OECD SIDSDISODIUM DISULPHITE

FOREWORDINTRODUCTION

Disodium disulphite
CAS N°: 7681-57-4

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1OECD SIDSDISODIUM DISULPHITE

SIDS Initial Assessment Reportfor 13th SIAM
(Bern , 6-9 November 2001)
Chemical Name:

Disodium disulphite

CAS No:7681-57-4

Sponsor Country:

Republic of Korea/ ICCA(BASF)

National SIDS Contact Point in Sponsor Country:
Dr. Moon-Soon LEE
National Institute of Environmental Research
Gyeongseo-dong, Seo-gu, Incheon, 404-170, Korea
Tel : 82-32-560-7113
Fax : 82-32-568-2037
E-mail : mslee416@me.go.kr
History:This HPV chemical was assigned to Korea in 1999. In 2000, ICCA (BASF)
proposed to be co-sponsor and prepared the draft documents (Dossier, SIAR,
SIAP). It was submitted to the SIDS Contact Point of Korea on Nov. 2000. The
draft documents were revised by Korea after discussion with BASF. Robust Study
Summaries were prepared according to the new RSS templates by Korea. The
revised draft was sent to BASF for a detailed discussion on Aug 2001. In themeantime, Korea performed an acute toxicity test with fish. After agreement, thedocuments were finalized and the checklist was developed by Korea.
Testing:

No testing
Testing( )( x ) Acute toxicity to Fish

Comments :Deadline for circulation:
Date of Circulation:
Revised : September 2001

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SIDS INITIAL ASSESSMENT PROFILECAS No.

7681-57-4

Chemical Name

Disodium disulphite

O
Structural Formula

+

O Na

+

Na O S SOORECOMMENDATIONS
The chemical is currently of low priority for further work.

SUMMARY CONCLUSIONS OF THE SIAR
Human Health
Disodium disulphite is rapidly eliminated as sulphate in humans and dogs. When sulphite is present in the tissues insufficiently high concentrations, it may be metabolized to inorganic thiosulphate that is then excreted in the urine.
The acute toxicity of oral LD50 in rats is 1,540 mg/kg bw. In decedents, toxicity was observed to the stomach andliver, and the gastro-intestinal tract was filled with blood. For repeated dose toxicity, disodium disulphite was given
to rats through diet for 30 to 104 weeks. The predominant effect was the induction of stomach lesions due to local
irritation and was characterized as forestomach and glandular stomach hyperplasias and inflammation. There wereno signs of local toxicity (stomach irritation) at ca. 217 mg/kg bw/day, and the lowest dose where this effectoccurred was ca. 454 mg/kg bw/day as actual intake dose [NOAEL for local (stomach irritation), rats, oral feed : ca.
217 mg/kg bw/day]. From the same dietary study in rats, the NOAEL for systemic effects was the highest dosetested (942 mg/kg bw/day).
The results of genotoxic tests in vitro are equivocal but there is no evidence that disodium disulphite is genotoxic invivo. It was not carcinogenic in rats that received disodium disulphite via feed for 104 weeks. N o reproduction
toxicity of disodium disulphite was observed for a period of up to 2 years and over three generations (NOAEL,
fertility, oral feed: ca. 942 mg/kg bw/day ). No developmental toxicity and teratogenic effects appeared in rats or
rabbits at the highest dose tested (NOAEL 110 and 123 mg/kg bw/day, respectively).
This chemical is not irritating to the skin, but irritating to the eyes . In humans, urticaria and asthma with itching,edema, rhinitis, and nasal congestion were reported. An immunological pathogenesis of these reactions is still not
clear. In a non-guideline study, no indication of skin sensitization for guinea pig was observed. In a few cases
allergic contact dermatitis as well as positive patch-testing was observed. With respect to wide spread use, it is notconsidered as a skin sensitizer. Disodium disulphite is unlikely to induce res piratory sensitization but may enhance
symptoms of asthma in sensitive individuals. Given the wide-spread use, the number of cases is considered to be
low.
Environment
Boiling point, melting point and vapour pressure are not relevant for disodium disulphite. Also, testing for theendpoint of biodegradability, is not appropriate due the chemical not being an organic chemical. Bioaccumulation is
not expected. For the boiling point, decomposition occurred at 150 oC to form sulfur dioxide. This chemical will bemainly transported to the water compartment when released to environmental compartments since it is highly watersoluble (470 g/L at 20? ). The lo w KOC (2.447) indicates that disodium disulphite is so mobile in soil that it may notstay in the terrestrial compartment. Instead it has a potential to leach into the groundwater.
The chemical has been tested in a limited number of aquatic species. In an acute toxicity test with fish, the 96 hrLC50 was >100 mg/L. For algae, the 72 hr-EC 50 was 48.1 mg/L. For daphnids, the acute 48 hr-EC50 was 88.76 mg/L,

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OECD SIDSDISODIUM DISULPHITE

and the chronic 21day-NOEC was >10 mg/L. Therefore, a PNEC of 0.1 mg/L for aquatic organisms was obtained
from the chronic NOEC for daphnids using an assessment factor of 100.
Exposure
In 1999, estimates for the world market of sodium salts of sulphites, without China and the Russian Federation,amounted to approx. 330,000 tonnes/ year. These are distributed as follows : 20,000 tonnes in Germany, 60,000
tonnes in the rest of Europe and 250,000 tonnes in the rest of the world. Disodium disulphite is a basic chemical andused in chemical synthesis. Exposure to consumer may occur, but the extent of this exposure is unknown. There is apotential for exposure to the respiratory tract, skin and eyes during manufacture or formulation of the chemical into
products.
In Korea, the total production of disodium disulphite was about 3,200 tonnes/year in 1998. The chemical is used intanning agents, food additives, bleaching agents, photography and reducing agents but the amount for each use
pattern is not available. There is no exposure data for the environment and humans at the present time.

NATURE OF FURTHER WORK RECOMMENDED
No recommendation.

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FULL SIDS SUMMARYCAS NO : 7681-57-4

SPECIESPROTOCOL

RESULTSPHYSICAL-CHEMICAL
2.1
Melting Point

NA

2.2
2.3
2.4
2.5

Boiling Point
Density
Vapour Pressure
Partition Coefficient(Log POW)
2.6 A
Water Solubility
B
pH
pKa
2.12
Oxidation:
Reduction Potential
ENVIRONMENTAL FATE
AND PATHWAY
3.1.1
Photodegradation
3.1.2
Stability in Water

NA
NA

150 °C(decomposes to form sulfur dioxide)
Decomposed
1480 kg/m3
Not relevant-3.7 at 25 °C

NA
NA
-

470 g/L at
20 °C
pH 3.5~5.0 (50 g/L) at 20 °C
No data
-

-

3.2
3.3

-

Not relevant
Not relevant (Dissociates in water tosodium cations, disulfite anions andsulfur dioxide)
No data
Not relevant-

Not relevant (inorganic compounds)

Oryzias latipes
Salmo gairdneri
Daphnia magna

OECD TG 203
Other (DIN38412)
Other(79 / 831 / EWG)

LC 50 (96 hr) >100 mg/L
LC 50 (96 hr) >147 mg/L and < 215 mg/L
EC 50 (48 hr) =88.76 mg/L

Scenedesmus
subspicatus
Daphnia magna

OECD TG 201

EC 50 (72 hr) =48.1mg/L

OECD TG 211

LC 0 (21 d ) > 10 mg/L
NOEC (21 d ) > 10 mg/L

Monitoring Data
Transport andDistribution
3.5
Biodegradation
ECOTOXICOLOGY
4.1
Acute/Prolonged
Toxicity to Fish
4.2
Acute Toxicity to
Aquatic
Invertebrates
4.3
Toxicity to Aquatic
Plants e.g. Algae
4.5.2
Chronic Toxicity to
Aquatic
Invertebrates
4.6.1
Toxicity to Soil
Dwelling Organisms
4.6.2
Toxicity to
Terrestrial plants(4.6.3)
Toxicity to Other
Non- Mammalian
Terrestrial Species(Including Birds)
TOXICOLOGY
5.1.1
Acute Oral Toxicity
5.1.2
Acute Inhalation
Toxicity
5.1.3
Acute Dermal
Toxicity
5.2.1
Skin irritation
5.2.2
Eye irritation
5.3

Skin sensitization

No data
No relevant data available
No data

Rat

OECD TG 401

LD 50 = 1540 mg/kg
No data
No data

RabbitRabbitOECD TG 404
OECD TG 405

Not irritating
Irritating

Guinea pig

Other(Standardized skinsensitization test)

Not sensitizing

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CAS NO : 7681-57-4
5.4

Repeated DoseToxicity

5.5

Genetic Toxicity In
Vitro
Bacterial Test
(Gene mutation)

A

B

5.6
5.7
5.8

5.9

5.11

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SPECIESPROTOCOL

RESULTS

Rat

Other(multigeneration
study)NOAEL= 217 mg Na2S2O 5 /kg bw/day(0.5 % in the diet) for local toxicity
NOAEL = 942 mg Na2S2O5 /kg bw/day(2 % in the diet) for systemic toxicity

S. typhimurium
E. coliS. typhimurium

OECD 471
Other
Other(Ames assay)

Non-Bacterial In
Vitro Test
(Chromosomal
aberrations)
Genetic Toxicity In
Vivo
Carcinogenicity
Toxicity to
Reproduction

CHL

Other
(cytogenetic)

Negative (With &without metabolic
activation)
Negative(With & w ithout metabolic
activation)
positive(Without metabolic activation)negative(Without metabolic activation)

Rat

Other(cytogenetic)

negative

Rat
Rat

No tumorigenesis
NOAEL = 942 mg of Na2S2O 5 /kg
bw/day (2 % in the diet)

Developmental
Toxicity/
Teratogenicity
Experience with
Human Exposure

Rat
RabbitOther
Other(multigeneration
study)
Other
Other
Patch test
(dermatitis)
Patch-tests(ocular
hypersensitivity)
Inhalation,
ingestion

Positive

human

UNEP PUBLICATIONSNOAEL = 110 Na2S2O 5 mg/kg bw/day
NOAEL = 123 Na2S2O 5 mg/kg bw/day

negative
Asthma, anaphylaxis

OECD SIDSDISODIUM DISULPHITE

SIDS INITIAL ASSESSMENT REPORT
1. IDENTITY• OECD Name :Disodium disulphite• Synonym :Dinatriumdisulfit
Disodium disulphite
Disodium metabisulfite
Disodium pyrosulfite
Disulfurous acid, disodium salt (9CI)
Natriumdisulfit
P yrosulfurous acid, disodium salt (8CI)
Sodium disulfite
Sodium metabisulfite
Sodium pyrosulfite• CAS Number :7681-57-4• Molecular Formula :Na2S 2O 5• Structural Formula :

O

+

O Na

+

Na O S S
OO• Degree of Purity :> 98 % w/w• Physical-chemical properties- Melting Point :150 ? (decomposition)- Boiling Point :- Vapour Pressure : - Water Solubility : 470 g/L at 20?
-3.7 at 25?
- Log Pow :• Classification in member countries
Not classified as a toxic chemical in the Toxic Chemicals Control Act, Republic of Korea

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2. GENERAL INFORMATION ON EXPOSURE
In 1999, the estimates of the world market for sodium salts of sulfites without China and RussianFederation amounted to approx. 330,000 tonnes/year. These are distributed as follows: 20,000
tonnes in Germany, 60,000 tonnes in the rest Europe and 250,000 tonnes in the rest of the world.
Disodium disulphite is a basic chemical and used in synthesis. It is also used in tanning agents,
food/foodstuff additives, bleaching agents, photography, etc. Total production of disodium
disulphite in Korea was about 3,200 tonnes/year in 1998 (MOE , Korea, 1998). There is no
exposure data for the environment and humans at the present time.
2.1 Environmental Fate
Testing for the endpoint of biodegradability is not appropriate due the chemical not being anorganic chemical. Also, bioaccumulation is not expected. The product may lead chemical
consumption of oxygen in biological sewage treatment plants or in natural water. Inhibition of
degradation activities in sewage treatment plants is not to be expected from the introduction of low
concentrations. The substance can release sulphur dioxide under acid conditions, but this is not
likely to occur under normal natural environmental conditions.
Disodium disulphite dissolves in water and forms sodium cations, disulfite anions, and sulfur
dioxide. Depending on the pH-value, sulfur dioxide, sodium hydrogen sulfite or sodium sulfite arepresent in the aqueous solution.
Photodegradation of disodium disulphite in water is not relevant because it is quickly ionized inwater.
The evaluation of the fugacity model for disodium disulphite is not relevant because it is an
inorganic chemical, very soluble in water (470 g/L)
2.2 Human Exposure
Exposure to consumers may occur but the extent of this exposure is unknown. Several occupationaland consumer exposure cases have been reported. An occupational asthma in laundry workers(Le-Stradic-Reygagne, 1991), dermatitis and asthma in a photographic technician (Jacobs et al,1992), occupational bronchospasm (Vallon et al., 1995), a case of asthma after ingesting a disodium
disulphite containing salad (Baker et al., 1981) and a case of intermittent urticaria (Wuethrich et al.,1993) indicate that this chemical could have an impact on sensitive individuals. No data is available
regarding human exposure in Korea.

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3. HUMAN HEALTH HAZARDS
3.1 Effects on Human Health3.1.1 Toxicokinetics & Metabolism
It was stated that a rapid and quantitative elimination of disodium disulphite as sulfate wasobserved in man and dog (Rost, 1993). When sulphite is present in the tissues in sufficiently highconcentrations, it may be metabolized to inorganic thiosulphate excreted in the urine. Sulphite may
damage DNA chains, presumably by a reaction involving free radicals. However, mammaliantissues are largely protected against hazards from sulphite by its oxidation to the relatively nontoxic sulphate (Renner, 1983).
3.1.2 Acute Toxicity
Acute toxicity data are reported in literature for rats and other species. Oral LD50s of 1540 and 2480
mg/kg bw in rats have been reported (Hoechst AG, 1987; NTIS, 1972). The acute LD 50 by oral
exposure in rat is 1540 mg/kg bw and deaths were observed at 1250 mg/kg and above. In the deadanimals, the following gross observations were seen; the gastro-intestinal tract was filled withblood, reddened mucosa of the stomach and the dark colored liver, but unusual gross abnormalities
were not found in surviving rats (Hoechst AG, 1987).
Conclusion :The acute oral LD50 in rats is 1540 mg/kg bw. In decedents, toxicity was observed to the stomach,liver and the gastro-intestinal tract was filled with blood.
3.1.3 Repeated Dose Toxicity
An assessment of repeated dose toxicity was performed using a multigeneration study with Wistar
rats (Til et al., 1972). Rats were exposed to disodium disulphite in a supplemented diet withthiamine (ca. 2 mg/kg bw) since sulfites are known to break down thiamine. Twenty
animals/dose/sex received a diet containing 0, 0.125, 0.25, 0.5, 1.0 or 2.0 % of disodium disulphite(i.e. actual doses of ca. 48, 106, 217, 454, and 942 mg/kg/day) for 104 weeks (F0- and F1generations) or for 30 weeks (F2-generation).
The general condition of the animals was good during the first 72 weeks of the F0-generation, as
was the case in the next generation. Overall, survival in the sulphite groups was generally higher
than in the controls, except in the case of males of the F1-generation given 2 % sulphite. However,no deaths occurred in the females of the same dose group. The body weights of the F0-generation
were comparable in all groups irrespective of treatment. There was a marginal reduction in bodyweight gain in both sexes of F1-and F2-generation rats given 2 % disodium disulphite.
A marginally reduced hemoglobin content, hematocrit and erythrocyte count occurred in F0generation males at the 2 % dose at week 52, 78 and 100, and the F1-generation males at 2 %showed an increase in leukocyte count at week 102. All rats in the highest dose group showedindications of occult blood in the feces of all generations; this also occurred at other doses,
however, only sporadically.
Pathological changes attributable to feeding sulfites were only observed in the stomach. A raised
and thickened limiting ridge and small amounts of a reddish brown flocky material in the mucous
layer of the glandular stomach were seen grossly in the two highest doses. Lesions weremicroscopically characterized as forestomach and glandular stomach hyperplasia or inflammation,
and were seen mostly in the 1 and 2 % dose groups (seen mainly at 2 years in the F0- and F1UNEP PUBLICATIONS

