SULFURIC ACID CAS N°: 7664-93-9, Lecture notes of Toxicology

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FOREWORD INTRODUCTION

SULFURIC ACID

CAS N°: 7664-93-

SIDS Initial Assessment Report

for

th

SIAM

(Orlando, Florida, 23-26 January, 2001)

Chemical Name : Sulfuric acid

CAS no: 7664-93-

Sponsor Country : France

National SIDS Contact Point in Sponsor Country:

Mme. Laurence Musset

Bureau des substances et préparations

Ministère de l'environnement

20 avenue de Ségur

75302 Paris 07 SP

France

History: The national peer review consisted of a presentation and critical

discussion at a national panel of experts in toxicology and

ecotoxicology from administration, university and industry and

nominated by the ministry of environment. In parallel, a review was

performed by the national institute on environmental and industrial

risk (INERIS) by request from the ministry of environment. For this

particular substance, only the verification of the most relevant

underlying study reports or publications was performed.

Testing completed : none

Comments:

1).” Concerns have been raised that confounding factors could not be fully excluded.

Because sulfuric acid is a direct-acting toxicant, and because it is unlikely to reach the reproductive organs,

reproductive effects in mammals are not likely to occur following exposure to sulfuric acid by any route. In

a developmental toxicity/teratogenicity study conducted by inhalation with sulfuric acid aerosol, the

NOAEL for maternal toxicity appears to be 20 mg/m3 in mice and rabbits. No evidence of foetotoxicity or

teratogenicity was seen in either species.

Environment

Sulfuric acid is a strong mineral acid that dissociates readily in water to sulfate ions and hydrated protons,

and is totally miscible with water. Its pKa is 1.92 at 25 °C. At pH 3.92, for example, the dissociation is 99

%, and sulfate ion concentration is 1.2 x 10-4^ moles = 11.5 mg/l. So at environmentally relevant

concentrations, sulfuric acid is practically totally dissociated, sulfate is at natural concentrations and any

possible effects are due to acidification. This total ionisation will imply also that sulfuric acid, itself, will not

adsorb on particulate matters or surfaces and will not accumulate in living tissues.

The NOECs selected were obtained on a natural (cold water) lake artificially contaminated by the

controlled addition of sulfuric acid:

• NOEC in phytoplankton community structure = pH 5.6 = 0.13 mg/l sulfuric acid
• NOEC in zooplankton population repartition = pH 5.6 = 0.13 mg/l sulfuric acid.
• NOEC in fish population recruitment = pH 5.93 = 0.058 mg/l sulfuric acid

There is only one validated NOEC available for warm water fish ( Jordanella floridae ), 0.025 mg/l, which is

derived from the LOEC/2.

Exposure

Estimated worldwide production of sulfuric acid is 160 million ton/year. The main uses are non dispersive

(industrial uses). In some countries, sulfuric acid is approved for agricultural use. The occurrence of sulfuric

acid in the environment comes mainly from the hydrolysis of sulfur oxides produced by combustion

processes (natural and anthropogenic), wet deposition, generally as a mixture with nitrogen oxides and nitric

acid and not from the manufacturing and use of the acid. The emissions to the aquatic environment

generally occur from manufacturing industrial locations after neutralisation and are mainly in the form of

sulfate ions. Alternatively, following manufacturing and use, it can enter the terrestrial environment as

stable gypsum (calcium sulfate).

NATURE OF FURTHER WORK RECOMMENDED

Environment: the collection of information about exposure during agricultural use should be considered.

Health: the collection of information about occupational exposure to sulfuric acid mist should be considered

due to the carcinogenic potential.

