450
GLP: yesother TS: compound FDA 71-37, sodium benzoate,
as supplied by the Food and Drug
Administration

Reliability:(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint

Flag:
10-AUG-2001
Type:
Species:
Strain:Route of admin.:
Exposure period:
Doses:
Result:
Method:Year:
Test substance:

Result:Reliability:
Flag:
10-AUG-2001
Type:
Species:
Strain:Route of admin.:
Exposure period:
Doses:
Result:
Method:Year:
Test substance:

182

(74)
other: Host mediated assay
mouse
no datagavagesingle application
50, 500 or 5000 mg/kg
negative
other: EPA

Sex: male

GLP: yesother TS: compound FDA 71-37, sodium benzoate,
as supplied by the Food and Drug
Administration
No elevation of mutant frequencies in Salmonella
Typhimurium G46 and no increase in recombinantfrequencies in Saccharomyces cerevesiae D3(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(74)
other: Host mediated assay
mouse
no datagavagesingle application
50, 500 or 5000 mg/kg
negative
other: EPA

Sex: male

GLP: yesother TS: compound FDA 71-37, sodium benzoate,
as supplied by the Food and Drug Administration
UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Result:Reliability:
Flag:
10-AUG-2001

Type:
Species:
Strain:Route of admin.:
Exposure period:
Doses:
Result:
Method:Year:
Test substance:

Result:Reliability:
Flag:
10-AUG-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
elevation of mutant frequencies in Salmonella
typhimurium TA 1530 in the intermediate doselevel; Not dose dependent and negative at
multiple dose exposure.
(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(74)

other: Host mediated assay
mouse
Sex: maleno datagavageonce daily for 5 consecutive days
50, 500 or 5000 mg/kg
negative
other: EPA
GLP: yesother TS: compound FDA 71-37, sodium benzoate,
as supplied by the Food and Drug
Administration
no elevation of mutant frequencies in Salmonella
Typhimurium G46; no elevation of mutant
frequencies in Salmonella typhimurium TA 1530;
no increase in recombinant frequencies in
Saccharomyces cerevesiae D3(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(74)

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

rat
Fischer 344
oral feed
18-24 months

Sex: male/female

continuously in dietno1 or 2 % in diet (see remarks)
negative
yesOECD Guide-line 451 "Carcinogenicity Studies"
GLP: no data
other TS: sodium benzoate, purity not noted
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Method:Remark:Result:Reliability:
Flag:
10-AUG-2001
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Result:Control Group:
184

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
Groups of 50 male and 52 female Fischer 344
rats, four to five weeks old, received diets
containing 1% (500 mg/kg bw per day) or 2%(1000 mg/kg bw per day) sodium benzoate for
18-24 months. Controls, consisting of 25 maleand 43 female rats, received basal diet.
Food intake was adequately controlled to
avoid an excess; tap water was available adlibitum.
Mean compound consumption:
1 % in diet: m: 141 +- 9.7 mg/d
f: 102 +- 11.8 mg/d
2 % in diet: m: 280 +- 9.8 mg/d
f: 202 +- 10.5 mg/d
about 40 rats including control animals diedduring the first 16 months of the experimental
period (pneumonia with abscess) about 100 rats
including control animals died after 16 monthsof hemorrhagic pneumonia (infection)
Survival was very poor in all groups, due tointercurrent sialodacryoadenitis and mycoplasma
infections. All surviving animals weresacrificed between 18 and 25 months, all were
autopsied, and various tissues were examinedhistopathologically. No adverse clinical signs
directly attributable to treatment wereobserved, and only negligible differences inaverage body weight and mortality rate wereseen between the treated and control groups.
Although a variety of tumours occurred among
treated and control rats of each sex, they wereof similar type and incidence; no evidenceof carcinogenicity.
(1) valid without restriction
Guideline study
Critical study for SIDS endpoint
(66)
mouse
other: Albino Swiss
drinking water
lifelong

Sex: male/female

continuously in drinking water
no data
2 % in drinking water
negative
yes
UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Method:Year:
Test substance:
Method:Remark:Result:Reliability:

Flag:
10-AUG-2001
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Result:Control Group:
Method:BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
other: see below
GLP: no data
other TS: sodium benzoate, purity not noted
In the main study, a 2% solution of sodium
benzoate (purity, 99%) was administered in thedrinking-water to groups of 50 male and 50
female five-week-old mice for their lifetime.
Groups of 100 males and 100 females were used as
untreated controls. Both treated and control
animals were 'carefully checked'; their bodyweights were measured weekly, and grosspathological changes were recorded. The animals
were either allowed to die or were sacrificed
when moribund. Complete necropsies were
performed on all animals, and the liver,spleen, kidneys, bladder, thyroid, heart,pancreas, testes, ovaries, brain, nasal
turbinates, at least four lobes of thelungs, and organs with gross pathologicalchanges were examined histologically.
50 males and 50 females were treated; 99 males
and 99 females served as controls; average
daily intake: 119.2 mg (f) or 124.0 mg (m)The average daily intake of sodium benzoate was
124.0 mg for males and 119.2 mg for females on
the basis of daily water consumption of 6.2 and5.9 ml, respectively. The dose of sodium
benzoate was equivalent to 6200 mg/kg bw per day
for males and 5960 mg/kg bw per day for females.
Treatment had no effect on survival or theincidence of tumours.
(2) valid with restrictions
This study is sufficiently reliable due to a
sufficient number of animals and a detailed
histopathological examination.
Critical study for SIDS endpoint(64)
rat
Fischer 344

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5. TOXICITYYear:
Test substance:
Remark:Result:26-JAN-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
GLP:
DEN-PH model; final, general protocol:
Group 1: single i.p. dose ofdiethylnitrosamine, repeated treatment withthe test compound from week 2, hepatectomy
at week 3, sacrifice at week 8.
Group 2: single i.p. dose ofdiethylnitrosamine, hepatectomy at week 3,
sacrifice at week 8.
Group 3: single i.p. dose of saline, repeatedtreatment with the test compound from week 2,
sacrifice at week 8.
The enhancing effects of chemicals on
induction of preneoplastic form of glutathione
S-transferase positive foci was measured bycomparing the GST-P positive foci in liverslices of treated and control animals.
positive(83)

5.8 Toxicity to ReproductionType:other: 2 year carcinogenicity study
Species:rat
Sex: male/female
Strain:Fischer 344
Route of admin.: oral feed
Exposure Period: 18 - 24 months
Frequency oftreatment:
continuously in diet
Duration of test: 24 months
Doses:
1 or 2 % in dietControl Group:
yes
NOAEL Parental:
2 %Method:other: OECD 451
Year:
GLP: no data
Test substance:other TS: sodium benzoate, purity not noted
Result:No evidence of compound related effects in thetestes or ovaries of treated rats.
Reliability:(2) valid with restrictions
In the 2 yr feeding study, reproductive organs
were examined macroscopically andhistologically.
Flag:
Critical study for SIDS endpoint
10-AUG-2001
(66)

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5. TOXICITYBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

Species:
Sex:
Strain:Route of admin.:
Exposure Period:
Frequency oftreatment:
Duration of test:
Doses:
Control Group:
Method:Year:
GLP:
Test substance:
Remark:A 4-generation reprotoxicity test with benzoic
acid revealed no reproductive effects.
Therefore no indication for reproductive
toxicity testing for the benzoic acid sodium
salt.
See IUCLID on benzoic acid (CAS# 65-85-0); thedata on the sodium salt should be similar.
Flag:
Critical study for SIDS endpoint
10-AUG-2001

5.9 Developmental Toxicity/Teratogenicity
Species:rat
Sex: female
Strain:WistarRoute of admin.: gavage
Exposure period: Day 6-15 of gestation
Frequency oftreatment:
once daily
Duration of test:
Doses:
1.75; 8; 38 or 175 mg/kg/dControl Group:
yes
NOAEL Maternalt.: >= 175 mg/kg bw
NOAEL Teratogen.: >= 175 mg/kg bw
Method:EPA OPPTS 870.3700
Year:
GLP: no data
Test substance:other TS: sodium benzoate, purity not noted
Remark:This endpoint has been studied several times
by several other investigators/groups and allreported results similar to the study
mentioned above.
Result:no effect on nidation or on maternal or fetal
survival; the number of abnormalities of softand skeletal tissues did not differ fromnumber in controls; maternal toxicity was
not reported at any dose applied
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Reliability:
Flag:
10-AUG-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(84) (85)Species:rat
Sex: female
Strain:WistarRoute of admin.: oral feed
Exposure period: whole gestation period (20 d)
Frequency oftreatment:
continuously in diet
Duration of test:
Doses:
1, 2, 4 or 8 % in diet (700 to 5600 mg/kg)
Control Group:
yes
NOAEL Maternalt.: = 1400 mg/kg bw
NOAEL Teratogen.: = 1400 mg/kg bw
Method:other
Year:
GLP: no data
Test substance:other TS: sodium benzoate, purity not noted
Remark:
The mean food consumption was calculated fromgraph:<= 2 % in diet: approx. 20
mg/kg/day
4 % in diet: approx. 12
mg/kg/day
8 % in diet: approx. 2.5 mg/kg/day
The mean compound consumption was calculated
from graph:
1 % in diet: approx. 700 mg/kg/day
2 % in diet: approx. 1400 mg/kg/day
4 % in diet: approx. 2800 mg/kg/day
8 % in diet: approx. 5600 mg/kg/day
Result:A study using pregnant Wistar rats, dosed with
700, 1400, 2800, 5600 mg/kg sodium benzoate in
the diet during the entire gestation showed nostatistical difference in organ and boneabnormalities of fetuses between experimentalgroups and controls; growth of treated offsprings
was similar to controls in rats dosed with
1400 mg/kg/day; reduced food intake anddecreased body weight of the pregnant rats
especially in the 5600 mg/kg group; 100%
perinatal death rate; organ abnormalities offetuses involved eye, brain and kidneys, inaddition abnormalities of the skeletal systemwere found in rats dosed with >2800 mg/kg/day.

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Conclusion:

Reliability:

Flag:
10-AUG-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
The authors concluded that the effects on thedams and fetuses at the 2800 and 5600 levels
were due to reduced maternal feed intake inthese groups, leading to malnutrition.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(86)

Species:mouse
Sex: female
Strain:
CD-1
Route of admin.: gavage
Exposure period: Day 6-15 of gestation
Frequency oftreatment:
once daily
Duration of test:
Doses:
1.75; 8; 38 or 175 mg/kg/dControl Group:
yes
NOAEL Maternalt.: >= 175 mg/kg bw
NOAEL Teratogen.: >= 175 mg/kg bw
Method:EPA OPPTS 870.3700
Year:
GLP: no data
Test substance:other TS: sodium benzoate, purity not noted
Result:No effect on nidation or on maternal or fetal
survival; the number of abnormalities of softand skeletal tissues did not differ fromcontrols; maternal toxicity was not reported
at any dose applied.
Reliability:(1) valid without restriction
Guideline study
Flag:
Critical study for SIDS endpoint
10-AUG-2001(85)
Species:
rabbitStrain:other: Dutch-belted
Route of admin.: gavage
Exposure period: Day 6-18 of gestation
Frequency oftreatment:
once daily
Duration of test:
Doses:
2.5; 12; 54 or 250 mg/kg/dControl Group:
yes
NOAEL Maternalt.: 250 mg/kg bw
NOAEL Teratogen.: 250 mg/kg bw
Method:EPA OPPTS 870.3700
Year:

UNEP PUBLICATIONS

Sex: female

GLP: no data

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Test substance:
Result:Reliability:
Flag:
10-AUG-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
other TS: sodium benzoate, purity not notedNo effect on nidation or on maternal or fetal
survival; the number of abnormalities of softand skeletal tissues did not differ fromcontrols; maternal toxicity was not reported
at any dose applied.
(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(85)

Species:hamster
Sex: female
Strain:other: golden; outbred
Route of admin.: gavage
Exposure period: Day 6-10 of gestation
Frequency oftreatment:
once daily
Duration of test:
Doses:
3, 14, 65 or 300 mg/kg/dControl Group:
yes
NOAEL Maternalt.: 300 mg/kg bw
NOAEL Teratogen.: 300 mg/kg bw
Method:EPA OPPTS 870.3700
Year:
GLP: no data
Test substance:other TS: sodium benzoate, purity not noted
Result:No effect on nidation or on maternal or fetal
survival; the number of abnormalities of softand skeletal tissues did not differ fromcontrols; maternal toxicity was not reported
at any dose applied.
Reliability:(1) valid without restriction
Guideline study
Flag:
Critical study for SIDS endpoint
10-AUG-2001(85)
Species:rat
Sex: female
Strain:Sprague-Dawley
Route of admin.: i.p.
Exposure period: day 9-11 of gestation
Frequency oftreatment:
once daily
Duration of test:
Doses:
100, 315 or 1000 mg/kg/dControl Group:
other: sodium chloride 90 or 600 mg/kg/d
NOAEL Teratogen.: 315 mg/kg bw
Method:
Year:
GLP:

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Test substance:
Remark:Result:26-JAN-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

no further information available
1000 mg/kg: increased rate of in utero deaths,
reduced fetal body weight(87)

Species:rat
Sex: female
Strain:Sprague-Dawley
Route of admin.: i.p.
Exposure period: day 12-14 of gestation
Frequency oftreatment:
once daily
Duration of test:
Doses:
100, 315 or 1000 mg/kg/dControl Group:
other: sodium chloride 90 or 600 mg/kg/d
NOAEL Teratogen.: 315 mg/kg bw
Method:Year:
GLP:
Test substance:
Remark:no further information available
Result:1000 mg/kg: reduced fetal body weight,
increased rate of in utero deaths, grossanomalies in fetuses
26-JAN-2001(87)
Species:hen
Sex:
Strain:
Leghorn
Route of admin.: other
Exposure period: once
Frequency oftreatment:
single injection in eggs
Duration of test:
Doses:
highest level tested: 5 mg/egg
Control Group:yes
Method:Year:
GLP:
Test substance:
Remark:Fresh fertile eggs were used, 4 test
conditions were used: injection via the aircell and via the yolk twice, preincubation 0 h
and 96 h; total number of eggs treated:
approx. 100.
Result:
LD50 (injection via air cell at 96 h):
4.74 mg/egg; no teratogenic effects in thedeveloping chicken embryo.
26-JAN-2001(88)

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5. TOXICITYBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

Species:hen
Sex:
Strain:other: Ross I stock
Route of admin.: other
Exposure period: once
Frequency oftreatment:
single injection
Duration of test:
Doses:
highest level tested: 0.1 mg/embryo
Control Group:yes
Method:other: Chick Embryotoxicity Screening Test
(CHEST)
Year:
GLP:
Test substance:
Result:no embryotoxicity was observed at aconcentration of 100 ug/embryo
26-JAN-2001(89)
Species:other: chick embryo neural retina Sex:
cells

Strain:Route of admin.: other: in vitro
Exposure period: 24 hours
Frequency oftreatment:
single treatment
Duration of test: 7 days
Doses:
up to cytolethal or solubility limit
Control Group:yes
Method:other: Chick embryo retina cell (CERC) assay
Year:
GLP:
Test substance:other TS: purchased from Sigma Chemical
Method:The chemical was dissolved in Gibco medium 199
or DMSO and adjusted to pH 7.2. At least fiveconcentrations were tested, with six flasks perconcentration.
7-10 E+06 cells were dispersed in 3ml culture
medium, plus the test chemical, and incubatedfor 18-24 hours.
Cell aggregates were counted and the mediumchanged to Gibco 199 without the test chemical.
The cells were cultured for an additional 6
days. Protein content was measured by the Lowry
method and glutamine synthetase activity
measured by a spectrophotometric assay.
Statistics: pairwise comparisons among treatmentgroups were done by ANOVA and concentrationresponse relationships analyzed by general linear
methods (SAS, 1987). A chemical was classified as
active if there was a significant concentrationdependent decrease in glutamine
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Result:19-MAY-2000

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
synthetase activity, protein content or aggregate
size; or increasing trend in aggregate number andat least one concentration group that wassignificantly different (p<0.05) from the control.
Sodium benzoate was classified as inactive in
the CERC assay with LOEL at >34.7mM.
(90)

5.10 Other Relevant Information
Type:
Remark:23-OCT-1995
Type:
Remark:23-OCT-1995
Type:
Remark:Metabolism
The experimental study on the inducibility of
the hepatic and renal hippurate-synthesizing
system by gradually increasing daily i.p. doses(125-375 mg/kg, given between 17 and 21 days) of
sodium benzoate to mice showed no effects.
Sodium benzoate did not induce its own
metabolizing system.
(91)
Metabolism
A 15 mM aqueous solution of sodium benzoate
was shown to inhibit in vitro thenoradrenaline-induced aggregation of platelets
from healthy volunteers by blocking thecyclo-oxygenase-thromboxane enzyme system.
(92)

23-OCT-1995

Metabolism
Six female volunteers (case I) and three malevolunteers (case II) were orally given(case I) 33 or 66 mg sodium benzoate in a softdrink or (case II) a sodium benzoate solution
at a dosage of 20 mg/kg bw..
In case I, 66 to 86 % of the administered dose
was excreted in urine within 3 hours as
hippuric acid (maximum at 0 to 30 minutes); in
case II, approx. 89 % of the administereddose was excreted in urine within 5 hours as
hippuric acid (maximum at 0 to 1 hour).
In case I, the concentration of hippuric acidrecovered to the predose level after 3 hours,
while in case II the concentration of hippuric
acid did not recover to the predose levelwithin 5 hours.
(93)

Type:

Metabolism
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Remark:23-OCT-1995
Type:
Remark:23-OCT-1995
Type:
Remark:23-OCT-1995
Type:
Remark:23-OCT-1995
Type:
Remark:10-AUG-2001
194

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
After i.p. injection of 2.5 to 10 mmol sodium
benzoate/kg bw in male Sprague-Dawley rats,changes in metabolic levels of the liver andin amino acid levels in liver and plasma werenoted.
(94)
Metabolism
Sodium benzoate inhibited the dissolution ofhydrochlorothiazide (HCT) in vitro. In
bioavailability studies with 6 male volunteers,
the rate of increase in meanurine volume after intake of HCT-sodium
benzoate was 6:1 compared to HCT alone.
(95)
Metabolism
In an in vitro study with gastric mucosa frompatients with asthma, atopic eczema andurticaria, the release of histamine andprostaglandin was significantly increased bysodium benzoate at a concentration of 0.4 %.
The mucosa of control persons did not react tosodium benzoate.
(62)
Metabolism
In experiments with isolated rat hepatocytes
and mitochondria, sodium benzoate atconcentrations from 0 to 2.0 mM inhibited
gluconeogenesis (max. 67 %) and urea
production (max. 52 %) in a dose-dependent
manner by depletion of acetyl CoA.
(96)

Toxicity:
I.p. injection of 7.5 mmol/kg ammonium acetatealone produced 10 % mortality in male Swiss
albino mice. Subsequent i.p. administration of
7.5 mmol/kg sodium benzoate resulted in 100 %mortality.
Pretreatment of mice with carbamyl glutamate(2-20 mmol/kg), a structural analogue ofN-acetyl glutamate, reduced mortality to 20 %.
The protective effect of carbamyl glutamate isaccompanied by an increase in urea production
and of carbamyl phosphate synthetase activity.
(97)
UNEP PUBLICATIONSOECD SIDS
5. TOXICITY
Type:
Remark:10-AUG-2001
Type:
Remark:10-AUG-2001

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
Effect on ammonia levels:
Male SD-rats received i.p. injections of saline,
L-norvaline (1 mmol/kg), L-methionine-SRsulfoximine (250 umol/kg), sodium benzoate(2.5-10 mmol/kg) in saline, either alone orin combination. L-norvaline and L-methionine-SRsulfoximine caused an increase in theconcentration of ammonia in plasma and in liver(interference with urea and glutamine
formation). Subsequent injection of sodium
benzoate failed to alleviate ammonia levels,and on the contrary, caused further increase.
Sodium benzoate itself resulted in higher
levels of ammonia in plasma and liver.
Application of glycine did not lower ammonia
levels indicating that other factors besides
glycine may also be necessary for the removalof sodium benzoate.
(98)

Liver perfusion:
In isolated perfused rat liver (livers of male
Wistar rats, body weight 120-150 g), additionof sodium benzoate to the perfusion medium led
to a rapid and marked stimulation of glutamate
release from the liver (maximal glutamate
efflux: 0.9 umol/min/g), which was fully
reversible. Benzoate concentrations as low as
15 uM were effective to stimulate glutamate
release significantly. Simultaneously benzoate
inhibits urea and glutamine synthesis anddiminishes hepatic ammonia uptake.
(99)

5.11 Experience with Human Exposure
Remark:case-report: A 34 year old man reported in1985 recurrent swelling of the upper lips andgums associated with the presence of afissured tongue since he was 10 years old. In
1980 episodes became more frequent and werecaused by the ingestion of different foods,
including wine, sausages, and"hot foods".
Each time, remission occurred spontaneously
within 2 weeks. The patient reacted positivein a double-blind challenge test with sodium
benzoate (see chapter 4.3).
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23-OCT-1995