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generation, and at 30 weeks in the F2-generation). At the 0.5 % dose, a few forestomach lesions
were seen in the F2-generation rats. Other non-neoplastic lesions observed in treated groups werecomparable to controls. In section 3.1.5 information on neoplastic changes are reported. No
histologic changes were noted in the gonads. Section 3.1.6 of this SIAR describes the reproductive
effects seen in this experiment.
In summary, no signs of systemic toxicity were observed. Therefore, the NOAEL for systemic toxicity
was the highest dose tested. The only major finding in this study was local irritation in the stomach. The
repeated dose where no stomach irritation occurred in the F0-generation was 0.5 % in the diet. Taking
the loss of sulphite into account, the actual dose was 0.44 % Na2S 2O 5 that is equivalent to an intake of
217 mg Na2S2O5 /kg bw/day. The lowest dose where local effects occurred in the F0-generation was 1.0% in the diet that is equivalent to an intake of 454 mg Na2S 2O5/kg bw/day.
Conclusion :Disodium disulphite primarily caused stomach lesions due to local irritation under the conditions of
the present study. There were no signs of local toxicity at ca. 217 mg/kg bw /day, and the lowest
dose where this effect occurred was ca. 454 mg/kg bw/day as actual intake dose (NOAEL &LOAEL for local toxicity, rats, oral feed: ca. 217 mg/kg bw/day & 454 mg/kg bw/day). From thesame dietary study in rats, the NOAEL for systemic toxicity was the highest dose tested (NOAEL
for systemic toxicity, rats, oral feed: ca. 942 mg/kg bw/day).
3.1.4 Genetic Toxicity
Genetic Toxicity in vitro
Disodium disulphite was not mutagenic in the Ames assay performed with and without S-9 mix,
using both standard plate and preincubation test conditions (NTIS , 1978; BASF AG, 1989). Nor did
it induce chromosomal aberrations in a Chinese hamster fibroblast cell line (Ishidate et al., 1984).
However, there were other in vitro bacterial assays with positive results (Pagano and Zeiger, 1987;
Pagano et al., 1990; De Giovanni-Donelly, 1985). Sensitivity to mutation by bisulfite was shown instrains which carried cytosines in the appropriate context in the putative target region of DNA,
since bisulfite has been suggested to cause cytosine deamination in single stranded DNA. In
summary they mentioned that bisulfite was a weak mutagen in bacteria when cytosines were foundas CCC and CCCCCC runs, but not in CCCC or GC runs (De Giovanni-Donelly 1985, Pagano andZeiger, 1987). These positive results also suggest that the SO3- radical is responsible for the
mutagenic activity (Pagano et al., 1990) and clearly depends on the specific test condition such as
pH value. The proper pH range (pH 4.4 to 5.6) for mutagenicity was also determined (Pagano andZeiger, 1987). However, their doses were not clearly presented. If very high doses were used, thepositive effects could be attributed to an impurity. No data on purity was given. These positive in
vitro studies referred above could not support that the substance is clearly genotoxic since the free
radical-mediated mutagenic effects are generally very transient. Moreover, such mutagenic
mechanism does not seem to be relevant to in vivo condition where the autooxidation of disodium
disulphite occurred (Renner 1983).
Genetic Toxicity in vivo
No adverse effect on bone marrow chromosomes was observed in rats as a result of disodium
disulphite treatment by gavage (NTIS, 1972 and Maxwell et al., 1974). Likewise, an evaluation formutagenicity in a dominant lethal assay showed no substance-related effect attributable to disodium
disulphite given by feed (NTIS, 1979).
Conclusion :The genetic toxicity of this chemical is equivocal in vitro but the substance is not genotoxic underin vivo condition.
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3.1.5. Carcinogenicity
The study described in section 3.1.3 (disodium disulphite given in the diet with 0.125, 0.25, 0.5,
1.0, 2.0 %, i.e. ca. 48, 106, 217, 454, and 942 mg/kg/day as actual dose and supplemented withthiamine due to its breakdown by sulphite) using rats by Til et al. (1972) is not a conventional
carcinogenicity study as the animals were mated to determine reproductive performance.
Nevertheless, this data is sufficient to assess the carcinogenic potential of disodium disulphite sinceanimals were maintained for 104 weeks, the usual time frame for a carcinogenicity bioassay, andsuitable histologic examinations were performed. In this regard, the number of lymphoreticularpulmonary tumors in males decreased with increasing levels of sulphite. The incidence of thyroid
and pituitary tumors in control males was exceptionally low, whereas those noted in the various test
groups represented numbers normally found in the strain of Wistar rats used. All other neoplasms
occurred in a sporadic manner with no apparent relationship between number, location or type oftumors and the treatment.
Conclusion :Disodium disulphite was not carcinogenic to rats.
3.1.6. Reproduction Toxicity
As described in section 3.1.3, rats were treated with 0, 0.125, 0.25, 0.5, 1.0, and 2.0 % of disodium
disulphite (ca. 0, 48, 106, 217, 454, and 942 mg/kg bw /day actual doses) in a supplemented dietwith thiamine, since sulphites are known to break down thiamine (Til et al., 1972). The F0generation was mated at week 21 of treatment. Half of ht e animals were mated again at week 34.
Animals from the 1st litter were selected at weaning to become the F1a-generation. The F1ageneration was mated at weeks 12 and 30 to produce F2a - and F2b-generations. Animals from theF2a litters were mated to produce F3a- and F3b-generations by pairing on weeks 14 and 22.
Body weight was not reduced in any treatment group in the F0-generation. There was a marginal
reduction in body weight in both sexes of the 2 % group in the F1- and the F2-generations.
Results in successive generations showed no substantial treatment-related effects in terms offertility, the number of animals/litter or the birth weight or mortality of the young. During lactation
the body weight of the young in the 2 % group was generally lower than the controls and the lowerdosed groups. In the F1a- and the F1b-generation offspring (F2a and F2b pups) dietary levels of 1
and 2 % disodium disulphite were associated with decreased body weight on days 8 and 21. Thiseffect was primarily transient for the F2a pups, since animals of the 1 % group recovered their bodyweight after weaning and the 2 % group nearly recovered their body weight as compared to thecontrol. The F2b pups were discarded after weaning. This reduced body weight was probably not atrue substance-related effect since it could be due to a higher initial body weight in the control
groups. Furthermore, these body weight changes were within or were not dramatically different
from the control values of the F1 pups. A reduction in the number of F2a-generation offspring (F3apups) was observed in the 0.5, 1.0, and 2.0 % dose groups, but it was not dose-dependent and did
not occur in the F2b-generation offspring (F3b pups).
No pronounced effects were observed on reproductive performance in any generation and no effects
on gonads were seen histologically ; thus, the NOAEL for reproduction toxicity was the highest
dose 2 % in the diet that is equivalent to 942 mg/kg bw /day as actual dose.
Conclusion :There is no suggestive evidence of reproductive toxicity in rats that received orally 942 mg/kg
bw/day of disodium disulphite as actual dose (2 % in the diet). The NOAEL (rat, fertility, F0, F1,
F2, F3, oral feed) was 942 mg/kg bw/day.
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3.1.7. Developmental Toxicity
When pregnant Wistar rats were exposed to 0, 1, 5, 24, 110 mg/kg bw/day by gavage for 6-15 daysof gestation (NTIS, 1972), disodium disulphite had no effect on nidation, on maternal and fetal
survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did
not differ from the numbers occurring in the sham-treated controls. Thus, the NOAELs for maternal
toxicity and teratogenicity as well as embryo/fetotoxicity were the highest dose tested.
NOAEL, rats, maternal toxicity, oral:
110 mg/kg bw/day
NOAEL, rats, teratogenicity, oral:
110 mg/kg bw/day
NOAEL, rats, embryo/fetotoxicity, oral:
110 mg/kg bw/day
Pregnant rabbits (Dutch-belted) were treated by gavage on days 6-18 of gestation with 0, 1.23, 5.71,
26.5 or 123 mg/kg bw /day of disodium disulphite, and were sacrificed on day 29 (NTIS, 1974).
Again, the test substance had no clear effect on nidation, or on maternal or fetal survival. The
number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ fromthe number occurring spontaneously in the sham-treated controls. The NOAELs for maternal
toxicity, teratogenicity and embryo/fetotoxicity were the highest dose tested.
NOAEL, rabbits, maternal toxicity, oral:
123 mg/kg bw/day
NOAEL, rabbits, teratogenicity, oral:
123 mg/kg bw/day
NOAEL, rabbits, embryo/fetotoxicity, oral:
123 mg/kg bw/day
Conclusion :Disodium disulphite showed no evidence of developmental toxicity or teratogenicity. The NOAELs
were established at 110 mg/kg bw/day in rats and 123 mg/kg bw/day in rabbits, respectively.
3.1.8. Other: Irritation (Human data); Sensitisation; Corrosivity
There are only a few animal studies relating to irritation of disodium disulphite. These two studies
show disodium disulphite is not irritating to the skin but irritating to the eyes of rabbits (Hoechst
AG, 1987). Regarding skin sensitization in animals, no guideline studies were available for anassessment, however, in one study with guinea pigs which was not well-documented, no indicationof sensitization was observed. In humans urticaria and asthma with itching, edema, rhinitis, andnasal congestion are reported (Le-Stradic-Reygagne, 1991; Baker, 1981; Vallon, 1995; Valero,
1993; Sanz, 1992; Wüthrich et al., 1993). An immunological pathogenesis of these are not stillclear. In a few cases allergic contact dermatitis, as well as positive patch-testing was observed(Jacobs, 1992; Apetato, 1986; Sokol, 1990; Petersen, 1990; Larame, 1989; Vestergaard andAndesen, 1995).
Conclusion :Disodium disulphite is not irritating to the skin but irritating to the eyes. It is not considered as skinsensitizer and also unlikely to induce respiratory sensitization but may enhance symptoms ofasthma in sensitive individuals.

3.2 Initial Assessment for Human Health
Acute toxicity of disodium disulphite is likely to be low since the LD50 by oral exposure in rat is1540 mg/kg bw. This chemical is not irritating to the skin, but irritating to the eyes with risk ofserious damage.
For repeated dose toxicity, in long term dietary studies (30 to 104 weeks) in rats, the predominant
effect was the induction of stomach lesions due to local irritation and was characterized as
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forestomach and glandular stomach hyperplasias and inflammation. There were no signs of local
toxicity at ca. 217 mg/kg bw/day, and the lowest dose where this effect occurred was ca. 454 mg/kg
bw/day as actual intake dose (NOAEL for local toxicity: ca. 217 mg/kg bw/day). From the same
dietary study in rats, the NOAEL for systemic toxicity was the highest dose tested (NOAEL, rats,
oral feed : ca. 942 mg/kg bw/day).
The results of genotoxic tests in vitro are equivocal but there is no evidence demonstrating that
disodium disulphite is genotoxic in vivo.
Reproduction toxicity of disodium disulphite was not observed (NOAEL, rats, fertility, oral feed:ca. 942 mg/kg bw). No developmental toxicity and teratogenic effects were observed in rats or
rabbits (NOAEL, rats, maternal toxicity/teratogenicity/embryo/fetotoxicity, oral : 110 mg/kg bw;
NOAEL, rabbits, maternal toxicity/teratogenicity/embryo/fetotoxicity, oral: 123 mg/kg bw).
It was not carcinogenic in rats that received disodium disulphite via feed.
In humans, urticaria and asthma with itching, edema, rhinitis and nasal congestion were reported.
An immunological pathogenesis of these reactions is not still clear. In a non-guideline study, no
indication of skin sensitization with guinea pigs was observed. In a few cases allergic contact
dermatitis as well as positive patch-testing was observed. With respect to wide spread use, it is notconsidered as a skin sensitizer. Disodium disulphite is unlikely to induce respiratory sensitization
but may enhance symptoms of asthma in sensitive individuals. Given the wide-spread use, thenumber of cases is considered to be low.

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13OECD SIDSDISODIUM DISULPHITE

4. H AZARDS TO THE ENVIRONMENT
4.1 Aquatic Effects
The following acute toxicity tests with aquatic organisms were available:
Medaka (Oryzias latipes) : LC50 (96 h) >100 mg/L, nominal concentration (MOE, Korea ,2001)
Rainbow trout (Salmo gairdneri) : LC 50 (96 hr) >147 mg/L and <215mg/L, nominal concentration(BASF, 1981)
Water flea (Daphnia magna) : EC50 (48 h) = 88. 76 mg/L, nominal concentration (BASF, 1989)
Algae (Scenedesmus subspicatus) : EC50 (72 h) = 48.1 mg/L, nominal concentration (BASF, 1989)
Bacteria (Pseudomonas putida) : EC50 (17 h) = 56.1 mg/L, nominal concentration (BASF, 1988)
The following chronic toxicity test with aquatic organisms was available:
Water flea (Daphnia magna ) : 21d-NOEC > 10 mg/L (BASF, 1993). The test concentrations were 1,
5, and 10 mg/L.
4.2 Terrestrial Effects
There is almost no data available on the terrestrial organisms. A study showed that treatment of
tomato leaves with different concentrations of disodium disulphite induced degradation of green
pigments and protein. The author suggested that SO2 might be responsible for the decreased protein
content of treated leaves. However, the value of KOC (2.477) is low implying that it is very mobile
in soil. Therefore given the low potential for exposure in terrestrial compartment, significant
toxicity in terrestrial organism is unlikely.
4.3 Other Environmental Effects
There is no available information.
4.4 Initial Assessment for the Environment
Testing for the endpoint of biodegradability is not appropriate due the chemical not being anorganic chemical. Also, bioaccumulation is not expected. As mentioned above, the low Koc (2.447)
indicates that disodium disulphite is so mobile in soil that it may not stay in the terrestrial
compartment. Instead it has a potential to leach into the groundwater.
From the experimental acute toxicity result of the most sensitive organism, 48.1 mg/L (72 hr-EC50
for algae; Scenedesmus subspicatus), an assessment factor 100 was applied to determine PNEC of
0.481 mg/L. From a chronic toxicity value of > 10 mg/L (21days-NOEC for Daphnia magna), a
PNEC of 0.1 mg/L was derived by applying an assessment factor of 100. Therefore the lowest
PNEC was determined to be 0.1 mg/L.

14

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE

5. CONCLUSIONS AND RECOMMENDATIONS
5.1 Conclusions
Physical/Chemical property, production, use and distribution
In 1999, estimates for the world market of sodium salts of sulphites, without China and the Russianfederation, amounted to approx. 330,000 tonnes/year. Total production of disodium disulphite in
Korea was about 3,200 tonnes/year. Disodium disulphite is a basic chemical and used in synthesis.
The substance is also used in tanning agents, food/foodstuff additives, bleaching agents,
photography, etc.
Environment
The estimated distribution shows water is the main target compartment for disodium disulphite. The
substance has no considerable potential for bio- and geoaccumulation (logPOW-3.7, measured).
Biodegradation or elimination tests may not be appropriate since disodium disulphite is an
inorganic substance. Disodium disulphite dissolves in water and forms sodium cations, disulfite
anions, and sulfur dioxide. Photodegradation is not relevant under environmental conditions.
The following acute toxicity tests with aquatic organisms were available:
Medaka (Oryzias latipes) : LC50 (96 h) >100 mg/L, nominal concentration (MOE, Korea ,2001)
Rainbow trout (Salmo gairdneri) : LC 50 (96 hr) >147 mg/L and <215mg/L, nominal concentration(BASF, 1981)
Water flea (Daphnia magna) : EC50 (48 h) = 88. 76 mg/L, nominal concentration (BASF, 1989)
Algae (Scenedesmus subspicatus ) : EC50 (72 h) = 48.1 mg/L nominal concentration (BASF, 1989)
Bacteria (Pseudomonas putida) : EC50 (17 h) = 56.1 mg/L nominal concentration (BASF, 1988)
The following chronic toxicity test with aquatic organisms w as available:
Water flea (Daphnia magna ) : 21d-NOEC > 10 mg/L (BASF, 1993). The test concentrations were 1,
5, and 10 mg/L.
From a chronic toxicity value of 10 mg/L (21days-NOEC of Daphnia magna ), a PNEC of 0.1 mg/L
was derived by applying an assessment factor of 100.
Human Health
Acute toxicity of disodium disulphite is likely to be low since the LD50 for oral exposure in rats is1540 mg/kg bw. This chemical is not irritating to the skin, but irritating to the eyes with risk ofserious damage.
In long term dietary studies (30 to 104 weeks) in rats, the predominant effect was the induction of
stomach lesions due to local irritation and was characterized as forestomach and glandular stomach
hyperplasias and inflammation. There were no signs of local toxicity at ca. 217 mg/kg bw/day, andthe lowest dose where this effect occurred was ca. 454 mg/kg bw /day as actual intake dose
(NOAEL for local toxicity: ca. 106 mg/kg bw /day) in the F0 generation. From the same dietary
study in rats, the NOAEL for systemic toxicity was the highest dose tested (NOAEL, rats, oral feed:ca. 942 mg/kg bw/day).
The results of genotoxic tests in vitro are equivocal but there is no evidence that disodium disulphite
is genotoxic in vivo.
Reproductive toxicity of disodium disulphite was not observed (NOAEL, rats, fertility, oral feed: ca.
942 mg/kg bw). No developmental toxicity or teratogenic effects appeared in rats or rabbits(NOAEL, rats, maternal toxicity/teratogenicity/embryo/fetotoxicity, oral: 110 mg/kg bw; NOAEL,
rabbits, ma ternal toxicity/teratogenicity/embryo/fetotoxicity, oral: 123 mg/kg bw).
It was not carcinogenic in rats that received disodium disulphite via feed.
In humans, urticaria and asthma with itching, edema, rhinitis, and nasal congestion have beenreported. An immunological pathogenesis of these reactions is still unclear. In a few cases allergic
contact dermatitis as well as positive patch-testing was observed. Given the wide-spread use, theUNEP PUBLICATIONS

15

OECD SIDSDISODIUM DISULPHITE

number of cases is considered to be low.
5.2 Recommendations
The chemical is currently of low priority for further work.

16

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE

6. REFERENCES
Apetato M, M.S.J. Marques. Contact dermatitis caused by sodium metabisulphite. Contact
Dermatitis. 14, 194, 1986
Baker G.J., P. Collett, D.H. Allen. Bronchospasm induced by metabisulfite-containing foods anddrugs. Med J Aust. 2, 614-617, 1981
BASF AG, Department of ecology, unpublished data (80/339), 06.January. 1981
BASF AG, Department of ecology, unpublished data (0897/88), 10.May. 1989
BASF AG, Department of ecology, unpublished data (0897/88), 21.July. 1989
BASF AG, Department of ecology, unpublished data (0897/88), 29.July. 1989
BASF AG, Department of ecology, unpublished data (2057/93), 15.December. 1993
BASF AG, Department of Toxicology, Unpublished study (89/380), 09.October. 1989
BASF AG, Safety data sheet, 30.October. 2000
De Giovanni-Donnelly, R. The mutagenicity of sodium bisulfite on based-substitution strains of S.
typhimurium. Teratogen. Carcinogen. Mutagen. 5, 195-203, 1985
Eastman Kodak Co., U.S. Toxic Substance Control Act Submission, Microfiche No. OTS 0557795,
Old Doc ID:86940000099, 1980
Hoechst AG, Unpublished studies (87.1374), 04.September. 1987a
Hoechst AG, Unpublished studies (87.1241), 11.August. 1987b
Hoechst AG, Unpublished studies (87.1293), 21.August. 1987c
Hoppe, J. O. and , F. C. Goble. The intravenous toxicity of sodium bisulfite. J. Pharmacol. Exp.
Therap. 101, 101-6, 1951
Ishidate, M., T. Sofuni, K. Yoshikawa, M. Hayashi, T. Nohmi, M. Sawada, A. Mastuoka. Primary
mutagenicity screening of food additives currently used in Japan. Fd. Chem. Toxic. 22, 623-636,
1984
Jacobs M C, R.J.G. Rycroft. Contact dermatitis and asthma from sodium metabisulfite in aphotographic technician. Contact Dermatitis. 33, 65-66, 1992
Larame B, P.M. Bedard, J. Hebert. Contact dermatitis to sulfating agents. J Allergy Clin Immunol.
28, 197, 1989
Le-Stradic-Reygagne A. in: Sodium metabisulfite, Documentation of threshold limit values.
ACGIH, Cincinnati, 1991
Maxwell, W.A. and Newell, G.W. Mol. Environ. Aspects Mutagenesis, Proc. Publ.. Rochester Int.
Conf. Environ. Toxic. 6th, 223-252, 1974
Ministry of Environment(MOE), Korea(1998), Survey on Circulation Volume of Chemicals in
Korea a)Ministry of Environment(MOE), Korea(2001), The Toxicity of Disodium disulphite to Fish (tested
by KRICT) b)
National Technical Information Service (NTIS), U.S. Department of Commerce, Study of the
UNEP PUBLICATIONS

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OECD SIDSDISODIUM DISULPHITE

Mutagenic Effect of Sodium Meta-Bisulfite (71-22), PB-221 825, July 1972
National Technical Information Service (NTIS), U.S. Department of Commerce, Teratologic
Evaluation of Compound FDA 71-22 (Sodium Meta-Bisulfite), Prepared for the FDA, PB-221 795,
Sept. 1972
National Technical Information Service (NTIS), U.S. Department of Commerce, Teratologic
Evaluation of Compound FDA 71-22. Sodium Meta-Bisulfite in Rabbit, PB-267 194, July 1974
National Technical Information Service U.S. Department of Commerce (NTIS), Microbial
Mutagenesis Testing of Substances: Compound Report F76-004 Sodium Meta-Bisulfite, PB 89193684,1978
National Technical Information Service (NTIS), U.S. Department of Commerce, Study of the
Mutagenic Effect of Sodium Meta-Bisulfite (76-73) by Dominant Lethal Test in Rats, PB-299 836,
May 1979
Pagano, D.A. E. Zeiger, A. Stack. Autoxidation and mutagenicity of sodium bisulfite. Mutation Res.
228, 89-96, 1990
Pagano, D. G. and E. Zeiger. Condition affecting the mutagenicity of sodium bisulfite in S
typhimurium. Mutation Res. 179, 159-66, 1987
Pekhov, A.P, V.N. Reshetnikova. Test strains of E. Coli for the detection of chemical mutagens.
Bull. Exp. Biol. Med. (USSR) 84, 1043-5, 1977
Petersen P.E, R.B.Evans, M.A.Johnstone, W.R Handerson. Evaluation of ocular hypersensitivity todipovalyl epinephrine by component eye-drop testing. J Allergy Clin Immunol. 85, 954-958, 1990
Renner, H.W. and J. Wever. Attempts to induce cytogenetic effects with sulphite in sulphite oxidasedeficient chinese Hamsters and mize. Fd Chem. Toxic. 21(2), 123-127, 1983
Rost, E. Handbuck der Lebensmittelchemie, Band 1, S. 993, Springer-Verlag (1993) cited in :Toxicological Evaluation of Certain Food additives and contaminants. WHO Food Addiives Series
21, 1986
Sanz J, A. Martorell, I Torro, J.C. Cerda, V Alvarez. Intolerance to sodium metabisulfite in children
with steroid-dependent asthma. J Investig Allergol Clin Immunol. 2, 36-38, 1992
Singh, S.N., N.Yumus., N. Singh. Effect of Sodium Metabisulphite on Chlorophy II, Protein andNitrate Reductase Activity of Tomato Leaves. Sci. Total Environ. 92, 269-274, 1990
Sokol W.N, I.B. Hydick. Nasal congestion, urticaria, and angioedema, caused by IgE-mediatedreaction to sodium metabisulfite. J. Allerg Clin Immunol. 65, 233-238, 1990
Til, H.P. , V.J. Feron, A.P. De Groot. The toxicity of sulfite. I. Long-term feeding andmultigeneration studies in rats. Fd. Cosmet. Toxicol. 10, 291-310, 1972
Valero A.L., M. Bescos, P Amet, A. Malet. Bronchial asthma caused by occupational sulfite
exposure. Allergol Immnol (Madrid). 21, 221-224, 1993
Vallon C, J. Sainte-Laudy, M. Nasr. Allergie et exposition professionnelle aux composessoufres:questions posees. Allerg Immunol (Paris). 27, 83-87, 1995
Wüthrich B, M.K. Kagi, J. Hafner. Disulfite-induced acute intermittent urticaria with vasculitis.
Dermatology. 187, 290-292, 1993

18

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE

SIDS DOSSIER

Disodium Disulphite
CAS No. 7681-57-4

Sponsor Country : Republic of Korea/ICCA(BASF)DATE : September 2001

UNEP PUBLICATIONS

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OECD SIDSDISODIUM DISULPHITE

CONTENTSSIDS PROFILESIDS SUMMARY

1.