FULL SIDS SUMMARY

CAS N° 7664-93-9 SPECIES PROTOCOL RESULTS PHYSICO-CHEMICAL

2.1 Melting point 10.4-10.5 °C (sulfuric acid 100 %) 3 °C (sulfuric acid 98 %) -32 °C (sulfuric acid 93 %) -38 °C (sulfuric acid 78 %) -44 °C (sulfuric acid 74 %) -64 °C (sulfuric acid 65 %) 2.2 Boiling point 290 °C at 1013 hPa (sulfuric acid 100 %) 310-335 °C at 1013 hPa (sulfuric acid 98 %) 2.3 Density 1.835 at 20 °C (sulfuric acid 93-100 %) 2.4 Vapour pressure < 0.001 hPa at 20 °C 0.004 hPa at 50 °C 1.3 hPa at 145.8 °C 2.5 Partition coefficient Not relevant for ionisable compounds 2.6 Water solubility Miscible pKa = 1. 2.7 Density 1.835 at 20 °C (sulfuric acid 93-100 %) 2.11 Oxidising properties Powerful acidic oxidizer which can cause ignition or explosion in contact with many materials. 2.12 Additional remarks Vigorous reaction when water added to sulfuric acid. ENVIRONMENTAL FATE AND PATHWAY 3.1.2 Stability in water Strong acid : dissociates in water to sulfate and hydrated proton 3.3.1 Transport between environmental compartments

Very mobile in soil. Mobility increases with the dilution in water. Wet acidic deposition on soils are 75 % sulfuric acid

ECOTOXICOLOGY

4.1 Acute/prolonged toxicity to fish

Lepomis macrochirus

Brachydanio rerio

pH decreasing each 96 hours ISO 7346/

LC50 96h = 16-28 mg/l (pH 3.25 to 3.5) LC50 24h = 82 mg/l

4.2 Acute toxicity to aquatic invertebrates

Daphnia magna ISO 6341^ EC50 24h = 29 mg/l

4.3 Toxicity to aquatic plants e.g. algae

Epilimnetic phytoplankton in a natural lake

Phytoplankton community structure study

NOEC = 0.13 mg/l (pH 5.6)

LC0 = 0.718 mg/1/3.5h LC50 = 1.470 mg/1/3.5h 5.2.1 Skin irritation/corrosion Rabbit, Guinea-pig, Human

Rabbit, Human

FDA, FSHA, Federal Register V37, 1972

CFR, DOT 1986 (rabbit) and 1988 (human) + Hill top Chamber

Not irritating

Not irritating

5.2.2 Eye irritation/Corrosion Rabbit

Rabbit

Rabbit

Rabbit

OECD TG 405

Directive 79/831/EEC, Annex V, part B

US, FHSA (CFR,

1979. and NAS 1138 Committee (1977)

US.FHSA Fed. Reg. Vol 38 (187) Part II and 16 CFR 1500. (1973) and Draize method (1944)

Sulfuric acid 10%: not irritating

Sulfuric acid 10%: not irritating

Sulfuric acid 10% (0.01 ml): slightly irritating Sulfuric acid 10% (0.05 ml): severely irritating Sulfuric acid 10% (0.1 ml): severely irritating

Sulfuric acid 10%: severe irritant

Sulfuric acid 5%: moderate irritant 5.4 Repeated Dose Toxicity by Inhalation

Rat (réf. 74)

Rat (réf. 106)

Rat (réf. 111)

Rat (réf. 26)

Rat (réf. 25)

Guinea pig (réf. 111)

Guinea pig (réf. 26)

Guinea pig (réf. 25)

Guinea pig (réf. 184)

Guinea pig (réf. 168)

Guinea pig (réf. 2)

Guinea pig (réf. 3)

Rabbit (réf. 165)

Rabbit (réf. 64)

Rabbit (réf. 63)

Rabbit (réf. 155)

Rabbit (réf. 160)

OECD TG 412

Other

Other

Other

Other

Other

Other

Other

Other

Other

Other

Other

Other

Other

Other

Other

Other

a NOEL/NOAEL can not be identified NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

Repeated Dose Toxicity by Inhalation (continued)

Rabbit (réf. 154)

Rabbit réf. 156)

Rabbit (réf. 167)

Monkey (réf. 2)

Monkey (réf. 3)

Mouse (réf. 168)

Hamster (réf. 105)

Dog (réf. 110)

Other

Other

Other

Other

Other

Other

Other

Other

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

NOEL/NOAEL not indicated

A.