196

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1
Upon elimination of sodium benzoate and anotherfood additive, tartrazine, from the usual diet,complete remission of the clinicalmanifestation occurred.
(57)

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1(1) Additional references:
Safety data sheet Bayer AG, Leverkusen, 07.01.92
DSM datasheet.
(2) Janssen Chimica (1987/88)(3) Meylan W. and Howard P. 1999. EPIWin Modeling Program.
Syracuse Research Corporation. Environmental Science
Center, 6225 Running Ridge Road, North Syracuse, NY
13212-2510(4) Additional reference:safety data sheet Bayer AG, Leverkusen, 07.01.92.
(5) DSM safety data sheet.
(6) safety data sheet Bayer AG, Leverkusen, 07.01.92(7) Meylan W. and Howard P. 1999. EPIWin Modeling Program.
Syracuse Research Corporation. Environmental Science
Center, 6225 Running Ridge Road, North Syracuse, NY
13212-2510(8) Additional reference:
Hartke, K. In: Hartke, K. & Mutschler, E., ed., Deutsches
Arzneibuch, 9. Ausgabe, Bd. 3, Wissenschaftliche
Verlagsgesellschaft, Stuttgart, 2426-2428 (1986).
(9) Budavari, S. (ed.), The Merck Index. An encyclopedia ofchemicals, drugs, and biologicals. 11th ed., Rahway, New
Jersey, 1357 (1989)(10) Hartke, K. In: Hartke, K. & Mutschler, E., ed., Deutsches
Arzneibuch, 9. Ausgabe, Bd. 3, Wissenschaftliche
Verlagsgesellschaft, Stuttgart, 2426-2428 (1986)(11) Sunshine, I., CRC Handbook of analytical toxicology. The
Chemical Rubber Co., Cleveland, 282-283 (1969)(12) Meylan W. and Howard P. (1999) EPIWin Modeling Program.
Syracuse Research Corporation. Environmental Science
Center, 6225 Running Ridge Road, North Syracuse, NY
13212-2510

UNEP PUBLICATIONS

197

OECD SIDS
6. REFERENCES

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1(13) Additional references:
Battersby, N.S. & Wilson, V., Appl. Environ. Microbiol.
55:433-439 (1989)
Birch, R.R. et al., Chemosphere 19, 1527-1550 (1989)
Commission of the European Communities,
Degradation/Accumulation Subgroup; Ring-Test Programme
1981-1982; Assessement of the biodegradability ofchemicals in water by manometric respirometry (1982).
DeFulvio, S. et al. Biotic Degradation of organic
compounds in seawater: shake-flask method. Rapp. Istisan
1123-3117(1985) Grbic-Galic, D. & Young, L.Y., Appl.
Environ. Microbiol. 50,292-297 (1985)
King, E.F. & Painter, H.A., Ring-test programme 1981-82.
Assessment of biodegradability of chemicals in water bymanometric respirometry, Commission of the European
Communities, Luxembourg, Contract No. W/81/217 (1983)
Kobayashi, T. et al., Water Sci. Technol. 21, 55-65(1989) Nyholm, N. and Kristensen, P. Ecotox. Environ.
Safety 23:161-172 (1992)
Richterich, K. & Steber, J., Chemosphere 19,1643-1654(1989) Shlomi, E.R. et al., Microb. Ecol. 4, 249-261(1978)(14) Salanitro, J.P. et al., Water Sci. Technol. 20, 125-130(1988)(15) Battersby, N.S. & Wilson, V., Appl. Environ. Microbiol.
55, 433-439 (1989)(16) Courtes, R.,et al., Ready Biodegradability Test in
Seawater: A New Methodological Approach. Ecotox Environ.
Safety 31:142-148 (1995)(17) Birch, R.R. et al., Chemosphere 19, 1527-1550 (1989)(18) Commission of the European Communities,
Degradation/Accumulation Subgroup; Ring-Test Programme
1981-1982; Assessment of the biodegradability ofchemicals in water by manometric respirometry (1982).
(19) DeFulvio, S. et al. Biotic Degradation of organic
compounds in seawater: shake-flask method. Rapp. Istisan
1123-3117 (1985)(20) Nyholm, N. and Kristensen, P.
23:161-172 (1992)

198

UNEP PUBLICATIONS

Ecotox. Environ. Safety

OECD SIDS
6. REFERENCES

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1(21) King, E.F. & Painter, H.A., Ring-test programme 1981-82.
Assessment of biodegradability of chemicals in water bymanometric respirometry, Commission of the European
Communities, Luxembourg, Contract No. W/81/217 (1983)(22) Richterich, K. & Steber, J., Chemosphere 19, 1643-1654(1989)(23) Grbic-Galic, D. & Young, L.Y., Appl. Environ. Microbiol.
50, 292-297 (1985)(24) Kobayashi, T. et al., Water Sci. Technol. 21, 55-65(1989)(25) Shlomi, E.R. et al., Microb. Ecol. 4, 249-261 (1978)(26) Nyholm, N. & Kristensen, P., Screening test methods forassessment of biodegradability of chemical substances in
sea water. Commission of the European Communities, Water
Quality Institute Denmark, Contract No.
84-B-6601-11-001-11-N (1987)(27) De Fulvio, S. et al., Rapp. Istisan, 85/27 (1985)(28) Sleat, R. & Robinson, J.P., J. Gen. Microbiol. 129,141-152 (1983)(29) Kuhn, E.P. et al., Appl. Environ. Microbiol. 54, 490-496(1988)(30) Additional reference:
Ewell, W.S. et al., Environ. Toxicol. Chem. 5, 831-840(1986)(31) Geiger, D.L. et al., Acute toxicities of organic
chemicals to fathead minnows (Pimephales promelas),Vol. 2, University of Wisconsin, 139-140 (1985)(32) Ewell, W.S. et al., Environ. Toxicol. Chem. 5, 831-840(1986)(33) Additional reference:
Anderson, B.G., Sewage Works J. 18, 82-87 (1946)(34) Anderson, B.G., Sewage Works J. 18, 82-87 (1946)(35) Nikkilae, O.E., Fette, Seifen, Anstrichmittel 57, 494-98(1955)(36) Hatanaka, J. et al., Jpn. J. Exp. Med. 52, 243-253 (1982)
UNEP PUBLICATIONS

199

OECD SIDS
6. REFERENCES

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1(37) King, A.D., Jr. and Halbrook, W.U., J. Food Sci. 52,
1252-1254, 1266 (1987)(38) King, A.D., Jr. et. al., Appl. Microbiol. 18, 166-173(1969)(39) Roland, J.O. and Beuchat, L.R., J. Food Sci. 49, 402-406(1984)(40) Roland, J.O. et al., J. Food Prot. 47, 237-241 (1984)(41) Schelhorn, M. v., Dtsch. Lebensmitt. Rdsch. 47, 128-34(1951)(42) Rahn, O. and Conn, J.E., Industr. Engin. Chem. 36, 185-87(1944)(43) Deuel, H.J., Jr. et al., Food Res. 19, 1-12 (1954)(44) Smyth, H.F., Jr. & Carpenter, C.P., J. Ind. Hyg. Toxicol.
30, 63-68 (1948)(45) Loeser, E., Bayer AG data, Akute orale Toxizitaet (1977)(46) Hager, G.P. et al., J. Am. Pharm. Assoc. 31, 253-255(1942)(47) RCC NOTOX, Primary skin irritation/corrosion study withnatrium benzoate in rabbits (study no. 014658). RCC NOTOX
B.V., 's-Hertogenbosch(48) Loeser, E., Bayer AG data, Untersuchungen zur Haut- undSchleimhautvertraeglichkeit (1977)(49) Stol, M. et al., Biomaterials 9, 273-276 (1988)(50) RCC NOTOX, Acute eye irritation/corrosion study withnatrium benzoate in rabbits (study no. 014669). RCC NOTOX
B.V., 's-Hertogenbosch(51) Brasch, J. et al., Dermatosen 41, 71-76 (1993)(52) Nethercott, J.R. et al., J. Occ. Med. 26, 734-736 (1984)(53) Toxicity profile benzoic acid and its common salts(1989). BIBRA UK.
(54) Young E. et al. (1987)
200

J. Royal Coll. Physicians 21:241.

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1(55) BIBRA profile 1989.
(56) Primary references:
Doeglas HMG. (1975) Br. J. Derm. 93:135.
Freedman BJ. (1977) Clin. Allergy 7:407.
Genton G. et al. (1985) J. Allergy Clin Immun. 76:40.
Juhlin L. et al. (1972) J. Allergy Clin Immun. 50: 2.
Moneret-Vautrin DA. (1986) J. Allergy Clin Immun.
78:1039. Ortolani C. et al. (1986) J. Allergy Clin Immun.
77:151. Rosenhall L. (1982) Eur J Respir. Dis. 63:410.
Tarlo SM. & Broder I. (1980) J. Allergy Clin Immun.
65:226.
(57) Pachor, M.L. et al., Oral Surg. Oral Med. Oral Pathol.
67, 393-395 (1989)(58) Van Bever, H.P. et al., Allergy 44, 588-594 (1989)(59) Vieluf, D. et al., Arch. Dermatol. Res. 281, 544-591(1990)(60) Pevny, I. et al., Dermatosen 29, 123-130 (1981)(61) Michils, A. et al., Lancet 337, 1424-1425 (1991)(62) Schaubschlaeger, W.W. et al., Int. Arch. Allergy Appl.
Immunol. 96, 97-101 (1991)(63) Additional references:
Fanelli, G.M. & Halliday, S.L., Arch. Int. Pharmacodyn.
144, 120-125 (1963) Kieckebusch, W. & Lang, K., Arzneim.Forsch. 10, 1001-1003 (1960)
Rost, E. et al., Arb. a. d. Kaiserl. Gesundheitsamte 45,425-490 (1913)
White, A., Yale J. Biol. Med. 13, 759-768 (1941)(64) Toth, B., Fundam. Appl. Toxicol. 4, 494-496 (1984)(65) Fujitani, T., Toxicol. Lett. 69, 171-179 (1993)(66) Sodemoto, Y. & Enomoto, M., J. Environ. Pathol. Toxicol.
4, 87-95 (1980)(67) Fanelli, G.M. & Halliday, S.L., Arch. Int. Pharmacodyn.
144, 120-125 (1963)(68) Kieckebusch, W. & Lang, K., Arzneim.-Forsch. 10, 10011003 (1960)
UNEP PUBLICATIONS

201

OECD SIDS
6. REFERENCES

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1(69) White, A., Yale J. Biol. Med. 13, 759-768 (1941)(70) Rost, E. et al., Arb. a. d. Kaiserl. Gesundheitsamte 45,425-490 (1913)(71) Additional references:
Ishidate M. and Yoshikawa K. Arch. Toxicol. Suppl. 4:4144 (1980) Prival, M.J. et al., Mutat. Res. 260, 321-329(1991)(72) Ishidate, M., Jr. et al., Food Chem. Toxicol. 22, 623-636(1984)(73) Additional references:Abe, S. & Sasaki, M., J. Nat. Cancer Inst. 58, 1635-1641(1977) Ishidate M. and Yoshikawa K. Arch. Toxicol.
Suppl. 4:41-44(1980)(74) Litton Bionetics Inc., Mutagenic evaluation of compound
FDA 71-37, Sodium Benzoate, Food and Drug Administration,
Washington, D.C., PB 245453, 95 S. (1974)(75) Ishidate, M., Jr. & Odashima, S., Mutat. Res. 48, 337-354(1977)(76) Prival, M.J. et al., Mutat. Res. 260, 321-329 (1991)(77) Abe, S. & Sasaki, M., J. Nat. Cancer Inst. 58, 1635-1641(1977)(78) Xing, W. & Zhang, Z., Mutat. Res. 241, 109-113 (1990)(79) Njagi, G.D.E. & Gopalan, H.N.B., Mutat. Res. 102, 213-219(1982)(80) Nonaka, M., Environ. Mol. Mutagen. 14, 143 (1989)(81) Ishizaki, M. & Ueno, S., J. Food Hyg. Soc. Japan 30,
447-451 (1989)(82) Ishidate M. and Yoshikawa K.
44(1980)

Arch. Toxicol. Suppl. 4:41-(83) Ito, N. et al., CRC Critical Rev. Toxicol. 19, 385-415(1989)(84) Additional references:
Daston, G.P. et al. Fund Appl Toxicol. 26:203-210.
(1995) Jelinek, R. et al., Indian J. Exp. Biol. 23:588202

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

BENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

595 (1985) Minor, J.L. & Becker, B.A., Toxicol. Appl.
Pharmacol.19:373 (1971) Verrett, M.J. et al., Toxicol.
Appl. Pharmacol.56:265-273 (1980)(85) Food and Drug Research Laboratories, Inc., Teratologic
evaluation of FDA 71-37 (Sodium benzoate). East Orange,
New Jersey, Food and Drug Administration, Washington,
D.C., PB 221777 (1972)(86) Onodera, H. et al., Eisei Shikenjo Hokoku 96, 47-55(1978)(87) Minor, J.L. & Becker, B.A., Toxicol. Appl. Pharmacol. 19,373 (1971)(88) Verrett, M.J. et al., Toxicol. Appl. Pharmacol. 56, 265273(1980)(89) Jelinek, R. et al., Indian J. Exp. Biol. 23, 588-595(1985)(90) Daston, G.P. et al.
(1995)

Fund Appl Toxicol.

26:203-210.

(91) Qureshi, I.A. et al., Biochem. Int. 19, 657-666 (1989)(92) Williams, W.R. et al., Clin. Exp. Allergy 19, 533-537(1989)(93) Fujii, T. et al., J. Food Hyg. Soc. Japan, 32, 177-182(1991)(94) Palekar, A.G. & Kalbag, S.S., Biochem. Med. Metabol.
Biol. 46, 52-58 (1991)(95) Hashem, F. & El-Din, E.E.Z., Pharm. Ind. 54, 381-384(1992)(96) Ji, H. & Tremblay, G.C., Biochem. Arch. 9, 33-40 (1993)(97) O'Connor, J.E. et al., Eur. J. Pediatr. 148, 540-542(1989)(98) Palekar, A.G. et al., Biochem. Med. Metab. Biol. 41,
64-69(1989)(99) Haeussinger, D. et al., Biochem. J. 264, 837-843 (1989)

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7. RISK ASSESSMENTBENZOATESDATE: 10-AUG-2001
SUBSTANCE ID: 532-32-1

7.1 End Point Summary

7.2 Hazard Summary

7.3 Risk Assessment

204

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S e t( POTASSIUM BENZOATE; CAS: 582-25-2)

Existing Chemical
CAS No.
EINECS Name
EINECS No.
Molecular Formula

ID: 582-25-2
582-25-2
potassium benzoate
209-481-3
C7H6O2.K

Producer Related Part
Company:
Creation date:

Bayer Corporation
21-OCT-1999

Substance Related Part
Company:
Bayer Corporation
Creation date:21-OCT-1999

Memo:

Bayer Corporation

Printing date:
Revision date:
Date of last Update:

10-AUG-2001

Number of Pages:

21

10-AUG-2001

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

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1. GENERAL INFORMATIONPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

1.0.1 OECD and Company Information
Type:
Name:

Street:Town:
Country:lead organisation
American Chemistry Council (formerly Chemical
Manufacturers Association), Benzoates HPV
Panel
1300 Wilson Boulevard
22209 Arlington, VA
United States

10-AUG-2001
Type:
Name:
Country:

cooperating company
ATOFINA Chemicals, Inc
United States

10-AUG-2001
Type:
Name:
Street:Town:
Country:

cooperating company
Bayer Corporation
100 Bayer Road
PA 15205-9741 Pittsburgh
United States

06-JUL-2000
Type:
Name:
Country:

cooperating company
DSM Fine Chemicals
Netherlands

06-JUL-2000
Type:
Name:
Country:

cooperating company
Noveon, Inc.
United States

10-AUG-2001
Type:
Name:
Country:

cooperating company
Velsicol Chemical Corporation
United States

06-JUL-2000
1.0.2 Location of Production Site

1.0.3 Identity of Recipients
206

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1. GENERAL INFORMATIONPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

1.1 General Substance Information
1.1.0 Details on Template
1.1.1 Spectra

1.2 Synonyms

1.3 Impurities

1.4 Additives

1.5 Quantity

1.6.1 Labelling

1.6.2 Classification

1.7 Use Pattern
1.7.1 Technology Production/Use

1.8 Occupational Exposure Limit Values

1.9 Source of Exposure

1.10.1 Recommendations/Precautionary Measures
1.10.2 Emergency Measures

1.11 Packaging

1.12 Possib. of Rendering Subst. Harmless

1.13 Statements Concerning Waste
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1. GENERAL INFORMATIONPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

1.14.1 Water Pollution
1.14.2 Major Accident Hazards
1.14.3 Air Pollution

1.15 Additional Remarks

1.16 Last Literature Search
Type of Search:
Date of Search:

Internal and External
07-SEP-1999

Remark:Only HPV endpoints: TOXLINE data base andinternal studies

10-AUG-2001
1.17 Reviews

1.18 Listings e.g. Chemical Inventories

208

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2. PHYSICO CHEMICAL DATAPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

2.1 Melting Point
Value:
Method:Adapted Joback
Year:
GLP:
Testsubstance:
Reliability:
Flag:
10-AUG-2001

330.6 degree C
other: (calculated) MPBPWIN (v1.31) Program;
Method1999
noother TS: molecular structure(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(1)

2.2 Boiling Point
Value:
Method:Year:
GLP:
Testsubstance:
Reliability:
Flag:
10-AUG-2001

464.9 degree C
other: (calculated) MPBPWIN (v1.31) Program;
Adapted Stein and Brown Method1999
noother TS: molecular structure(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(1)

2.3 Density
2.3.1 Granulometry

2.4 Vapour Pressure
Value:
Method:Year:
GLP:
Testsubstance:
Reliability:
Flag:
10-AUG-2001.00000000489 hPa at 25 degree C
other (calculated): MPBPWIN (v1.31) Program;
Modified Grain Method1999
noother TS: molecular structure(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(1)

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2. PHYSICO CHEMICAL DATAPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

2.5 Partition Coefficientlog Pow:
Method:Year:
GLP:
Testsubstance:
Reliability:
Flag:
10-AUG-2001-2.269other (calculated): Log Kow(version 1.65
estimate)1999
noother TS: molecular structure(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(1)

2.6.1 Water Solubility
Value:
Method:Testsubstance:
Reliability:
Flag:
10-AUG-2001
Value:
Method:Year:
GLP:
Testsubstance:
Reliability:
Flag:
10-AUG-2001

556 g/l at 20 degree C
otherother TS: sodium benzoate(2) valid with restrictions
Data from Handbook or collection of data
Critical study for SIDS endpoint(2)> 1000 g/l at 25 degree C
other: (calculated) WSKOW v1.36 Program
1999
noother TS: molecular structure(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(1)

2.6.2 Surface Tension

2.7 Flash Point

2.8 Auto Flammability

2.9 Flammability

210

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2. PHYSICO CHEMICAL DATAPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

2.10 Explosive Properties

2.11 Oxidizing Properties

2.12 Additional Remarks

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3. ENVIRONMENTAL FATE AND PATHWAYSPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

3.1.1 Photodegradation
Type:
air
Conc. of subst.: at 25 degree C
INDIRECT PHOTOLYSIS
Sensitizer:
OH
Conc. of sens.: 1560000 molecule/cm3
Rate constant: .0000000000017775 cm3/(molecule * sec)
Degradation:
50 % after 72.2 hour(s)Method:other (calculated): AOP Program (v1.89)
Year:
1999
GLP: noTest substance:other TS: molecular structure
Reliability:(2) valid with restrictions
Accepted calculation method
Flag:
Critical study for SIDS endpoint
10-AUG-2001(1)

3.1.2 Stability in Water
Type:
Method:Year:
Test substance:
Remark:GLP:
Based on structure and organic chemistry rules(e.g. bonding in organic molecules, activationenergy, reactivity, transformations, addition,
substitution, elimination) no hydrolysis will
occur at pH ranges 4 - 11.