GENERAL INFORMATION

1.01

SUBSTANCE INFORMATION

1.02

1.1

1.2
1.3
1.4
1.5
1.6
1.7

1.8
1.9
1.10

2.
2.1
2.2
2.3
2.4
2.5
2.6

2.7
2.8
2.9
2.10
2.11
2.12
2.13

20

A. CAS-NUMBER
B. NAME (IUPAC-NAME)
C.NAME (OECD NAME)
D.CAS DESCRIPTOR
E. EINECS-NUMBER
F. MOLECULAR FORMULAG.
STRUCTURAL FORMULA
H.
SUBSTANCE GROUPI.
SUBSTANCE REMARKJ.
MOLECULAR WEIGHTOECD INFORMATIONA.
SPONSOR COUNTRY
B.
LEAD ORGANISATIONC.
NAME OF RESPONDER (COMPANY)
GENERAL SUBSTANCE INFORMATIONA.
TYPE OF SUBSTANCE
B.
PHYSICAL STATEC.
PURITYSYNONYMS
IMPURITIESADDITIVESQUANTITYLABELLING AND CLASSIFICATION (USE AND/OR TRANSPORTATION)
USE PATTERN
A.
GENERAL USE PATTERNB.
USES IN CONSUMER PRODUCTS
OCCUPATIONAL EXPOSURE LIMIT VALUE
SOURCES OF EXPOSURE
ADDITIONAL REMARKSPHYSICAL-CHEMICAL DATAMELTING POINT
BOILING POINT
DENSITY (RELATIVE DENSITY)
VAPOUR PRESSURE
PARTITION COEFFICIENT n-OCTANOL/WATER
WATER SOLUBILITYA.
SOLUBILITYB.
pH VALUE, pKa VALUEFLASH POINT (LIQUIDS)
AUTO FLAMMABILITY (SOLID/GASES)
FLAMMABILITYEXPLOSIVE PROPERTIESOXIDISING PROPERTIESOXIDATION:REDUCTION POTENTIAL
ADDITIONAL REMARKSA.
PARTITION CO-EFFICIENT BETWEEN SOIL/SEDIMENT AND WATER (Kd)
B.
OTHER REMARKSUNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE

3.

ENVIRONMENTAL FATE AND PATHWAYS

3.1
3.1.1
3.1.2
3.1.3
3.2
3.3

STABILITYPHOTODEGRADATIONSTABILITY IN WATERSTABILITY IN SOIL
MONITORING DATA (ENVIRONMENT)
TRANSPORT AND DISTRIBUTION BETWEEN ENVIRONMENTAL COMPARTMENTS INCLUDING
ESTIMATED ENVIRONMENTAL CONCENTRATIONS AND DISTRIBUTION PATHWAYS
TRANSPORT
THEORETICAL DISTRIBUTION (FUGACITY CALCULATION)
MODE OF DEGRADATION IN ACTUAL USE
BIODEGRADATION
BOD-5, COD OR RATIO BOD-5/COD
BIOACCUMULATION
ADDITIONAL REMARKSA.
SEWAGE TREATMENT
B.
OTHER

3.3.1
3.3.2
3.4
3.5
3.6
3.7
3.8

4.

ECOTOXICITY

4.1
4.2

4.7
4.8
4.9

ACUTE/PROLONGED TOXICITY TO FISH
ACUTE TOXICITY TO AQUATIC INVERTEBRATESA.
DAPHNIAB.
OTHER AQUATIC ORGANISMSTOXICITY TO AQUATIC PLANTS e.g., ALGAETOXICITY TO MICROORGANISMS
CHRONIC TOXICITY TO AQUATIC ORGANISMS
CHRONIC TOXICITY TO FISH
CHRONIC TOXICITY TO AQUATIC INVERTEBRATES(e.g., DAPHNIA REPRODUCTION)TOXICITY TO TERRESTRIAL ORGANISMSTOXICITY TO SOIL DWELLING ORGANISMSTOXICITY TO TERRESTRIAL PLANTSTOXICITY TO OTHER NON-MAMMALIAN TERRESTRIAL SPECIES(INCLUDING BIRDS)
BIOLOGICAL EFFECTS MONITORING (INCLUDING BIOMAGNIFICATION)
BIOTRANSFO RMATION AND KINETICS
ADDITIONAL REMARKS5.

TOXICITY

5.1
5.1.1
5.1.2
5.1.3
5.1.4
5.2
5.2.1
5.2.2
5.3
5.4
5.5

ACUTE TOXICITYACUTE ORAL TOXICITYACUTE INHALATION TOXICITYACUTE DERMAL TOXICITYACUTE TOXICITY BY OTHER ROUTES OF ADMINISTRATIONCORROSIVENESS/IRRITATIONSKIN IRRITATION/CORROSION
EYE IRRITATION/CORROSION
SKIN SENSITISATIONREPEATED DOSE TOXICITYGENETIC TOXICITY IN VITROA.
BACTERIAL TESTB.
NON-BACTERIAL IN VITRO TESTGENETIC TOXICITY IN VIVOCARCINOGENICITYTOXICITY TO REPRODUCTION
DEVELOPMENTAL TOXICITY / TERATOGENICITYOTHER RELEVANT INFORMATION

4.3
4.4
4.5
4.5.1
4.5.2
4.6
4.6.1
4.6.2
4.6.3

5.6
5.7
5.8
5.9
5.10

UNEP PUBLICATIONS

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OECD SIDSDISODIUM DISULPHITE

5.11

A.
SPECIFIC TOXICITIES (NEUROTOXICITY, IMMUNOTOXICITY etc.)
B.
TOXICODYNAMICS, TOXICOKINETICS
EXPERIENCE WITH HUMAN EXPOSURE

6.

REFERENCES
Note:

22

Data elements in the SIDSUNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE

SIDS PROFILE
1.01 A.
1.01 C.
1.01 D.
1.01 G.
1.2

CAS No.
CHEMICAL NAME
(OECD Name)CAS DESCRIPTORSTRUCTURAL FORMULAOTHER CHEMICAL IDENTITY
INFORMATION

1.5

QUANTITY

1.7

USE PATTERN

1.9

SOURCES AND LEVELS OFEXPOSURE

7681-57-4
Disodium disulphite(EINECS)
Not applicable
Na2S2O5
Dinatriumdisulfit
Disodium disulphite
Disodium metabisulfite
Disodium pyrosulfite
Disulfurous acid, disodium salt (9CI)
Natriumdisulfit
Pyrosulfurous acid, disodium salt (8CI)
Sodium disulfite
Sodium metabisulfite
Sodium pyrosulfite
100 000 - 500 000 tonnes per annum (World)
1,000-5,000 tonnes per annum (Korea)
Wide -dispersive use(tanning agents, food/foodstuff additives, bleaching
agents, photography, etc.)

ISSUES FORDISCUSSION(IDENTIFY, IF
ANY)UNEP PUBLICATIONS

23

OECD SIDSDISODIUM DISULPHITE

SIDS SUMMARYCAS NO: 7681-57-4

STUDY
Y/N

Y/N

Y

Y/N

Y/N

Y/N

Y/N

Y/N

N

Y

N

Y

N

Y

N

Y

N

Y

N

Y
Y
Y

N
N
N

Y
Y
Y

N
N
N

Y
Y
Y

N
N
N

PHYSICAL-CHEMICAL DATA
2.1
2.2
2.3
2.4
2.5
2.6
2.12

3.1.1
3.1.2
3.2
3.3
3.5

Melting Point
Boiling Point
Density
Vapour Pressure
Partition Coefficient
Water Solubility
pH and pKa values
Oxidation: Reduction potential
OTHER P/C STUDIES RECEIVEDENVIRONMENTAL FATE andPATHWAY
Photodegradation
Stability in water
Monitoring data
Transport and Distribution
Biodegradation
OTHER ENV FATE STUDIES RECEIVEDN

N

ECOTOXICITY
4.1
4.2
4.3
4.5.2
4.6.1
4.6.2
4.6.3

5.1.1
5.1.2
5.1.3
5.4
5.5

5.6
5.8
5.9
5.11

24

Acute toxicity to Fish
Acute toxicity to Daphnia
Toxicity to Algae
Chronic toxicity to Daphnia
Toxicity to Soil dwelling organisms
Toxicity to Terrestrial plants
Toxicity to Birds
OTHER ECOTOXICITY STUDIESRECEIVEDTOXICITY
Acute Oral
Acute Inhalation
Acute Dermal
Repeated Dose
Genetic Toxicity in vitro. Gene mutation. Chromosomal aberration
Genetic Toxicity in vivo
Reproduction Toxicity
Development / Teratogenicity
Human experience
OTHER TOXICITY STUDIES RECEIVED

Y
Y
Y
Y
N
Y
N

Y
N
Y
Y

Y
N
N
Y

Y

Y
Y
Y
Y
Y
Y

Y
N
N
N
N
N

Y
N
N
Y

N
Y
N
N

N
N
N
N

Y
Y
Y
Y
N

Y

N

UNEP PUBLICATIONS

N

N

N
N
N
N
N
N
N

N

N

Y

Y

N

Y

N
N
N
N

N
Y
Y
Y
Y
Y

N
N
N
N
N
N

Y
Y
Y
Y
Y
Y

N
N
N
N
N
N

OECD SIDSDISODIUM DISULPHITE

1.

GENERAL INFORMATION

1.01

SUBSTANCE INFORMATIONA.

CAS number

B.

Name (IUPAC name)

Disodium disulphiteC.

Name (OECD name)

Disodium disulphite (EINECS)D.

CAS Descriptor

7681-57-4

Not Applicable since disodium disulphite is not a complex chemical.
E.

EINECS -Number

231-673-0

F.

Molecular Formula

Na2S2O5G.

Structural Formula+O+

Na O SOO NaSOSmiles Code : [Na]OS[=O][=O]S[=O]O[Na]H.

Substance GroupNot applicable

I.

Substance Remark (Indicate the substance remark as prescribed in the EINECS Inventory, if possible)
Not applicable since no prescription in the EINECS Inventory.

J.

Molecular Weight

1.02

OECD INFORMATIONA.

Sponsor Country:

B.

Lead Organisation:
Name of Lead Organisation: National Institute of Environmental ResearchContact person:
Dr. Moon-Soon LEE
Address:
Street:Gyeongseo-dong, Seo-gu
Postal code 404-170
Town:
IncheonCountry:
Republic of Korea
Tel:82-32-560-7113
Fax:
82-32-568-2037
E-mail :mslee416@me.go.kr

C.

Name of responder

Name :
Address :190.10

Republic of Korea/ICCA (BASF)(Information on a responder should be provided when companies respond to Lead
Organisation or SIDS Contact Points.)

same as above
same as above

UNEP PUBLICATIONS

25

OECD SIDS
1.1

DISODIUM DISULPHITE

GENERAL SUBSTANCE INFORMATION

A.

Type of Substanceelement [ ]; inorganic [x]; natural substance [ ]; organic [ ];organometallic [ ]; petroleum product [ ]B.

Physical State (at 20 °C and 1.013 hPa)gaseous [ ]; liquid [ ]; solid [x]C.

Purity> 98 % w/w

1.2

SYNONYMS
Dinatriumdisulfit
Disodium disulphite
Disodium metabisulfite
Disodium pyrosulfite
Disulfurous acid, disodium salt (9CI)
Natriumdisulfit
Pyrosulfurous acid, disodium salt (8CI)
Sodium disulfite
Sodium metabisulfite
Sodium pyrosulfite

1.3

IMPURITIESCAS No:
EINECS No:
Name:Value:
Remarks:
CAS No:
EINECS No:
Name:Value:
Remarks:
CAS No:
EINECS No:
Name:Value:
Remarks:
CAS No:
EINECS No:
Nam e:
Value:
Remarks:
CAS No:
EINECS No:
Name:Value:
Remarks:

26[Indicate CAS No., chemical name (IUPAC name is preferable), percentage, if possible
EINECS number.]

ClLess than 0.05 %S2O32Less than 0.05 %heavy metals
Less than 0.001 %Fe
Less than 0.002 %Insolubles
Less than 0.005 %UNEP PUBLICATIONSOECD SIDS
1.4

DISODIUM DISULPHITE

ADDITIVES (e.g. stabilising agents, inhibitors etc. Indicate CAS No., chemical name (IUPAC name ispreferable), percent age, if possible EINECS number), the component of the UVCB (substance with no definedcomposition) should be indicated here.)
CAS No:
EINECS No:
Name:Value:
Remarks:

1.5

QUANTITY [Information on production or import levels should be provided in figures or ranges (e.g. 1,0005,000, 5,000-10,000 tonnes, etc.) per responder or country and the date for which those ranges apply should begiven. For EU Member states, only indicate the EU import figure. Give an estimation of the global production
quantity in the remarks field. Information on the number of producers in the country and the source of
information should also be given in the remarks field.]
Estimated production

Remarks:

Reference :1.6- World wide : 100,000 – 500,000 tonnes per annum (1999)- Korea : 3,200 tonnes per annum (MOE, 1998)(If possible, indicate if the substance was produced and/or imported
during the 12 months following adoption of the EU regulation on
existing chemicals.)
Ministry of Environment (MOE), K orea(1998), Survey on Circulation Volume ofChemicals in Korea.

LABELLING AND CLASSIFICATION [If possible, enter information on labelling and classification, suchas labelling and classification system, existence of specific limit, symbols, nota, R-Phrases and S-Phrases of
EC Directive 67/548/EEC. See HEDSET Explanatory Note.]
LabellingType:
Specific limits:
Symbols:
Nota:
R-phrases:
S-phrases:
Text of S-phrases:
Remarks:
Classification
Type:
Category of danger:
R-phrases:
Remarks:*Disodium disulphite is not classified as toxic chemicals in Korea

1.7

USE PATTERNA.
General [Data on use pattern have to be given by assigning main types according to their exposure relevance(i.e. non-dispersive use, use in closed systems, use resulting in inclusion into or onto matrix and wide dispersive use),
industrial categories (e.g. basic chemical industry, chemical industry, agricultural industry, personal and domestic use)
and use categories such as colouring agents, intermediates, solvents, adhesives, cleaning/washing agents, fertilizers,
impregnation agents, surface-active, etc. If available, give an estimation of different uses in percentage terms.](a)Type of Use:

Category:main
industrial

Wide dispersive use
Chemical Industry

UNEP PUBLICATIONS

27

OECD SIDSDISODIUM DISULPHITE

use

Tanning agents

(b)

main
industrialuse

Non dispersive use
Personal and domestic use
Food/foodstuff additives

(c)

main
industrialuse

Non dispersive use
Personal and domestic use
Bleaching agents

(d)

main
industrialuse

Non dispersive use
Personal and domestic use
Photography

Remarks:

Reference:

General use of Disodium disulphite in the world are shown above. Among 3,200 tonnes consumed in
Korea, most of them are used for Tanning agents, Food/foodstuff additives. Information of other use is notavailable
Ministry of Environment (MOE), Korea (1998), Survey on Circulation Volume of Chemicals in Korea.

B.
Uses in Consumer Products (If the chemical is present in consumer products as marketed give details of formof products function (e.g. detergent etc.), and percent in product and physical state of product as marketed (e.g. aerosol,
powder or liquid))
Function
Remarks:
Reference:

1.8

Amount present

Physical state

Information of other use is not available.

OCCUPATIONAL EXPOSURE LIMIT VALUE (Indicate the type of occupational exposure limit value
including short-term exposure limit value. If a value does not exist, give the hygiene standard of the producer
company if available. See also 5.11.)

Exposure limit valueType:
TLV (KO)
Value:
5 mg/m3 (8 hr TWA)
Short term exposure limit value
Value:
Length of exposure period
Frequency:
Remarks:
Reference:
Industrial safety and health act in Korea (1998)
Exposure limit valueType:
TLV (US)
Value:
5 mg/m3
Short term exposure limit value
Value:
Length of exposure period
Frequency:
Remarks:
Reference:
ACGIH Documentation of the TLV and Biological Exposure Indices (1991)
Exposure limit value
Type:
Value:REL (US)
5 mg/m3 (10 hr TWA)

Short term exposure limit value
Value:
Length of exposure period
Frequency:
Remarks:
Reference:
NIOSH pocket guide to chemical hazards (1994)

28

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1.9

DISODIUM DISULPHITE

SOURCES OF EXPOSURE
Describe sources of potential human [other than concentration of chemicals in the workplace and indoor
environment (see 5.11)], or environmental exposure, including emission data (e.g. quantities per media withinformation such as time dimensions of release, indication of type of release (e.g. point source or diffuse), typeof estimating (e.g. average or worst case), uncertainties in estimation), for all phases of the life cycle of thechemical, if available, including manufacturing and user areas.
For environmental exposure, indicate the production process briefly, number of sites of manufacture and, thebasis for concluding that the process is "closed" if applicable.
Also an indication of measured exposure levels (expressed in an appropriate form, e.g. geometric mean andstandard deviation) can be mentioned here. Any information that will help to focus the assessment of exposure(either quantitative or quantitative in nature) can be mentioned, if available.)
Source:Remarks:
Reference:

the most probable human exposure would be occupational exposure, which may occur
through dermal contact at workplaces.
NIOSH National Occupational Exposure Survey 1983

1.10

ADDITIONAL REMARKS

A.

Options for disposal [Mode of disposal (e.g. incineration, release to sewage system, etc.) for each category
and type of use, if appropriate; recycling possibility]
Remarks:
Reference:B.

Other remarks
Remarks:
Reference:

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2.

2.1

DISODIUM DISULPHITE

PHYSICAL-CHEMICAL DATAMELTING POINT (If more than one, identify the recommended value.)
Value:
Decomposition:
Sublimation:
Method:GLP:
Remarks:
Reference:

Yes [x] No [ ] Ambiguous [ ]Yes [ ] No [ ] Ambiguous [ ]Yes [ ] No [ ] ? [x]Solid temperature 150 °C (decompose to form sulfur dioxide )BASF AG safety data sheet sodium metabisulfite, 06. January. 1999

2.2 BOILING POINT (If more than one, identify the recommended value.)
Value:
Pressure:
Decomposition:
Method:GLP:
Remarks:
Reference:

Yes [x] No[ ] Ambiguous [ ]Yes [ ] No [ ] ? [x]not relevant (decomposition)

2.3 DENSITY (relative density) (Where applicable, indicate the relative density of the substance.)
Type:
Value:
Temperature:
Method:GLP:
Remarks:
Reference:

2.4

Yes [ ] No [ ] ? [x]BASF AG safety data sheet sodium metabisulfite, 06. January. 1999

VAPOUR PRESSURE (if more than one, identify the recommended value)
Value:
Temperature:
Method:GLP:
Remarks:
Reference:

2.5

Relative Density
1.48 g/cm 3
15 °C

°C
Yes [ ] No [ ] ?[ ]not relevant

PARTITION COEFFICIENT log POW (if more than one, identify the recommended value)

Log POW :Temperature:
Method:GLP:
Remarks:
Reference :

-3.7
25 °C
calculated [ ]; measured [x]Yes [ ] No [ ] ?[x]log POW strongly depend on pH value
BASF AG Physical/chemical, unpublished investigation, report BRU 88.
221, 02. November. 1988

2.6

WATER SOLUBILITY (if more than one, identify the recommended value)A.

Solubilitya) Preferred result
Value: 470 g/l

30

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE

Temperature:
Description:

0 °C
Miscible[ ]; Of very high solubility [ ]; Of high solubility [x]; Soluble [ ];Slightly soluble [ ]; Of low solubility [ ]; Of very low solubility [ ]; Not soluble[ ]MethodGLP:
Remarks :Reference:

Yes [ ] No [ ] ?[x]BASF AG, Sicherheitsdatenblatt Natriumdisulfit, 30.October. 2000b)
Value:
Temperature:
Description:

640 g/l25 °C
Miscible[ ]; Of very high solubility [ ]; Of high solubility [x]; Soluble [ ];Slightly soluble [ ]; Of low solubility [ ]; Of very low solubility [ ]; Not soluble[ ]Method:GLP:
Remarks:
Reference:c)Value:
Temperature:
Description:
Method:GLP:
Remarks:
Reference:

B.