B.

G ENETIC TOXICITY I N VITRO

Bacterial test (Gene mutation)

Non-bacterial In Vitro test (Chromosomal aberrations)

S. typhimurium

E. coli

Developing embryos of Sphaerechinus granularis and Paracentrotus lividus

Chinese hamster Ovary (CHO) K1 cells

Other

Other

Other

Other

- (with metabolic activation) - (without metabolic activation) - (without metabolic activation)

• (without metabolic activation)

• (with metabolic activation)

• (without metabolic activation 5.7 Carcinogenicity Rat (réf. 187)

Rat (réf. 187)

Mouse (réf. 187)

Hamster (réf. 105)

Rat (réf. 55)

Guinea pig (réf. 54)

Other

Other

Other

Other

Other

Other

Local and weak carcinogen, (gastric intubation)

Local and weak carcinogen, (intratracheal instillation)

Local and weak carcinogen, (gastric intubation)

No evidence of carcinogenic potential (inhalation, mist)

No carcinogenic effect, (inhalation, mist)

No carcinogenic effect (inhalation, mist) 5.9 Developmental toxicity / Teratogenicity

Mouse

Rabbit

Similar to OECD TG 414 (inhalation)

Similar to OECD TG 414 (inhalation)

NOAEL maternal = 20 mg/m

NOEL teratogenicity = 20 mg/m

NOAEL maternal = 20 mg/m

NOEL teratogenicity = 20 mg/m 5.10 Other data 49 articles/reviews included in the IUCLID dossier for additional information 5.11 Experience with human exposure

50 articles/epidemiological studies included in the IUCLID dossier

A very minor agricultural use (about 0.025 %) is as desiccant for potato crops.

In the workplace, sulfuric acid can exist as an acid mist. This situation can occur because sulfur

trioxide generates very dense sulfuric acid mists with atmospheric humidity. However, this occurs

only in the event of accidental leakage of sulfur trioxide, and is not a result of normal activity.

Other sulfuric acid uses that are important sources of sulfuric acid mists in the workplace are:

• car and industrial batteries loading
• metal sheets cleaning for surface treatment
• electro-chemical production of zinc and copper : sulfuric acid is driven off as fine droplets by

evolved hydrogen.

• Loading and discharging of sulfuric acid

Occupational exposure limit values for different countries are presented in Annex I. For most of the

countries (e.g. USA, France, Japan, Finland) the limit value for an 8 hour-exposure is 1 mg/m

except for Germany : MAK value, 8 hours : 0.1 mg/m3.

Sulfuric acid occurrence in the environment mainly comes from hydrolysis of sulfur oxides

produced by combustion processes (natural and anthropogenic) wet deposition, generally as mixture

with nitrogen oxides and nitric acid and not from manufacturing. The emissions to the aquatic

environment generally occur from manufacturing industrial locations after neutralisation and are

mainly in the form of sulfate ions. Alternatively, following manufacturing and use, it can enter the

terrestrial environment as stable gypsum (calcium sulfate).

Sulfuric acid use in agriculture as desiccant for potato crops is reported in UK (Food and

Environment Protection Act, 1985, Part III, Control of Pesticides Regulations 1986, Evaluation of

Fully Approved or Provisionally Approved Products, Evaluation on Sulphuric Acid, April 1998). In

1992, 90 685 ha of potato crops were treated with 77% w/w sulfuric acid. Doses ranged from 112

l/ha to 335 l/ha, which means a total consumption of about 40 000 t sulfuric acid in this agricultural

use.

3. ENVIRONMENT

3.2. Effects on the aquatic environment

Preliminary remarks

Quality criteria: The principal quality criteria for acceptance of data are that the test procedure

should be well described (with reference to an official guideline) and that the toxicant

concentrations must be measured with an adequate analytical method.

Four situations can be distinguished and are summarised in the following table according to criteria

defined in IUCLID system.