26-JAN-2001
3.1.3 Stability in Soil

3.2 Monitoring Data (Environment)

3.3.1 Transport between Environmental Compartments
Type:fugacity model level III
Media:
other: air - water - soil - sediment
Air (Level I):
Water (Level I):
Soil (Level I):
Biota (L.II/III):
Soil (L.II/III):
Method:other: EPIWin Modeling Program

212

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3. ENVIRONMENTAL FATE AND PATHWAYS

Year:
Result:
Air
Water
Soil

Distribution(percent)
1.61e-007
45.3
54.6

Sediment

Reliability:
Flag:
10-AUG-2001

Half-Life
(hr)
144
360
360

0.0755POTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

Emissions Fugacity(kg/hr)(atm)
1000
4.83e-019
1000
1.38e-020
1000
6.16e-019

1.44e+003

0Persistence Time: 421 hr
Reaction Time:520 hrAdvection Time:
2.21e+003 hr
Percent Reacted: 80.9
Percent Advected: 19.1
(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(1)

3.3.2 Distribution

3.4 Mode of Degradation in Actual Use

3.5 Biodegradation
Type:
Inoculum:
Degradation:
Method:Year:
Test substance:
Reliability:
Flag:
10-AUG-2001

aerobic
80.9 % after 22 dayother: (calculated) Fugacity Level III
1999
GLP: noother TS: molecular structure(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint
(1)

Type:
aerobic
Inoculum:
activated sludge, domestic
Concentration:
50 mg/l related to Test substance
Degradation:
ca. 90 % after 7 day
Result:readily biodegradable
Method:OECD Guide-line 301 B "Ready Biodegradability:
Modified Sturm Test (CO2 evolution)"

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3. ENVIRONMENTAL FATE AND PATHWAYS

Year:
Test substance:
Remark:Test condition:
Reliability:
Flag:
10-AUG-2001
Type:
Inoculum:
Concentration:
Degradation:
Method:Year:
Test substance:
Method:Remark:Result:Reliability:
Flag:
10-AUG-2001
Type:
Inoculum:
Method:Year:
Test substance:
Remark:1981
GLP: no data
other TS: sodium benzoate
See IUCLID on sodium benzoate (CAS# 532-32-1);
the biodegradation of the potassium salt would
be similar to the sodium salt.
temperature = 25 degree C(1) valid without restriction
Guideline study
Critical study for SIDS endpoint(3)
anaerobic
other bacteria: anaerobic sewage, domestic andindustrial
50 mg/l related to DOC (Dissolved Organic
Carbon)93 % after 7 dayother: see below
GLP: no data
other TS: sodium benzoate
2-3 g sludge plus sodium benzoate (concentrationequivalent to 50 mg Carbon/liter or 85 mg
substance/l).
Controls and tests done in triplicate.
Temperature = 35 degree C.
Measured gas production (CH4 + CO2).
See IUCLID on sodium benzoate (CAS# 532-32-1);
the biodegradation of the potassium salt would
be similar to the sodium salt.
Degradation is expressed as percentage oftheoretical methane production based on the
stoichiometry of degradation.
(2) valid with restrictions
Critical study for SIDS endpoint
(4)

GLP:
See IUCLID on benzoic acid (CAS# 65-85-0); thepotassium salt is expected to immediately
dissociate and form benzoic acid in an aqueous
environment.

10-AUG-2001

214

POTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

3.6 BOD5, COD or BOD5/COD Ratio

3.7 Bioaccumulation
Species:
Exposure period:
Concentration:
BCF:
Elimination:
Method:Year:
Test substance:
Result:3.16
other: (calculated) BCF Program (v2.13)
GLP: noother TS: molecular structure
Estimated Log BCF = 0.500 (BCF = 3.162)
Log Kow (estimated) : 1.87
Log Kow (experimental): 1.87
Log Kow used by BCF estimates:

Reliability:
Flag:
10-AUG-2001

1.87

Equation Used to Make BCF estimate:
Log BCF = 0.50 (Ionic; Log Kow dependent)(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint(1)

3.8 Additional Remarks

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OECD SIDS
4. ECOTOXICITYPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

AQUATIC ORGANISMS
4.1 Acute/Prolonged Toxicity to Fish
Type:
Species:
Exposure period:
Unit:
LC50:
Method:Year:
Test substance:
Remark:Result:other: ECOSAR calculations
other: fresh water fish
96 hour(s)g/lAnalytical monitoring: no> 1000other: ECOSAR (v 0.99)
1999
GLP: noother TS: molecular structure
ECOSAR class: Neutral organics. Chemical may
not be soluble enough to measure the predictedeffect.
ECOSAR Class Organism
Duration End Pt
mg/L===========================================================
Neutral Organic SAR: Fish 14-day
LC50
1.13e+006(Baseline Toxicity)
Neutral Organics: Fish
96-hr
LC50
Neutral Organics: Fish
14-dayLC50
Neutral Organics: Fish
30-dayChV
Reliability:(2) valid with restrictions
Accepted calculation method
Flag:
Critical study for SIDS endpoint
10-AUG-2001
Type:
Species:
Exposure period:
Unit:
Method:Year:
Test substance:
Remark:(1)

Analytical monitoring:
GLP:
See IUCLID on sodium benzoate (CAS# 532-32-1);
the toxicity of the potassium salt would be
similar to the sodium salt.

10-AUG-2001

216

1.23e+006
1.13e+006
79360.031

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITYPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

4.2 Acute Toxicity to Aquatic Invertebrates
Type:
Species:
Exposure period:
Unit:
EC50:
Method:Year:
Test substance:
Remark:Result: ECOSAR

Daphnia magna (Crustacea)
48 hour(s)g/lAnalytical monitoring: no
978other: ECOSAR (v 0.99)
1999
GLP: noother TS: molecular structure
ECOSAR class: Neutral organics. Chemical may
not be soluble enough to measure the predictedeffect.
Class
Organism
Duration End Pt
mg/L===========================================================
Neutral Organics: Daphnid
48-hr
LC50
9.78e+005
Neutral Organics: Daphnid
16-dayEC507746.435
Neutral Organics: Mysid Shrimp 96-hr
LC50
7.45e+006
Reliability:(2) valid with restrictions
Accepted calculation method
Flag:
Critical study for SIDS endpoint
10-AUG-2001
(1)
Type:
Species:
Exposure period:
Unit:
Method:Year:
Test substance:
Remark:Flag:
10-AUG-2001

Analytical monitoring:
GLP:
See IUCLID on sodium benzoate (CAS# 532-32-1);
the toxicity of the potassium salt would be
similar to the sodium salt.
Critical study for SIDS endpoint

4.3 Toxicity to Aquatic Plants e.g. Algae
Species:
Endpoint:
Exposure period:
Unit:
EC50:
Method:Year:other algae: Green Algae
biomass
96 hour(s)g/lAnalytical monitoring: no478
other: ECOSAR (v 0.99)
1999
GLP: noUNEP PUBLICATIONS

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OECD SIDS
4. ECOTOXICITYPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

Test substance:other TS: molecular structure
Remark:ECOSAR class: Neutral organics.
Result:ECOSAR Class
Organism
Duration End Pt

mg/L=============================================================
Neutral Organics: Green Algae
96-hr EC50
4.78e+005
Neutral Organics: Green Algae
96-hr
ChV
4053.982
Reliability:(2) valid with restrictions
Accepted calculation method
Flag:
Critical study for SIDS endpoint
10-AUG-2001(1)

4.4 Toxicity to Microorganisms e.g. Bacteria
Type:Species:
Exposure period:
Unit:
Method:Year:
Test substance:
Remark:Analytical monitoring:
GLP:
See IUCLID on sodium benzoate (CAS# 532-32-1);
the toxicity of the potassium salt would be
similar to the sodium salt.

10-AUG-2001

4.5 Chronic Toxicity to Aquatic Organisms
4.5.1 Chronic Toxicity to Fish
4.5.2 Chronic Toxicity to Aquatic Invertebrates

218

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4. ECOTOXICITYPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

TERRESTRIAL ORGANISMS

4.6.1 Toxicity to Soil Dwelling Organisms
4.6.2 Toxicity to Terrestrial Plants
4.6.3 Toxicity to other Non-Mamm. Terrestrial Species

4.7 Biological Effects Monitoring

4.8 Biotransformation and Kinetics

4.9 Additional Remarks

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OECD SIDS
5. TOXICITYPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

5.1 Acute Toxicity
5.1.1 Acute Oral Toxicity
Type:Species:
Strain:Sex:
Number of
Animals:
Vehicle:Value:
Method:Year:
Test substance:
Reliability:
Flag:
10-AUG-2001
Type:
Species:
Strain:Sex:
Number of
Animals:
Vehicle:Value:
Method:Year:
Test substance:
Reliability:
Flag:
10-AUG-2001
Type:
Species:
Strain:Sex:
Number of
Animals:
Vehicle:Value:
Method:
Year:

220

LD50
rat

> 10000 mg/kg bw
GLP:other TS: potassium benzoate; purity not noted(4) not assignable
Original reference in foreign language
Critical study for SIDS endpoint
(5)
LD50
mouse

> 10000 mg/kg bw
GLP:other TS: potassium benzoate; purity not noted(4) not assignable
Original reference in foreign language
Critical study for SIDS endpoint(5)
LD50
guinea pig> 10000 mg/kg bw
GLP:

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Test substance:
Reliability:
Flag:
10-AUG-2001

POTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

other TS: potassium benzoate; purity not noted(4) not assignable
Original reference in foreign language
Critical study for SIDS endpoint(5)

5.1.2 Acute Inhalation Toxicity
Type:Species:
Strain:Sex:
Number of
Animals:
Vehicle:Exposure time:
Value:
Method:Year:
Test substance:
Remark:GLP:
See IUCLID on benzoic acid (CAS# 65-85-0); theloss of acidity due to the potassium salt
should decrease toxicity.

10-AUG-2001
5.1.3 Acute Dermal Toxicity
Type:Species:
Strain:Sex:
Number of
Animals:
Vehicle:Value:
Method:Year:
Test substance:
Remark:GLP:
See IUCLID on benzoic acid (CAS# 65-85-0); theloss of acidity due to the potassium salt
should decrease toxicity.

10-AUG-2001
5.1.4 Acute Toxicity, other Routes

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5. TOXICITYPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

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:
Remark:GLP:
See IUCLID on sodium benzoate (CAS# 532-32-1);
the irritating ability of the potassium salt
would be similar to the sodium salt.

10-AUG-2001
5.2.2 Eye Irritation
Species:
Concentration:
Dose:
Exposure Time:
Comment:
Number of
Animals:
Result:EC classificat.:
Method:Year:
Test substance:
Remark:GLP:
See IUCLID on sodium benzoate (CAS# 532-32-1);
the irritating ability of the potassium salt
would be similar to the sodium salt.

10-AUG-2001
5.3 Sensitization

222

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5. TOXICITYPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

5.4 Repeated Dose Toxicity
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Control Group:
Method:Year:
Test substance:
Remark:Sex:

GLP:
See IUCLID on sodium benzoate (CAS# 532-32-1);
the toxicity of the potassium salt would be
similar to the sodium salt.

10-AUG-2001

5.5 Genetic Toxicity 'in Vitro'
Type:
System oftesting:
Concentration:
Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:
Result:Reliability:

Flag:
10-AUG-2001

Bacillus subtilis recombination assay
Bacillus subtilis H17, M45
1-20 mg/disk; vehicle: water and ethanol(1:1)

with and without
positive
GLP:
other TS: potassium benzoate; purity not noted
Authors judged results as positive.
(3) invalid
Significant methodological deficiencies: onedose tested
Critical study for SIDS endpoint
(6)

Type:
System oftesting:
Concentration:

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5. TOXICITY

Cytotoxic Conc.:
Metabolicactivation:
Result:
Method:Year:
Test substance:
Remark:POTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

GLP:
See IUCLID on sodium benzoate (CAS# 532-32-1);
the toxicity of the potassium salt would be
similar to the sodium salt.

10-AUG-2001

5.6 Genetic Toxicity 'in Vivo'
Type:
Species:
Strain:Route of admin.:
Exposure period:
Doses:
Result:
Method:Year:
Test substance:
Remark:Cytogenetic assay
Sex:

GLP:
See IUCLID on sodium benzoate (CAS# 532-32-1);
the toxicity of the potassium salt would be
similar to the sodium salt.

10-AUG-2001

5.7 Carcinogenicity
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Post. obs.
period:Doses:
Result:Control Group:
Method:
Year:

224

Sex:

GLP:

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Test substance:
Remark:POTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

See IUCLID on sodium benzoate (CAS# 532-32-1);
the toxicity of the potassium salt would be
similar to the sodium salt.

10-AUG-2001

5.8 Toxicity to Reproduction
Type:
Species:
Sex:
Strain:Route of admin.:
Exposure Period:
Frequency oftreatment:
Duration of test:
Doses:
Control Group:
Method:Year:
GLP:
Test substance:
Remark:A 4-generation reprotoxicity test with benzoic
acid revealed no reproductive effects. Therefore
no indication for reprotoxicity for the benzoic
acid potassium salt.
See IUCLID on benzoic acid (CAS# 65-85-0); theloss of acidity due to the potassium salt should
decrease toxicity.
10-AUG-2001

5.9 Developmental Toxicity/Teratogenicity
Species:
Strain:Route of admin.:
Exposure period:
Frequency oftreatment:
Duration of test:
Doses:
Control Group:
Method:
Year:

Sex:

GLP:

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5. TOXICITY

Test substance:
Remark:POTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

See IUCLID on sodium benzoate (CAS# 532-32-1);
the toxicity of the potassium salt would be
similar to the sodium salt.

10-AUG-2001

5.10 Other Relevant Information

5.11 Experience with Human Exposure

226

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

POTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2(1) Meylan W. and Howard P. 1999. EPIWin Modeling Program.
Syracuse Research Corporation. Environmental Science
Center, 6225 Running Ridge Road, North Syracuse, NY
13212-2510(2) Budavari, S. (ed.), The Merck Index. An encyclopedia ofchemicals, drugs, and biologicals. 11th ed., Rahway, New
Jersey, 1357 (1989)(3) Salanitro, J.P. et al., Water Sci. Technol. 20, 125-130(1988)(4) Battersby, N.S. & Wilson, V., Appl. Environ. Microbiol.
55: 433-439 (1989)(5) Kravets-Bekker A.A. & Ivanova O.P. 1970. Faktory Vnesh.
Sredy Ikh Znachenie Zdorov'ya Naseleniya No.2, 125: in
BIBRA Toxicity Profiles, BIBRA International, GreatBritain.
(6) Ishizaki, M. & Ueno, S., J. Food Hyg. Soc. Japan 30,
447-451 (1989)

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7. RISK ASSESSMENTPOTASSIUM BENZOATEDATE: 10-AUG.-2001
SUBSTANCE ID: 582-25-2

7.1 End Point Summary

7.2 Hazard Summary

7.3 Risk Assessment

228

UNEP PUBLICATIONSOECD SIDSBENZYL ALCOHOLI U C L I D D a t a S e t( BENZYL ALCOHOL; CAS: 100-51-6)

Existing Chemical
CAS No.
EINECS NameEC No.
TSCA Name
Molecular Formula

ID: 100-51-6
100-51-6
benzyl alcohol
202-859-9
Benzenemethanol
C7H8O

Producer Related Part
Company:
Creation date:

Bayer Corporation
15-JUL-1999

Substance Related Part
Company:
Bayer Corporation
Creation date:
15-JUL-1999
Memo:

Bayer Corporation

Printing date:
Revision date:
Date of last Update:

14-FEB-2002

Number of Pages:

82

14-FEB-2002

Chapter (profile):
Chapter: 1, 2, 3, 4, 5, 6, 7, 8, 10
Reliability (profile): Reliability: without reliability, 1, 2,
3, 4
Flags (profile):
Flags: without flag, confidential, nonconfidential, WGK (DE), TA-Luft (DE),Material Safety Dataset, Risk Assessment,
Directive 67/548/EEC, SIDSUNEP PUBLICATIONS

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OECD SIDS
1. GENERAL INFORMATIONBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

1.0.1 Applicant and Company Information
Type:
Name:
Street:Town:
Country:lead organisation
American Chemistry Council, Benzoates Panel
1300 Wilson Boulevard
22209 Arlington, VA
United States

14-DEC-2000
Type:
Name:
Country:

cooperating company
B.F. Goodrich
United States

26-MAY-2000
Type:
Name:
Country:

cooperating company
Bayer Corporation
United States

14-DEC-2000
Type:
Name:
Country:

cooperating company
DSM Fine Chemicals
Netherlands

14-DEC-2000
Type:
Name:
Country:

cooperating company
Elf Atochem NA
United States

26-MAY-2000
Type:
Name:
Country:

cooperating company
Velsicol Chemical Corporation
United States

26-MAY-2000
Type:
Name:

lead organisation
American Chemistry Council, Benzoates Panel

16-JAN-2001

230

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATIONBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

1.0.2 Location of Production Site, Importer or Formulator
1.0.3 Identity of Recipients
1.0.4 Details on Category/Template

1.1.0 Substance Identification
1.1.1 General Substance Information
1.1.2 Spectra

1.2 Synonyms and Tradenames

1.3 Impurities

1.4 Additives

1.5 Total Quantity

1.6.1 Labelling
1.6.2 Classification
1.6.3 Packaging

1.7 Use Pattern
1.7.1 Detailed Use Pattern
1.7.2 Methods of Manufacture

1.8 Regulatory Measures
1.8.1 Occupational Exposure Limit Values
1.8.2 Acceptable Residues Levels

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1. GENERAL INFORMATION

1.8.3 Water Pollution
1.8.4 Major Accident Hazards
1.8.5 Air Pollution
1.8.6 Listings e.g. Chemical Inventories

1.9.1 Degradation/Transformation Products
1.9.2 Components

1.10 Source of Exposure

1.11 Additional Remarks

1.12 Last Literature Search

1.13 Reviews

232

UNEP PUBLICATIONSBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

OECD SIDS
2. PHYSICO-CHEMICAL DATABENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

2.1 Melting Point
Value:-15.2 degree C

Method:Test substance:other: Handbook value
other TS: benzyl alcohol, purity not noted

Reliability:(2) valid with restrictions
Data from Handbook or collection of data
Critical study for SIDS endpoint

Flag:
14-FEB-2002(1)

Value:-15.3 degree C

Test substance:other TS: benzyl alcohol, purity not noted

12-FEB-2002(2)

2.2 Boiling Point
Value:

205.3 degree C at 1013 hPa

Method:Test substance:other: Handbook value
other TS: benzyl alcohol, purity not noted

Reliability:(2) valid with restrictions
Data from Handbook or collection of data
Critical study for SIDS endpoint

Flag:
14-FEB-2002
Value:(1)
205.4 degree C at 1013 hPa

19-JAN-2001(2)

2.3 Density
Type:
Value:

density
1.041 g/cm³ at 24 degree C

Method:Test substance:other: Handbook value
other TS: benzyl alcohol, purity not noted

Reliability:(2) valid with restrictions
Data from Handbook or collection of data

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OECD SIDS
2. PHYSICO-CHEMICAL DATABENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Flag:
14-FEB-2002

Critical study for SIDS endpointType:
Value:

density
1.0442 g/cm³ at 22.5 degree C(1)

19-JAN-2001(2)

2.3.1 Granulometry

2.4 Vapour Pressure
Value:.03 hPa at 20 degree C

Test substance:other TS: benzyl alcohol, purity not noted

Flag:
12-FEB-2002

Critical study for SIDS endpoint

Value:.09 hPa at 30 degree C

Test substance:other TS: benzyl alcohol, purity not noted

Flag:
12-FEB-2002

Critical study for SIDS endpoint

Value:.67 hPa at 50 degree C

Flag:
19-JAN-2001

Critical study for SIDS endpoint

(2)

(2)

(2)

2.5 Partition Coefficientlog Pow:

1.1

Method:other (calculated): Leo, A.: CLOGP-3.54 MedChem
Software 1989. Daylight, Chemical Information
Systems, Claremont, CA 91711, USA

Reliability:(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint

Flag:

234

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATABENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

06-JUN-2001(3)

log Pow:

1.1

Method:other (measured)

Remark:Flag:
14-FEB-2002

experimentally determined
Critical study for SIDS endpoint(4)

2.6.1 Solubility in different media
Solubility in:
Value:

Water
40 g/l at 20 degree C

Flag:
14-FEB-2002

Critical study for SIDS endpoint

Solubility in:
Value:

Water
44 g/l at 50 degree C

Flag:
14-FEB-2002

Critical study for SIDS endpoint

(5)

(5)

2.6.2 Surface Tension

2.7 Flash Point
Value:
Type:

101 degree C
closed cup

Method:other: DIN 51758

19-JAN-2001(5)

2.8 Auto Flammability
Value:
Remark:19-JAN-2001

ignition temperature: 435 degree C(2)

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OECD SIDS
2. PHYSICO-CHEMICAL DATABENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

2.9 Flammability

2.10 Explosive Properties
Result:19-JAN-2001

other: explosive limits: lower 1.3 % by vol.,upper 13.0 % by vol. at 170 degree C and 1.013
bar(2)

2.11 Oxidizing Properties

2.12 Dissociation Constant

2.13 Viscosity

2.14 Additional Remarks

236

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

3.1.1 Photodegradation
Type:
air
Light source:
Sun light
INDIRECT PHOTOLYSIS
Sensitizer:
OH
Conc. of sens.: 1560000
Rate constant: .0000000000082541 cm³/(molecule * sec)
Degradation:
50 % after 1.3 day(s)Method:Year:
GLP:
Test substance:other (calculated): AOPWin version 1.89
1999
noother TS: molecular structure

Remark:Experimental Database Structure Match:experimental OH rate constant= 22.9 E-12
cm3/molecule-sec.
(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint

Reliability:
Flag:
14-FEB-2002(6)

3.1.2 Stability in Water
Remark:Flag:
26-JAN-2001

Based on structure and organic chemistry rules(e.g. bonding in organic molecules, activationenergy, reactivity, transformations, addition,
substitution, elimination) no hydrolysis will
occur at pH ranges 4 - 11.
Critical study for SIDS endpoint

3.1.3 Stability in Soil
3.2.1 Monitoring Data (Environment)
3.2.2 Field Studies

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OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

3.3.1 Transport between Environmental Compartments
Type:Media:
Method:Remark:Result:fugacity model level III
other: other: air - water - soil - sediment
other: EPIWin Modeling Program
Modeling was performed using equal releases(10,000 kg/hr) and equal distribution to allcompartments.
Distribution
Half-Life
Emissions
Fugacity(percent)(hr)(kg/hr)
(atm)

Air
Water
Soil
Sediment

1.51
50.0
48.4
0.0923

Reliability:
Flag:
14-FEB-2002

11.2
360
360
1440

1000
1000
1000
0

2.95e-011
6.71e-012
1.7 e-010
5.52e-012

Persistence Time: 287 hr
Reaction Time:353 hrAdvection Time:
1.54e+003 hr
Percent Reacted: 81.3
Percent Advected:(2) valid with restrictions
Critical study for SIDS endpoint(6)

3.3.2 Distribution

3.4 Mode of Degradation in Actual Use

3.5 Biodegradation
Type:
Inoculum:
Concentration:
Degradation:

aerobic
activated sludge
100 mg/l
92 - 96 % after 28 day(s)Method:ModifiedOECD Guide-line 301 C"Ready Biodegradability:

Year:
GLP:
Test substance:

MITI Test (I)"1981
no dataother TS: benzyl alcohol, purity not noted

Remark:slugde conc.: 30 mg/l

238

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3. ENVIRONMENTAL FATE AND PATHWAYSBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Reliability:
Flag:
14-FEB-2002(1) valid without restriction
Critical study for SIDS endpoint

Type:
Inoculum:
Degradation:
Method:Closedaerobic
predominantly domestic sewage> 90 % after 30 day(s)OECD Guide-line 301 D "Ready Biodegradability:

Year:
GLP:
Test substance:(7)

Bottle Test"1972
noother TS: benzyl alcohol, purity not noted

Remark:Reliability:
Flag:
29-JAN-2001

related to BOD(1) valid without restriction
Critical study for SIDS endpoint

Type:
Inoculum:
Contact time:
Degradation:
Result:anaerobic
anaerobic sludge
28 day(s)
100 % after 7 day(s)readily biodegradable

Method:Year:
GLP:
Test substance:other: see below
1982
no dataother TS: commercial grade benzyl alcohol,
purity > 95%

Method:

A 10% anaerobic sludge inoculum was transferred
to 160 ml serum bottles previously amended with50 ppm carbon (related to test substance) using
strict anaerobic techniques. Methane production
from test bottles vs. controls was monitored
weekly for 4 weeks or until net production
occurred. At that time, the bottles wereamended again with the same substrate and methane
production monitored to confirm the observation.
All data were obtained from duplicate bottles.
Methane was measured using a flame ionization
detector on a Perkin-Elmer Model 900 GC equippedwith a 3-m Tenax-G.C. column.