Sorbe, Sicherheitstechnische Kenndaten chemischer Stoffe, p.97, 28. Erg. Lfg.
12/92

540 g/l25 °C
Miscible[ ]; Of very high solubility [ ]; Of high solubility [x]; Soluble [ ];Slightly soluble [ ]; Of low solubility [ ]; Of very low solubility [ ]; Not soluble [ ]Yes [ ] No [ ] ?[x]Richardson, M.L. and S. Gangolli. The Dictionary of Substances and their Effects.
Royal Society of Chemistry. p. 19, 1995

pH Value, pKa value
pH Value:
Concentration:
Temperature:
Method:GLP:
pKa value:
Remarks:
Reference:

2.10

Yes [ ] No [ ] ?[x]3.5-5.0
50 g/l20 °C
Yes [ ] No [ ] ?[x]BASF AG, Sicherheitsdatenblatt Natriumdisulfit, 30. October. 2000

EXPLOSIVE PROPERTIES
Results:

Explosive under influence of a flame[ ];More sensitive to friction than m -dinitrobenzene [ ];More sensitive to shock than m-dinitrobenzene [ ]; Not explosive [x]; Other [ ]Method:GLP:
Yes [ ] No [ ] ?[x]Remarks:
because of chemical structure
Reference:
BASF AG, Sicherheitstechnik, interne Mitteilung,
29.October.1999

2.11 OXIDIZING PROPERTIES
Results:
Method:GLP:
Remarks:

Maximum burning rate equal or higher than reference mixture [ ];Vigorous reaction in preliminary test [ ]; No oxidising properties [x]; Other [ ]Yes [ ] No [ ] ?[x]because of chemical structure

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Reference:

2.12

DISODIUM DISULPHITE
BASF AG, Sicherheitstechnik, interne Mitteilung, 29. October. 1999OXIDATION: REDUCTION POTENTIAL(Where applicable, indicate the redox potential and the conditions under which it was measured.)
Value:
Method:GLP:
Remarks:

No data available
Yes [ ] No [ ] ?[x]2.13

ADDITIONAL DATA

A.

Partition co-efficient between soil/sediment and water (Kd)
Value:KOC :Method:GLP:
Remarks:
Reference:

B.

32

2.447
calculated by PCKOCWIN V. 1.63
Yes [ ] No [ ] ?[x]very high mobility in soil.
BASF AG, department of ecology, unpublished calculation, 18, December.1998

Other data
(e.g. Henry's Law constant, fat solubility, surface tension (of aqueous solution), adsorption/desorption on soil,
particle size distribution, etc.)

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE

3.

ENVIRONMENTAL FATE AND PATHWAYS[Reporting of studies should give the test method, test conditions (laboratory versus field studies), test results(e.g. % degradation in specified time period) and reference. Information on breakdown products (transient andstable) should be provided when available.]

3.1

STABILITY

3.1.1

PHOTODEGRADATION
(a)
Type:
Air [ ]; Water [ ]; Soil [ ]; Other [ ]Light source:
Sun light [ ]; Xenon lamp [ ]; Other [ ]Light spectrum:.nm
Relative intensity:(based on intensity of sunlight)
Spectrum of substance:(e.g. lambda (max.)[> 295 nm] and epsilon[max] or epsilon [295 nm])nm
Concentration of Substance:
Temperature:°C
Direct photolysis:
Half life:
Degradation:% (weight/weight) after . . . .(exposure time)
Quantum yield:
Indirect Photolysis:
Type of sensitizer:
Concentration of sensitizer
Rate constant (radical): cm 3/molecule*sec
Degradation:
Method:calculated [ ]; measured[ ](e.g. OECD, other (with the year of publication or updated of the method used))
GLP:
Yes [ ] No [ ] ? [ ]Test substance:.
Remarks:
Molecules with an adsorbance maximum of light with wavelength range of 290-600
nm electrons may get promoted from bonding orbitals to antibonding orbitals(eg. π → π* transitions). The molecule is then in a so-called exited state. But
molecules with the basic structure RS-SR has an adsorption maximum near by 300
nm and a single bound. Additionally the molecule needs a chromophore group like a
conjugated double bonds. Heteroatoms like oxygen makes so-called n → n*transition are principle also possibly but commonly at longer wavelength. Due tothese chemical features probably it does not seem that disodium disulphite
undergoes photochemical reactions neither in air (totally soluble in water) nor inwater depending on its chemical structure.
Reference:

3.1.2

STABILITY IN WATERType:
Half life:
Degradation:
Method:GLP:Test substance:
Remarks:

Abiotic (hydrolysis)[ ] ; biotic (sediment)[ ](T 1/2 :)at pH at °C after (exposure time)
Yes [ ] No [ ] ? [ ]purity:Disodium disulphite dissolves in water forming sodium cations, disulfite anions,and sulfur dioxide. Depending on the pH-value, sulfur dioxide, sodium hydrogensulfite or sodium sulfite is present in aqueous solution.

Reference:

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3.3

TRANSPORT AND DISTRIBUTION BETWEEN ENVIRONMENTAL COMPARTMENTS
INCLUDING ESTIMATED ENVIRONMENTAL CONCENTRATIONS AND DISTRIBUTIONPATHWAYS

3.3.2

THEORETICAL DISTRIBUTION (FUGACITY CALCULATION)a) Preferred result
Media:
Method:Results:

Remarks:
Reference:

3.4

IDENTIFICATION OF MAIN MODE OF DEGRADABILITY IN ACTUAL USE
Results:
Remarks:
Reference:

3.5

Air-biota[ ]; Air-biota-sediment -soil-water[ ]; Soil-biota[ ]; Water-air[ ];Water-biota[ ]; Water-soil[ ]; Other[ ];Fugacity level I[ ]; Fugacity level? [ ]; Fugacity level III[ ];Fugacity level IV [ ]; Other (calculation) [ ]; Other(measurement)[ ]In air%In water%
In soil%In sediment %Not relevant

No data available

BIODEGRADATION
Type:
aerobic [ ]; anaerobic [ ]Inoculum:
adapted [ ]; non-adapted [ ];Concentration of the chemical:
related to COD [ ]; DOC [ ]; test substance [ ]Medium:water [ ]; water-sediment [ ]; soil [ ]; sewage treatment [ ]Degradation:% after (time)
Results:
readily biodeg. [ ]; inherently biodeg. [ ];under test condition no biodegradation observed [ ], other [ ]Kinetic (e.g. Zahn-Wellens-Test)% in(time)
Method:GLP:
Yes [ ] No [ ] ? [ ]Test substance:
purity:Remarks:
Not relevant (inorganic compounds). Elimination test can not be carried out cause itis an inorganic substance. The product may lead chemical consumption of oxygen in
biological sewage works or natural water. Inhibition of degradation activity inactivated sludge is not to be anticipated during correct introduction of low
concentrations. The substance develops sulphurdioxide in acid milieu.
Reference:

3.6

BOD5,COD OR RATIO BOD5/COD
BOD5Method:Concentration:
Value:GLP:
COD
Method:Value:
GLP:
Ratio BOD5/COD:
Remarks:
Reference:

34

mg/L related to COD [ ]; DOC [ ]; Test substance [ ];= mg O2/L
Yes [ ] No [ ] ? [x]= mg O2/g
Yes [ ] No [ ] ? [ ]Not relevant (inorganic compounds)

UNEP PUBLICATIONSOECD SIDS
3.7

DISODIUM DISULPHITE

BIOACCUMULATION
Species:
Exposure period:
Temperature:
Concentration:
BCF:
Elimination:
Method:Type of test:
GLP:
Test substance:
Remarks:
Reference:mg/L
Yes [ ] No [ ] ? [ ](e.g. OECD, other (with the year of publication or updated of the method used))
calculated [ ] ; measured [ ]static [ ]; semi-static [ ]; flow -through [ ]; other (e.g. field test) [ ]Yes [ ] No [ ] ? [ ]Not expected

3.8

ADDITIONAL REMARKSA.

Sewage treatment (information on treatability of the substance)
Results:
Remarks:
Reference:B.

No data available

Other information (information that will help to focus the exposure assessment (either qualitative or
quantitative)
Results:
Remarks:
Reference:

No data available

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4.

ECOTOXICITY

4.1

ACUTE/PROLONGED TOXICITY TO FISH(a)Type of test:
Species:
Exposure period:
Results:
Analytical monitoring:
Method:GLP:Test substance:
Remarks:
Reference :(b)Type of test:
Species:
Exposure period:
Results:
Analytical monitoring:
Method:GLP:Test substance:
Remarks:
Reference :static [x]; semistatic [ ]; flow-through [ ]; other[ ];open-system[ ]; closed system[ ]Oryzias latipes
96 hr
LC50 (96 hr) > 100 mg/L
Yes[ ] No[x] ? [ ]OECD TG 203
Yes[x] No[ ] ? [ ]98.3 %
Ministry of Environment (MOE), Korea (2001), The Toxicity of disodium disulphite
to Fish (tested by KRICT)

static [x]; semistatic [ ]; flow-through [ ]; other[ ];open-system[ ]; closed system[ ]Salmo gairdneri (Fish, estuary, fresh water)
96 hr
LC50(96 hr) > 147 and < 215 mg/L
Yes[ ] No[x] ? [ ]other : German Industrial Standard Guideline Number, DIN 38412 Group L, Part 1
and 15; 1979
Yes[ ] No[x] ? [ ]approx.98 %, BASF AG No 80/339
BASF AG, Dept. of Toxicology, unpublished result (80/339) 06. January. 1981

4.2

ACUTE TOXICITY TO AQUATIC INVERTEBRATESA.

Daphnia
Type of test:
Species:
Exposure period:
Results:

Analytical monitoring:
Method:GLP:Test substance:
Remarks:
Reference :B.

static [x]; semistatic [ ]; flow -through [ ]; other[ ];open-system[ ]; closed-system[ ]Daphnia magna
48 hr
EC0 (48 hr) = 62.5 mg/L
EC50 (48 hr) = 88.76 mg/L
EC100 (48 hr) = 125.0 mg/L
Yes[ ] No[ ] ? [x]Other: EEG guideline 79/831/EWG, appendix V, part of C "Acute toxicity for
Daphnia"
Yes[ ] No[x] ? [ ]purity > 98 % (w/w), BASF Sulphite-factory RCA B 306
BASF AG, Dept. of Ecology ; unpublished result (0897/88), 10. May. 1989

Other aquatic organisms
No data available.

4.3

TOXICITY TO AQUATIC PLANTS (e.g. algae)
Species:
End point:
Exposure period:

36

Scenedesmus subspicatus (Algae)
Biomass [x]; Growth rate [ ]; Other [ ]72 hr , 96 hr

UNEP PUBLICATIONSOECD SIDS
Results:

Analytical monitoring:
Method:GLP:Test substance:
Remarks:
Reference :4.4

DISODIUM DISULPHITE
Biomass :EC20 (72 hr) = 39.2 mg/mL
EC50 (72 hr) = 48.1 mg/mL
EC90 (72 hr) = 60.0 mg/mL
EC20 (96 hr) = 20.0 mg/mL
EC50 (96 hr) = 39.8 mg/mL
EC90 (96 hr) = 58.0 mg/mL
Yes[ ] No[ ] ? [x]other: OECD Guide-line 201 “ Algae, Growth Inhibition Test”
open-system[ ]; closed-system[ ]Yes[ ] No[x] ? [ ]purity > 98 % (w/w)
BASF AG , Dept. of Ecology, unpublished result (0897/88), 21. July. 1989

TOXICITY TO BACTERIA(a) Preferred result
Type of test:
Species:
Exposure period:
Results:

Analytical monitoring:
Method:GLP:Test substance:
Remarks:
Reference:(b)
Type of test:
Species:
Exposure period:
Results:
Analytical monitoring:
Method:GLP:Test substance:
Remarks:

Reference:

Aquatic [x]; Field [ ]; Soil [ ]; Other [ ]Pseudomonas putida (Bacteria)
17 hr
EC10 (17 hr) = 30.8 mg/L
EC50 (17 hr) = 56.1 mg/L
EC90 (17 hr) =115.1 mg/L
Yes[ ] No[ ] ? [x]other: DIN 38412, part 8, Determination of inhibitory effect on the cell
multiplication
Yes[ ] No[x] ? [ ]purity > 98 % (w/w)
BASF AG, Dept. of Ecology, unpublished result (0897/88), 29. July. 1989

Aquatic [ ]; Field [ ]; Soil [ ]; Other [ ]Salmonella typhimurium, Escherichia coli, and Pseudomonas aeruginosahr
EC ( h) = mg/L
Yes[ ] No[ ]Yes[ ] No[ ] ? [x]Salmonella typhimurium 59143, Escherichia coli ES-1, and Pseudomonas
aeruginosa 8602 were not viable to disodium disulphite concentration of 800, 1000,
and 2000 ppm, respectively, in gelatin medium. In rehydrated bone meal,
Salmonella typhimurium showed no viability in 2 out of 4 cases at 4000 ppm.
Abalaka, J.A., R.H. Deibel. A comparative study of the lethal effect of
metabisulphite on the viability of three bacterial species in bone meal and gelatin.
Microbios. 27 (108), 79-88, 1980

4.5

CHRONIC TOXICITY TO AQUATIC ORGANISMS

4.5.1

CHRONIC TOXICITY TO FISH
No data available.

4.5.2 CHRONIC TOXICITY TO AQUATIC INVERTEBRATESType of test:
Species:
Endpoint:
Exposure period:
Unit:static [ ]; semistatic [x]; flow-through [ ]; other[ ]; open-system[ ];closed-system[ ]Daphnia magna
Mortality [ ];Reproduction rate[x]; other[ ]21 days
mg/L

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OECD SIDS
Results:
Analytical monitoring:
Method:GLP:Test substance:
Remarks:
Reference:

DISODIUM DISULPHITENOEC > 10.0 mg/L
LC0 > 10.0 mg/L
Yes[ ] No[x] ? [ ]other: OECD Guideline 202, part 2: “Daphnia sp., Reproduction test”.
Yes[x] No[ ] ? [ ]purity > 98 % (w/w)
BASF AG, Dept. of Ecology, unpublished result (2057/93), 15. December. 1993

4.6

TERRESTRIAL ORGANISMS

4.6.1

TOXICITY TO SOIL DWELLING ORGANISMS
No data available.

4.6.2

TOXICITY TO TERRESTRIAL PLANTS
Species:
End-point:
Exposure period:
Results:
Method:GLP:Test Substances:
Remarks:

Reference:

Tomato leaves
Emergence [ ]; Growth [ ]; Other [x]
5 hr

Yes [ ] No [ ] ? [x]purityTreatment of tomato leaves with different concentration of disodium disulphite
induced degradation of green pigments and protein. Chlorophyll content was
reduced by 71.15 % and protein by 42.85 % in treated leaves at a concentration of660 µg/mL as compared with controls.
Singh, S.N., M. Yumus, N.Singh. Effect of Sodium Metabisulphite on Chlorophyll,
Protein and Nitrate Reductase Activity of Tomato Leaves. Sci. Total Environ. 91,
269-74,1990

4.6.3

TOXICITY TO OTHER NON-MAMMALIAN TERRESTRIAL SPECIESNo data available.

4.7

BIOLOGICAL EFFECTS MONITORING
No data available.

4.8

BIOTRANSFORMATION AND KINETICSNo data available.

4.9

ADDITIONAL REMARKSNo data available.

38

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5.

TOXICITY

5.1

ACUTE TOXICITY

5.1.1

ACUTE ORAL TOXICITY(a) Preferred Result
Type:
Species/strain
Value:
Method:GLP:Test substance:
Remark:Reference:
(b)
Type:
Species/strain
Value:
Method:GLP:Test substance:
Remark:Reference:

(c)
Type:
Species/strain
Value:
Method:GLP:Test substance:
Remark:Reference:

LD0[ ]; LD50[x] LD100[ ]; LDLo[ ]; Other [ ]RatLD50= 1,540 mg/kg
Discriminating dose : 0, 800, 1250, 1600, 2000 mg/kg bw
OECD TG 401
Yes[x] No[ ]?[ ]Disodium disulphite-powder, purity min. 96 %, other TS
Hoechst AG (1987); unpublished studies (87.1374), 04. September. 1987

LD0[ ]; LD50[x] LD100[ ]; LDLo[ ]; Other [ ]RatLD50= 2,480 mg/kg
Discriminating dose : unknown
Not specified
Yes[ ] No[ ]? [x]Disodium disulphite purity : unknown
National Technical Information Service U.S. Department of Commerce (NTIS),
FDA 71-22, PB 221 825 (1972)

LD0[ ]; LD50[x]; LD100[ ]; LDLo[ ]; Other [ ]Sheep2,515 mg/kg
Discriminating dose : N/A
Yes[ ] No[ ]? [x]Nikolaev, K. and Dzhidzheva, V. Vet-Med Nauki 10 (4), 61-5, 1973

5.1.2

ACUTE INHALATION TOXICITY
No data available

5.1.3

ACUTE DERMAL TOXICITY
No data available

5.1.4

ACUTE TOXICITY, OTHER ROUTES OF ADMINISTRATION
(a)
Type:
Species/strain
Route of Administration:
Exposure time:
Value:
Method:GLP:Test substance:
Remarks:
Reference:

LC0[ ]; LC50[ ]; LC100[ ]; LCLo [ ]; Other [ ]LD0[ ]; LD50[x]; LD100[ ]; LDLo [ ]; Other [ ]Rat/Sherman
i.m.[ ]; i.p [ ]; i.v. [x]; infusion [ ]; s.c. [ ]; Other [ ]approximately 115 mg/kg bw
Yes[ ] No[x] ?[ ]Disodium disulphite
Hoppe, J. O., F. C. Goble. The intravenous toxicity of sodium bisulfite. J.
Pharmacol. Exp. Therap. 101, 101-6, 1951

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(b)
Type:

LC0[ ]; LC50[ ]; LC100[ ]; LCLo [ ]; Other [ ]LD0[ ]; LD50[x]; LD100[ ]; LDLo [ ]; Other [ ]Species/strain
Mouse/Albino Webstar
Route of Administration: i.m.[ ]; i.p [ ]; i.v. [x]; infusion [ ]; s.c. [ ]; Other [ ]Exposure time:
Value:
approximately 130 mg/kg bw
Method:GLP:
Yes[ ] No[x] ?[ ]Test substance:
Disodium disulphite
Remarks:
Reference:
Hoppe, J. O., F. C. Goble. The intravenous toxicity of sodium bisulfite. J.
Pharmacol. Exp. Therap. 101, 101-6, 1951
(c)
Type:

LC0[ ]; LC50[ ]; LC100[ ]; LCLo [ ]; Other [ ]LD0[ ]; LD50[x]; LD100[ ]; LDLo [ ]; Other [ ]Species/strain
RabbitRoute of Administration: i.m.[ ]; i.p [ ]; i.v. [x]; infusion [ ]; s.c. [ ]; Other [ ]Exposure time:
Value:
approximately 65 mg/kg bw
Method:GLP:
Yes[ ] No[x] ?[ ]Test substance:
Disodium disulphite
Remarks:
Reference:
Hoppe, J. O., F. C. Goble. The intravenous toxicity of sodium bisulfite. J.
Pharmacol. Exp. Therap. 101, 101-6, 1951
(d)
Type:

LC0[ ]; LC50[ ]; LC100[ ]; LCLo [ ]; Other [ ]LD0[ ]; LD50[x]; LD100[ ]; LDLo [ ]; Other [ ]Species/strain
Hamster/Golden Syrian
Route of Administration: i.m.[ ]; i.p [ ]; i.v. [x]; infusion [ ]; s.c. [ ]; Other [ ]Exposure time:
Value:
approximately 95 mg/kg bw
Method:GLP:
Yes[ ] No[x ] ?[ ]Test substance:
Disodium disulphite
Remarks:
Reference:
Hoppe, J. O., F. C. Goble. The intravenous toxicity of sodium bisulfite. J.
Pharmacol. Exp. Therap. 101, 101-6, 1951

5.2

CORROSIVENESS/IRRITATION

5.2.1

SKIN IRRITATION(a)
Species/strain
Results:
Classification:
Method:GLP:Test substance:
Remarks:

Reference:

40

Rabbit/Albino New ZealandHighly corrosive [ ] ; corrosive [ ]; Highly irritating [ ]; Irritating [ ]; Moderate
irritating [ ]; Slightly irritating [ ]; Not irritating [x]Highly corrosive (cause severe burns) [ ]; Corrosive (caused burns) [ ];Irritating [ ]; Not irritating [x]OECD Guideline 404 "Acute Dermal Irritation/Corrosion" 19981
Yes[x] No[ ] ?[ ]Disodium disulphite-powder, min. purity 96 %, Other TS
500 mg of the chemical was prepared into a paste with a saline solution (NaCl 0.9%) and applied to the animal semiocclusively over a 2.5 x 2.5 cm2 area. The skin
was evaluated after 30-60 min, as well as 24, 48 and 72 h after the patch wasremoved.
Hoechst AG (1987); unpublished studies (87.1241)

UNEP PUBLICATIONSOECD SIDS
5.2.2

EYE IRRITATION/CORROSION(a) Preferred result
Species/strain
Results:
Classification:
Method:GLP:Test substance:
Remarks:
Reference:

5.3

RabbitHighly corrosive [ ] ; corrosive [ ]; Highly irritating [ ]; Irritating [x]; Moderate
irritating [ ]; Slightly irritating [ ]; Not irritating [ ]Irritating [x]; Not irritating [ ]; Risk of serious damage to eyes [ ]OECD TG 405 (1987)
Yes[x] No[ ] ?[ ]Disodium disulphite-powder, min. purity 96 %, other TS
Hoechst AG (1987); unpublished result (87.1293).