Table: Quality criteria for acceptance of ecotoxicity data

Case Detailed description

of the test

Accordance with

scientific guidelines

Measured

concentration

Conclusion:

reliability level

I + + +

[1] :

valid without

restriction

II ± ± ±

[2] :

valid with

restrictions; to

be considered

with care

III insufficient or - - -

[3] :

invalid

IV the information to give an adequate opinion

is not available

[4] :

not assignable

Publications were assigned validity 4 when they could not be checked directly. Validity 3 was

assigned systematically when no clear description was given of the test substance. This approach is

important for sulfuric acid, as sources for sulfuric acid production can be recovery from many

processes leading to various impurities.

Analytical monitoring reported in the IUCLID file refers to pH measurements. At concentrations

reported in publications and study reports, the toxicity has been assumed to be due to acidity only,

because at these low concentrations, sulfate quantities added are below most of natural medium

concentrations. So the sulfuric acid environmental risk assessment is in fact acidity risk assessment.

3.2.1 Aquatic effects

3.2.1.1. Effects in fish

The acute toxicity of sulfuric acid in fish has been reported in 10 different publications, leading to 8

LC50 values in 24, 48 or 96 hours duration. Only two references were assigned validity 2 : one

study performed according to the international standard ISO7346/1, in a 24 hours static test in

Brachydanio rerio , not under GLP, giving an LC50 24 hours of 82 mg/l. The other one was

obtained in a study where Lepomis macrochirus were exposed successively 96 hours to each pH

tested (from pH 7.5 original water to pH 5.0, 4.5, 3.5, 3.25 and 3.0. However the LC50 48 hours

was retained as a worst case one and measured as being from pH 3.25 to pH 3.5, which gives a

value of 16 to 28 mg/l sulfuric acid. No LC50 was found lower than Lepomis macrochirus one in all

publications assigned validity 3 or 4.

The chronic toxicity of sulfuric acid in fish was assessed in 6 publications reporting laboratory tests.

5 validity 2 NOEC values were derived, 3 of them being in the same range: NOECs for embryo

survival and time for hatching of Salvelinus fontinalis (pH 5.2 and pH 5.5 giving substance

concentrations 0.31 mg/l and 0.15 mg/l), and a NOEC for weight of young Salvelinus fontinalis

produced in 10 month (pH 5.56, giving 0.13 mg/l). The fourth NOEC is far lower, being derived

from a LOEC on fry growth of Jordanella floridae in 45 days of pH 6.0 (0.049 mg/l) giving 20 %

inhibition, which, divided by 2 can give a NOEC of 0.025 mg/l.

The difference between Salvelinus fontinalis and Jordanella floridae is their optimal temperature :

Salvelinus is a cold water fish (Brook trout), and Jordanella a warm water fish. The difference in

physiology could explain the difference in sensitivity.

aquatic plants/algae, presence/lack of predators for smaller fish). Moreover it integrates effects of

successive one-year exposures to pH 6.49 and 6.13, which models a progressive acidification by

sulfuric acid deposition.

The zooplankton community study was also analysed by identifying the species and counting the

organisms. A NOEC for population repartition (from copepod to cladoceran dominance) was pH

5.59 (0.13 mg/l). This NOEC integrates not only reproductive success, but also prey/predator

relationships (presence/lack of suitable food as smaller invertebrates or aquatic plants/algae,

presence/lack of fish predators). Here also it integrates effects of successive one-year exposures to

pH 6.49, 6.13, 5.93 and 5.64.

The phytoplankton community structure was also studied, giving a NOEC of pH 5.6 (0.13 mg/l)

(chlorophyte increase and species shift to large inedible Gymnodium sp.). This NOEC integrates not

only algae growth rate, but also consumption by invertebrates and fish, and also effects of

successive one year exposures to pH 6.49, 6.13, 5.93.