(8)

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OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Remark:Test condition:

Reliability:
Flag:
23-MAR-2001
Type:
Inoculum:
Concentration:

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

100 % mineralisation (CH4-Production) in 1 weekwith sludge from Jackson, MI waste-treatment
plant 100 % mineralisation (CH4-Production) in 2
weeks with sludge from Adrian, MI wastetreatment plant
The test bottles were incubated at 35 degree C
in the dark. Substrates were kept under an
atmosphere of 90% N2 and 10% H2(2) valid with restrictions
Critical study for SIDS endpoint(9)

Contact time:
Degradation:

anaerobic
domestic sewage
50 µg/l related to DOC (Dissolved Organic
Carbon)2 month> 75 % after 2 month

Method:Year:
GLP:
Test substance:other: see below
1984
no dataother TS: benzyl alcohol, purity not noted

Method:Reliability:
Flag:
23-MAR-2001

Sludge samples collected from primary andsecondary anaerobic digesters were diluted to
10 % and incubated anaerobically with 50 ug
Carbon per ml (related to test substance).
All compounds were tested in triplicate. Gas
production was measured by gas chromatography
and by a pressure transducer. Biodegradation
was determined by net increase in gas pressure
in bottles amended with test chemicals over
non-amended controls.
Degradation is expressed as percentage oftheoretical methane production based on the
stoichiometry of degradation.
The test bottles were incubated at 35 degree C
in the dark.
Substrates were kept under atmospheres of 10%
CO2 and 90% N2.
(2) valid with restrictions
Critical study for SIDS endpoint
(10)

Type:
Degradation:

aerobic
62 % after 5 day(s)Result:

Test condition:

240

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Method:ClosedGLP:OECD Guide-line 301 D"Ready Biodegradability:

Bottle Test"noRemark:19-JAN-2001

related to ThODType:
Degradation:

aerobic
77 % after 20 day(s)Method:ClosedOECD Guide-line 301 DGLP:

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6(11)"Ready Biodegradability:

Bottle Test"noRemark:19-JAN-2001

related to ThODType:
Inoculum:
Degradation:

aerobic
activated sludge, adapted
95 % after 28 day(s)Method:other: Closed bottle test

Remark:Test concentration: 2 - 5 mg/l
Degradation related to ThOD

(11)

19-JAN-2001

(12)

Type:
Inoculum:
Degradation:

aerobic
domestic sewage
89.2 % after 5 day(s)Method:GLP:other: respirometric diluting methodno

Remark:19-JAN-2001

related to ThODType:
Inoculum:
Degradation:

aerobic
activated sludge, industrial
88.9 % after 5 day(s)Test substance:other TS

(13)

UNEP PUBLICATIONS

241OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Method:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

17-JAN-2001

Radio-respirometric study using radio-labeledchemicals by activated sludge and in a complex
photographic processing effluent using
acclimated industrial sludge.
Concentration of test substance was 0.1 or
0.2ml of radioactive substrate(27,000-400,000
dpm).
Samples were incubated in the dark at ambient
temperature.
14CO2 recovery without effluent = 85.7% after
5 days14CO2 recovery in presence of effluent = 88.9%
after 5 days
benzyl-alcohol-7-14C (carbinol-14C) obtained
from New England Nuclear Corporation, Boston,
Massachusetts.
(14)

Type:
Degradation:

aerobic
85 % after 5 day(s)Remark:Test substance:

GLP:

no

Remark:19-JAN-2001

related to ThOD

Remark:The activity of degradation is at aconcentration of 100 mg/l not hindered in amodel plant (Ascomat)(8)19-JAN-2001
Remark:19-JAN-2001(15)

Biodegradation characteristics: biodegraded
completely in a short time by general
microorganisms.
(16)

3.6 BOD5, COD or BOD5/COD Ratio
Method:Year:
Method:Remark:19-JAN-2001

ThOD: 2515.1 mg/l
(13)

3.7 Bioaccumulation
BCF:
242

.31
UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Method:Year:
Test substance:other: (calculated) BCF Program (v2.13)
1999
other TS: molecular structure

Result:Reliability:

Estimated Log BCF = -0.503 (BCF = 0.3141)(2) valid with restrictions
Accepted calculation method
Critical study for SIDS endpoint

Flag:
14-FEB-2002(6)

3.8 Additional Remarks
Remark:27-MAY-1993

ThOD
2520 mg/g
COD
2520 mg/g
BOD51560 mg/g
Influence on biological purification plants:
adapted 1180 mg/l degradable(17)

UNEP PUBLICATIONS

243

OECD SIDS
4. ECOTOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

AQUATIC ORGANISMS

4.1 Acute/Prolonged Toxicity to Fish
Type:
Species:
Exposure period:
Unit:
LC50:

staticPimephales promelas
96 hour(s)
mg/l
460

Method:Year:
GLP:
Test substance:other: see below
1976
no dataother TS: reagent grade benzyl alcoholpurchased from Curtin Matheson Scientific,
Inc.

Method:Juvenile fathead minnows were obtained from
Environmental Reserach Laboratory, Duluth.
All fish used for the test were 4 to 8 weeks
of age, 1.1 to 3.1 cm in length, andacclimated for at least 48 hr before testing.
Test solutions were prepared by adding aweighed amount of chemical to 4 liters of Lake
Superior water (all concentrations arenominal). Water temperature during the test
was 18-22 degree C.
Range-finding tests were done and definitive
tests were conducted with 10 fish percontainer, 20 fish per concentration.
Complete immobilization was considered thebiological endpoint and equated with death.
Standard graphical procedures were followed todetermine LC50 (American Public Health Assn.,
1971) Analyses of test water was done fordissolved oxygen and pH at the beginning and 1
or 2 times during the test.
1 hour LC50 = 770 mg/l
24 hour LC50 = 770 mg/l
48 hour LC50 = 770 mg/l
72 hour LC50 = 480 mg/l(2) valid with restrictions
Critical study for SIDS endpoint(18)

Result:Reliability:
Flag:
23-MAR-2001

244

UNEP PUBLICATIONS(Fish, fresh water)
Analytical monitoring: noOECD SIDS
4. ECOTOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Type:Species:
Exposure period:
Unit:
LC0:
LC50:
LC100:

staticLeuciscus idus
48 hour(s)
mg/l
630
646
662

Method:other: Bestimmung der Wirkung vonWasserinhaltsstoffen auf
Fische, DIN 38412 Teil 15
1983
noother TS: benzyl alcohol, purity not noted

Year:
GLP:
Test substance:(Fish, fresh water)
Analytical monitoring: no

Reliability:
Flag:
12-FEB-2002(2) valid with restrictions
Critical study for SIDS endpoint

Type:
Species:
Exposure period:
Unit:
LC50:

staticPetromyzon marinus
24 hour(s)
mg/l
>= 5

GLP:

(19)

Analytical monitoring: nonoRemark:17-JAN-2001

larvae; screening test

Species:
Exposure period:
Unit:
LC0:

Carassius auratus
24 hour(s)
mg/l
>= 5

(20)
(Fish, fresh water)
Analytical monitoring:

17-JAN-2001
Species:
Exposure period:
Unit:
LC0:
GLP:
Remark:(21)
Cyprinus carpio
48 hour(s)(Fish, fresh water)
Analytical monitoring: no

136
noTesting of acute oral toxicity
Unit: mg/kg

UNEP PUBLICATIONS

245

OECD SIDS
4. ECOTOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

17-JAN-2001
Species:
Exposure period:
Unit:
LC0:

(22)
Lepomis macrochirus
24 hour(s)
mg/l
>= 5

(Fish, fresh water)
Analytical monitoring:

17-JAN-2001(21)

Species:
Exposure period:
Unit:
LC50:

Lepomis macrochirus
96 hour(s)mg/l
10Remark:12-FEB-2002

The static test was directed to simulate acutespill circumstances. The test substances were
pipetted or poured undiluted directly into theaquaria with fish. There was no preparation ofdefined concentrations according to guideline.
No analytical monitoring was done.
Aeration was not used during the first 24 hrs
thus allowing chemicals to act in an
uninterrupted state at the onset of the test
period.
(4) not assignable
Significant methodological deficiencies(23)

Species:
Exposure period:
Unit:
LC50:

Menidia beryllina
96 hour(s)mg/l
15Remark:The static test was directed to simulate acutespill circumstances. The test substances were
pipetted or poured undiluted directly into theaquaria with fish. There was no preparation ofdefined concentrations according to guideline.
No analytical monitoring was done.
Aeration was not used during the first 24 hrs
thus allowing chemicals to act in an
uninterrupted state at the onset of the test
period.
(4) not assignable
Significant methodological deficiencies(23)

Reliability:

Reliability:
12-FEB-2002

246(Fish, fresh water)
Analytical monitoring:(Fish, estuary, marine)

UNEP PUBLICATIONS

Analytical monitoring:OECD SIDS
4. ECOTOXICITY

Species:
Exposure period:
Unit:
LC0:

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Salmo trutta (Fish, fresh water, marine)
24 hour(s)mg/lAnalytical monitoring:>= 5

17-JAN-2001(21)

4.2 Acute Toxicity to Aquatic Invertebrates
Species:
Exposure period:
Unit:
EC0:
EC50:
EC100:

Daphnia magna
24 hour(s)
mg/l
300
400
500

Method:other: Daphnien-Kurzzeittest, DIN 38412 Teil
11, Bestimmung der Wirkung vonWasserinhaltsstoffen auf Kleinkrebse
1983
noother TS: benzyl alcohol, purity not noted

Year:
GLP:
Test substance:(Crustacea)
Analytical monitoring: no

Reliability:
Flag:
14-FEB-2002(2) valid with restrictions
Critical study for SIDS endpoint

Species:
Exposure period:
Unit:
TGK :

Daphnia magna
48 hour(s)
mg/l
360

(Crustacea)

Method:GLP:other: acutenoimmobilisation test

Reliability:
Flag:
06-JUN-2001(2) valid with restrictions
Critical study for SIDS endpoint

Species:
Exposure period:
Unit:
EC0:
EC50:
EC100:

Daphnia magna
24 hour(s)
mg/l
26
55
100

(19)

Analytical monitoring: no(24)(Crustacea)

UNEP PUBLICATIONS

Analytical monitoring: no247

OECD SIDS
4. ECOTOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

GLP:

no

Reliability:
16-JAN-2001(2)

valid with restrictions(25)

4.3 Toxicity to Aquatic Plants e.g. Algae
Species:
Endpoint:
Exposure period:
Unit:
EC50:

Chlorella pyrenoidosa (Algae)
other: Inhibition of photosynthesis
3 hour(s)mg/lAnalytical monitoring: no data
95

Method:Year:
GLP:
Test substance:other: see below
1982
no dataother TS: benzyl alcohol purchased from
Aldrich Chemical Co. Wisconsin, USA. Purity >95%

Method:Photosynthesis was assayed by following theuptake of 14CO2 from NaH 14CO3(Amersham/Searle, Ontario, Canada). Plastic
culture flasks containing 9.9 ml of cellsuspension (1.0 x 10+E5 cells/ml), 0.1 ml
radioisotope and 0.01 ml of test chemical wereincubated for 3 hours.
Five concentrations, ranging from 0 to 100
ppm, were tested and replicated five times.
Photosynthetic activity was assayed according
to Stratton et al. (1979) Appl. Environ.
Microbiol. 38: 537-43.
Per cent inhibition values were calculated
relative to photosynthetic activity in thesolvent controls and EC50 values determined by
Probit analysis.
Analyses for significant differences were
performed using Dunnett's test and Duncan's
multiple range test.
Cultures were maintained in a liquid nitrogenfree medium at 20 degree C and a lightintensity of 7000 lux on a 12 hour light-darkcycle.
(2) valid with restrictions
Critical study for SIDS endpoint

Test condition:

Reliability:
Flag:

248

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

14-FEB-2002(26)

Species:
Endpoint:
Exposure period:
Unit:
EC50:

Haematococcus pluvialis (Algae)
other: Inhibition of photosynthesis
4 hour(s)mg/lAnalytical monitoring: no
2600

Method:other: according to Tuempling v.W. (Fortschritte
Der Wasserchemie. 14 S: 205-213 (1972) using a
Warburg apparatus
noother TS: benzyl alcohol, purity not noted

GLP:
Test substance:
Reliability:
Flag:
29-JAN-2001(2) valid with restrictions
Critical study for SIDS endpoint

Species:
Exposure period:
Unit:
TGK :

Scenedesmus quadricauda (Algae)
96 hour(s)mg/lAnalytical monitoring:
640

Method:other: cell multiplication inhibition test

Remark:Reliability:
Flag:
06-JUN-2001

green algae(2) valid with restrictions
Critical study for SIDS endpoint

Species:
Endpoint:
Exposure period:
Unit:
EC50:

Anabaena cylindrica (Algae)
other: Inhibition of photosynthesis
3 hour(s)mg/lAnalytical monitoring:90

Remark:17-JAN-2001

blue-green algae

Species:
Endpoint:
Exposure period:
Unit:
EC0:

Anabaena inaequalis (Algae)
other: Inhibition of photosynthesis
3 hour(s)mg/lAnalytical monitoring:
30

(19)

(24)

(26)

UNEP PUBLICATIONS

249

OECD SIDS
4. ECOTOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Remark:17-JAN-2001

blue-green algae

Species:
Endpoint:
Exposure period:
Unit:
EC50:

Anabaena variabilis (Algae)
other: Inhibition of photosynthesis
3 hour(s)mg/lAnalytical monitoring:
35

Remark:17-JAN-2001

blue-green algae

Species:
Endpoint:
Exposure period:
Unit:
EC50:

Scenedesmus quadricauda (Algae)
other: Inhibition of photosynthesis
3 hour(s)mg/lAnalytical monitoring:79

GLP:
Remark:17-JAN-2001

(26)

(26)

no
green algae(26)

4.4 Toxicity to Microorganisms e.g. Bacteria
Type:Species:
Exposure period:
Unit:
EC0:

aquatic
Escherichia coli
48 hour(s)
mg/l
1000

Method:GLP:other: cell multiplication test
noReliability:
Flag:
06-JUN-2001(2) valid with restrictions
Critical study for SIDS endpoint

Type:
Species:
Unit:
EC10:

aquatic
Pseudomonas putida
mg/l
658

Method:other: Test according to Bringmann and Kuehn(cell multiplication inhibition test)

250(Bacteria)
Analytical monitoring: no(24)

UNEP PUBLICATIONS(Bacteria)
Analytical monitoring: noOECD SIDS
4. ECOTOXICITYGLP:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
noRemark:Reliability:
Flag:
06-JUN-2001

Exposure period: 16-18 h(2) valid with restrictions
Critical study for SIDS endpoint

Type:
Species:
Exposure period:
Unit:
EC50:

aquatic
Photobacterium phosphoreum (Bacteria)
30 minute(s)mg/lAnalytical monitoring: no71.42

Method:GLP:other: Microtox
no

(19)

19-JAN-2001
Type:
Species:
Exposure period:
Unit:
EC50:
GLP:

(27)
aquatic
Photobacterium phosphoreum (Bacteria)
5 minute(s)mg/lAnalytical monitoring: no50
no19-JAN-2001
Type:
Species:
Exposure period:
Unit:
IC50 :
GLP:
Remark:(28)
aquatic
other bacteria: Aerobic heterotrophic
49 hour(s)mg/lAnalytical monitoring:2100
no19-JAN-2001

Inhibition of respiration;
prolonged incubation compared with ISO 8192
(29)

Type:
Species:
Exposure period:
Unit:
IC50 :

aquatic
other bacteria: Nitrosomonas
24 hour(s)mg/lAnalytical monitoring:390

UNEP PUBLICATIONS251

OECD SIDS
4. ECOTOXICITY

Method:GLP:
Remark:19-JAN-2001

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

other: Inhibition of nitrification, comparablewith ISO/DIS 9509
noInhibition of N-oxidation(29)

4.5 Chronic Toxicity to Aquatic Organisms
4.5.1 Chronic Toxicity to Fish
4.5.2 Chronic Toxicity to Aquatic Invertebrates

252

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

TERRESTRIAL ORGANISMS

4.6.1 Toxicity to Sediment Dwelling Organisms
4.6.2 Toxicity to Terrestrial Plants
4.6.3 Toxicity to Soil Dwelling Organisms
4.6.4 Toxicity to other Non-Mamm. Terrestrial Species

4.7 Biological Effects Monitoring

4.8 Biotransformation and Kinetics

4.9 Additional Remarks
Remark:Aedes aegypti, eggs

(72h)

LD50 160 l/ha
LD90 251 l/ha
Aedes aegypti, larval stage L1(24h)
LD50 105 l/ha
LD90 132 l/ha
aegypti, larval stage L3-L4(24h) LD50 129 l/ha
LD90 184 l/ha
Aedes scutellaris, eggs(72h) LD50 160 l/ha
LD90 265 l/ha
Aedes scutellaris, larval stage L1 (24h) LD50 110 l/ha
LD90 151 l/ha
Aedes scutellaris, larval stage L3-L4(24h) LD50 126 l/ha
LD90 172 l/ha
19-JAN-2001

UNEP PUBLICATIONS

Aedes

(30)

253

OECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

5.0 Toxicokinetics, Metabolism and Distribution

5.1 Acute Toxicity
5.1.1 Acute Oral Toxicity
Type:Species:
Sex:
Value:

LD50
rat
male
= 1610 mg/kg bw

Method:GLP:Test substance:otherno dataother TS: benzyl alcohol, purity not noted

Reliability:

Flag:
12-FEB-2002(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint
(31)

Type:
Species:Sex:
No. of Animals:
Vehicle:Value:

LD50
mouse
male/female
10
other: corn oil= 1580 mg/kg bw

Method:GLP:Test substance:other: see below
no dataother TS: commercial grade benzyl alcohol

Method:Mice were dosed on full stomachs by intubation.
All animals were observed for toxic signs andtime of death for 2 weeks.
The LD50 was computed by the method of
Litchfield & Wilcoxon(1949).
Toxic signs: depression, death(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(32) (33)

Remark:Reliability:

Flag:
12-FEB-2002

254

UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Type:Species:
Strain:Sex:
No. of Animals:
Vehicle:Value:

LD50
rat
other: Osborne-Mendel
male/female
10
other: neat
= 1230 mg/kg bw

Test substance:other TS: commercial grade benzyl alcohol

Method:12-FEB-2002

Groups of 10 young adult Osborne-Mendel rats,
evenly divided by sex were fasted forapproximately 18 hrs prior to treatment.
Animals were dosed by intubation. All animals
were observed for toxic signs and time of deathfor 2 weeks.
The LD50 was computed by the method of
Litchfield & Wilcoxon (1949).
Toxic signs: depression, excitability, coma,death(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
(32)

Type:
Species:Value:

LD50
rat= 2080 mg/kg bw

Method:GLP:Test substance:other: no data
no dataother TS: benzyl alcohol, purity not noted

Reliability:(4) not assignable
Secondary literature; Original reference not

Remark:Reliability:

available
Flag:
12-FEB-2002

Critical study for SIDS endpoint

Type:
Species:Value:

LD50
rabbit= 1040 mg/kg bw(34) (33)12-FEB-2002
Type:(34) (35)LD50

UNEP PUBLICATIONS

255

OECD SIDS
5. TOXICITY

Species:Value:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

rat= 3100 mg/kg bw

16-JAN-2001
Type:
Species:Value:

(36)
LDLo
rat
ca. 1040 - 3120 mg/kg bw

16-JAN-2001
Type:
Species:Value:

(37)
LD50
mouse
= 1150 mg/kg bw

16-JAN-2001
Type:
Species:Value:

(38)
LDLo
mouse
ca. 1040 mg/kg bw

16-JAN-2001
Type:
Species:Value:(37)
LDLo
guinea pig
ca. 1040 - 2600 mg/kg bw

16-JAN-2001(37)

5.1.2 Acute Inhalation Toxicity
Type:Species:
Exposure time:
Value:

LC50
rat
4 hour(s)> 4.178 mg/l

Method:GLP:otherno data

Test substance:other TS: benzyl alcohol, purity not noted

Flag:
12-FEB-2002

Critical study for SIDS endpoint

Type:
Species:

LC50
rat

256

(39)

UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Exposure time:
Value:

4 hour(s)ca. 8.8 mg/l

Remark:19-JAN-2001

Extrapolation according to Haber`s law: LC50(8h) = 1000 ppm.
(36)

Type:
Species:
Exposure time:
Value:

LC50
rat
4 hour(s)> .9 mg/l

Remark:19-JAN-2001

LC33 (4h) = 200 ppm.