SKIN SENSITIZATION
(a)
Type:
Species/strain:
Results:
Classification:
Method:GLP:Test substance:
Remarks:
Reference:

5.4

DISODIUM DISULPHITE

Guinea pig
Sensitizing [ ]; Not sensitizing [x]; ambiguous [ ](If possible, according to EC Directive 67/548/EEC)
Sensitizing [ ]; Not sensitizing [ ]Standardized skin sensitization test
Yes [ ] No [ ] ? [x]0/10 guinea pigs responded positively
Eastman Kodak Co., U.S. Toxic Substance Control Act Submission, Microfiche No.
OTS 0557795, Old Doc ID:86940000099, 1980

REPEATED DOSE TOXICITY(a) Preferred Result
Species/strains:
Rat / Wistar
Sex:
Female [ ]; Male [ ]; Male/Female [x]; No data [ ]Route of administration: Feeding(p.o)
Exposure period:
104 weeks (F0 and F1 generations), 30 weeks (F2 generations)
Frequency of treatment: Daily
Post exposure observation period:
Dose:0, 0.125, 0.25, 0.5, 1.0, 2.0 % in feed
Control group:
Yes [x]; No [ ]; No data [ ]Concurrent no treatment [x]; Concurrent vehicle [ ]; Historical [ ]NOAEL:
local toxicity : 0.44 % (as actual dose) or 0.5 % (in the diet)system toxicity : 1.91 % (as actual dose) or 2 % (in the diet)
LOAEL:
0.92 % (actual dose) or 1.0 % (in the diet)Results:
The most sensitive criteria of sulphite damage in the present studies turned out to be
the presence of occult blood in the faeces and changes in gastric morphology. At 0.5% of this chemical, neither these nor any of the other criteria were affected. Taking
the loss of sulphite into account, the NOAEL was 0.44 % Na2S2O5 whichcorresponds to an intake of 217 mg Na2S2O5 /kg b.w./day.
Method:Other (multigeneration study)
GLP:
Yes [ ]; No [x]; ? [ ]Test substance:source : Amsterdamsche Chinine Fabriek, purity : 95-99 % (as calculated from SO2
determination)
Remark:The actual doses were 0, 0.098, 0.215, 0.44, 0.92, 1.91 % (sulphit loss occurred)
Reference:
Til, H.P., V.J. Feron, A.P. De Groot. The toxicity of sulfite. I. Long-term feeding andmultigeneration studies in rats. Fd. Cosmet. Toxicol. 10, 291-310, 1972(b)Species/strains:
Sex:
Route of administration:
Exposure period:

Rat / Wistar
Female [ ]; Male [ ]; Male/Female [x]; No data [ ]Feeding (p.o)
8 or 12 weeks

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OECD SIDSDISODIUM DISULPHITE

Frequency of treatment: Daily
Post exposure observation period:
Dose:
4, 6 % in feed
Control group:
Yes [x]; No [ ]; No data [ ]Concurrent no treatment [x]; Concurrent vehicle [ ]; Historical [ ]
NOEL:
LOEL:
Results:
Feeding sulfite induce hyperplastic fundic glands and dilated glands.
Method:Subchronic study
GLP:
Yes [ ]; No [ ]; ? [x]Test substance:
Remark:The animals were fed on thiamine-supplemented feed, which was mixed with 4 or 6
% test substance
Reference:
Beems, R.B., B.J. Spit, H.B.W.M. Koeter, V.J. Feron. Nature and Histogenesis ofsulfite-induced gastric lesions in rats. Exp. Mol. Pathol. 36 (3), 316-25, 1982(c)Species/strains:
RabbitSex:
Female [ ]; Male [x]; Male/Female [ ]; No data [ ]Route of administration: i.v.
Exposure period:
3 weeks
Frequency of treatment: 3 times/day and 5 d/weeks
Post exposure observation period:
Dose:
10, 20, 40 mg/kg
Control group:
Yes [x]; No [ ]; No data [ ]Concurrent no treatment [x]; Concurrent vehicle [ ]; Historical [ ]NOEL:> 40 mg/kg in feed
LOEL:
Results:
The test was performed using 3 animals/dose (2 animals in control). During theexperimental period (21 days), no dead animals were observed. Neither
macroscopic nor microscopic changes were observed in the heart, lung, liver, spleen
and kidney. Intravenous injection caused the formation of 2-3 cm long thrombus.
The addition of 6 % parenamin (protein hydrolysate) could hinder this thrombus
formation.
Method:GLP:
Yes [ ]; No [x]; ? [ ]Test substance:
Remark:Reference:
Hoppe, J. O., F. C. Goble. The intravenous toxicity of sodium bisulfite. J.
Pharmacol. Exp. Therap. 101, 101-6, 1951(d)Species/strains:
Pig / other: Hollaendische Landrasse
Sex:
Female [ ]; Male [ ]; Male/Female [x]; No data [ ]Route of administration: Oral feed
Exposure period:
15-19 or 48-51 weeks
Frequency of treatment: Daily
Post exposure observation period:
Dose:
0.06, 0.16, 0.35, 0.83, 1.72 % in feed
Control group:
Yes [x]; No [ ]; No data [ ]Concurrent no treatment [x]; Concurrent vehicle [ ]; Historical [ ]NOEL:
0.35 % in feed
LOEL:
Results:
Method:The testing was performed using 20 each of male and female animals for dosegroups. The animals were given thiamine-supplemented feed. At 1.72 % dose, thefeed intake and body weight were reduced. The mortality was not affected. The
thiamine content in urine and liver was reduced dose-dependently and it was lower
than control animals at 1.72-% dose. In another study 15 each of male and female
animals with 1.72 % sodium metasulfite (paired feeding study), no effect on feedintake and weight gain was observed. Hematological examination showed nochange in comparison with control. Besides these, no indication of blood in feces
was observed. Each 14 animals of male and female were sacrificed after 15-19

42

UNEP PUBLICATIONSOECD SIDS

GLP:
Test substance:
Remark:Reference:

DISODIUM DISULPHITE
weeks and the remaining animals were sacrificed after 48-51 weeks. Relative organ
weight was increased in heart, kidney and spleen at 0.83 % and 1.72 % doses and inliver at 1.72 % dose. Alteration of stomach and darkening of cecum were formed at
0.83 % and 1.72 % doses. At three doses, hyperplastic in stomach mucosa wasobserved. Epithelial hyperplasia and neutrophilic leucocyte in the gullet was also
observed. In the mucosa of blind gut at 0.83 and 1.72 % dosing, pigmented
macrophage often appeared. In the highest dose, lipid-containing Kupffer’s cells
were frequently observed in the liver.
Yes [ ]; No [x]; ? [ ]source : Amsterdamsche Chinine Fabriek, purity : 95-99 %Til, H.P., V.J. Feron, A.P. De Groot. The toxicity of sulfite. II. Short and long-term
feeding studies in pigs. Fd. Cosmet. Toxicol. 10, 463-472, 1972

5. 5

GENETIC TOXICITY IN VITROA.

BACTERIAL TEST(a) Preferred Result
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:
Precipitation conc:
Genotoxic effects:

Method:GLP:Test substance:
Remarks:
Reference:
(b)
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:
Precipitation conc:
Genotoxic effects:

Method:GLP:Test substance:
Remarks:
Reference:

Bacterial reverse mutation assay
Salmonella typhimurium TA98, TA100, 1537 & 1538
20 - 5000 µg /plateWith [ ]; Without [ ]; With and Without [x]; No data [ ]With metabolic activation : not observed
Without metabolic activation : not observed+ ? With metabolic activation :[ ] [ ] [x]Without metabolic activation : [ ] [ ] [x]OECD TG 471 (1983)
Yes [ ]; No [x]; ? [ ]Source : BASF Aktiengesellschaft Purity : 98 %Standard Plate Test; Preincubations test
BASF AG, Dept. Toxicology, unpublished result (89/380), 09.October.1989

Bacterial reverse mutation assay
Salmonella typhimurium TA98, TA100, 1535, 1537 & 1538
Escherichia coli WP 2 (uvrA)
0.3 – 10000.0 µg/plateWith [ ]; Without [ ]; With and Without [x]; No data [ ]With metabolic activation : 333.3 µg/plate
Without metabolic activation : 10000 µg/plate+ ? With metabolic activation :[ ] [ ] [x]Without metabolic activation : [ ] [ ] [x]Other
Yes [ ]; No [ ]; ? [x]Source : Baker Chemical Co., Phillipsburg
1. National Technical Information Service U.S. Department of Commerce (NTIS),
Microbial Mutagenesis Testing of Substances : Compound Report F76-004 Sodium
Meta-Bisulfite, PB 89-193684 (1978)

UNEP PUBLICATIONS

43OECD SIDSDISODIUM DISULPHITE
2. Prival, M.J., Simmon,V.F. , Mortelmans, K.E. Bacterial mutagenicity testing of
49 food ingredients gives very few positive results. Mutat. Res. 260 (4), 321-329,
1991

(c)
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:
Precipitation conc:
Genotoxic effects:

Method:GLP:Test substance:
Remarks:
Reference:

(d)
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:
Precipitation conc:
Genotoxic effects:

Method:GLP:Test substance:
Remarks:
Reference:

(e)
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:
Precipitation conc:
Genotoxic effects:

Method:GLP:Test substance:
Remarks:
Reference:

44

Bacterial reverse mutation as say
Salmonella typhimurium TA1530
Not specified
With [ ]; Without [x]; With and Without [ ]; No data [ ]With metabolic activation : mg/plate
Without metabolic activation : no data+ ?
With metabolic activation :[ ] [ ] [ ]Without metabolic activation : [ ] [ ] [x]Other(Ames1975)
Yes [ ]; No [ ]; ? [x]-Green, S., J. Present and future uses of mutagenicity tests for assessment of thesafety of food additives. Environ. Pathol. Toxicol., 1, 49-54, 1977

Bacterial reverse mutation assay
Salmonella typhimurium TA 92, 94, 98, 100, 1535 &1537
maximum dose 50 mg/plateWith [ ]; Without [ ]; With and Without [x]; No data [ ]With metabolic activation : not observed
Without metabolic activation : not observed+ ? With metabolic activation :[ ] [ ] [x]Without metabolic activation : [ ] [ ] [x]Other (Ames 1975)
Yes [ ]; No [ ]; ? [x]Provided by Japan Food Additive Association, Purity : 95 %Ishidate, M., T. Sofuni, K. Yoshikawa, M. Hayashi, T. Nohmi, M. Sawada, A.
Mastuoka. Primary mutagenicity screening of food additives currently used inJapan. Fd. Chem. Toxic. 22, 623-636, 1984

Bacterial reverse mutation assay
Salmonella typhimurium TA 1530
no details
With [ ]; Without [ ]; With and Without [ ]; No data [x]Positive
With metabolic activation :mg/plate
Without metabolic activation :mg/plate+ ? With metabolic activation :[ ] [ ] [ ]Without metabolic activation : [ ] [ ] [ ]Yes [ ];No [ ]; ? [x]disodium disulphite
The article is not to explain, by which system was found the positive reaction.
Maxwell, W. A. and Newell, G. W. Mol. Environ. Aspects Mutagenesis, Proc. Publ.
Rochester Int. Conf. Environ. Toxic. 6th , 223-252,1973

UNEP PUBLICATIONSOECD SIDS
(f)
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:
Precipitation conc:
Genotoxic effects:

Method:GLP:Test substance:
Remarks:
Reference:

(g)
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:
Precipitation conc:
Genotoxic effects:

Method:GLP:Test substance:
Remarks:
Reference:

(h)
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:
Precipitation conc:
Genotoxic effects:

Method:GLP:Test substance:
Remarks:
Reference:

(i)
Type:
System of testing:

DISODIUM DISULPHITE
Bacterial reverse mutation assay
Salmonella typhimurium TA 97
With [ ]; Without [x]; With and Without [ ]; No data [ ]With metabolic activation :mg/plate
Without metabolic activation : no data
+ ? With metabolic activation :[ ] [ ] [ ]Without metabolic activation : [x] [ ] [ ]Yes [ ]; No [ ]; ? [x]The study indicates that the mutagenic action of sodium metabisulfite depends on
incubation conditions (temperature, pH, content of mannitol, ethanol etc.)
Pagano, D., A. E. Zeiger, A. Stack. Autoxidation and mutagenicity of sodium
bisulfite. Mutation Res. 228, 89-96, 1990

Bacterial reverse mutation assay
Escherichia coli AP 16, AP 18
With [ ]; Without [x]; With and Without [ ]; No data [ ]With metabolic activation :Without metabolic activation :mg/plateno data+ ? With metabolic activation :[ ] [ ] [ ]Without metabolic activation : [x] [ ] [ ]Yes [ ]; No [x ]; ? [ ]Pekhov, A.P, V.N. Reshetnikova. Test strains of E. coli for the detection of chemicalmutagens. Bull. Exp. Biol. Med. (USSR) 84, 1043-5, 1977

Bacterial reverse mutation assay
Salmonella typhimurium G 46, C 207, 3076, TA 98, 100, 1535, 1537
With [ ]; Without [ ]; With and Without [x ]; No data [ ]With metabolic activation : no data
Without metabolic activation : no data
+ ? With metabolic activation :[x] [ ] [ ]Without metabolic activation : [ ] [ ] [x]Yes [ ]; No [x ]; ? [ ]Source : E.Merck, Darmstadt
Spot test
Subba Rao, V. and A.S .Aiyar. Mutagenicity evaluation studies with food additives
and radiolytic products of sugars. Proc. Symp. Mutagen. Carcinogen Teratogen
Chem. 88, 104-14, 1975

Bacterial reverse mutation assay
Salmonella typhimurium G 46 : TA 92, 1535, 100, SB 2802, 2061(his G46)
TR 3243 : TA88, 110, 90, 97(his D6610)

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OECD SIDS

Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:
Precipitation conc:
Genotoxic effects:

Method:GLP:Test substance:
Remarks:

Reference:

(j)
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:
Precipitation conc:
Genotoxic effects:

Method:GLP:Test substance:
Remarks:
Reference:

(k)
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:
Precipitation conc:
Genotoxic effects:

Method:GLP:Test substance:
Remarks:
Reference:

46

DISODIUM DISULPHITE
D 3052 : TA 1538, 98(his D3052)
C3076 : TA1537, 1977(his C3076)
0.01-0.64 M/plateWith [ ]; Without [x]; With and Without [ ]; No data [ ]With metabolic activation : mg/plate
Without metabolic activation : 0. 32 M
+ ? With metabolic activation :[ ] [ ] [ ]Without metabolic activation : [x] [ ] [ ]Yes [ ]; No [ ]; ? [x]Source : Sigma Chemical Co.
Sodium metabisulfite showed a weak m utagenicity in the above system. Thesesystems are characterized by mutation in his G46 or D6610. No mutagenicity wasobserved in other systems.
Pagano, D. G. and E. Zeiger. Condition affecting the mutagenicity of sodium
bisulfite in S. typhimurium . Mutation Res. 179, 159-66, 1987

Bacterial reverse mutation assay
Salmonella typhimurium G 46 : TA 92, 1950, 2410, GW 19, TS 24
0, 0.1, 0.5, 1.0, 1.5, 2.0 M
With [ ]; Without [x]; With and Without [ ]; No data [ ]With metabolic activation :mg/plate
Without metabolic activation : not specified+ ? With metabolic activation :[ ] [ ] [ ]Without metabolic activation : [x] [ ] [ ]Yes [ ]; No [ ]; ? [x]source : Fisher Scientific Co. mixture of disodium disulphite and sodium
metabisulfite
De Giovanni-Donnelly, R. The mutagenicity of sodium busulfite on basedsubstitution strains of S. typhimurium. Teratogen. Carcinogen. Mutagen. 5, 195-203,
1985

Host mediated assay
Salmonella typhimurium G 46, TA 1530/ Mouse
5 %(w/v)
With [ ]; Without [ ]; With and Without [ ]; No data [ ]With metabolic activation :Without metabolic activation :mg/plate
mg/plate+ ? With metabolic activation :[ ] [ ] [x]Without metabolic activation : [ ] [ ] [ ]Yes [ ]; No [ ]; ? [x]

1. National Technical Information Service U.S. Department of Commerce (NTIS),
Study of the Mutagenic Effect of Sodium Meta- Bisulfite (71-22), PB -221 825(1972)
2. Maxwell, W. A. and G. W. Newell. Mol. Environ. Aspects Mutagenesis, Proc.
Publ. Rochester Int. Conf. Environ. Toxic. 6th (1973), 223-252 ,1974

UNEP PUBLICATIONSOECD SIDSB.

DISODIUM DISULPHITE

NON -BACTERIAL TEST(a) Preferred Results
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:

Cytogenetic assay
CHL-cellup to 0.125
mg/mL
With [ ]; Without [x]; With and Without [ ]; No dat a [ ]With metabolic activation :mg/plate
Without metabolic activation : not observed

Precipitation conc:
Genotoxic effects:
With metabolic activation :Without metabolic activation :Method:GLP:Test substance:
Remarks:
Reference:

(b)
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:

Yes [ ]; No [ ]; ? [x]Source : Japan Food Additive Association, Purity : 95 %Ishidate, M., T. Sofuni, K. Yoshikawa, M. Hayashi, T. Nohmi, M. Sawada, A.
Mastuoka. Primary mutagenicity screening of food additives currently used inJapan, Fd. Chem. Toxic. 22, 623-636, 1984

Cytogenetic assay
Embryonic lung cell WI-38
2.5, 25, 250 µg/mL
With [ ]; Without [x]; With and Without [ ]; No data [ ]With metabolic activation :Without metabolic activation :mg/plate
mg/plate

With metabolic activation :Without metabolic activation :+ ? [ ] [ ] [ ][x] [ ] [ ]Precipitation conc:
Genotoxic effects:

Method:GLP:Test substance:
Remarks:
Reference:

(c)
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:+ ? [ ] [ ] [ ][ ] [ ] [x]Yes [ ]; No [ ]; ? [x]Test substance indicates the inhibition of cell division and remarkabledamage (aberration) in anaphase cells.
1. National Technical Information Service U.S. Department of Commerce (NTIS),
Study of the Mutagenic Effect of Sodium Meta- Bisulfite (71-22), PB -221 825(1972)
2. Maxwell, W. A. and G. W. Newell. Mol. Environ. Aspects Mutagenesis, Proc.
Publ. Rochester Int. Conf. Environ. Toxic. 6th (1973), 223-252 (1974)

Cytogenetic assay
Human embryonic lung cell WI-38
mg/plate
With [ ]; Without [x]; With and Without [ ]; No data [ ]With metabolic activation :Without metabolic activation :mg/plate
mg/plate

Precipitation conc:
Genotoxic effects:
With metabolic activation :Without metabolic activation :Method:GLP:Test substance:
Remarks:+ ? [ ] [ ] [ ][x] [ ] [ ]Yes [ ]; No [ ]; ? [x]The result showed non-correlation with other testing systems. No detailed
experimental information.