3.2.1.5 Toxicity in micro-organisms

A multispecies-microcosm test was performed : the structure and function of naturally derived

periphytic communities on polyurethane foam artificial substrates were monitored. The artificial

substrates were suspended at 1m depth in a man-made outdoor ponds. After 21 days substrates were

collected. pH was set in different ponds to 8.34-7.61-6.90-6.61-5.34-3.33. The control pond was pH

Significant effects on protozoan species richness were observed in this test at a pH = 5.33.

Therefore the NOEC for species richness was 6.61. In this experiment, the sulfuric acid

concentration calculation is more problematic, because the initial pH in the ponds is far from

neutrality, and alkaline (pH 8.36). So the assumption that pH is only the result of sulfuric acid

dilution in water, which was an approximation in pH 6.7 Canadian Lake 223 experiments, is here

completely false. Ignoring the buffering capacity of the pond water, it is therefore impossible to

derive a NOEC as sulfuric acid mg/l.

Discussion

It is remarkable that sensitivity to pH is not universal among species and related ecosystems : for

example at pH 6.0, Jordanella floridae fry growth already begins to be inhibited.

Some interesting examples are also salamanders : Ambystoma jeffersonianum eggs have hatching

success > 90 % only at pH 6 at 10 °C, and at pH 5 to 6 at 5 °C. Eggs do not hatch successfully

above pH 6. And Ambystoma maculatum eggs hatch only from pH 7 to 9.

The sulfuric acid hazard assessment is in fact hazard assessment of acidity. All the observations

made and the results derived would be the same for any strong acid, provided the anion has no

toxicity in any species at environmentally relevant strong acid concentrations.

4. HUMAN HEALTH

4.2 Effects on Human Health

Preliminary remarks:

9 Reliability of the studies was evaluated using the criteria for reliability categories adapted from

Klimisch et al. (1997) and Rosner (1994). Reliability is differentiated and thus classified into 4

categories/codes as described below. In this scoring system, studies conducted and reported

according to internationally accepted test guidelines and in compliance with GLP have the

highest grade of reliability and should be used as reference standards.

ƒ 1 : Reliable without restriction :

1a GLP guideline study (OECD, EC, EPA, FDA, etc…) 1b Comparable to guideline study 1c Test procedure in accordance with national standard methods (AFNOR, DIN, etc) 1d Test procedure in accordance with generally accepted scientific standards and described in sufficient detail

ƒ 2: Reliable with restrictions

2a Guideline study without detailed documentation 2b Guideline study with acceptable restrictions 2c Comparable to guideline study with acceptable restrictions 2d Test procedure in accordance with national standard methods with acceptable restrictions 2e Study well documented, meets generally accepted scientific principles, acceptable for assessment 2f Accepted calculation method 2g Data from handbook or collection of data

ƒ 3: Not reliable

3a Documentation insufficient for assessment 3b Significant methodological deficiencies 3c Unsuitable test system

ƒ 4: Not assignable

4a Abstract 4b Secondary literature 4c Original reference not yet available 4d Original reference not translated (e.g. Russian) 4e Documentation insufficient for assessment

9 Studies selected for discussion are identified in the following tables by a black bullet (•).

4.2.1 Mode of action of the chemical, toxicokinetics and metabolism

Sulfuric acid is corrosive and irritating and causes direct local effects on the skin, eyes and

gastrointestinal tracts after direct exposure to sufficient concentrations. Small droplets of sulfuric

acid (aerosol/mist) can also be inhaled and cause direct local effects on respiratory tract. The effects

of inhaled sulfuric acid aerosols will depend on many factors: - exposure concentrations; - exposure

time; - particle size of the aerosol, which determines the location in the respiratory tract where

sulfuric acids aerosols will deposit; - humidity, both in the environment and in the respiratory tract,

which determines the particle size; - endogenous ammonia that can neutralize sulfuric acid; - pattern

of respiration and the inhalation route (oral or nasal); - buffering capacity of the airways; - species

studied (e.g. respiratory tract dimension and architecture) (see ref. 10, 102, 144).