Type:
Species:Sex:
No. of Animals:
Vehicle:Exposure time:
Value:

LC50
rat
no data6other: neat
4 hour(s)8.9 mg/l

Test substance:

no dataResult:Exposure to 2000 ppm kills either 2/6, 3/6 or
4/6 rats.
Therefore benzyl alcohol is considered to beof moderate toxicity.
(41)

07-SEP-2000(40)

5.1.3 Acute Dermal Toxicity
Type:Species:Value:

LD50
rabbit= 2000 mg/kg bw

Method:GLP:Test substance:otherno dataother TS: benzyl alcohol, purity not noted

Flag:
29-JAN-2001

Critical study for SIDS endpoint

Type:
Species:Value:

LD50
guinea pig< 5 ml/kg bw

Method:GLP:otherno data(42)

UNEP PUBLICATIONS

257

OECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Test substance:other TS: benzyl alcohol, purity not noted

Flag:
29-JAN-2001

Critical study for SIDS endpoint(43) (35)5.1.4 Acute Toxicity, other Routes
Type:Species:Route of admin.:Value:

LD50
rat
i.p.
> 400 - 800 mg/kg bw

19-JAN-2001

(44)

Type:
Species:
Strain:Sex:
Route of admin.:Value:

LD50
mouse
CD-1
male
i.p.
= 1000 mg/kg bw

Remark:14-FEB-2002

Acute toxicity after 4 h.

Type:Species:
Strain:Sex:
Route of admin.:Value:

LD50
mouse
CD-1
male
i.p.
= 650 mg/kg bw

Test substance:other TS: benzyl alcohol, purity not noted

Remark:14-FEB-2002

Acute delayed toxicity after 7 d.

Type:Species:Route of admin.:Value:

LD50
guinea pig
i.p.
> 400 - 800 mg/kg bw

(45)

(45)

19-JAN-2001

(44)

Type:
Species:Route of admin.:Value:

LD50
rat
s.c.
= 1700 mg/kg bw

Test substance:other TS: benzyl alcohol, purity not noted

258

UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

14-FEB-2002
Type:
Species:Route of admin.:Value:

(46)
LD50
mouse
s.c.
= 950 mg/kg bw

19-JAN-2001
Type:
Species:Route of admin.:Value:(38)
other: LDLO
rabbits.c.
ca. 2080 mg/kg bw

19-JAN-2001
Type:
Species:Route of admin.:Value:

(37)
LD50
rat
i.v.
= 314 mg/kg bw

19-JAN-2001

(47)

Type:
Species:Route of admin.:Value:

LD50
rat
i.v.
= 53 mg/kg bw

Remark:19-JAN-2001

Rapid injection

Type:
Species:Route of admin.:Value:

LD50
mouse
i.v.
= 324 mg/kg bw

19-JAN-2001
Type:
Species:Route of admin.:Value:

(47)

(48)
LD50
mouse
i.v.
ca. 105 mg/kg bw

Remark:19-JAN-2001

LD50 value depends on speed of injection

Type:
Species:Route of admin.:Value:

LD50
mouse
i.v.
= 1460 mg/kg bw(49)

UNEP PUBLICATIONS

259

OECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

19-JAN-2001
Type:
Species:
Strain:Sex:
Route of admin.:Value:(47)
other: LDLO
mouse
CD-1
male
i.v.
ca. 135 mg/kg bw

14-FEB-2002
Type:
Species:Route of admin.:Value:(50)
other: LDLO
dogi.v.
ca. 50 mg/kg bw

19-JAN-2001

(47)

Type:
Species:Route of admin.:Value:

LD50
rat
other
= 410 mg/kg bw

Remark:19-JAN-2001

Application: intra-arterial.
(47)

5.2 Corrosiveness and Irritation
5.2.1 Skin Irritation
Species:Result:rabbitnot irritating

Method:OECD Guide-line 404 "Acute Dermal
Irritation/Corrosion"
no dataother TS: benzyl alcohol, purity not noted

GLP:
Test substance:
Reliability:
Flag:
14-FEB-2002(1) valid without restriction
Critical study for SIDS endpoint

Species:
Concentration:
Exposure Time:
Result:rabbit10 other: mg
24 hour(s)slightly irritating

260

(49)

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5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Method:GLP:Test substance:other: see remarks
no dataother TS: benzyl alcohol, purity not noted

Flag:
14-FEB-2002

Critical study for SIDS endpoint

Species:
Exposure:
Exposure Time:
Result:rabbitOpen
24 hour(s)moderately irritating

Method:other: see remarks

Remark:mg/animal, open,

Exposure time: 24 h, clipped skin, 100(51) (36)observation time: 72 h.
14-FEB-2002(52)

Species:Result:rabbitnot irritating

Method:other: see remarks

Remark:19-JAN-2001

Exposure time: 24 h, ear, ca. 500 mg/animal,semi-occlusive, observation time: 7 d.
(53)

Species:Result:guinea pig
moderately irritating

Method:other: see remarks

Remark:Exposure time: 24 h, depilated skin, dose:
undiluted material, no other data, open,
observation time: no data.

19-JAN-2001(44)

Species:Result:guinea pig
slightly irritating

Method:other: see remarks

Remark:19-JAN-2001

Exposure time: 24 h, clipped flank,
dose: 8 mg/animal (30 % in unspecified
solvent), open, observation time: no data.
(54)

Species:Result:guinea pig
slightly irritating
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OECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Method:other: see remarks

Remark:19-JAN-2001

Exposure time: 24 h, shaved flanks,
dose: 26 mg/animal (25 % unspecified solvent),
intradermally, observation time: no data.
(55)

Species:Result:guinea pig
not irritating

Method:other: see remarks

Remark:19-JAN-2001

Exposure time: 24 h, clipped skin,
100 mg/animal, open, observation time: 72 h.
(52)

Species:Result:human
irritating

Method:other: Closed Patch Test

Remark:19-JAN-2001

Observation time: 24/48 h, 0.05 % in either
ethanol or a cream base produced irritation in
18 of 614 subjects.
(56)

Species:Result:human
irritating

Method:other: Uncovered Patch Test

Remark:19-JAN-2001

0.5 % in petrolatum induced contact urticaria
in 7 of 32 volunteers.
(57)

Species:Result:humanslightly irritating

Method:other: Patch Test

Remark:19-JAN-2001

Exposure time: 48 h, ca. 50 mg/person (30 % in
acetone), observation time: up to 120 h.
(52)

Species:Result:other: Male nude mouse
highly irritating

Method:other: see remarks

262

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5. TOXICITY

Remark:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

19-JAN-2001

Exposure time: 24 h, 10 % in purified water,
occlusive, observation time: no data.
(58)

Species:Result:other: mini-pig
not irritating

Method:other: Patch Test

Remark:Exposure time: 48 h, clipped skin,
50 mg/animal, observation time: no data.

19-JAN-2001(52)

5.2.2 Eye Irritation
Species:Result:rabbitmoderately irritating

Method:OECD Guide-line 405 "Acute Eye
Irritation/Corrosion"
no dataother TS: benzyl alcohol, purity not noted

GLP:
Test substance:
Reliability:
Flag:
14-FEB-2002(1) valid without restriction
Critical study for SIDS endpoint

Species:Result:rabbithighly irritating

Method:GLP:Test substance:other: see remarks
no dataother TS: benzyl alcohol, purity not noted

Remark:Flag:
14-FEB-2002

Exposure time: 24 h, dose: 750 microg., no other
data.
Critical study for SIDS endpoint(51) (36)Species:
Concentration:
Result:rabbit4 %not irritating

Method:Test substance:other: see remarks
other TS: benzyl alcohol, purity not noted

Remark:4 % aqueous solution, tested for stability, noother data.
Critical study for SIDS endpoint
(59)

Flag:
14-FEB-2002(49)

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5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Species:Result:rabbitnot irritating

Method:other: see remarks

Remark:Exposure time: 4 d, 2 drops of a 0.08 %aqueous solution, no other data.

19-JAN-2001(38)

Species:Result:rabbitmoderately irritating

Method:other: see remarks

Remark:ca. 100 mg/animal, observation time: 7 d.

19-JAN-2001(53)

5.3 Sensitization
Type:
Species:Result:Draize Testguinea pig
not sensitizing

Test substance:other TS: benzyl alcohol, purity not noted

Flag:
14-FEB-2002

Critical study for SIDS endpoint

Type:
Species:Result:(54)
Guinea pig maximization test
guinea pig
not sensitizing

Test substance:other TS: benzyl alcohol, purity not noted

Flag:
14-FEB-2002

Critical study for SIDS endpoint

Type:
Species:Result:(54)
Freund's complete adjuvant test
guinea pig
sensitizing

Test substance:other TS: benzyl alcohol, purity not noted

Flag:
14-FEB-2002(54)

Critical study for SIDS endpoint

264

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5. TOXICITY

Type:
Species:Result:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
Open epicutaneous test
guinea pig
sensitizing

Test substance:other TS: benzyl alcohol, purity not noted

Flag:
14-FEB-2002

Critical study for SIDS endpoint

Type:
Species:Result:(54)
Patch-Testhumansensitizing

Test substance:other TS: benzyl alcohol, purity not noted

Remark:Flag:
14-FEB-2002

Maximum incidence of sensitization: 1 %.
Critical study for SIDS endpoint(60) (61) (62)Type:
Species:Result:
Test substance:

Patch-Testhumansensitizing
other TS: benzyl alcohol, purity not noted

14-FEB-2002
Type:
Species:Result:
Test substance:(63) (64)Patch-Testhumanambiguous
other TS: benzyl alcohol, purity not noted

14-FEB-2002
Type:
Species:(57)
Patch-Test
human

Test substance:other TS: benzyl alcohol, purity not noted

Remark:Two patients with contact dermatitis were
found to be sensitised by benzyl alcohol: 1
per cent in petrolatum(65)

14-FEB-2002
Type:
Species:
Test substance:

Patch-Testhumanother TS: benzyl alcohol, purity not noted
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OECD SIDS
5. TOXICITY

Remark:14-FEB-2002
Type:
Species:

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
A previously to balsam of Peru sensitised
patient reacted on patch testing with benzyl
alcohol: 0.5 per cent in olive oil.
(66)
other
laboratory animal

Method:other: additional animal studies are reported

Test substance:other TS: benzyl alcohol, purity not noted

14-FEB-2002
Type:
Species:
Method:Test substance:(68) (69) (70) (67)
other
human
other: additional data
other TS: benzyl alcohol, purity not noted

14-FEB-2002 (71) (72) (73) (74) (75) (76) (77) (78) (79) (80)(81) (82) (83) (84) (85) (86) (87) (88) (89) (90)(91) (92) (93) (94) (95) (96)Type:
Species:Result:
Test substance:other: Application to shaved skinguinea pig
not sensitizing
other TS: benzyl alcohol, purity not noted

14-FEB-2002
Type:
Species:Result:
Test substance:(38)
other: Intradermal application
guinea pig
not sensitizing
other TS: benzyl alcohol, purity not noted

14-FEB-2002
Type:
Species:Result:
Test substance:(38)
other: Maximization Test
human
not sensitizing
other TS: benzyl alcohol, purity not noted

14-FEB-2002

266

(97)

UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

5.4 Repeated Dose Toxicity
Type:Sub-chronic
Species:rat
Strain:other: F344/N
Route of administration: gavage
Exposure period:
13 w
Frequency of treatment:
Post exposure period:
Doses:
Control Group:
NOAEL:

Sex: male/female

daily
no
50, 100, 200, 400, 800 mg/kg/d
yes
400 mg/kg bw

Year:
GLP:
Test substance:

1981
yes
other TS: technical grade benzyl alcohol(purity =99%)

Method:Groups of 10 rats of each sex were administered
0, 50, 100, 200, 400, or 800 mg/kg benzyl
alcohol in corn oil by gavage, 5 days/week for
13 weeks (dose volume = 5 ml/kg).
Rats were housed five/cage with feed and water
available ad libitum.
Animals were observed twice daily; moribund
animals were sacrificed. Animal weights wererecorded weekly. At the end of the study,
survivors were sacrificed.
A necropsy was performed on all animals;
histolgic exams performed on all vehicle
controls and animals in the 800 mg/kg group.
Brains were examined from rats in the 400
mg/kg group.
Biochemistry and hematolgy studies were not
performed.
8/10 male rats dosed with 800 mg/kg diedduring w 7 and 8.
Rats of the high dose group exhibited clinicalsigns indicative of neurotoxicity including
staggering, respiratory difficulty, andlethargy. Hemorrhages occurred around the mouthand nose, and there were histologic lesions
in the brain, thymus, skeletal muscle, andkidney.
There were reductions in relative weight gainin male rats dosed with 800 mg/kg and infemale rats dosed with 200 mg/kg or more.
No notable changes in bw gain or compound-

Remark:Result:UNEP PUBLICATIONS

267

OECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
related histopathologic lesions were observedin rats from thelower dose groups.
In the 2-y study, however, no notable changes
were found on bw or bw gain at 200 or
400 mg/kg/d.

Reliability:
Flag:
14-FEB-2002

NOAEL = 400 mg/kg/day (based on investigatedparameters and taking into account the bw
results of 2-y study)(1) valid without restriction
GLP, Comparable to Guideline study
Critical study for SIDS endpoint
(98)

Type:
Sub-chronic
Species:mouse
Sex: male/female
Strain:B6C3F1
Route of administration: gavage
Exposure period:
13 w
Frequency of treatment: daily
Post exposure period:noDoses:
50, 100, 200, 400, 800 mg/kg/dControl Group:
yes
NOAEL:
200 mg/kg bw
Year:
GLP:
Test substance:=99%)
Method:Remark:Result:

268

1981
yes
other TS: technical grade benzyl alcohol (purity
Groups of 10 mice of each sex were administered
0, 50, 100, 200, 400, or 800 mg/kg benzyl alcohol
in corn oil by gavage, 5 days/week for 13 weeks(dose volume = 5 ml/kg).
Mice were housed five/cage with feed and water
available ad libitum.
Animals were observed twice daily; moribund
animals were sacrificed. Animal weights wererecorded weekly. At the end of the study,
survivors were sacrificed.
A necropsy was performed on all animals;
histolgic exams performed on all vehicle
controls and animals in the 800 mg/kg group.
Brains were examined from mice in the 400 mg/kg
group and from all mice dying before the end of
the study.
Biochemistry and hematolgy studies were not
performed.
Staggering after dosing occurred during thefirst 2 w of the study in mice dosed with
800 mg/kg.
UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Reliability:
Flag:
14-FEB-2002

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
There were reductions in relative weight gainin male mice dosed with 400 or 800 mg/kg, andin female mice dosed with 200 mg/kg or more.
No notable changes in bw gain or compoundrelated histopathologic lesions were observedin mice from the lower dose groups. In the 2-ystudy, however no notable changes were foundon bw or bw gain at 200 mg/kg/d.
NOAEL = 200 mg/kg/day (based on investigatedparameters and taking into account the bw
results of 2-y study)(1) valid without restriction
GLP, Comparable to Guideline study
Critical study for SIDS endpoint
(98)

Type:
Chronic
Species:rat
Strain:Fischer 344
Route of administration: gavage
Exposure period:
103 weeks
Frequency of treatment: 5 d/w
Post exposure period:noDoses:
200, 400 mg/kg/dControl Group:
yes
NOAEL:
400 mg/kg bw

Sex: male/female

Year:
GLP:
Test substance:

1981
yes
other TS: technical grade benzyl alcohol(purity = 99%)

Method:Groups of 50 rats of each sex wereadministered 0, 200, or 400 mg/kg benzyl
alcohol in corn oil by gavage, 5 days/week
for 103 weeks. The rats were placed on the
study at 8-9 weeks of age.
All animals were observed twice daily andclinical signs recorded at least once permonth.
Body weights were recorded once per week forthe first 12 weeks,then once a month
thereafter.
Animals found moribund and those surviving to
the end of the study were humanely killed.
Necropsy was performed on all animals;
histological exams performed on all female ratsand vehicle controls, and high dose rats thatdied before month 22, and male rats with grosslesions.
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OECD SIDS
5. TOXICITY

Remark:Result:Reliability:
Flag:
14-FEB-2002

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
Biochemistry and hematolgy studies were not
performed.
No effect on bw gain or mortality wasobserved. No apparent compound-related nonneoplastic responses were observed.
(1) valid without restriction
GLP, Comparable to Guideline study
Critical study for SIDS endpoint
(98)

Type:
Chronic
Species:mouse
Strain:B6C3F1
Route of administration: gavage
Exposure period:
103 w
Frequency of treatment: 5 d/w
Post exposure period:noDoses:
100, 200 mg/kg/dControl Group:
yes
NOAEL:
200 mg/kg bw

Sex: male/female

Method:Year:
GLP:
Test substance:other: OECD 451
1981
yesother TS: technical grade benzyl alcohol(purity = 99%)

Method:Benzyl alcohol (purity, 99%) was given togroups of 50 B6C3F1 mice of each sex, eight tonine weeks of age, at a dose of 0, 100, or 200
mg/kg bw per day in corn oil by gavage on
five days a week for 103 weeks. The doses wereselected on the basis of those found to induce
neurotoxic effects (lethargy and staggering)in short-term studies.
The mice were observed twice daily, and theirbody weights were recorded weekly for the
first 12 weeks and once a month thereafter.
Gross necropsy was performed on all animals,
and 50 tissues and organs, including brain,
liver, kidney, and stomach, fromall vehicle controls, animals at the high dose,and animals at the other doses that died before

Remark:270

22 months or had gross lesions were examinedhistologically.
Biochemistry and hematolgy studies were not
performed.

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Result:Reliability:
Flag:
14-FEB-2002

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
The mean body weights of treated and control
mice werecomparable throughout the study. The survivalof control females was significantly lower thanthat of animals at the high dose after week 74,
but no other differences in survival were seen:
68% of control, 66% of low-dose, and 70% of highdose males; and 50% of control, 62% of low-dose,and 72% of high-dose females. No significant
treatment-related effects were noted at gross
necropsy or histopathological examination.
No increase was seen in the incidence ofhepatocellular or forestomach neoplasia.
(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint
(98)

Type:
Sub-acuteSpecies:mouse
Sex: male/female
Strain:B6C3F1
Route of administration: oral feed
Exposure period:
10 dFrequency of treatment: continuously in diet
Post exposure period:noDoses:
2.08; 2.5 or 3 % in diet (approx. 3012,
3750 or 4500 mg/kg/d)Control Group:
yes
NOAEL:
3750 mg/kg bw
LOAEL:
4500 mg/kg bw
GLP:
Test substance:

no dataother TS: sodium benzoate (specific grade)purchased from Wako

Method:Sodium benzoate, mixed with the powdered diet,was fed to groups of 12 rats (6 males, 6
females) for 10 days.
Animals were observed for body weight gain andclinical signs 5 day/ week.