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47

OECD SIDS
Reference:

DISODIUM DISULPHITE
Green, S., J. Present and future uses of mutagenicity tests for assessment of thesafety of food additives. Environ. Pathol. Toxicol. 1, 49-54, 1977

(d)
Type:
Recombination assay
System of testing:
Saccharomyces cerevisiae D 3
Concentration:
mg/plate
Metabolic activation:
With [ ]; Without [x]; With and Without [ ]; No data [ ]Results:
Negative
Cytotoxicity conc:
With metabolic activation :mg/plate
Without metabolic activation : mg/plate
Precipitation conc:
Genotoxic effects:+ ? With met abolic activation :[ ] [ ] [ ]Without metabolic activation : [ ] [ ] [x]Method:GLP:
Yes [ ]; No [ ]; ? [x]Test substance:
Remarks:
Reference:
Green, S., J. Present and future uses of mutagenicity tests forassessment of the safety of food additives. Environ. Pathol. Toxicol. 1, 49-54,
1977
(e)
Type:
System of testing:Concentration:
Metabolic activation:
Results:
Cytotoxicity conc:

Recombination assay
Saccharomyces cerevisiae D 3
0.1 %(w/v)
With [ ]; Without [ ]; With and Without [ ]; No data [ ]Negative
With metabolic activation :mg/plate
Without metabolic activation :mg/plate

Precipitation conc:
Genotoxic effects:
With metabolic activation :Without metabolic activation :Method:GLP:Test substance:
Remarks:
Reference:

5. 6

Yes [ ]; No [ ]; ? [x]Provided by FDA U.S, no detail information
1. National Technical Information Service U.S. Department of Commerce (NTIS),
Study of the Mutagenic Effect of Sodium Meta- Bisulfite (71-22), PB -221 825(1972)
2. Maxwell, W. A. and G. W. Newell. Mol. Environ. Aspects Mutagenesis, Proc.
Publ. Rochester Int. Conf. Environ. Toxic. 6th (1973), 223-252 (1974)

GENETIC TOXICITY IN VIVO(a) Preferred Result
Type:
Species/Strains:
Sex:
Route of Administration:
Exposure period:
Doses:
Results:
Method:GLP:Test substance:
Remarks:
Reference:48+ ? [ ] [ ] [ ][ ] [ ] [ ]Cytogenetic assay
Rat/Albino
Female [ ]; Male [x]; Male/Female [ ]; No data [ ]OralMax. 5 days
0, 30, 700, 1200 mg/kg
Negativechromosome aberration test
Yes [ ]; No [ ]; ? [x]Provided by FDA US, no detail information
No adverse effect on bone marrow cells.
1. National Technical Information Service U.S. Department of Commerce (NTIS),
Study of the Mutagenic Effect of Sodium Meta- Bisulfite (71-22), PB -221 825(1972)UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE
2. Maxwell, W. A. and G. W. Newell. Mol. Environ. Aspects Mutagenesis, Proc.
Publ. Rochester Int. Conf. Environ. Toxic. 6th (1973), 223-252 (1974)

(b)
Type:
Species/Strains:
Sex:
Route of Administration:
Exposure period:
Doses:
Results:
Method:GLP:Test substance:
Remarks:

Reference:

Cytogenetic assay
Chinese Hamster, Mouse
Female [ ]; Male [ ]; Male/Female [x]; No data [ ]Gavage2 times applications
Equivalent to 660 mg/ kg (normal animal), 330 mg/kg (deficient animal) SO2
Negative
Other
Yes [ ]; No [ ]; ? [x]Disodium disulphite
The study was performed using sulfite-oxidase deficient and normal animals.
Sulfite-oxidase deficiency was obtained by molybdenum -deficient diet and tungsten
supply. As a protein control, animals treated with cyclophosphamid were used.
Renner, H. W. and J .Wever. Attempts to induce cytogenetic effects with sulphite insulphite oxidase-deficient Chinese Hamsters and mice. Food Chem. Toxicol. 21,
123-7,1983

(c)
Type:
Rodent dominant lethal assay
Species/Strains:
Rat/Sprague-Dawley
Sex:
Female [ ]; Male [x]; Male/Female [ ]; No data [ ]Route of Administration: Oral feed
Exposure period:
10 weeks
Doses:
0,125, 417, 1250 mg/kg daily
Results:
Negative
Method:The positive control was triethylenemelamine given in the drinking water at a doseof 0.6 mg/L. The diet was supplemented with 50 mg/kg in corn oil. The controls (+and-) were fed a diet with the corn oil alone. After the 10 wk treatment, 40 male rats
from the vehicle control group and 20 from each TS and positive control group wereindividually housed and paired with 2 virgin females for 7 days. Each female wassacrificed 15-19 d after the 1st d of cohabitation. To investigate the dominant lethal
effect the following were investigated : total implants, total dead implants, total live
implants, preimplantation loss. Total corpora lutea were also recorded.
GLP:
Yes [ ]; No [ ]; ? [x]Test substance:source : J.T. Baker Chemical Co.
Remarks:
Reference:
National Technical Information Service U.S. Department of Commerce (NTIS),
Study of the Mutagenic Effect of Sodium Meta-Bisulfite (76-73) by DominantLethal Test in Rats, PB -299 836 (1979)
(d)
Type:
Species/Strains:
Sex:
Route of Administration:
Exposure period:
Doses:
Results:
Method:GLP:Test substance:
Remarks:
Reference:

Dominant lethal assay
Rat
Female [ ]; Male [x]; Male/Female [ ]; No data [ ]Oralsingle dose30, 700, 1200 mg/kg (single dose)
Negativeother
Yes [ ]; No [ ]; ? [x]Disodium disulphite
No adverse effect
1. National Technical Information Service U.S. Department of Commerce (NTIS),
Study of the Mutagenic Effect of Sodium Meta- Bisulfite (71-22), PB -221 825(1972)
2. Maxwell, W. A. and G. W. Newell. Mol. Environ. Aspects Mutagenesis, Proc.
Publ. Rochester Int. Conf. Environ. Toxic. 6th (1973), 223-252 (1974)

UNEP PUBLICATIONS

49

OECD SIDS
(e)
Type:
Species/Strains:
Sex:
Route of Administration:
Exposure period:
Doses:
Results:
Method:GLP:Test substance:
Remarks:

Reference:

(f)
Type:
Species/Strains:
Sex:
Route of Administration
Exposure period:
Doses:
Results:
Method:GLP:Test substance:
Remarks:

Reference:

5. 7

DISODIUM DISULPHITE
Micronucleus assay
Hamster, Mouse
Female [ ]; Male [ ]; Male/Female [x]; No data [ ]Gavageflushing out of bone marrow cell 30 and 6 hour after 2 times application
Equivalent to 660 mg/kg (normal animal), 330 mg/kg (deficient animal) SO2
Negative
Other (Schimd 1973)
Yes [ ]; No [ ]; ? [x]Disodium disulphite
The study was undertaken using sulfite-oxidized deficient and normal animals.
Sulfite-oxidase deficiency was obtained by molybdenum -deficient diet and tungsten
supply. As a protein control, animals treated with cyclophosphamid were used.
Renner, H. W. and J .Wever. Attempts to induce cytogenetic effects with sulphite insulphite oxidase-deficient Chinese Hamsters and mice. Food Chem. Toxicol. 21,
123-7 ,1983

Sister chromatid exchange assay
Hamster, Mouse
Female [ ]; Male [ ]; Male/Female [x]; No data [ ]s.c.
animals killed 30 and 6 hour after 2 equal dose
Equivalent to 50 mg/kg, 660 mg/kg (normal animal), 165 mg SO2/kg (enzyme
deficient animal) calculated as SO2
Negative
other (Schwarzacher & Wolf, 1974)
Yes [ ]; No [ ]; ? [x]Disodium disulphite
The study was undertaken using sulfite-oxidase deficient and normal animals.
Sulfite-oxidase deficiency was obtained by molybdenum -deficient diet and tungsten
supply. As a protein control, animals treated with cyclophosphamid were used.
Renner, H. W. and J. Wever. Attempts to induce cytogenetic effects with sulphite insulphite oxidase-deficient Chinese Hamsters and mice. Food Chem. Toxicol. 21,
123-7,1983

CARCINOGENECITY(a) Preferred Result
Species/Strains:
Rat / Wistar
Sex:
Female [ ]; Male [ ]; Male/Female [x]; No data [ ]Route of Administration: p.o.
Exposure period:
104 weeks
Frequency of treatment:
Postexposure observation period:
Doses:
0; 0.125; 0.25; 0.5; 1; 2 % in dietControl group:
Yes [x]; No [ ]; No data [ ];Concurrent no treatment [x]; Concurrent vehicle [ ]; Historical [ ]Results:
Negative
Method:GLP:
Yes [ ]; No [x]; ? [ ]Test substance:source : Amsterdamsche Chinine Fabriek, purity : 95-99 %Remarks:
multiple generation study referred 5.4, 5.8
Regarding neoplatic findings, the number of lymphoreticular pulmonary tumors inmales decreased with increasing levels of sulphite. The incidence of thyroid andpituitary tumors in control males was exceptionally low, whereas those noted in thevarious test groups represented numbers normally found in the strain of rats used.
All other neoplasms occurred in a random manner.
Reference:
Til, H.P., V.J. Feron, A.P. De Groot. The toxicity of sulfite. I. Long-term
feeding and multigeneration studies in rats. Fd. Cosmet. Toxicol. 10, 291-310, 1972

50

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITEb)
Species/Strains:
Rat
Sex:
Female [ ]; Male [ ]; Male/Female [ ]; No data [x]Route of Administration: Drinking water
Exposure period:
about 3 years
Frequency of treatment:
Daily
Postexposure observation period:
Doses:
Equivalent to 350, 750 ppm as SO2
Control group:
Yes [x]; No [ ] ; No data [ ];Concurrent no treatment [x]; Concurrent vehicle [ ]; Historical [ ]Results:
The study was undertaken for 2.5 years and 3 generations per dose group wereused 13-19 animals. Effect of feed and water intake on the feces excretion,
reproduction, lactation or incidence of tumor was not observed (NOEL > 750
ppm).
Method:3 generation study
GLP:
Yes [ ]; No [ ]; ? [x]Test substance:
Disodium disulphite
Remarks:
Reference:
Lockett, M. F. and I. L. Natoff. A study of toxicity of sulphite. J. Pharm. Pharmacol.
12, 488-96 (1960), cited in: Toxicological Evaluation of Certain Food Additives andContaminants, WHO Food Additives Series 21, 30th Meeting of the Joint
FAO/WHO Expert Committee on Food Additives,1986

5. 8

TOXICITY TO REPRODUCTION(a) Preferred Result
Type:
Fertility [ ]; One generation study [ ]; Two generation study [x]; Other [ ]Species/Strains:
Rat / Wistar
Sex:
Female [ ]; Male [ ]; Male/Female [x]; No data [ ]Route of Administration: Oral feed
Exposure period:
104 weeks (F0, F1-generation), 30 weeks (F2-generation)
Frequency of treatment:
Once a day
Postexposure observation period:
Premating exposure period: Male: 21 weeks Female: 21 weeks
Duration of test:
until the weaning of the F3 animals
Doses:
0.125, 0.25, 0.5, 1.0, 2.0 % in feed
Control group:
Yes [x]; No [ ]; No data [ ];Concurrent no treatment [x]; Concurrent vehicle [ ]; Historical [ ]NOAEL parental := 1.91 % (actual dose), 2 % (in the diet)
NOAEL F1 Offspring:= 1.91 % (actual dose), 2 % (in the diet)
NOAEL F2 Offspring:= 1.91 % (actual dose), 2 % (in the diet)Results:
No pronounced effects were observed on reproductive performance in any
generation and no effects on gonads were seen histologically
Method:continuous breeding
GLP:
Yes [ ]; No [ ]; ? [x]Test substance:source : Amsterdamsche Chinine Fabriek, Holland, purity : 95-99 %Remarks:
Reference:
Til, H.P., V.J. Feron, A.P. De Groot. The toxicity of sulfite. I. Long-term feeding andmultigeneration studies in rats. Fd. Cosmet. Toxicol. 10, 291-310, 1972
(b)
Type:
Fertility [x]; One generation study [ ]; Two generation study [ ]; Other [x]Species/Strains:
Rat
Sex:
Female [ ]; Male [ ]; Male/Female [ ]; No data [x]Route of Administration: Drinking water
Exposure period:
Lifetime
Frequency of treatment:
Daily
Postexposure observation period:
Premating exposure period: Male:
Female:Duration of test:
Doses:
Equivalent to 350, 750 ppm SO2
Control group:
Yes [x]; No [ ]; No data [ ];UNEP PUBLICATIONS

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OECD SIDSDISODIUM DISULPHITE

Concurrent no treatment [x]; Concurrent vehicle [ ]; Historical [ ]NOEL parental := 750 ppm
NOEL F1 Offspring:= 750 ppm
NOEL F2 Offspring:= 750 ppm
Results:
The study was undertaken for 2.5 years and 3 generations. Per dose group 13-19
animals were used. Effect of feed and water intake on the feces excretion,
reproduction, lactation or incidence of tumor were not observed. Detailed
description was not given (NOEL > 750 ppm).
Method:GLP:
Yes [ ]; No [ ]; ? [x]Test substance:
Disodium disulphite
Remarks:
Reference:
Lockett, M. F. and I. L. Natoff. A study of toxicity of sulphite. J. Pharm. Pharmacol.
12, 488-96 (1960), cited in: Toxicological Evaluation of Certain Food Additives andContaminants, WHO Food Additives Series 21, 30th Meeting of the Joint
FAO/WHO Expert Committee on Food Additives, 1986

5. 9

DEVELOPMENTAL TOXICITY/TERATOGENICITY(a) Preferred Result
Species/strain:
Sex:
Route of administration:
Duration of the test:
Exposure period:
Frequency of treatment:
Doses:
Control group:

Rat / Wistar
Female [x]; male [ ]; Male/Female [ ]; No data [ ]Gavageday 20 of gestation
day of 6-15 of gestation
Daily
0, 1, 5, 24, 110 mg/kg bw
Yes [x]; No [ ]; No data [ ];Concurrent no treatment [x]; Concurrent vehicle [ ]; Historical [ ]NOAEL Maternal Toxicity :110 mg/kg bw/day
NOAEL Teratogenicity : 110 mg/kg bw/day
Results:
Test substance did not cause any effect in implantation or survival rate in maternal
and fetus. In comparison with control, no significant change was observed in thenumber of anomaly in soft and skeletal tissues.
GLP:
Yes [ ]; No [ ]; ?[x]Test substance:
disodium disulphite (FDA 71-22)
Remarks:
Reference:
National Technical Information Service U.S. Department of Commerce (NTIS),
Teratologic Evaluation of FDA 71-22 (Sodium Meta-Bisulfite), PB-221 795 (1972)(b)Species/strain:
Rabbit/Dutch
Sex:
Female [x]; male [ ]; Male/Female [ ]; No data [ ]Route of administration:
GavageDuration of the test:day 29 of gestation
Exposure period:
6th –18th pregnated days
Frequency of treatment:
Daily
Doses:
0, 1.23, 5.71, 26.5, 123 mg/kg bw
Control group:
Yes [x]; No [ ]; No data [ ];Concurrent no treatment [ ]; Concurrent vehicle [x]; Historical [ ]NOAEL Maternal Toxicity:= 123 mg/kg bw/day
NOAEL Teratogenicity: = 123 mg/kg bw/day
Results:
No clear effect on nidation, or on maternal or fetal survival. In comparison with
control, no change was observed in the number of anomaly in soft and skeletal
tissues.
GLP:
Yes [ ]; No [ ]; ?[x]Test substance:
Disodium disulphite (FDA 71-22)
Remarks:
Reference:
National Technical Information Service U.S. Department of Commerce (NTIS),
Teratologic Evaluation of Compound FDA 71-22. Sodium Meta-Bisulfite in Rabbit,
PB-267 194 (1974)

52

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE(c)
Species/strain:
Sex:
Route of administration:
Duration of the test:
Exposure period:
Frequency of treatment:
Doses:
Control group:

Hamster
Female [x]; male [ ]; Male/Female [ ]; No data [ ]Gavageno details
6th –10th pregnated days
Daily
0, 1, 6, 26, 120 mg/kg
Yes [ ]; No [ ]; No data [ ];Concurrent no treatment [ ]; Concurrent vehicle [x]; Historical [ ]NOEL Maternal Toxicity: 120 mg/kg bw/day
NOEL Teratogenicity:
120 mg/kg bw/day
Results:
Test substance did not cause any effect in implantation or survival rate in maternal
and fetus. In comparison with control, no change was observed in the number ofanomaly in soft and skeletal tissues.
GLP:
Yes [ ]; No [ ]; ?[x]Test substance:
Disodium disulphite
Remarks:
Reference:
National Technical Information Service U.S. Department of Commerce (NTIS),
Teratologic Evaluation of Compound FDA 71-22. Sodium Meta-Bisulfite in Rabbit,
PB-267 194 (1974)(d)Species/strain:
Sex:
Route of administration:
Duration of the test:
Exposure period:
Frequency of treatment:
Doses:
Control group:

Rat / Wistar
Female [x]; male [ ]; Male/Female [ ]; No data [ ]Drinking water
3 weeks before mating to 20th pregnated day
Daily4750, 9500 mg/L (25, 50 mM)
Yes [x]; No [ ]; No data [ ];Concurrent no treatment [x]; Concurrent vehicle [ ]; Historical [ ]NOEL Maternal Toxicity:
NOEL Teratogenicity
Results:
Tested with normal and tungsten - treated animals. The tungsten brought about
sulfite-oxidized deficiency. It could not identify any adverse effect induced by
disodium disulphite in reproduction or teratogenicity.
GLP:
Yes [ ]; No [ ]; ?[x]Test substance:
Remarks:
Reference:
Dulak, L., G.Chiang, A.F. Gunnison. A sulphite oxidase-deficient rat model:
Reproductive toxicology of sulphite in the female. Food Chem. Toxicol. 22, 599607, 1984

5. 10

OTHER RELEVANT INFORMATIONA.

Specific toxicities
Type:
Results:

Remarks:
Reference:

B.

Sensory irritation
Sodium metabisulfite aerosol actively evoked sensory irritation to upper respiratory
tract in mice, due to presence of bis ulfite anion formed in slightly alkaline pH of
nasal mucosa.
Alarie, Y., Wakisaka I., Oka S. Sensory irritation by sulfite aerosol. Environ.
Physiol. Biochem. 3 (4), 182-4, 1973.

Toxicodynamics, toxicokinetics
(a)
Type:
Results:
Remarks:

Metabolism
The literature states that a rapid and quantitative elimination of disodium disulphite

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Reference:

(b)
Type:
Results:
Remarks:

Reference:

5. 11

as sulfate was observed in man and dog.
Rost. E., Handbuch der Lebensmittelchemie, Band 1, S.993, Springer- Verlag(1933) cited in : Toxicological Evaluation of Certain Food additives andContaminants, WHO Food Additives Series 21 (1986)

Metabolism
The study describes comparative metabolic examinations of injected sulfite in rats,
rabbits and monkeys for the purpose of estimating the in vivo function of sulfite
oxidase. The excretion rate was 1: 0.34: 0.2 in rats, rabbits and monkeys,
respectively. If it is assumed that man clears sulfite similarly to the rhesus monkey,
it would appear that the rat is not a good model for prediction of human toxicity.
Gunnison, A. F. et al., Toxicol. Appl. Pharmacol. 42, 99-109 (1977)

EXPERIENCE WITH HUMAN EXPOSURE
(a)
Type:
Results:

Remarks:
Reference:

(b)
Type:
Results:
Remarks:

Reference:

(c)
Type:
Results:

Remarks:
Reference:

(d)
Type:
Results:

54

DISODIUM DISULPHITE

Respiratory disease
Four cases of respiratory diseases probably due to the exposure or handling of sulfur
derivates were presented. The responsibility of theses compounds stands on theclinical history, biological cellular tests and for one of them on the evolution under ametabisulfite-free diet and a positive oral provocation test at 5 mg.
Vallon C, J. Sainte-Laudy, M. Nasr. Allergie et exposition professionnelle aux
composes soufres:questions posees. Allerg Immunol (Paris), 27, 83-87, 1995

Asthma6 or 20 presented a positive reaction, confirmed in 4 of 20 by double-blind
challenge.
Oral challenge tests were carried out with sodium metabisulfite solution doses of 5,
10, 25, 50 and 100 mg in 20 children aged 7-14 years with steroid-dependent
brochial asthma.
Sanz J, A. Martorell, I Torro, J.C. Cerda, V Alvarez. Intolerance to sodium
metabisulfite in children with steroid-dependent asthma. J Investig Allergol Clin
Immunol. 2, 36-38, 1992

Life-threatening asthma
Sodium metabisulfite in food and drugs provoked life-threatening asthma. In one
case, a 67-yr-old woman developed severe asthma almost immediately afteringesting a salad with a vinegar based dressing (the vinegar contained sodium
metabisulfite). During oral challenge studies 2 weeks later, she developed severe
bronchospasm within 30 min of ingesting sodium metabisulfite. In another case, a
23- yr-old woman developed rapid deterioration of moderately severe asthma
following administration of an infusion of dexamethasone (24 mg) and an injectionof metaclopromide (metoclopramide) (10 mg); both drugs contained sidium
metabisulfite. Challenge reactions to sodium metabisulfite were positive. Orally
administered dexamethasome which did not contain sodium metabisulfite induced
no bronchospasm. The patient improved significantly during 6 months on a sodium
metabisulfite free diet. It was suggested that the use of sodium metabisulfite as apreservative and anti-oxidant may need re-evaluation.
Baker G.J., P. Collett, D.H. Allen. Bronchospasm induced by metabisulfitecontaining foods and drugs. Med J Aust. 2, 614-617, 1981

Dermal disease
acute urticaria attack.