The effects of sulfuric acid are the result of the H+ ion (local deposition of H+, pH change) rather

than an effect of the sulfate ion. Sulfuric acid per se is not expected to be absorbed or distributed

throughout the body. The acid will rapidly dissociate and the anion will enter the body electrolyte

pool, and will not play a specific toxicological role (102, 144). This is supported by experiments

which have studied the active component in inorganic acids on various endpoints, using different

Rat (NS)

185 (1950)

Inhalation, whole body

diluted SA (10- 60% w/v)

7 h

3.5 h

1-

LC 0

LC 100

LC 0

LC 100

0.461 mg/l/7h

0.699 mg/l/7h

0.718 mg/l/3.5h

1.470 mg/l/3.5h RAT (NS)

93 (1982)

Inhalation NS 2 h NS LC 50 0.510 mg/l/2h

• MOUSE (CD-1)

150 (1976)

Inhalation, whole body

SO3 + humid air

4 h

8 h

1

LC 50

LC 50

0.850 mg/l/4h

0.600 mg/l/8h

• Mouse (NS)

185 (1950)

Inhalation, whole body

diluted SA (10- 60% w/v)

7 h 1-

LC 0

LC 40

0.461 mg/l/7h

0.699 mg/l/7h Mouse (NS)

93 (1982)

Inhalation NS 2h NS LC 50 0.320 mg/l/2h

Rabbit (NS)

185 (1950)

Inhalation, whole body

diluted SA (10- 60% w/v)

7 h

3.5 h

1-

LC 0

LC 50

LC 0

LC 50

0.699 mg/l/7h

1.610 mg/l/7h

0.718 mg/l/3.5h

1.470 mg/l/3.5h NS: Not specified, SA: sulfuric acid

In rats, mice and rabbits, as well as in guinea pigs, concentration of acid aerosol, time of exposure

and particle size are important factors in determining lethality by inhalation. Among the different

species tested, the guinea pigs appear to be the most sensitive to the acute inhalation effects of

sulfuric acid mist/aerosol. For the guinea pig, the apparent LC50 for an 8 hour-exposure period to

sulfuric acid mist/aerosol with a particle size of about 1μm, ranges from 0.018 to 0.050 mg/l

depending on the age of the animals. Younger guinea pigs seem to be more sensitive to sulfuric acid

aerosol than older animals.

According to the duration of exposure, the LC 50 appear to be about 0,375 - 0,425 mg/l in rats,

0.600 - 0.850 mg/l in mice, and 1.470 - 1.610 mg/l in rabbits, when taking into account the more

reliable/relevant studies.

The sensitivity of the guinea pig may be caused by its tendency for bronchoconstriction and

laryngeal spasm compared to other small laboratory animals.

The main macroscopic and/or microscopic alterations observed in respiratory tract after acute

exposure to sulfuric acid aerosol were hemorrhage, edema, atelectasis and thickening of the alveolar

wall in the lung of guinea pigs, hemorrhage and edema of the lungs and/or ulceration of the

turbinate, trachea and larynx in rats and mice. These lesions are related to the corrosive/irritant

effect of sulfuric acid.

No data are available on the acute dermal toxicity or on acute toxicity by other routes for sulfuric

acid.

4.2.3 Irritation and Corrosiveness

4.2.3.1 Skin irritation

According to Annex I of the Directive 67/548/EEC, sulfuric acid is classified as C; R 35: Corrosive;

Causes severe burns. Specific concentration limits are: C; R35 for concentration ≥ 15 % and Xi;

R36/38 when concentrations are ≥ 5%, and < 15 %.

The skin irritation studies, that could be checked, were performed using diluted sulfuric acid and are

summarized in the following table.