Remark:At the end of the experiment, surviving animals
were necropsied. Organ weights, clinicalchemistry and histlogical examinations were
performed.
Benzyl alcohol will rapidly be metabolized tobenzaldehyde and so to benzoic acid (sodium
benzoate is the salt of benzoic acid).
Therefore the data of sodium benzoate can also
be supportive in the repeat dose endpoint.
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OECD SIDS
5. TOXICITY

Result:Reliability:

Flag:
14-FEB-2002

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
the mean compound consumption was calculated
according to Lehman, Food Drug Off. Q. Bull.
18, 66 (1954)
All mice in the 3.0 %-group showed increased
sensitivity to stimuli and 1/5 male and 2/5
females showed convulsions; 2/5 females died;liver weights of males and females and kidneyweights of females were dose-dependently
increased; histopathologic examination showedenlarged hepatocytes, single cell necrosis andvacuolation of hepatocytes in all livers frommales; no histopathologic changes of thekidney were described; serum cholesterol,
lipid levels and cholinesterase were increasedin males.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint
(99)

Type:
Sub-acuteSpecies:rat
Sex: male/female
Strain:other: F344/N
Route of administration: gavage
Exposure period:
16 dFrequency of treatment: daily
Post exposure period:noDoses:
125, 250, 500, 1000, 2000 mg/kg/dControl Group:no data specified
Test substance:other TS: technical grade benzyl alcohol(purity = 99%)

Remark:No. of animals: 5/sex/dose.

Result:All male and female rats dosed with 2000 mg/kg
died. 2/5 male and 3/5 female rats dosed with
1000 mg/kg died. Rats in the 2 highest dosegroups were lethargic after dosing.
Other toxic responses in these 2 dose groups
included blood around the mouth and nose,
subcutaneous hemorrhages, and blood in theurinary and gastrointestinal tract. Animals
administered lower doses had no compound-related
histologic lesions.
(98)

14-FEB-2002
Type:
Species:272

Sub-acutemouse
UNEP PUBLICATIONS

Sex: male/female

OECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Strain:B6C3F1
Route of administration: gavage
Exposure period:
16 dFrequency of treatment: daily
Post exposure period:
no data specified
Doses:
125, 250, 500, 1000, 2000 mg/kg/dControl Group:no data specified
Test substance:other TS: technical grade benzyl alcohol(purity = 99%)

Remark:Result:No. of animals: 5/sex/dose.
All male and female mice dosed with 2000 mg/kg
died. 1/5 male and 2/5 female mice dosed with
1000 mg/kg died. Mice of each sex in the 2highest dose groups were lethargic after dosing.
Other toxic responses in these 2 dose groups
included blood around the mouth and nose,
subcutaneous hemorrhages, and blood in theurinary and gastrointestinal tract and in theurinary bladder. Animals administered lower
doses had no compound-related histologic lesions.
(98)

14-FEB-2002

Species:rat
Strain:no data
Route of administration: inhalation
Exposure period:
no dataFrequency of treatment: 4 h/d
Post exposure period:
no data specified
Doses:
216-270 ppm
Control Group:no data specified
NOAEL:

Sex: male

270 ppm

Test substance:other TS: benzyl alcohol, purity not noted

Remark:Result:No. of animals: 6.
Subacute exposure to male rats for 4 h periods
produced no clinical or pathologic signs of
toxicity.
(40)

14-FEB-2002

Species:rat
Strain:no data
Route of administration: gavage
Exposure period:
3 w
Frequency of treatment: 6 d/w
Post exposure period:noDoses:
50, 150, 500 mg/kg
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Sex: male/female273

OECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Control Group:yes

Test substance:other TS: benzyl alcohol, purity not noted

Remark:Result:No. of animals: 5/sex/dose.
The compound was administered in propylene
glycol. Increases in weight were the same inall groups, and there were no pathologicaleffects on blood or organs.
(38)

14-FEB-2002

Species:mouse
Sex: no data
Strain:no data
Route of administration: gavage
Exposure period:
8 dFrequency of treatment: daily
Post exposure period:
no data specified
Doses:
325, 645, 1300, 2595 mg/kg/dControl Group:no data specified
Test substance:other TS: benzyl alcohol, purity not noted

Remark:Result:No. of animals: no data.
Decreased muscle coordination, a "hunched"appearance, depression, and fur changes werereported in mice given 645 mg/kg but not in
those receiving 325 mg/kg or below. At 1300
mg/kg, animals additionally suffered breathingdifficulties,

14-FEB-2002

discharge from the eyes, and various CNS
effects, and death occurred on day 1 in all
mice given 2595 mg/kg.
(100)

5.5 Genetic Toxicity 'in Vitro'
Type:
System of testing:Ames test
S. typhimurium TA 98, TA 100, TA 1535,
TA 1537
Concentration:
up to 6666 ug/ml
Cytotoxic Concentration: >/= 3333 ug/plate
Metabolic activation:with and without
Result:
Method:Year:274

negative
other: similar to OECD Guide-line 471;
protocol according to Haworth, et.al. (1983)
1983
UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

GLP:
Test substance:yesother TS: technical grade benzyl alcohol(purity = 99%)

Method:Separate trials were done using metabolic
activation with Aroclor 1254-induced S9 frommale Syrian hamster liver andmale Sprague-Dawley rat liver.
(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(98)

Reliability:
Flag:
14-FEB-2002

Type:
System of testing:
Metabolic activation:
Result:other: Point-mutation
E. coliwith and without
negative

Test substance:other TS: benzyl alcohol, purity not noted

Flag:
14-FEB-2002

Critical study for SIDS endpoint(101) (102)Type:
System of testing:Concentration:

Cytogenetic assay
CHO cells
up to 5000 ug/ml

Cytotoxic Concentration: none noted
Metabolic activation:
without
Result:negative
Method:Year:
GLP:
Test substance:

Result:Reliability:
Flag:
14-FEB-2002

other: similar to OECD 473; Galloway S.M. etal., Environ. Mutagen. 7, 1-52 (1985)
1989
yesother TS: technical grade benzyl alcohol(purity = 99%)
No significant increase in chromosome
aberrations was observed after exposure to
benzyl alcohol in the absence of S9.
(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(103) (98) (104)Type:
Cytogenetic assay
System of testing:
CHO cells
Concentration:
up to 5000 ug/ml
Cytotoxic Concentration: none noted
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OECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Metabolic activation:
Result:
Method:Year:
GLP:
Test substance:

Result:Reliability:

Flag:
14-FEB-2002

withpositive

other: similar to OECD 473; according to
Galloway S.M. et al. Environm. Mutagen.7, 1-52
(1985)
1989
no dataother TS: technical grade benzyl alcohol(purity = 99%)
A significant increase in chromosome
aberrations was observed after exposure to
benzyl alcohol in the presence of S9.
(1) valid without restriction
Similar to Guideline study
Critical study for SIDS endpoint(103) (98) (104)Type:
Cytogenetic assay
System of testing:
CHO cells
Concentration:
16 –5000 ug/ml
Cytotoxic Concentration: none noted
Metabolic activation:with and without
Result:equivocal
Method:Year:
GLP:
Test substance:other: similar to guideline study
1989
yesother TS: technical grade benzyl alcohol(purity = 99%)

Result:Sister chromatid exchange (SCE) an equivocal
response with and without metabolic
activation.
(1) valid without restriction
Similar to Guideline study

Reliability:

Flag:
14-FEB-2002
Type:
System of testing:Result:Remark:Flag:
12-FEB-2002
276

Critical study for SIDS endpoint(98)
Bacillus subtilis recombination assay
B. subtilis M 45, H 17
positive
limited data
Critical study for SIDS endpoint(105)
UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Type:
Mouse lymphoma assay
System of testing:L5178Y cells
Concentration:
up to 5000 ug/ml
Cytotoxic Concentration: >/= 3500 ug/ml
Metabolic activation:with and without
Method:GLP:Test substance:

Result:Reliability:Flag:other: similar to OECD 476; according to Myhr G.
et al., Prog. Mutat. Res. 5, 555-586 (1985)
yesother TS: technical grade benzyl alcohol(purity = 99%)
Benzyl alcohol induced an increase intrifluorothymidine-resistant cells in theabsence, but not in the presence of, S9
activation. The effect was associated with
toxicity.
(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint

14-FEB-2002

(98)

Type:
other: transformation assay
System of testing:
BALB/c-3T3 cells
Concentration:
5 to 20 mM
Cytotoxic Concentration: The cytotoxic response (millimolarLD50) = 17.9.
Metabolic activation:
without
Result:positive
Method:Year:
GLP:
Test substance:

Method:other: Matthews E.J.,J. Tissue Culture Methods
10, 157-164 (1986),Matthewy E.J. et al.,Environm. Health Perspect. 101[Suppl 2], 319-345 (1993)
1993
no dataother TS: Supplied by Radian Corp. (Houston,
TX); purity not noted
The A31-1-13 clone of BALB/c-3T3 cells was used
to evaluated the transforming potential ofnumerous chemicals including benzyl alcohol.
Each transformation assay contained astandard clonal survival assay, a co-culture
clonal survival assay, and a transformation
assay.
For each test, chemical-induced transformation
was detected using 18-20 vessels per doseseeded with 3.2x10(e4) cells/vessel.
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Remark:Result:278

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
Each dose was applied to cell cultures for 48
hrs. days 2-4, using standard procedures.
A total of 3 to 6 test chemicals were includedin each transformation experiment and each wastested at four treatment doses in at least two
independent trials.
The doses covered a range of cytotoxicity
responses of approximately 10-100% relativecloning efficiency.
Each test chemical in each experiment wasevaluated as sufficiently positive(statistically significant at two or moredoses), limited activity (statisticallysignificant at one dose at 99% conf. or two at
95% conf.), sufficiently negative ( nostatistically significant responses),or limited negative (no cytotoxity or abnormal
positive control). The number of type I-III
transformed foci were identified
microscopically considering their various
different phenotypic properties.
REFERENCES:
Matthews E.J.,J. Tissue Culture Methods 10,
157-164 (1986),
Matthews E.J. et al., Environm. Health
Perspect. 101 [Suppl 2], 319-345 (1993)
Benzyl alcohol (BA) was tested as a codedsample.
The author noted that BA can be oxidized by air
and may have been altered during the treatment
period. They state that BA was noncytotoxic
to BALB/c-3T3 cells and that the statisticalsensitivities for trial 1 and 2 were 2 and38/110, respectively. BA was evaluated as
active in this assay with actual and estimatedrank t-statistics both 1.95.
For the purpose of this study benzyl alcohol(BA) was grouped as a noncytotoxic,
nonmutagenic, noncarcinogenic chemical.
Notations for BA were: reacts with acid, air,acid chlorides and is temperature sensitive.
BA's potential to be oxidized by air was noted
as a potential confounding factor.
It had limited activity in the first test andWas sufficiently positive in the second.
It, therefore, was given the overall
evaluation of active in the transformation
assay. The cytotoxic response (millimolarLD50) 17.9.
In trial 1 BA concentrations ranged 5 to 20mM
UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
with an increase in transformation only notedat the 10mM concentration (85% coculture
clonal survival).
RESULT: 7.36foci/vessel - rank order 2(p</=0.001) -limited active mean t-statistic
2.11
In trial 2 BA concentrations ranged 5 to 20mM
with an increase in transformation noted at
the 10mM concentration (95% coculture clonal
survival;p</=0.001) and 15mM concentration(84% coculture clonal survival;p</= 0.01
to 0.05).

Reliability:

Flag:
14-FEB-2002

Fewer foci were observed in the second trial.
RESULT: 0.609 foci/vessel - rank order 38 –sufficient positive mean t-statistic 1.79
The positive control B(a)P performed well.
The number of foci/vessel for the neg control
was 7.36 and 0.609 in Trials 1 and 2,
respectively.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint
(106)

Type:
System of testing:
Metabolic activation:
Result:Reliability:

14-FEB-2002

Ames test
S. typhimurium TA 98, TA 100, TA 1535,
TA 1537
with and without
negative(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
(107)

Type:
System of testing:

Metabolic activation:
Result:Ames test
S. typhimurium TA 98, TA 100, TA 1535,
TA 1537, TA
1538
without
negative

16-JAN-2001
Type:
System of testing:(108)
Ames test
S. typhimurium TA 98, TA 100, TA 1535,
TA 1537
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5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Metabolic activation:
Result:Remark:16-JAN-2001

with and without
negative

Rat and hamster liver S-9 mix.
(109) (104)Type:
System of testing:
Metabolic activation:
Result:Ames test
S. typhimurium TA 98, TA 100
without
negative

16-JAN-2001

(110)

Type:
System of testing:
Metabolic activation:
Result:Ames test
S. typhimurium TA 92, TA 94, TA 98,
TA 100, TA 1535, TA 1537
withnegative

16-JAN-2001

(111)

Type:
System of testing:
Metabolic activation:
Result:Ames test
S. typhimurium TA 98, TA 1535
no datanegative

16-JAN-2001

(112)

Type:
System of testing:
Metabolic activation:
Result:other: Point-mutation
E. coli WP2 uvrA
no datanegative

16-JAN-2001

(105)

Type:
System of testing:Result:Bacillus subtilis recombination assay
B. subtilis M 45, H 17
positive

16-JAN-2001
(113)
Type:
System of testing:
Metabolic activation:
Result:other: Point-mutation
E. coli WP2 uvrA
without
negative

16-JAN-2001
Type:
280

(113)
Cytogenetic assay
UNEP PUBLICATIONSOECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

System of testing:

CHL cells

Result:negative

16-JAN-2001(111) (114)Type:
System of testing:
Metabolic activation:
Result:Mouse lymphoma assay
L5178Y tk+/tk- cellswith and without
ambiguous

16-JAN-2001(115) (116) (104)Type:

Ames test
System of testing:
Metabolic activation:
Result:S. typhimurium TA 100
without
negative

16-JAN-2001

(117)

Type:
System of testing:
Metabolic activation:
Result:Sister chromatid exchange assay
CHO cellswith and without
positive

16-JAN-2001

(104)

Type:
System of testing:Concentration:
Metabolic activation:
Result:other: DNA Double Strand Breaks
rat hepatocytes
0, 1, 3, 10 mM in 1 % DMSO
no dataambiguous

Method:Year:
GLP:
Test substance:other: in vitro alkaline elution assay
1994
no datano data

Remark:16-JAN-2001

Positive only in the highest dose.
(118) (119)5.6 Genetic Toxicity 'in Vivo'
Type:
Species:
Strain:Micronucleus assay
mouse
Sex: maleother: ddY strain, obtained from Shizuoka
Agricultural Cooperative Association forLaboratory Animals, Shizuoka, Japan
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5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Route of admin.:
Exposure period:
Doses:
Result:i.p.
24 h50, 100, 200 mg/kg
negative

Method:OECD Guide-line 474 "Genetic Toxicology:
Micronucleus Test"
1983
no dataother TS: benzyl alcohol, purity not noted

Year:
GLP:
Test substance:
Remark:Result:Mortality
0
50
100
200
(4 doses)
100
Mitomycin C
2.0

No. of animals: 6/dose.
There was no indication of micronucleus
induction at any dose tested.
1 Dose (mg/kg)
MNPCE (%)
PCE (%)
0.23 +/-0.18
0.23 +/-0.15
0.27 +/-0.12
0.12 +/-0.10

48.8 +/-6.2
55.5 +/-4.0
51.8 +/-9.5
48.7 +/-5.2

0/6
0/6
0/6
0/6

0.20 +/-0.14

63.1 +/-4.1

0/6

2.63 +/-0.32*

43.8 +/-1.1

0/6

MNPCE = Micronucleated polychromaticerythrocyte

Reliability:
Flag:
14-FEB-2002

PCE = polychromatic erythrocyte* = (P < 0.01)(1) valid without restriction
Guideline study
Critical study for SIDS endpoint
(120)

Type:
Species:
Strain:Route of admin.:
Exposure period:
Doses:
Result:other: replicative DNA synthesis
rat
Fischer 344
gavageonce
0, 300, 600 mg/kg bw
negative

Method:other: according to Uno Y. et al., Toxicol.
Lett. 63, 191-199, 201-209 (1992)
1994
no datano dataYear:
GLP:
Test substance:

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Sex: maleOECD SIDS
5. TOXICITY

Result:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Flag:
14-FEB-2002

Benzyl alcohol did not induce replicative DNA
synthesis in rat hepatocytes following oral
treatment.
Critical study for SIDS endpoint
(121)

Type:
Species:
Strain:Route of admin.:
Exposure period:
Doses:
Result:other: replicative DNA synthesismouse
B6C3F1
gavageonce
0, 400, 800 mg/kg bw
negative

Method:other: according to Uno Y. et al.,
Toxicol.Lett.63,191-199,201-209 (1992),
1995
no datano dataYear:
GLP:
Test substance:
Result:Flag:
23-MAR-2001

Sex: male

Benzyl alcohol did not induce replicative DNA
synthesis in mice hepatocytes following oral
treatment.
Critical study for SIDS endpoint
(122)

Type:
Species:
Strain:Route of admin.:
Exposure period:
Doses:

Drosophila SLRL test
Drosophila melanogaster
Sex: maleother: Canton S
drinking water
72 hrs0, 5000 (unit not given) in 5 % succrose
solution

Method:Year:
GLP:
Test substance:

other
1994
no dataother TS: purity: 99.8 %Result:no evidence for mutagenicity

19-JAN-2001
Type:
Species:
Strain:Route of admin.:
Exposure period:
Doses:(123)
Drosophila SLRL test
Drosophila melanogasterother: Canton S
i.p.
once
0, 8000 (unit not given)
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Sex: male283

OECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Method:Year:
GLP:
Test substance:

other
1994
no dataother TS: purity.99.8 %Result:19-JAN-2001

no evidence for mutagenicity(123)

5.7 Carcinogenicity
Species:rat
Strain:other: F344/N
Route of administration: gavage
Exposure period:
103 w
Frequency of treatment: 5 d/w
Post exposure period:noDoses:
200, 400 mg/kg/dResult:negative
Control Group:
yes

Sex: male/female

Method:Year:
GLP:
Test substance:

OECD Guide-line 451 "Carcinogenicity Studies"1981
yesother TS: technical grade benzyl alcohol(purity =99%)

Method:Benzyl alcohol was administered in corn oil by
gavage to groups of 50 Fischer 344/N rats ofeach sex at a dose of 0, 200, or 400 mg/kg bw
per day on five days a week for 103 weeks.
The rats were observed twice daily, and bodyweights were recorded weekly for the first 12
weeks and once a month thereafter.
Gross necropsy was performed on all animals; and49 tissues and organs, including brain,kidney, pancreas,

Remark:Result:284

and skeletal muscle, from all female rats andfrom male rats in the vehicle control and highdose groups and those in the other groups thatdied before 22 months or which had grosslesions were examined histologically.
Biochemistry and hematolgy studies were not
performed.
The mean body weights of treated and control
animals were comparable throughout the study. No
compound-related clinical signs were observed,
although a sialodacryoadenitis viral infection
UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Reliability:

Flag:
14-FEB-2002

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
was widespread among the study animals in
the third month. The survival of treatedfemales was significantly lower than that ofvehicle controls: 70% of controls, 34% of
low-dose females, and 34% of high-dose
females; this was due to a much higher
incidence of accidental deaths related to thegavage process.
Survival among the male rats was comparable inall groups: 56% of controls, 54% at the low
dose, and 48% at the high dose.
Cataracts and retinal atrophy were observed at
Increased incidences in rats at the high dose.
The authors attributed this effect to theproximity of this group of animals to
fluorescent light for most of the study. An
increased incidence of hyperplasia of theforestomach epithelium was seen (notstatistically significant) in male rats:
control, 0/48; low dose, 0/19;
high dose, 4/50.
Haemorrhage and foreign material in the
respiratory tract seen in treated rats thatdied before the end of the study weresuggested by the authors to have been the
result of either direct deposition of material
into the lung during gavage 'accidents' or theanaesthetic properties of benzyl alcohol
resulting in reflux of gavage material andaspiration into the lungs. No pancreatic acinarcell adenomas were reported, and no othereffects of treatment were seen at gross
necropsy or histopathologicalexamination.
(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(124) (98)Species:mouse
Strain:B6C3F1
Route of administration: gavage
Exposure period:
103 w
Frequency of treatment: 5 d/w
Post exposure period:noDoses:
100, 200 mg/kg/dResult:negative
Control Group:
yes
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Sex: male/female

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OECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Method:Year:
GLP:
Test substance:

OECD Guide-line 451 "Carcinogenicity Studies"1981
yesother TS: technical grade benzyl alcohol(purity =99%)