UNEP PUBLICATIONSOECD SIDS
Remarks:
Reference:

(e)
Type:
Results:
Remarks:
Reference:

(f)
Type:
Results:
Remarks:

Reference:
(g)
Type:
Results:
Remarks:
Reference:

(h)
Type:
Results:
Remarks:
Reference:

(i)
Type:
Results:
Remarks:

Reference:

(j)
Type:
Results:
Remarks:

Reference:
(k)
Type:
Results:

DISODIUM DISULPHITE
Case report of a 47-year-old man with severe acute intermittent urticaria. A placebocontrolled oral challenge test with 50 mg sodium disulfite
Wüthrich B, M.K. Kagi, J. Hafner. Disulfite-induced acute intermittent urticariawith vasculitis, Dermatology. 187, 290-292, 1993

Patch-test
positive
Case report of contact dermatitis and asthma from sodium metabisulfite in aphotographic technician. Patch-test with sodium metabisulfite 5 % pet.
Jacobs M C, R.J.G. Rycroft. Contact dermatitis and asthma from sodium
metabisulfite in a photographic technician. Contact Dermatitis. 33, 65-66, 1992

Patch-test
positive
Case report of a 39-year old man with dermatitis. Patch-test with sodium
metabisulfite 2, 5, and 10 % in water. Control tests at 10 % in 5 subjects were all
negative.
Apetato, M., Marques, M., S., J.; Contact Dermatitis 14, 194, (1986)

Occupational asthma
Two cases of occupational asthma in laundry workers exposed to sodium
metabisulfite have been reported.
Le-Stradic-Reygagne A, in: Sodium metabisulfite, Documentation of threshold limit
values. ACGIH, Cincinnati, 1991

Patch-test
negative
Patch-tests in five patients with ocular hypersensitivity to eyes-drops also among
other compounds.
Petersen P.E, R.B.Evans, M.A.Johnstone, W.R Handerson. Evaluation of ocular
hypersensitivity to dipovalyl epinephrine by component eye-drop testing. J Allergy
Clin Immunol. 85, 954-958, 1990

Patch-test
positive
A thirty-year old male with erythematous vesiculapular skin eruptions with extreme
pruritus on both hands showed positive patch-test reaction to DSD (10, 20, and 50
mg in pet.). Three controls were negative. Single oral provocation test with DS (5,30, 50, and 100 mg in citric acid) gave neither skin nor pulmonary manifestations.
Larame B, P.M. Bedard, J. Hebert. Contact dermatitis to sulfating agents. J Allergy
Clin Immunol. 28, 197, 1989

Patch-test
positive
A 31-year-old woman with psoriasis developed acute allergic contact dermatitis
during topical drug trial. Patch testing with ingredients showed a positive reaction to
DSD (1 and 0.2 % in pet.).
Vestergaard LL., K. E Andersen. Am. J. Contact Dermatitis. 6, 174-175, 1995

Anaphylaxis
A case of metabisulfite induced anaphylaxis is presented in which convincing
evidence of an IgE-mediated mechanism of action was found. The patientdemonstrated urticaria, angioedema, nasal congestion, and apparent nasal polypswelling following provocative challenge with sodium metabisulfite. Skin test to
metabisulfite was positive as was a basophil histamine release test when the

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OECD SIDSDISODIUM DISULPHITE
patient's cells were incubated with metabisulfite. A review of metabisulfite induced
allergic reactions in which an IgE -mediated mechanism demonstrated is presented

Remarks:
Reference:

(l)
Type:
Results:

Remarks:
Reference:

56

Sokol W.N, I.B. Hydick. Nasal congestion, urticaria, and angioedema, caused by
IgE-mediated reaction to sodium metabisulfite. J. Allerg Clin Immunol. 65, 233238, 1990

Bronchospasm
A case is reported of a patient with episodes of bronchospasm requiring hospital
admission after handling disodium disulphite on the job. Skin tests for sodium
metasulfite at a concn 10 mg/mL were negative. A simple blind oral provocation testof sodium metasulfite (1, 5, 20, and 50 mg) in acid medium was positive at the 50mg dose, eliciting bronchial and nasal symptoms, and a decrease in CVF, FEVI, andPEF of more than 20 % over baseline values. The episode of bronchospasm has notrecurred in the workplace since exposure to disodium disulphite was eliminated.
Oral provocation with metasulfite in acid medium is considered as a good techniquefor confirming the diagnosis of these cases.
Valero, A.L., M. Bescos, P. Amat, and A. Malet. Bronchial asthma caused byoccupational sulfite exposure. Allergol. Immunopathol. (Madr). 21(6), 221-4, 1993

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE

6. REFERENCES
Abalaka, J.A., R.H. Deibel. A comparative study of the lethal effect of metabisulphite on the viability of three bacterial
species in bone meal and gelatin. Microbios. 27, 79-88, 1980
Alarie, Y., Wakisaka I., Oka S. Sensory irritation by sulfite aerosol. Environ. Physiol. Biochem. 3 (4), 182-4, 1973
American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values andBiological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH,ACGIH, 1418, 1991
Baker G.J., P. Collett, D.H. Allen. Bronchospasm induced by metabisulfite-containing foods and drugs. Med J Aust. 2,
614-617, 1981
BASF AG, Abt. Toxikologie, unpublished result (80/339), 14.January.1981
BASF AG, Abt. Toxikologie, unpublished result (84/200), 5.November.1984
BASF AG, Abt. Toxikologie, unpublished result (89/380), 09.October.1989
BASF AG, Abt. Toxikologie, unpublished result (23/355), 18.February.1974
BASF AG, Analytisches Labor, unpublished result (BRU 88.221)
BASF AG, Department of ecology, unpublished data, (80/339), 06.January.1981
BASF AG, Department of ecology, unpublished data, (0897/88), 29.July.1988
BASF AG, Department of ecology, unpublished data, (0897/88), 10.May.1989
BASF AG, Department of ecology, unpublished data, (0897/88), 21.July.1989
BASF AG, Department of ecology, unpublished data, (2057/93), 15.December.1993
BASF AG, Department of ecology, unpublished calculation, 18. December. 1998
BASF AG, Labor Oekologie, unpublished result, (0897/88)
BASF AG, Labor Oekologie, unpublished information, 23.June.1987
BASF AG Physical/chemical, unpublished investigation, report BRU 88.221, 02. November. 1988
BASF AG safety data sheet sodium metabisulfite, 06. January. 1999
BASF AG, Sicherheitstechnik, interne Mitteilung, 29.October.1999
BASF AG, Sicherheitsdatenblatt Natrium Disulfit Pulver P mind. 66 % SO2 (7/92)
BASF AG, Sicherheitsdatenblatt Natriumdisulfit, 30.October.2000
Beems, R.B., B.J. Spit, H.B.W.M. Koeter, V.J. Feron. Nature and Histogenesis of sulfite-induced gastric lesions in rats.
Exp. Mol. Pathol. 36 (3), 316-25, 1982
Bhagat, B. M. F. Lockett. J. Pharm. Pharmacol. 12, 690-4 (1960) cited in: Toxicological Evaluation of Certain Food
Additives and Contaminants, WHO Food Additives Series 21, 30th Meeting of the Joint FAO/WHO Expert Committee
on Food Additives,1986
Budavari, S. (ed.), The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ, Merck and Co.,
Inc., p. 1479, 1989
De Giovanni-Donnelly, R. The mutagenicity of sodium bisulfite on based-substitution strains of S. typhimurium .
Teratogen. Carcinogen. Mutagen. 5, 195-203, 1985
Dulak, L., G. Chiang, A.F. Gunnison. A sulphite oxidase-deficient rat model: Reproductive toxicology of sulphite in the

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OECD SIDSDISODIUM DISULPHITE

female. Food Chem. Toxicol. 22, 599-607, 1984
Eastman Kodak Co., U.S. Toxic Substance Control Act Submission, Microfiche No. OTS 0557795, Old Doc
ID:86940000099, 1980
Giffon, E., D. Vervloet, and J. Charpin. Suspicion on sulfites. Rev. Mal. Respir. 6(4), 303-10, 1989
Green, S., J. Present and future uses of mutagenicity tests for assessment of the safety of food additives. Environ.
Pathol. Toxicol. 1, 49-54, 1977
Gunnison, A. F. et al., Food Cosmet. Toxicol. 19, 221-32, 1981
Gunnison, A. F. et al., Toxicol. Appl. Pharmacol. 42, 99-109, 1977
Hoechst AG, Unpublished studies (87.1374), 04.September.1987a
Hoechst AG, Unpublished studies (87.1241), 11.August.1987b
Hoechst AG, Unpublished studies (87.1293), 21.August.1987
Hoppe, J. O., F. C. Goble. The intravenous toxicity of sodium bisulfite. J. Pharmacol. Exp. Therap. 101, 101-6, 1951
Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 33, 1988
International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I & II. Geneva, Switzerland:International Labour Office, p. 1343, 1983
Ishidate, M., T. Sofuni, K. Yoshikawa, M. Hayashi, T. Nohmi, M. Sawada, A. Mastuoka. Primary mutagenicity
screening of food additives currently used in Japan. Fd. Chem. Toxic. 22, 623-636, 1984
Jacobs M C, R.J.G. Rycroft. Contact dermatitis and asthma from sodium metabisulfite in a photographic technician.
Contact Dermatitis. 33, 65-66, 1992
Jaulmes, P. Personal communication (1964), cited in: Toxicological Evaluation of Certain Food Additives andContaminantes, WHO Food Additives Series 21, 30th Meeting of the Joint FAO/WHO Expert Committee on Food
Additives,1986
Larame B, P.M. Bedard, J. Hebert. Contact dermatitis to sulfating agents. J Allergy Clin Immunol. 28, 197, 1989
Le-Stradic-Reygagne A, in: Sodium metabisulfite, Documentation of threshold limit values. ACGIH, Cincinnati, 1991
Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 71st ed. Boca Raton, FL, CRC Press Inc., p. 4-106, 19901991
Lide, D.R. (ed.): CRC Handbook of Chemis try and Physics. 76th ed. Boca Raton, FL, CRC Press Inc., 1995-1996
Lockett, M. F., I. L. Natoff. A study of toxicity of sulphite. J. Pharm. Pharmacol. 12, 488-96 (1960), cited in:
Toxicological Evaluation of Certain Food Additives and Contaminants, WHO Food Additives Series 21, 30th Meetingof the Joint FAO/WHO Expert Committee on Food Additives,1986
Maxwell, W. A. and G. W. Newell. Mol. Environ. Aspects Mutagenesis, Proc. Publ. Rochester Int. Conf. Environ. Toxic.
6th, 223-252,1974
Miltgen. J., C.Marotel, F.Natali, F.Vaylet, P.L'Her. Clinical aspects and diagnosis of sulfite intolerance. Apropos of 9
patients. Service de pneumologie (Pr. P. L'Her), Hopital d'instruction des armees Percy, Clamart
Ministry of Environment(MOE), Korea(1998), Survey on Circulation Volume of Chemicals in Korea
Ministry of Environment (MOE), Korea (2001), The Toxicity of disodium disulphite to Fish (tested by KRICT)
National Technical Information Service U.S. Department of Commerce (NTIS), Study of the Mutagenic Effect of
Sodium Meta-Bisulfite (71-22), PB -221 825, 1972
National Technical Information Service U.S. Department of Commerce (NTIS), Microbial Mutagenesis Testing of

58

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Substances: Compound Report F76-004 Sodium Meta-Bisulfite, PB 89-193684,1978
National Technical Information Service U.S. Department of Commerce (NTIS), Study of the Mutagenic Effect of
Sodium Meta-Bisulfite (76-73) by Dominant Lethal Test in Rats, PB -299 836,1979
National Technical Information Service U.S. Department of Commerce (NTIS), Teratologic Evaluation of Compound
FDA 71-22. Sodium Meta-Bisulfite in Rabbit, PB-267 194,1974
National Technical Information Service U.S. Department of Commerce (NTIS), Teratologic Evaluation of FDA 71-22(Sodium Meta-Bisulfite), PB -221 795,1972
Newell, G.W. and Maxwell, W.A. Mutagenic effects of sodium metabisulfite (71-22); US Nat. Tech. Inform. Serv., Pb
Rep, p.104, 1972
Nikolaev, K., V. Dzhizheva. Acute toxicity of food containing sodium metabisulfite. Vet. Med. Nauki 10, 61-5, 1973
Pagano, D., A. E. Zeiger, A. Stack. Autoxidation and mutagenicity of sodium bisulfite. Mutation Res. 228, 89-96, 1990
Pagano, D. G., E. Zeiger. Condition affecting the mutagenicity of sodium bisulfite in S. typhimurium . Mutation Res.
179, 159-66, 1987
Pekhov, A.P, V.N. Reshetnikova. Test strains of E. coli for the detection of chemical mutagens. Bull. Exp. Biol. Med.
(USSR) 84, 1043-5, 1977
Petersen P.E, R.B. Evans, M.A. Johnstone, W.R Handerson. Evaluation of ocular hypersensitivity to dipovalyl
epinephrine by component eye-drop t esting. J Allergy Clin Immunol. 85, 954-958, 1990
Prival, M.J., V.F. Simmon, K.E. Mortelmans. Bacterial mutagenicity testing of 49 food ingredients gives very few
positive results. Mutat. Res. 260(4), 321-329, 1991
Renner, H. W., J .Wever. Attempts to induce cytogenetic effects with sulphite in sulphite oxidase-deficient Chinese
Hamsters and mice. Food Chem. Toxicol. 21, 123-7,1983
Richardson, M.L. and S. Gangolli. The Dictionary of Substances and their Effects. Royal Society of Chemistry. p. 19,
1995
Richardson, M.L. and S. Gangolli. The Dictionary of Substances and their Effects. Royal Society of Chemistry. p. 107,
1995
Sanz J, A. Martorell, I Torro, J.C. Cerda. V Alvarez. Intolerance to sodium metabisulfite in children with steroiddependent asthma. J Investig Allergol Clin Immunol. 2, 36-38, 1992
Singh, S.N., M.Yumus, N. Singh. Effect of Sodium Metabisulphite on Chlorophyll, Protein and Nitrate Reductase
Activity of Tomato Leaves. Sci. Total Environ. 92, 269-74, 1990
Sokol W.N, I.B. Hydick. Nasal congestion, urticaria, and angioedema, caused by IgE-mediated reaction to sodium
metabisulfite. J. Allerg Clin Immunol. 65, 233-238, 1990
Sorbe, Sicherheitstechnische Kenndaten chemischer Stoffe, p.97, 28. Erg. Lfg. 12/92
Subba Rao, V. and A.S. Aiyar. Mutagenicity evaluation studies with food additives and radiolytic products of sugars.
Proc. Symp. Mutagen. Carcinogen Teratogen Chem. 88, 104-14, 1975
Til, H.P. , V.J. Feron, A.P. De Groot. The toxicity of sulfite. I. Long-term feeding and multigeneration studies in rats. Fd.
Cosmet. Toxicol., 10, 291-310, 1972
Til, H.P. , V.J. Feron, A.P. De Groot. The toxicity of sulfite. II. Short and long-term feeding studies in pigs. Fd. Cosmet.
Toxicol. 10, 463-472, 1972
Toxicological Evaluation of Certain Food Additives and Contaminants, WHO Food Additives Series: 21, the 30th
Meeting of the Joint FAO/WHO Expert Committee on Food Additives, 11 June 1986, Cambridge University Press
Twarog, F.J. and D.Y.M. Leung. J. Am. Med. Assoc. 248, 2030-1, 1982

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Valero, A.L., M. Bescos, P. Amat, A. Malet. Bronchial asthma caused by occupational sulfite exposure. Allergol.
Immunopathol.(Madr). 21(6), 221-4, 1993
Vallon C, J. Sainte-Laudy, M. Nasr. Allergie et exposition professionnelle aux composes soufres:questions posees.
Allerg Immunol (Paris). 27, 83-87, 1995
Wüthrich B, M.K. Kagi, J. Hafner. Disulfite-induced acute intermittent urticaria with vasculitis. Dermatology. 187, 290292, 1993

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ROBUST STUDY SUMMARIESDisodium disulphite (CAS No. 7681-57-4)

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OECD SIDSDISODIUM DISULPHITE

PHYSICAL/CHEMICAL ELEMENTS
1) MELTING POINT
TEST SUBSTANCE
Ÿ Identity : Disodium Disulphite (CAS NO. 7681-57-4)⇒ Remarks : Source : BASF corporation, NR 80/339
Purity : 95 %METHODŸ Method/guideline followed : Not statedŸ GLP : No details
Ÿ Year : 1999
⇒ Remarks

RESULTSŸ Melting point value in ºC: Not statedŸ Decomposition : Yes --- 150ºC
Ÿ Sublimation (yes/no/ambiguous) : Not stated⇒ Remarks : solid temperature 150ºC (decompose to form sulfur dioxide)

CONCLUSIONS
Decomposition starts at 150ºC

DATA QUALITY
Ÿ Reliabilities : Reliable with restrictions.
⇒ Remarks

REFERENCES (Free Text)
BASF AG safety data sheet sodium metadisulfite, 06. January. 1999

OTHER
Ÿ Last changed : September, 2001
Ÿ Order number for sorting⇒ Remarks

62

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE
4) PARTITION COEFFICIENTTEST SUBSTANCE
Ÿ Identity : Disodium Disulphite(CAS NO. 7681-57-4)⇒ Remarks : Source : BASF corporation, NR 80/339
Purity : Natriumpyrosulfit 95 %1-Octano : > 99 %, Merck, Water : demineralizes
METHODŸ Method/guideline followed : Not statedŸ GLP : No details
Ÿ Year : 1998
⇒ Remarks :Test condition was not stated and Test chemical was analyzed by atomic absorption-spectrometric regulation.
RESULTSŸ Log Pow : -3.7
Ÿ Temperature : 25ºC
⇒ Remarks :- Measured result
substance name

Disodium
disulphite

substance content
C(octanol) X 10 -3:C(water) : g/L
g/L
2.58
15.1
6.71
60.3
16.0
30.1

Mean valuebalanced
distribution(Pow)a)Log Pow

1.7E10-4
1.1E10-4
5.3E10-4
2.2E10-4

-3.77
-3.95
-3.27
-3.7 ±0.3a) Pow = C (octanol) / C (water)
C : concentration of the substance in 1-octanol or water

CONCLUSIONSŸ Log Pow : –3.7.
⇒ Remarks
DATA QUALITY
Ÿ Reliabilities : Reliable with restrictions.
⇒ Remarks :REFERENCES (Free Text)
BASF AG Physical/chemical, unpublished investigation, report BRU 88.221, 02. November. 1988.
OTHER
Ÿ Last changed : September, 2001
Ÿ Order number for sorting⇒ Remarks

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OECD SIDSDISODIUM DISULPHITE
5) WATER SOLUBILITYTEST SUBSTANCE
Ÿ Identity : Disodium Disulphite (CAS NO. 7681-57-4)⇒ Remarks
METHODŸ Method/guideline followed : Not statedŸ GLP : No details
Ÿ Year : 1999
⇒ Remarks :RESULTSŸ Value(g/L) at Temperature : 470 g/L at 20ºC
Ÿ Description of solubility : high solubleŸ pH value and concentration at Temperature : Not statedŸ *pKa value at 25ºC : Not stated.
⇒ Remarks :CONCLUSIONSŸ Solubility in water : 470 g/L at 20ºC
⇒ Remarks : This chemical is high soluble in water with 20ºC .
DATA QUALITY
Ÿ Reliabilities : Reliable with restrictions.
⇒ Remarks :REFERENCES (Free Text). BASF AG, Sicherheitsdatenblatt Natriumdisulfit, 30.October. 2000
OTHER
Ÿ Last changed : September. 2001
Ÿ Order number for sorting⇒ Remarks