Skin irritation testing with sulfuric acid

Species, Test Type Ref. (year)

Protocol Doses Result

• RABBIT,^ G^ UINEA-^ PIG^ ,^ HUMAN^ , S KIN IRRITATION TEST ON ABRADED AND INTACT SKIN

135 (1975)

FDA, FSHA, Federal register V37, 1972

0.5 ml of sulfuric acid, 10 % Not irritating

• RABBIT,^ HUMAN^ , S TANDARD SKIN IRRITATION TEST AND H ILL TOP CHAMBERS TEST

134 (1990)

CODE OF F EDERAL REGULATION, DOT 1986 ( RABBIT) AND 1988 ( HUMAN ) + H ILL TOP CHAMBER

0.4 or 0.5 ml of sulfuric acid 10 % in standard test 0.2 ml of sulfuric acid 10 % in Chamber

Not irritating

Sulfuric acid 10 % appears not to be irritating to the skin in rabbit, guinea pig and human.

4.2.3.2 Eye irritation

The eye irritation studies conducted with diluted sulfuric acid are summarized in the following

table. Only available studies are presented.

Eye irritation testing with sulfuric acid

Specie, Test type

Ref. (year)

Protocol Doses^ Result

• RABBIT^95 (1992)

OECD Guideline 405 0.1 ml of sulfuric acid 10 %

Not irritating

• RABBIT^94 (1989)

Directive 79/831/EEC, Annex V, part B

0.1 ml of sulfuric acid 10 %

Not irritating

• RABBIT^68 (1980)

US.FHSA (CFR, 1979) and NAS 1138 Committee (1977)

0.01 ml, 0.05 ml, 0.1 ml of sulfuric acid 10 %

0.01ml: slightly irritating 0.05ml: severely irritating 0.1 ml: severely irritating

RABBIT, W ASHED AND UNWASHED EYE

128 (1982)

US.FHSA Fed. Reg. Vol. 38 (187) Part II and 16 CFR 1500.42 (1973) and Draize method (1944)

0.1ml of sulfuric acid 10 % or 5 %

10% : SEVERE IRRITANT

5%: MODERATE IRRITANT

Conflicting results are observed in eye irritation studies according to the protocol used (OECD/EU

or US). However, buffering and dilution effects of tears could explain the different conclusions

since sulfuric acid was instillated into the conjunctival sac of the eye in studies n° 95 and 94 while

acid was administered directly to the central corneal surface in experiments 68 and 128. In this last

study, the authors have observed that the washing procedure (eye washed 2 min. with tap water 30

sec. after exposure) reduced the time to onset of opacity induced by 5% sulfuric acid and slightly

decreased the severity of the iritis induced by 10 % sulfuric acid.

OECD SIDS

SULFURIC ACID

UNEP Publications

107

Repeated dose toxicity studies by inhalation conducted with sulfuric acid aerosol

Species (strain, sex)

Ref.(year)

Protocol

Duration,frequency

Administration

Doses

Particle

size(μm)

T°(C/F)RH (%)

End-point

Value (unit)/ results

R AT (A

LPK

:AP

SDF

, FEMALE

)

(^74) (^ IN PREP

.)

OECD

N

°

412

/^

D

IR

.

67/548/EECA

NN

.^ V,

B

GLP

28

DAYS

6 H

/D

,^5

D /WK

Inhalation,nose only

0.00,0.30,1,38, 5.58 mg/m

0.620.830.

~19.5°C~50 %

Death:Body and lung weight:Histopathology:Cell proliferation:

No death due to SANo alterationAlteration in larynx onlyAlteration in larynx only

Rat(Sprague-Dawley,male)

106 (1997)

other

30 or 90 days23.5 h/d, 7d/wkor intermittent

(12 h/d)

Inhalation,whole body

0, 20, 100, 150 μg/m3 (SA) ± 0.12, 0.20ppm (O3)

0.4 - 0.

22°C80%

Lung histopathology:Lung biochemicalanalyses:Morphometric analyses ofalveolar tissues:Body and lung weight:+O3:

No alterationsNo alterationNo change due to SA aloneNo alterationNo interaction

Rat(Sprague-Dawley,male)

111 (1979)

other

from 6 to 14

weeks, continuous

Inhalation,whole body

from 2.37 to 15

mg/m

0.3 - 0.