Method:Benzyl alcohol (purity, 99%) was given togroups of 50 B6C3F1 mice of each sex, eight tonine weeks of age, at a dose of0, 100, or 200 mg/kg bw per day in corn oil by
gavage on five days a week for 103 weeks. The
doses were selected on the basis of thosefound to induce neurotoxic effects (lethargy
and staggering) in short-term studies.
The mice were observed twice daily, and theirbody weights were recorded weekly for the
first 12 weeks and once a month thereafter.
Gross necropsy was performed on all animals,
and 50 tissues and organs, including brain,
liver, kidney, and stomach, from all vehicle
controls, animals at the high dose, andanimals at the other doses that died before 22
months or had gross lesions were examinedhistologically.
Biochemistry and hematolgy studies were not
performed.
The mean body weights of treated and control
mice were comparable throughout the study. The
survival of control females was significantly
lower than that of animals at the high dose
after week 74, but no other differences inRemark:Result:Reliability:
Flag:
14-FEB-2002

survival were seen: 68% of control, 66% of
low-dose, and 70% of high-dose males; and 50%of control, 62% of low- dose, and 72% of highdose females.
No significant treatment-related effects werenoted at gross necropsy or histopathologicalexamination. No increase was seen in theincidence of hepatocellular or forestomach
neoplasia.
(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(124) (98)Species:mouse
Strain:B6C3F1
Route of administration: i.p.
Exposure period:
22 d
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Sex: maleOECD SIDS
5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Frequency of treatment:
Post exposure period:
Doses:
Control Group:
Remark:Result:19-JAN-2001

once on day 1, 8, 15, 22
up to 1 a
3.75 umol (total dose) in trioctanoin
yes

35 mice received injections prior to weaning.
The mice were weaned at 4 weeks of age. All
surviving mice were killed at 12 months forenumeration of hepatomas.
Benzyl alcohol had no detectable activity forthe initiation of hepatic tumors on
administration to male mice prior to weaning.
(125)

5.8.1 Toxicity to Fertility
Type:Species:
Sex:
Strain:Route of administration:
Exposure Period:
Frequency of treatment:
Duration of test:
Doses:
Control Group:
NOAEL Parental:

other: 2 year gavage study
ratmale/female
Fischer 344
gavage103 weeks
5d/w
103 weeks
200, 400 mg/kg/d
yes
400 ml/kg bw

Method:Year:
GLP:
Test substance:other: OECD 451
1981
yesother TS: technical grade benzyl alcohol(purity = 99%)

Remark:Result:Benzyl alcohol was administered in corn oil.
No evidence of compound related effects in thetestes or ovaries of treated rats.
Changes noted in general in the reproductive
system were inconsequential.
(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(98)

Reliability:
Flag:
14-FEB-2002

Type:
Species:
Sex:
Strain:Route of administration:other: 2 year gavage study
mouse
male/female
B6C3F1
gavage

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5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Exposure Period:
Frequency of treatment:
Duration of test:
Doses:
Control Group:
NOAEL Parental:

103 weeks
5 d/w
103 weeks
100, 200 mg/kg/d
yes
200 ml/kg bw

Method:GLP:Test substance:other: OECD 451
yesother TS: technical grade benzyl alcohol(purity =99%)

Remark:Result:Benzyl alcohol was administered in corn oil.
No evidence of compound related effects in thetestes or ovaries of treated mice.
Changes noted in general in the reproductive
system were inconsequential.
(1) valid without restriction
GLP guideline study
Critical study for SIDS endpoint(98)

Reliability:
Flag:
14-FEB-2002

Type:
Species:
Strain:Route of administration:
Exposure Period:

Frequency of treatment:
Doses:
Control Group:
NOAEL Parental:
NOAEL F1 Offspring:
NOAEL F2 Offspring:other: 4 generation study
rat
no dataoral feed
generation 1 and 2: lifelong;
generation 3: 16 weeks;
generation 4: until breeding
continuously in diet
0.5 or 1 % in diet (approx. 375 or
750 mg/kg/day)yes>= 750 ml/kg bw>= 750 ml/kg bw>= 750 ml/kg bw

Test substance:other TS: benzoic acid

Remark:See IUCLID data set on benzoic acid
(CAS# 65-85-0). Benzyl alcohol will rapidly bemetabolized to benzaldehyde and so to benzoic
acid.
Therefore the data of benzoic acid can also be
supportive to state that benzyl alcohol is not
a reproductive (fertility and developmental)
toxicant.
No effects on fertility, lactation, growth andsurvival or the incidence of foetal
malformations were observed in a 4 generation

Result:288

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Flag:
06-JUN-2001

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
reproduction study with rats (20 m and 20 f)
exposed to 0.5% and 1.0% benzoic acid in the
diet.
Critical study for SIDS endpoint
(126)

Type:
Species:
Sex:
Route of administration:
Exposure Period:
Frequency of treatment:
Premating Exposure Period
female:Duration of test:
Doses:NOAEL Parental:

Fertility
rat
femaleoral unspecified
32 weeks
every second day
75 days
32 weeks
5 mg/kg
5 mg/kg bw

Test substance:other TS: benzaldehyde

Remark:Benzyl alcohol will rapidly be metabolized tobenzaldehyde and so to benzoic acid.
Therefore the data of benzaldehyde can also be
supportive to state that benzyl alcohol is not
a reproductive (fertility and developmental)
toxin.
No treatment related effects noted.
Critical study for SIDS endpoint(127) (128)

Result:Flag:
16-JAN-2001

5.8.2 Developmental Toxicity/Teratogenicity
Species:femaleStrain:Route of administration:
Exposure period:
Frequency of treatment:
Duration of test:
Doses:
Control Group:
LOAEL Maternal Toxicity :LOAEL Fetotoxicity :

mouse

Sex:

CD-1
gavageday 7-14 of gestation
daily
until 3 days afer pregnancy
750 mg/kg bw/day
yes
750 mg/kg bw
750 mg/kg bw

GLP:
Test substance:

no dataother TS: benzyl alcohol, purity not noted

Method:Benzyl alcohol dissolved in distilled water wasadministered by gavage at a dose of 750 mg/kg
bw per day to 50 mice on days 7-14 of
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Result:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
gestation; evidence of copulation wasconsidered the first day of gestation.
A control group of 50 animals received
distilled water only. All animals wereallowed to deliver their litters and nurse
their pups for three days, at which time
necropsies were performed.
Maternal body-weight gain and mortality,
mating, gestation, numbers of live and deadpups per litter, total litter weight on days 1
and 2 post partum, litter weight change
between days 1 and 3 post partum, and pup
survival on days 1 and 3 post partum wererecorded.
During the treatment period, 18 deaths werereported, allof which were attributed to treatment; afurther death was reported on day 15 ofgestation, the day after treatment
was terminated. Clinical signs of toxicity,
including hunched posture, tremors,
inactivity, prostration, hypothermia, ataxia,
dyspnoea, swollen or cyanotic abdomen, andpiloerection, were reported in up to 20 mice
during treatment. Piloerection was also
reported in some animals up to day 3 post
partum, but no other clinical signs were seen
after the period of administration.
No differences were observed in the mating or
gestation indices, the total number ofresorptions, the mean length of gestation, orthe number of live pups per litter between
treated and control groups. Maternal bodyweight, measured on days 4 and 7 of gestation,
was not significantly different from control
values; however, statistically significant
reductions were reported on day 18 ofgestation (P < 0.001) and on day 3
post partum (P < 0.05).
Maternal body-weight gain during days 7-18 ofgestation was significantly lower than that ofcontrols (P < 0.001). Significant reductions
in pup body weight were reported, including alower mean pup weight per litter on days 1(P < 0.01) and 3 post partum (P < 0.001),
a mean litter weight change between day 1 andday 3 post partum (P < 0.05), and a mean pup
weight change between days 1 and 3 post partum(P < 0.001). No differences in pup survival

290

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5. TOXICITY

Conclusion:

Reliability:

Flag:
14-FEB-2002

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
were observed by day 3 post partum.
The authors concluded that benzyl alcohol may
be a reproductive hazard, apparently on thebasis of the reductions in pup body weights,
an effect that was observedin conjunction with maternal toxicity evidenced
by increased mortality, reduced body weights,
and clinical toxicity during the period ofadministration. As effects were seenon the dams and fetuses at the only dose usedin this study, there was no NOAEL. The LOAEL
was 750 mg/kg bw per day.
(2) valid with restrictions
Meets generally accepted scientific standards,
well documented and acceptable for assessment
Critical study for SIDS endpoint(129) (130) (131)Species:femaleRoute of administration:
Exposure period:
Frequency of treatment:
Duration of test:
Doses:
Control Group:
NOAEL Maternal Toxity:
NOAEL Teratogenicity:

mouse

Sex:

gavagedays 6-15 of gestation
daily
until day 3 post partum
550 mg/kg bw
yes, concurrent vehicle
550 mg/kg bw
550 mg/kg bw

GLP:
Test substance:

no dataother TS: benzyl alcohol; purity not noted

Method:50 female mice were given benzyl alcohol at 550
mg/kg bw per day by gavage on days 6-15 ofgestation; a further 50 mice received the corn
oil vehicle. All dams were allowed todeliver naturally, and pups and dams wereobserved until day 3 post partum, when theexperiment was terminated. Body weight,
clinical observations, and mortality wererecorded daily throughout treatment and up to
day 3 post partum.
abstract only
Mortality was not significantly increased inanimals given benzyl alcohol over that in thecontrol group.
One treated mouse showing languid behaviour,
laboured breathing, and a rough coat died, but
no other deaths or clinical signs were

Remark:Result:UNEP PUBLICATIONS

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OECD SIDS
5. TOXICITY

Conclusion:

Reliability:
Flag:
14-FEB-2002

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
reported. Maternal body weight and body-weightgain during treatment and up to day 3 post
partum were virtually identical for treatedand control animals. All other parameters
examined, including gestation index, average
number of live pups per litter, and postnatal
survival and pup body weight on days 0 and 3
post partum, were not significantly different
from the control values.
The authors concluded that, at the predicted
LD10, benzyl alcohol had no significant
effects on the development of CD-1 mice.
The NOAEL was 550 mg/kg bw per day.
(2) valid with restrictions
Critical study for SIDS endpoint(132) (133)Species:
male/female
Strain:Route of administration:
Exposure period:

Frequency of treatment:
Duration of test:
Doses:
Control Group:
NOAEL Maternal Toxity:
NOAEL Teratogenicity:

rat

Sex:

no dataoral feed
generation 1 and 2: lifelong;
generation 3: 16 weeks;
generation 4: until breeding
continuously in diet4 generations
0.5 or 1% in diet (approx. 375 or 750
mg/kg/day)yes
750 mg/kg bw
750 mg/kg bw

Method:GLP:Test substance:otherno dataother TS: benzoic acid

Remark:See IUCLID data set on benzoic acid
(CAS# 65-85-0).
Benzyl alcohol will rapidly be metabolized tobenzaldehyde and so to benzoic acid. Therefore
the data of benzoic acid can also be
supportive to state that benzyl alcohol is not
a reproductive (fertility and development)
toxicant.
No effects on the dams or on the growth anddevelopment of the offspring were seen whengroups of 10 rats were fed diets containing up
to 1% benzoic acid during pregnancy andlactation.

Result:292

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5. TOXICITY

Flag:
06-JUN-2001

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
Critical study for SIDS endpoint(126)

Species:Route of administration:
Exposure period:

other: chicken embryoother11 to 18 d

Frequency of treatment:

1 injection before incubation or on
different d after incubation
0.01-0.02 ml/egg = 10-20 mg/egg
yes

Doses:
Control Group:
Remark:30-JAN-2001

Sex:

Injections of benzyl alcohol into the yolks offertile eggs, either before incubation, orfrom the 1. through the 7. d after the
beginning of their incubation give rise tomeningoceles, limb deformities, beak defects
such as, arched upper beaks, localized blebs
and generalized edema.
no post observation(134)

5.8.3 Toxicity to Reproduction, Other Studies

5.9 Specific Investigations

5.10 Exposure Experience
Remark:19-JAN-2001
Remark:Source:20-AUG-1992

Benzyl alcohol poisoning can cause thegasping syndrome in neonates. The infants
had a typical course of gradual neurologic
deterioration, severe metabolic acidosis,
the striking onset of gasping respirations,thrombocytopenia, hepatic and renal failure,
hypotension, cardiovascular collapse anddeath. In every infant, unmetabolized
benzyl alcohol was identified in the urine.
(135) (136) (137) (138) (139) (140) (141) (142)
Local anaesthesia occurred when neat benzyl
alcohol was applied to the (presumably
uncovered) skin or when 1 % aqueous
solution was injected intradermally.
Bayer AG Leverkusen(37)

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Remark:Source:20-AUG-1992
Remark:Source:15-JUL-1993

Remark:Source:20-AUG-1992
Remark:Source:20-AUG-1992
Remark:Source:22-MAR-1993
Remark:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

A methylprednisolone sodium succinate
formulation, containing 18 mg / dose of
benzyl alcohol, was well tolerated in humanvolunteers after i.v. injection.
No important drug-related side effects wereencountered.
Bayer AG Leverkusen(143)
Cases of allergic contact dermatitis, andeven systemic hypersensitivity have beenreported in humans.
Bayer AG Leverkusen(144) (145) (146) (147) (148) (149) (150)(151) (152) (153) (154) (155)
No contact allergy could be detected inhumans treated with a 10 % formulation of
benzyl alcohol (no other data).
Bayer AG Leverkusen(156)
Premature neonates may receive multiple
drugs in the neonatal intensive care unit,
some of which may contain benzyl alcohol As
there may be no safe lower dose of benzyl
alcohol in these patients, it would seem
prudent to avoid the use of multiple dosevials containing benzyl alcohol wheneveralternatives exist.
Bayer AG Leverkusen(157)
It also seems prudent to avoid the use of
products containing benzyl alcohol topregnant patients within whom the benzyl
alcohol molecule, given its small size,presumably crosses the placental barrier
into immature fetal tissues as readily as
it crosses the blood-brain barrier.
Bayer AG Leverkusen(158)

Source:24-FEB-1998

high levels of benzyl alcohol (5-500 ug/10
ml plasma) were found in uremic patients on
hemodialysis; benzyl alcohol was notdetected in normal controls.
Bayer AG Leverkusen
(159)

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Remark:Source:24-FEB-1998
Remark:Source:24-FEB-1998
Remark:Source:26-FEB-1998

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

In 2 long-term double blind studies onhumans comparing benzyl alcohol , placebo
and Catalin in the topical treatment ofprogressive cataract, rapid (2-3 weeks
treatment) reversal of incipient cataract
was obtained accompanied by a marked
improvement of vision and by asignificantly lower percentage of eyes
requirering surgery after 22 months oftreatment with benzyl alcohol than withplacebo and Catalin.
Bayer AG Leverkusen(160)
Study on healthy adult voluteers: Benzyl
alcohol is itself an effective anesthetic
and can reduce the pain of injection for
lidocain without adversely affecting
its anesthetic properties.
Bayer AG Leverkusen(161)
Benzyl alkohol is commonly used as apreservative in many injectable drugs andsolutions. A number of neonatal deaths andsevere respiratory and metabolic
complications in low-birth-weight prematureinfants have been associated with the useof this agent.
Bayer AG Leverkusen(162) (163) (164) (165) (166) (167) (168)

5.11 Additional Remarks
Type:

Metabolism

Remark:Humans, rabbits and rats readily oxidize
benzyl alcohol to benzoic acid, which, after
conjugation with glycine, is rapidly
eliminated as hippuric acid in the urine.

19-JAN-2001(169) (170) (171) (172) (173) (174) (175)

Type:

other

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Remark:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Source:24-FEB-1998

Bacillus subtilis spore rec-assay can be used
as a simple screening test taking the place ofanimal methods for detection of theallergenicity.
Bayer AG Leverkusen
(176)

Type:

other

Remark:yeast test: according to the author an aalternative to the contemporary mode of acutetoxicity testing testing. In the test, theincrease in the cell count after treatment inrelationship to the increase in cell count of
untreated cells is measured and expressed as"medium inhibitory concentration = IC 50 " :benzyl alcohol IC 50 = 277 mg/l
Bayer AG Leverkusen

Source:24-FEB-1998(177) (178)

Type:

other

Remark:Benzylalkohol differencially altered thespecific activity of subcellular rat
epididymal and testicular aldehyde
dehydrogenase activity as well as hepatic
aldehyde dehydrogenase activity.
Bayer AG Leverkusen

Source:24-FEB-1998(179) (180) (181) (182)

Type:

other

Remark:different concentrations of benzyl alcohol(1,2,5,10 % v/v)in sesame oil were
subcutaneously injected to rats. only
the 1 % benzyl alcohol produced an
insignificant increase in skin fold thickness.
Bayer AG Leverkusen

Source:24-FEB-1998
Type:

296

(183)
other

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5. TOXICITY

Remark:Source:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

In vitro, benzyl alcohol relaxes airway smoothmuscle, probably through the dercrease in
intracellular Ca2+ release by inhibiting
agonist-mediated phosphatidylionositol
turnover.
Bayer AG Leverkusen

24-FEB-1998
Remark:Source:(184)
Aseptic meningitis has been observed following
intrathecal administration ofradiopharmaceuticals that contain benzylalcohol as a preservative. Cisterna magna
injections of benzylalcohol in concentrations
as high as 10 times that normally used did not
produce meningitis in adult or immature dogs.
With 9 % benzyl alcohol, transient
respiratory arrest was observed in adult dogs
and death was observed in immature dogs; 7 %and 4.5 % benzyl alcohol produced clonicseizures in puppies.
Bayer AG Leverkusen

15-JUL-1993
Remark:Source:(185)
Injection of benzyl alcohol (700-900 mg/kg,
i.p.) caused rapid immobilization of mice. The
mice were immobilized within 2 min. andremained unresponsive (no righting reflex, nowink reflex, and no leg reflex) for about 30
min. The immobilizing effect was accompanied
by a marked hyperglycemia. Tracer studies
indicated that the hyperglycemic effect may
have resulted from increased gluconeogenesis.
Bayer AG Leverkusen

27-MAY-1993
Remark:Source:(186)
Benzyl alcohol used as a stabilizer for
antibiotics of aminoglycosid structure is thesubstance responsible for the displacement ofbilirubin from albumin. The free, unbound,
unconjugated bilirubin tends to diffuse into
the lipid of the brain of young Gunn rats withresultant kernicterus.
Bayer AG Leverkusen

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5. TOXICITYBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

15-JUL-1993
Remark:Source:(187)
Duodenal and jejunal brush border membrane
vesicle integrity was studied after in vitro
treatment of rabbit tissue with benzylalcohol.
The effect of the alcohol on gastric parietal
cell apical and microsomal membrane vesicle
integrity was also studied. Exposure ofvesicles to the alcohol caused concentration
dependent decreases in enclosed volume. Allconcentrations tested reduced the enclosed
volume of both gastric apical membrane vesicles
and gastric microsomes. The alcohol induced
disruption of the vesicle membranes appears toresult from a fluidising effect. The main
effect of the raised fluidity is to increase
membrane fragility.
Bayer AG Leverkusen

15-JUL-1993
Remark:Source:(188) (189)Benzyl alcohol as a fragrance ingredient usedin cosmetic and other products is lipophilic
and therefore has the potential to be readily
absorbed through skin.
The percutaneous absorption was determined invivo in rhesus monkeys. Absorption throughoccluded skin was high (56-80 %) in 24 h.
No correlation was seen between skinpenetration and the octanol-water partition
coefficient.
Under unoccluded conditions skin penetration
was reduced (32 %), because of evaporation of
the compound.
Bayer AG Leverkusen

27-MAY-1993
Remark:Source:(190)
After i.v. injection in mice, benzyl alcohol
was found to inhibit TBPS binding and to
stimulate GABA receptor mediated Cl influx
into brain vesicles.
Bayer AG Leverkusen

27-MAY-1993

298

(191)

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5. TOXICITY

Remark:Source:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Benzyl alcohol can cause hemolysis of humanand rabbit erythrocytes in the presence of 0.9% NaCl.
Bayer AG Leverkusen

15-JUL-1993
Remark:Source:(192) (193)
Benzyl alcohol produced up to 6-fold increases
in cAMP concentrations in purified humanperipheral blood lymphocytes. Significant but
less marked augmentation of cAMP was observedin human platelets, human granulocytes, andrabbit alveolar macrophages.
The mechanism of the alcohol-induced cAMP
accumulation is probably secondary to membrane
perturbation and consequent activation of
adenylate cyclase.
Bayer AG Leverkusen

15-JUL-1993
Remark:Source:(194)
Uncoupled sonic submitochondrial particles
from beef heart and rat liver were studied for
mitochondrial electron transport. Benzyl
alcohol was found to inhibit each of thesegments of the electron transport chain
assayed.
NADH oxidase and NADH-cytochrome c oxidoreductase required the lowest concentration
for inhibition, and cytochrome c oxidase
required the highest concentration.
Beef heart submitochondrial particles are lesssensitive to inhibition than are rat liver
particles.
Bayer AG Leverkusen

27-MAY-1993
Remark:(195)
Lactated Ringer`s solution containing 1.5 %benzyl alcohol can cause severe symptoms of
toxicity in cats including hyperesthesia
leading to depression, coma, and finallydeath. In the cat, only hippuric acid isformed, as this species lacks adequate
glucuronic acid conjugation capacity,
resulting in a decreased rate of metabolism.