70/77°F35-50%

Spontaneous locomotoractivity:Blood gas parameters:Learning ability:Pulmonary functions:Food/water intake; bodyweight:

Alteration (at 2.49 mg/m3)Alteration (at 6.5 mg/m3No alterationAlteration (at 4.05 mg/m3)No alteration

Rat(Fischer,male/female)

26 (1978)

other

6 months,6h/d, 5d/wk

Inhalation,whole body

0, 10 mg/m

(SA)

±

0.5 ppm (O3)

~ 1

82°F60%

Hematology/bloodchemistry:Lung histopathology:Body and lung weight:+O3:

No alterationAlteration (slight)No alterationNo interaction

Rat(Fischer,male)

25 (1977)

Other

2 to 7, 14, 21 or

28 days, frequency: NS

Inhalation,whole body

0, 5, 10, 20, 30,

100 mg/m

(SA)

±

1, 2 ppm (O3)

~ 1

70°F55%

DeathHematology/bloodchemistry:Lung histopathology:Body and lung weight:Lung lavage fluids:+O3:

No deathNo alterationNo alterationNo alterationNo alterationNo interaction

OECD SIDS

SULFURIC ACID

UNEP Publications

Repeated dose toxicity studies by inhalation conducted with sulfuric acid aerosol (continued)^108

Species (strain, sex)

Ref.(year)

Protocol

Duration,frequency

Administration

Doses

Particle

size(μm)

T°(C/F)RH (%)

End-point

Value (unit)/ results

Guinea pig(NS, NS)

(^111) (1979)

other

from 6 to 14

weeks, continuous

Inhalation,whole body

from 6.56 to 15

mg/m

0.2 - 0.

70/77°F35-50 %

Pulmonary functions:

No alterations

Guinea pigs(Hartley,male/female)

26 (1978)

other

6 months,6h/d, 5d/wk

Inhalation,whole body

0, 10 mg/m

(SA) ±

0.5 ppm (O3)

~ 1

82°F60 %

Hematology/blood chemistry:Lung histopathology:Body and lung weight:+O3:

No alterationAlteration (slight)No alterationNo interaction

Guinea pigs,(Hartley, female)

25 (1977)

other

2 to 7, 14, 21 or 28 days,frequency: NS

Inhalation,whole body

0, 5, 10, 20, 30,100 mg/m3 (SA) ±^ 1, 2 ppm (O3)

0.53, 1,1.

70°C 55%

DeathHematology/blood chemistry:Lung histopathology:Body and lung weight:Lung lavage fluid:+O3:

Death at > 20mg/m3No alterationAlteration at > 20mg/m3No alterationNo alterationNo interaction

Guinea pig(NS, NS)

(^184) (1958)

other

from 18 to 140

days, continuous

Inhalationwhole body

0, 1 to 4 mg/m

(medium or

coarse) up to 26 mg/m3(fine aerosol)

3.6-4.3or 0.9or 0.

NS NS

Respiratory tract histopathology:

Alterations (slight);medium size (0.9μm)aerosol was the mostactive

Guinea pig(Harley, female)

(^168) (1979)

other

7 days, continuous

Inhalation,whole body

38 to 220 mg/m

0.32 - 0.

NS NS

Mortality (LD50):

100 mg/m

Guinea pig,(Hartley,male/female)

2 (1973)

other

12 months

23 h/d

Inhalation,whole body

0.00,0.08, 0.10 mg/m

0.84,2.

22°C50 %

Body weight:Survival:Hematology/blood chemistry:Pulmonary function:Histopathology:

Alteration (small infemale)No deathNo alterationNo alterationNo alteration

Guinea pig,(Hartley,male/female)

3 (1975)

other

12 months22-23 h/d

Inhalation,whole body

0,

0.9 mg/m3 SA

or

0.08 mg/m3 SA

±

0.46 mg/m3 fly

ash

0.49,0.54 or2.

22°C50%

Body weight:Survival:Hematology/blood chemistry:Pulmonary functions:histopathology:+ pollutants

No alterationNo death due to exposureNo alterationNo alterationNo alterationNo interaction