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Source:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
This results in an accumulation of benzoic acid.
Benzoic acid has been shown to be extremely
toxic to cats, causing clinical signs similar
to those observed.
Bayer AG Leverkusen

15-JUL-1993
Remark:Source:(196)
50 mM benzyl alcohol fluidized proximal brushborder membranes prepared from human small
intestine and increased p-nitrophenylphosphatase activity in this membrane. This
agent also shifted the phase transition
temperature of the membrane and breakpointtemperature of this enzymatic activity.
Bayer AG Leverkusen

15-JUL-1993
Remark:Source:(197)
Microscopic examination revealed local nerve
degeneration when 5 % benzyl alcohol was
injected into the side of a cat’s face.
At 10 % local anaesthesia was produced.
Bayer AG Leverkusen

27-MAY-1993

Remark:Source:(198)

Benzyl alcohol displays a pronounced
antiarrhythmic-anti- fibrillatory effect, when
injected i.v. into dogs and rats withspontaneous or drug-induced arrhythmias.
Mechanisms which might be responsible for theantiarrhythmic effect: lengthening of theeffective refractory period, local andgeneral anaesthetic effects, changes ofosmolality. The i.v. injection of benzylalcohol in high doses, produces
intravascular haemolysis.
Bayer AG Leverkusen

27-MAY-1993
Remark:300(199)
The length of the oestrus cycle was reduced
when 0.52-2.1 d (1-4 mg/kg bw) benzyl alcohol
was injected into the uterus of each of 48
cows.

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Source:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

Bayer AG

Leverkusen

27-MAY-1993
Remark:Source:(200)
The in vitro effect of local anesthetic benzyl
alcohol was studied using isolated cells fromrat stomach. Lower concentrations of thealcohol increased the basal aminopyrine
accumulation and potentiated the secretory
response of parietal cells to histamine anddbcAMP.
At higher concentrations the alcohol
progressively inhibited both the basal 14-Caminopyrine accumulation and that stimulated
by histamine, dbcAMP or carbachol. While a low
concentration increased gastric microsomal(H-K)-ATPaseactivity, higher concentrations
inhibited enzyme activity to about 80 % of
those activities found in resting parietal
cells.
Bayer AG Leverkusen

15-JUL-1993
Remark:contact.
Source:(201)
Benzyl alcohol is a fairly efficientanesthetic for intact mucous membranes,
greatly surpassing procain. Its action is
not as lasting as that of cocain. It appears
that 1 % does not produce satisfactory
anesthesia of the tongue, even after 10 min.
Bayer AG

Leverkusen

27-MAY-1993
Remark:Source:(202)
Benzyl alcohol in non-toxic concentrations wasfound to markedly reduce the hemoglobin
minor/hemoglobin major ratio and to moderately
reduce the total hemoglobin induced by
DMSO or HMBA in mouse erythroleukemia (MEL)
cells, while only slightly decreasing theratio induced by hemin or butyrate.
Bayer AG Leverkusen

27-MAY-1993(203)

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Remark:Source:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

It was demonstrated that benzyl alcohol, aneutral local anesthetic, inhibits the uptake
and degradation of lowdensity lipoprotein andendocytosis of transferrin receptors ofguinea-pig leukemic B lymphocytes. This
inhibition is very rapid, concentration
dependant and reversible by simple washing.
Membrane fluidity of the living cells is also
modified.
Bayer AG Leverkusen

27-MAY-1993
Remark:Source:(204)
The tissue culture lethal dose (TCLD50) inmouse embryo cells was found to be 0.002
mg/ml.
Bayer AG Leverkusen

27-MAY-1993
Remark:Source:(205)
Benzyl alcohol is more toxic to infant
jaundiced (jj) than to non-jaundiced (Jj) Gunnrats. Before excretion as hippuric acid,benzyl alcohol is metabolized to benzoic
acid, a potent competitor for bilirubinalbumin binding sites. These pathways are
immature in newborns. Therefore thekernicterus in jj pups is probably due toincreased levels of unbound bilirubin.
Bayer AG Leverkusen

27-MAY-1993
Remark:Source:(206)
The plasma half-life of benzyl alcohol
administered as a 2.5 % solution in saline wasfound to be approximately 1.5 h in dogs
injected i.v. at doses of 52 and 105 mg/kg.
Bayer AG Leverkusen

27-MAY-1993
Remark:302(47)
Larger percentages of benzyl alcohol doses
were found in urine as benzoic acid in preterm
babies, while less hippuric acid appeared intheir urine than in term newborns.

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Source:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
These results indicate that hippuric acidformation is deficient in preterm neonates.
Bayer AG Leverkusen

27-MAY-1993
Remark:Source:(207)
In vitro studies of human liver alcohol
dehydrogenase (ADH) variants revealed thatbenzyl alcohol is slowly metabolized bybeta-2-ADH. Working with this solvent mightlead to toxic effects; these could beparticularly prominent in individuals
possessing the beta-2-ADH if they have a lower
capacity to eliminate them, or they could beparticularly prominent in those with beta-1ADH if they quickly convert them into toxic
aldehydes.
Bayer AG Leverkusen

27-MAY-1993
Remark:Source:(208)
Perfusing the anterior chamber of enucleatedrabbit eyes with 1.18 % benzyl alcohol, thecorneal endothelial cells changed theappearence and the corneas began to swell.
Bayer AG Leverkusen

24-AUG-1993
Remark:Source:(209)
The invitro effects of benzyl alcohol andbenzaldehyde on subcellular rat liver NADdependant alcohol and aldehyde dehydrogenase
were studied as a function of gender.
These effects were compared with those of the
primary substrates ethanol and acetaldehyde.
the results suggest metabolic competitions
between benzyl alcohol and ethyl alcohol forcatalysis by alcohol dehydrogenase.
Bayer AG Leverkusen

03-MAR-1998
Remark:(210)
Acute intravenous toxicity of benzyl alcohol
was determined in CD2F1 (0.05-0.2 ml/kg bw),
B6D2F1 (0.05-0.4 ml/kg) and C57BL/6 mice.

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Source:BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6
The lowest dose was a safe dose and thehighest one was the dose causing mortality inno more than half the animals of each group.
Clinical signs were convulsion, dyspnea andreduced mortility in all strains for
24 hours. The slight decrease in body weightin the first week following treatment returned
to normal in the second
week.
Bayer AG Leverkusen

03-MAR-1998

304

(211)

UNEP PUBLICATIONSOECD SIDSBENZYL ALCOHOL
6. ANALYT. METH. FOR DETECTION AND IDENTIFICATIONDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

6.1 Analytical Methods

6.2 Detection and Identification

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7. EFF. AGAINST TARGET ORG. AND INTENDED USES

7.1 Function

7.2 Effects on Organisms to be Controlled

7.3 Organisms to be Protected

7.4 User

7.5 Resistance

306

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SUBSTANCE ID: 100-51-6

OECD SIDS
8. MEAS. NEC. TO PROT. MAN, ANIMALS, ENVIRONMENTBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

8.1 Methods Handling and Storing

8.2 Fire Guidance

8.3 Emergency Measures

8.4 Possib. of Rendering Subst. Harmless

8.5 Waste Management

8.6 Side-effects Detection

8.7 Substance Registered as Dangerous for Ground Water

8.8 Reactivity Towards Container Material

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9. REFERENCES(1)BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6

CRC Handbook of Chemistry and Physics. 1999. David R.
Lide, ed. CRC Press, New York. p 3-52, #1836.

(2) Auer-Technikum, Auerges. mbH Berlin, 12. Ausg. 1988
(3) Calculation UWS-Produktsicherheit, Bayer AG 1991
(4) THOR database Pomona 89, MedChem Software 1989. Daylight,
Chemical Information Systems, Claremont, CA 91711, USA(5) Safety Data Sheet Bayer AG 12.10.1992(6) Meylan W. and Howard P. 1999. EPIWin Modeling Program.
Syracuse Research Corporation. Environmental Science
Center, 6225 Running Ridge Road, North Syracuse, NY
13212-2510(7) Biodegradation and Bioaccumulation Data of Existing
Chemicals Based on the CSCL Japan, Compiled under theSupervision of Chemical Products Safety Division, Basic
Industries Bureau MITI, Ed. by CITI, October 1992.
Published by Japan Chemical Industry Ecology-Toxicology& Information Center(8) Bayer AG data
(9) Horowitz, A. et al., Dev. Ind. Microbiol. 23, 435-444(1982)(10) Shelton D.R. and Tiedje J.M.
47(4):850-857. (1984)

Appl. Environ. Microbio.

(11) Meinck, F. et al., Industrie-Abwaesser, p. 41 (1968)(12) Gerike, P. and Gode, P., Chemosphere 21(6), 799-812(1990)(13) Wagner, R., Vom Wasser 47, 241-265 (1976)(14) Belly R.T. and Goodhue C.T. Proceedings of theInternational Biodegradation Symposium. 3:1103-1107(1976)(15) Wagner, R., Vom Wasser 42, 271-305 (1974)

308

UNEP PUBLICATIONSOECD SIDS
9. REFERENCES

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6(16) Urano, K. und Kato, Z., Journal of Hazardous Materials 13(2), 135-145 (1986)(17) NAPM (National Association of Photographic Manufacturers,
Inc., in cooperation with Hydroscience, Inc.):
Environmental Effect of Photoprocessing Chemicals, Vol I
and II. NAPM, Inc., 600 Mamaroneck Ave., Harrison, N.Y.,
10528 (1974)(18) Mattson, V.R. et al., EPA-600/3-76-097, Oct. 1976, PB-262
897(19) Knie, J. et al., Deutsche Gewaesserkundl. Mitt. 27 (3),77-79 (1983)(20) Applegate, V.C. et al., Special Scientific ReportFisheries No. 207, Washington, D.C., March 1957(21) Lipnick, R.L. et al., Environmental Toxicology andChemistry 4, 281-296, (1985)(22) Loeb, H.A. und Kelly, W.H., Special Scientific
Report-Fisheries No. 471, Washington, D.C. (1963)(23) Dawson, G.W. et al., Journal of Hazardous Materials 1,
303-318 (1975/77)(24) Bringmann, G. und Kuehn, R., Gesundheitsingenieur 80 (4),115-120 (1959)(25) Bringmann, G. und Kuehn, R., Z. Wasser Abwasser Forsch.
15(1), 1-6 (1982)(26) Stratton, G.W. und Corke, C.T., Environmental Pollution(Series A) 29 (1), 71-80 (1982)(27) Kaiser, K.L.E. et al., QSAR of acute toxicity ofmono-substituted benzene derivatives to photobacterium
phosphoreum. QSAR Environ. Toxicol., Proc. Int.
Workshop, 2nd Meeting Date 1986, Edited by Kaiser,
K.L.E., Reidel: Dordrecht, Neth., 153-168 (1987)(28) Ferard, J.F. et al., Sciences de l'eau 2 (2), 221-237(1983)(29) Blum, D.J.W. und Speece, R.E, Research Journal WPCF
63(3), 198-207 (1991)

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9. REFERENCES

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6(30) Sinniah, B., Transactions of the Royal Society ofTropical Medicine and Hygiene 77 (1), 35-38 (1983)(31) Loeser, E.: Bayer AG data, short report, 3. 11. 1978(32) Jenner, P. M. et al.: Fd. Cosmet. Toxicol. 2, 327-343(1964)(33) Opdyke, D. L. J.: Monograph on Fragrance Raw Materials.
Fd. Cosmet. Toxicol. 11, 1011-1013 (1973)(34) Graham, B. E., Kuizenga, M. H.: J. Pharmac. 84, 358-362(1945)(35) Opdyke, D. L. J.: Monograph on Fragrance Raw Materials.
Fd. Cosmet. Toxicol. 11, 1011-1013 (1973)(36) Smyth, H. F. et al.: Arch. Ind. Hyg. Occup. Med. 4, 119120(1951)(37) Macht, D. I.: J. Pharmac. exp. Ther. 11, 263-279 (1918)(38) Carter, D. V. et al.: J. Pharmacol., Suppl. 10, T149-T159(1958)(39) Bayer AG data, Report No. 19799, 12. 12. 1990(40) Patty`s Industrial Hygiene and Toxicology, Third Revised
Edition, Vol. 2C, pg. 4639 (1982), John Wiley and Sons
(41) Carpenter, C. P. et al.: J. Ind. Hyg. Toxicol. 31: 343346 (1949)(42) NPIRI: Raw Mater. Data Handb. Vol. 1, 6 (1974)(43) Jones W.H. Toxicity and Health Hazard Summary,
Laboratory of Industrial Medicine, Eastman Kodak Company,
Kodak Park.(1967)(44) Opdyke, D. L. J.: Fd. Cosmet. Toxicol. 11, 1011-1013(1973)(45) McCloskey, S.E. et al., J. Pharmaceut. Sciences 75, 702705 (1986)(46) NTP: Technical Report No. TR 343 (1989)

310

UNEP PUBLICATIONSOECD SIDS
9. REFERENCES

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6(47) Kimura, E. T. et al.: Toxicol. Appl. Pharmacol. 18, 60-68(1971)(48) Chvapil, M. et al.: Arch. int. Pharmacodyn. 85, 330-343(1962)(49) Bayer AG data, Report No. 19232, 6. 7. 1990
(50) Cebula, T. A. et al.: Infection and Immunity 44, 91-96(1984)(51) reported in NTP: Technical Report No. TR 343 (1989)(52) Motoyoshi, K. et al.: Cosmet. Toiletries 94, 41-48 (1979)(53) Thyssen, J.: Bayer AG data, short report, 2. 1. 1979(54) Klecak, G. et al.: J. Soc. Cosmet. Chem. 28, 53-64 (1977)(55) Sharp, D. W.: Toxicology 9, 261-271 (1978)(56) Takenaka, T. et al.: Parf. Cosm. Sav. 13, 699-706 (1970)(57) Emmons, W. W., Marks, J. G.: Contact Dermatitis 13, 258265 (1985)(58) Lashmar, U. T. et al.: J. Pharm. Pharmacol. 41, 118-121(1989)(59) Macht, D. I., Shohl, A. T.: J. Pharmac. exp. Ther. 16,
61-69 (1921)(60) Malten, K. E. et al.: Contact Dermatitis 11, 1-10 (1984)(61) Mitchell, J. C. et al.: Contact Dermatitis 8, 336-337(1982)(62) Nethercott, J. R.: Contact Dermatitis 8, 389-395 (1982)(63) Hayakawa, R. et al.: Skin Res. 30, 243-246 (1988)(64) Mitchell, D. M., Beck, M. H.: Contact Dermatitis 18,
301-302 (1988)

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9. REFERENCES

BENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6(65) Fisher (1975) cited in: Etain Cronin, Contact Dermatits,
Churchill Livingstone, Edinburgh, London, New York, 1980,
p. 807(66) Schultheiss (1957) cited in: Etain Cronin, Contact
Dermatitis, Churchill Livingstone, Edinburgh, London,
New York, 1980, p. 807(67) Kashima R. et al., Contact dermatitis 28, 235-242 (1993)(68) Kashima R. et al., Contact dermatitis 29, 26-32 (1993)(69) Maurer Th. Durr. Probl. Derm. 14, 114-151 (1985)(70) Sharp D.W., Toxicology 9, 261-271 (1978)(71) Adams R. M. in Maibach H.I., G.A. Gellin (eds.),
Occupational and Industrial Dermatology, Chicago, Year
Book Publishers, Inc., p. 345-352 (1982)(72) Aguirre A. et al., Contact Dermatitis 30, 52-53 (1994)(73) Angenelli G. et al., J. Appl. Cosmetol. 3, 223-236 (1985)(74) Arima Y. et al.,Skin Res. 31 [Suppl. 7], 221-225 (1989)(75) Brasch J. et al., Dermatosen 41, 71-76 (1993)(76) Commandeur C. et al., Allergy 47,337-339 (1992)(77) Conde-Salazar L. et al., Actas Dermo-Sif. 83, 383-386(1992)(78) Corazza M. et al., Contact Dermatitis 34, 74-75 (1996)(79) Edwards E.K., Cutis 28, 332-333 (1981)(80) Eiermann H.J. et al., J. Am. Acad. Dermatol. 6, 909-917(1982)(81) Fisher A.A. Contact Dermatitis, Lea & Febiger,
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343 (1989)(99) Fujitani, T., Toxicol. Lett. 69, 171-179 (1993)(100) BIBRA: Toxicity Profile Benzyl Alcohol (1989)(101) Fluck, E. R. et al.: Chem.-Biol. Interactions 15, 219-231(1976)(102) Leifer Z. et al., Mutat. Res. 87, 211-297 (1981)

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SUBSTANCE ID: 100-51-6(103) Anderson B.E. et al., Environm. Molec. Mutagen. 16 [Suppl
18] 55-137 (1990)(104) Zeiger, E. et al., Environ. Mutagen. Molec. Mutagen.
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347-482 (1994)(107) Florin, I. et al.: Toxicology 15, 219-232 (1980)(108) Milvy, P., Garro, A. J.: Mutat. Res. 40, 15-18 (1976)(109) Mortelmans, K. et al.: Environ. Mutagen. 8, Suppl. 7,
1-119(1986)(110) Rogan, E. G. et al.: Chem.-Biol. Interactions 58, 253-275(1986)(111) Ishidate, M. et al.: Fd. Chem. Toxic. 22, 623-636 (1984)(112) Wiessler, M. et al.: Carcinogenesis 4, 867-871 (1983)(113) Yoo, Y. S.: Osaka-shi Igakkai Zasshi 34, 267-288 (1985)(114) Ishidate, M. et al.: Mutat. Res. 195, 151-213 (1988)(115) McGregor, D. B. et al.: Environ. Mutagen. 12, 85-154(1988)(116) Myhr B. et al., Environm. Molec. Mutagen. 16, [Suppl 18],
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SUBSTANCE ID: 100-51-6(142) Santeiro, M. L.: Fl. J. Hosp. Pharm. 9, 17-19 (1989)(143) Novak, E. et al.: Toxicol. Appl. Pharmacol. 23, 54-61(1972)(144) Addo, H. A. et al.: Br. J. Dermatol. 107, 261-274 (1982)(145) Fisher, A. A.: Contact Dermatitis 1, 281-284 (1975)(146) Fregert, S., Hjorth, N.: Contact Dermatitis Newsletter 5,85-86 (1969)(147) Grant, J. A. et al.: New Engl. J. Med. 306, 108 (1982)(148) Lagerholm, B. et al: Acta allergologica 12, 295-298(1958)(149) Larsen, W. G.: Arch. Dermatol. 113, 623-626 (1977)(150) Larsen, W. G.: J. Am. Acad. Dermatol. 21, 880-884 (1989)(151) Lazzarini, S.: Contact Dermatitis 8, 349 (1982)(152) Schultheiss, E.: Derm. Wschr. 135, 629-633 (1957)(153) Shmunes, E.: Arch. Dermatol. 120, 1200-1201 (1984)(154) Shoji, A.: Contact Dermatitis 9, 510 (1983)(155) Wilson, J. P. et al.: Drug Intell. Clin. Pharm. 20, 689691 (1986)(156) De Groot, A. C. et al.: Contact Dermatitis 15, 218-222(1986)(157) Reynolds, P., Wilton, N.: Anesth. Analg. 69, 855-856(1989)(158) Weissmann, D. E., Rockoff, M. A.: Anesth. Analg. 70, 673674 (1990)(159) Bowen D. et al., Clinica Chimica Acta 61, 399-401 (1975)(160) Testa M. et al., J. Ocular Pharmacol. 3, 211-225 (1987)

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SUBSTANCE ID: 100-51-6(161) Williams J.M., N.R. Howe, J. Dermatol. Surg. Oncol. 20,
730-733 (1994)(162) Ahlfors C.E, G.R. Kaleem, Pediatric Res. 37, 192 A (1994)(163) Am. Acad. Pediatrics: Committee on Drugs, Pediatrics 99,
268-278 (1997)(164) Benda G.I. et al., Pediatrics 77, 507-512 (1986)(165) Cronin C.M. et al., Am. J. Perinatol. 8, 80-85 (1991)(166) Cronin C.M.G., Pediatrics 89, 1129-1130 (1992)(167) Ellenhorn M.J., Barceloux D.G., Medical Toxicology,
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SUBSTANCE ID: 100-51-6(197) Dudeja, P. K. et al.: Am. J. Physiol. 257, G809-G817(1989)(198) Duncan, D., Jarvis W. H.: Anaesthesia 4, 465-474 (1943)(199) Eichbaum, F. W., Yasaka, W. J.: Basic Res. Cardiol. 71,
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10. SUMMARY AND EVALUATION

10.1 End Point Summary

10.2 Hazard Summary

10.3 Risk Assessment

320

UNEP PUBLICATIONSBENZYL ALCOHOLDATE: 14-FEB.-2002
SUBSTANCE ID: 100-51-6