64

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE
10-1) ACUTE TOXICITY TO FISHTEST SUBSTANCE
Ÿ Identity: Disodium Disulphite (CAS NO. 7681-57-4)⇒ Remarks: Source : disodium disulphite, 98.3 %METHODŸ Method / guideline followed : OECD TG 203
Ÿ Type (test type) : static
Ÿ GLP : YesŸ Year : 2001(study performed)
Ÿ Species / Strain / Supplier : Oryzias latipes (Medaka)Ÿ Analytical monitoring : No
Ÿ Exposure period : 96 hours
Ÿ Statistical methods : Not relevant(limit test)⇒ Remarks– Test fish
·Age : 9 months·Body length : 3.2 ±0.1 cm·Body weight : 0.25 ±0.02 g–

Test condition:
ž Details of test: static
ž Dilution water source: underground water by passing through activated carbon and the membrane filter(1µm)ž Dilution water chemistry : not statedž Stock and test solution and how they are prepared: dilution water was used to prepare the stock solution
ž Concentrations dosing rate, flow -through rate, in what medium : control, 100 mg/L
ž Vehicle/solvent and concentrations : not used
ž Stability of the test chemicals solutions : not statedž Exposure vessel type : 5 L glass aquarium non-sealed (25 x 14 x 25 cm), light/dark=16/8 hr
ž Number of replicates, fish per replicate: no replicates, 7 fish per concentration
ž Water chemistry in test (O2, pH) in the control and one concentration where effects were observed : DO
4.8 - 8.6 ; pH : 6.25 - 7.39

– Test temperature range : 23.9 - 24.5ºC– Methods of calculating mean measured concentration: not relevant (limit test)
RESULTSŸ Nominal concentration (as mg/L) : 100.0
Ÿ Measured concentration (as mg/L) : not statedŸ Unit (results expressed in what unit) : mg/L
Ÿ Statistical results as appropriate : not relevantŸ Element value:
96 hr - LC50 > 100 mg/L
⇒ Remarks- Biological observations :žObservable symptoms of intoxication : All normal- Table showing cumulative mortality: no death was observed
Nominal conc. (mg/L)
0.0
100.0

Number of fish at the
beginning
7
7

24 hr
0
0

UNEP PUBLICATIONS

Cumulative number of dead fish
48 hr
72 hr
96 hr
0
0
0
0
0
0

65

OECD SIDSDISODIUM DISULPHITE

Nominal conc. (mg/L)
0.0
100.0

66

Number of fish at the
beginning
7
7

24 hr
0
0

UNEP PUBLICATIONS

Cumulative number of dead fish
48 hr
72 hr
96 hr
0
0
0
0
0
0

OECD SIDSDISODIUM DISULPHITE

Nominal conc. (mg/L)
0.0
100.0

Number of fish at the
beginning
7
7

24 hr
0
0

UNEP PUBLICATIONS

Cumulative number of dead fish
48 hr
72 hr
96 hr
0
0
0
0
0
0

67

OECD SIDS68

DISODIUM DISULPHITE

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE
10-2) ACUTE TOXICITY TO FISHTEST SUBSTANCE
Ÿ Identity : Disodium Disulphite (CAS NO. 7681-57-4)⇒ Remarks : Source : disodium disulphite, approx. 98 %, (B ASF AG No 80/339)

METHODŸ Method / guideline followed : (other) German Industrial Standard Guideline Number DIN 38412 Group L,
part 1 and part 15
Ÿ Type (test type) : static
Ÿ GLP: NoŸ Year : 1979
Ÿ Species / Strain / Supplier: rainbow trout (Salm o gairdneri), Obtained from Forellenhof fredelsloh 3413 morin
towards 1, FRG.
Ÿ Analytical monitoring : No
Ÿ Exposure period : 96 hours
Ÿ Statistical methods : Probit Analysis⇒ Remarks– Test fish
· Body length : 7.6 cm (avg.)· Body weight : 5.4 g (avg.)·Duration of adaptation : 3 days–

Test condition:
ž Details of test : static
ž Dilution water source : tap waterž Dilution water chemistry : reconstituted freshwater was prepared from demineralized tap water that was
resalted by the addition of 344 mg/L CaSO4.2H 2O, 124 mg/L MgSO 4.7H2O, 70 mg/L NaHCO 3 and 3
mg/L KCl, Oxygen content : > 6 mg/L, pH : 7 - 8
ž Stock and test solution and how they are prepared : not statedž Concentrations dosing rate, flow -through rate, in what medium : 0, 68.1, 100.0, 147.0, 215.0, 316.0 mg/L
were tested
ž Vehicle/solvent and concentrations : not statedž Stability of the test chemicals solutions: not statedž Exposure vessel type : All-glass aquarium non-sealed (30 x 22 x 24 cm)
ž Number of replicates, fish per replicate : 10 fish per concentration
ž Water chemistry in test (O2, pH) in the control and one concentration where effects were observed:
Oxygen content : > 6 mg/L, pH : 7 - 8
pH values during the test
Conc. mg/L
0.0
68.1
100.0
147.0
215.0
316.0

Starting pH
7.6
6.5
6.1
6.0
5.6
5.0

UNEP PUBLICATIONSEnding pH
7.4
7.1
6.8
5.0
4.3
2.7

69

OECD SIDS70

DISODIUM DISULPHITE

Conc. mg/L
0.0
68.1
100.0
147.0
215.0
316.0

Starting DO
8.8
7.7
7.1
6.1
5.9
2.8

Conc. mg/L
0.0
68.1
100.0
147.0
215.0
316.0

Starting pH
7.6
6.5
6.1
6.0
5.6
5.0

UNEP PUBLICATIONSEnding DO
8.5
8.6
8.4
8.9
9.2
9.9

Ending pH
7.4
7.1
6.8
5.0
4.3
2.7

OECD SIDSDISODIUM DISULPHITE

Conc. mg/L
0.0
68.1
100.0
147.0
215.0
316.0

Starting pH
7.6
6.5
6.1
6.0
5.6
5.0

UNEP PUBLICATIONSEnding pH
7.4
7.1
6.8
5.0
4.3
2.7

71

OECD SIDS72

DISODIUM DISULPHITE

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE
11) TOXICITY TO AQUATIC PLANTS (ALGAE)TEST SUBSTANCE
Ÿ Identity : Disodium Disulphite (CAS No. 7681-57-4)⇒ Remarks : Source : disodium disulphite, > 98 %(w/w)

METHODŸ Method : OECD Guideline 201 "Algae, Growth Inhibition Test".
Ÿ Test type : staticŸ Element basis : area under the curveŸ Exposure period : 72 hr, 96 hr
Ÿ GLP : No
Ÿ Year : 1989
Ÿ Species/Strain/Supplier : Scenedesmus subspicatus 86.81 SAG
Ÿ Analytical monitoring : No details
Ÿ Statistical methods : Not stated⇒ Remarks:– Test organism:· Laboratory culture : OECD - medium· Method of cultivation : Not stated· Controls:– Test condition:· Test temperature range : 20 ºC· Growth/test medium chemistry :· Dilution water source :Exposure vessel type : 100 mL-medium in a 250 mL -Erlenmeyer flaks·Water chemistry in test (pH) in at least one replicate of each concentration :pH

Conc.(mg/L)
0.0
7.8
15.6
31.3
62.5
125.0
250.0
500.0

0 hr
8.20
7.50
7.27
6.97
6.60
6.00
5.40
4.38

96 hr
7.90
8.00
7.90
7.70
4.80
3.30
2.90
2.80

·Stock solutions preparation :·Light levels and quality during exposure :– Test design:· Concentration : 7.8 – 500.0 mg/L
· Initial cell number in cells/mL : 1 x 104– Methods of calculating mean measured concentration : Not stated

RESULTSŸ

Nominal Concentration in mg/L : 7.8, 15.6, 31.3, 62.5, 125.0, 250.0, 500.0 (mg/L)

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OECD SIDS74

DISODIUM DISULPHITE

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE(1) 72 hr
EC20 : 39.2 mg/L
EC50 : 48.1 mg/L
EC90 : 60.0 mg/L

(2) 96 hr
EC20 : 20.0 mg/L
EC50 : 39.8 mg/L
EC90 : 58.0 mg/L
Ÿ Was control response satisfactory? Yes (cell density increased 54 times after 72 hr)
Ÿ Statistical results, as appropriate⇒ Remarks:– Biological observations· cell density of each flask at each measuring point
Duration of the test : 72 hr
Nominal Conc. (mg/L)
0.0
7.8
15.6
31.3
62.5
125.0
250.0
500.0

% of control
100.00121.41
113.19106.86
1.55
0.10
0.10
0.00

The EC - values are given in nominal concentration.
EC20 : 39.2 mg/L
EC50 : 48.1 mg/L
EC90 : 60.0 mg/L
Duration of the test: 96 hr
The EC - values are given in nominal concentration.
EC20 : 20 mg/L
EC50 : 39.8 mg/L
EC90 : 58 mg/L
·Growth curves
Nominal Conc.( mg/L )
0.0
7.8
15.6
31.3
62.5
125.0
250.0
500.0

% of control
100.00109.47
84.31
68.83
0.22
0.00
0.00
0.00

CONCLUSIONSUNEP PUBLICATIONS

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OECD SIDS76

DISODIUM DISULPHITE

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE

UNEP PUBLICATIONS

77

OECD SIDSDISODIUM DISULPHITE
12) ACUTE TOXICITY TO INVERTEBRATES (DAPHNIA)TEST SUBSTANCE
Ÿ Identity : Disodium disulphite (CAS NO. 7681-57-4)⇒ Remarks : Source : disodium disulphite, > 98 %(w/w), (BASF sulfite - factory RCA B 306)

METHODŸ Method : EEC guideline 79/831/EWG, appendix V, part of CŸ Test type : 48 hr, immobilization test
Ÿ GLP : No
Ÿ Year : 1989
Ÿ Analytical monitoring : No details
Ÿ Species/Strain/Supplier : Daphnia magna
Ÿ Test details : static
Ÿ Statistical methods : Probit Analysis⇒ Remarks:– Test organism :·Source, Supplier, any pretreatment, breeding method : The clone of Daphnia straus used was supplied by Institut
National de Recherche Climique Appliquee, France, in 1978. The Daphnids are cultured under standard
conditions in the laboratory for environmental analytics and ecology of the BASF AG Ludwigshafen bred.
· Age at study initiation : 2 - 24 hrs– Test condition:·Stock solution preparation : not stated· Test temperature range : 19 – 21 °C· Exposure vessel type : not stated· Dilution water source : not stated· Dilution water chemistry : hardness= 2. 88 [m mol/L];
Ca: Mg = approx. 4:1; alkalinity = 0.97 [m mol/L]· Lighting: Day : Night rhythm 16:8 hours
Density of light: approx. 5 Microstone/(m*m*s) in the Wavelength coverage of 400 - 750 nm· Water chemistry in tes t : Oxygen content : > 2 mg/L; pH=8.0– Element (unit) basis : immobilization– Test design (volume/animals : 2 mL, number of animals/vessel: 5, total number of animals/concentration: 20,
replicates : 4)
– Method of calculating mean measured concentrat ions : Not stated– Exposure period : 48 hr– Analytical monitoring : No

RESULTSŸ Nominal concentration (as mg/L) : 7.8, 15.6, 31.3, 62.5, 125.0, 250.0, 500.0
Ÿ Measured concentration (as mg/L) : not statedŸ Units (results expressed in what unit) : mg/L
Ÿ EC50 (48 hrs)=88.76 mg/L, NOEC=62.5 mg/L
Ÿ Statistical results, as appropriate : not stated⇒ Remarks :-78

Biological observations·Number immobilized as compared to the number exposed: none
·Concentration response with 95 % confidence limit

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE

Duration of the test : 3 hr
EC50 = 148.99 mg/L
CI 95% = 82.6 - 215.38 mg/L
EC0 = 62.5 mg/L
EC100 = 250 mg/L
Duration of the test : 24 hr
EC50 = 88.76 mg/L
CI 95% = 88.76 - 88.76 mg/L
EC0 = 62.5 mg/L
EC100 = 125 mg/L
Duration of the test : 48hr
EC50 = 88.76 mg/L
CI 95 % = 88.76 - 88.76 mg/L
EC0 = 62.5 mg/L
EC100 = 125 mg/L
Cumulative immobilization
Immobility numbers
Conc. [mg/L]
7.8
15.6
31.3
62.5
125.0
250.0
500.0
0.0

0h
0
0
0
0
0
0
0
0

3h
0
0
0
0
6
20
20
0

Immobility numbers
6h
0
0
0
0
20
20
20
0

24 h
0
0
0
0
20
20
20
0

48 h
0
0
0
0
20
20
20
0

·Was control response satisfactory : Yes
CONCLUSIONSFor Disodium disulphite, 24 hr-EC50 value was 88.76 mg/L. Experimental designs and results were well
documented and prescribed conditions in the guideline were well satisfied.
⇒ Remarks :DATA QUALITY
Ÿ Reliabilities : Reliable with restrictions.
⇒ Remarks :REFERENCES (Free Text)
BASF AG, Dept. of Ecology, unpublished data (0897/88) 10, May, 1989.
OTHER
Ÿ Last changed : September 2001
Ÿ Order number for sorting⇒ Remarks :UNEP PUBLICATIONS

79

OECD SIDSDISODIUM DISULPHITEHEALTH ELEMENTS
13) ACUTE TOXICITYTEST SUBSTANCE• Identity : Disodium disulphite -powder(CAS No. 7681-57-4)⇒ Remarks : Source : Hoechst AG, Purity : 96 % (2 % Na2SO3, 2 % Na2SO 4)

METHOD
•
•
•
•
•
•
•
•
•

Method/guideline followed : OECD TG 401
Type : Acute oral toxicity test
GLP : yesYear (study performed) : 1987
Species/Strain : Rat / Wistar
Sex : male and female
No. of animals per sex per dose : 5 animals/sex/dose
Vehicle : water
Route of administration : oral (gavage)

REMARKS FIELD FOR TEST CONDITIONS
•
•
•
•
•

Age : 7 weeks(male) and 8 weeks(female)
Doses : 800, 1250, 1600 mg/kg(female), 1250, 1600, 2000 mg/kg (male)
Volume administered : 10 mL/kg bw
Concentration : 8, 12.5, 16, 20 % (w/v)
Post dose observation period : 14 days

RESULTS•

LD 50 with confidence limits: 1540 (1290 - 1960, p=0.05) mg/kg bw (male/female)• Male : 1630 (1210 - 2260, p= 0.05) mg/kg bw• Female : 1420(1040– 2110, p=0.05) mg/kg bw
Number of deaths at each dose level:
Males : 1/5, 2/5 and 4/5 in the 1250, 1600 and 2000 mg/kg dose groups respectively
Females : 0/5, 1/5 and 4/5 in the 800, 1250 and 1600 mg/kg dose groups respectively•

REMARKS FIELD FOR RESULTS• Time of death
Dead animals were observed at day 1 after dosing for male and female.

Lethality–

80

Time of death

Dose(mg/kg)

male

femalemale

female

800
1250
1600
2000

1/5
2/5
4/5

0/5
1/5
4/5
-

1hr
1hr and 4 hr
all at 4 hr

0/5
1hr
all at 4 hr-

Description, severity, time of onset and duration of clinical signs a each dose level : The symptoms
observed in male and female animals were the reduction of activity, crouching, retracted flanks, ruffled fur,irregular breathing and a stiff-legged gait. Additionally, males in the 2 high dose groups displayed proneposition, contracted eyelids, and apathy. After the first day the symptoms were reversed in the surviving
animals.

UNEP PUBLICATIONSOECD SIDS–DISODIUM DISULPHITE

Necropsy findings, included doses affected : The g.i. tract was filled with blood, the mucosa of thestomach was lightly reddened and the liver was dark in color. At the end of the experiment the surviving
animals were sacrificed and were found to be free of any unusual gross abnormalities. Body weight gain
was not influenced by treatment.

CONCLUSIONSLD 50 was calculated to be 1540 mg/kg with a 95 % confidence interval of 1290 - 1960 mg/kg bw

DATA QUALITY•

Reliabilities : Reliable without restriction

REFERENCES (Free Text)
Hoechst AG, Unpublished studies (87.1374), 04.Sept.1987

OTHER
•
•

Last changed (administrative field for updating) : September 2001
Order number for sorting (administrative field)

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81

OECD SIDSDISODIUM DISULPHITE
GENETIC TOXICITY ELEMENTS

14) GENETIC TOXICITY IN VIVO (CHROMOSOMAL ABERRATIONS)TEST SUBSTANCE• Identity : Disodium disulphite (CAS No. 7681-57-4)⇒ Remarks : Provided by Food and Drug Administration, US

METHOD•

Method/guideline followed : other•Type (test type) : Cytogenetic in vivo assay•

GLP : No details•

Year (study performed) : 1972•

Species : Rat•

Strain : Albino•

Sex : male•

Route of administration : oral•

Doses/concentration levels : 0, 30, 700, 1200 mg/kg•

Exposure period : Animals were treated either one time and then sacrificed in 6, 24 or 48 h, or they weretreated once/day for 5 d, and then were sacrificed in 6 h after the last treatment.

•

Statistical methods : Chi-square test

REMARKS FIELD FOR TEST CONDITIONS-Age at study initiation : Unknown
No. of animals per dose : 5 animals/dose/time point (3 rats used in negative control)
Vehicle : Unknown
Duration of test : 1 to 5 days
Frequency of treatment : single & multiple (once a day for 5 day)
Sampling times and number of samples : 6, 24, 48 hr subsequent to intubation or 6 hr after last intubation(subacute), 50 bone marrow cells per animal were evaluated.
Control groups (e.g. vehicle, positive, negative) : The positive control was triethylenemelamine injected
i.p. at a dose of 0.4 mg/kg.
Clinical observations performed : not stated
Organs examined at necropsy : not statedCriteria for evaluating results : Number and type of chromosomal aberrations (except gabs), mitotic
index
Criteria for selection of M.T.D. : LD50

RESULTS••••

Effect on mitotic index
The mitotic index was reduced in the high dose groups after all single administration time points whichindicates that the test substance reached the bone marrow to a sufficient level
Genotoxic effects : negative
Statistical results, as appropriate

82

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE

36.0
1.3

Cell with
Rearrangemn
et(%)
7.2
0

Cell with morethan one typeof aberr.(%)
5.6
0

250

0.4

0

0

0.4

250
250
150
200
250

0.8
1.2
1.3
0
0.8

0
0
0
0
0

0
0
0
0
0

0.8
1.2
1.3
0
0.8

5
3
5
5
5

250
150
250
250
250

0
0.7
1.6
1.2
0.4

0
0
0
0
0

0
0
0
0
0

0
0.7
1.6
1.2
0.4

3
5
5
3

150
250
250
150

2.6
0.8
0.8
0.7

0
0.4
0
0

0
0
0
0

2.6
1.2
0.8
0.7

Dosagemg/kg)

time

MitoicIndex(%)

No.of
AnimalNo.of cell

Cell with
Breaks(%)

TEM(0.4)
(-)

24
6

2.05
1.95

5
3

250
150

30

6

2.20

5

700
1200
(-)
30
700

6
6
24
24
24

2.25
1.90
2.10
2.05
2.20

5
5
3
4
5

1200
(-)
30
700
1200

24
48
48
48
48

1.65
2.20
1.70
1.60
1.80

(-)
30
700
1200

SA
SA
SA
SA

1.75
2.35
2.15
2.10

Cell with
Aberr .(%)
37.6
1.3

* SA : Sub acute (5 days treatments)

REMARKS FIELD FOR RESULTS−−−−

Mortality at each dose level by sex : not stated
Description, severity, time of onset and duration of clinical signs at each dose level : not stated
Body weight changes by dose and sex : not stated
Food/water consumption changes by dose and sex : not stated

CONCLUSIONSNo adverse effect on bone marrow chromosomes was observed as a result of disodium disulphite treatment.

DATA QUALITY• Reliability : Reliable with restriction

REFERENCES (Free Text)
1.
2.

National Technical Information Service U.S. Department of Commerce(NTIS), Study of the Mutagenic Effectof Sodium Meta-Bisulfite (71-22), PB-221 825, July 1972
Maxwell, W.A. and Newell, G.W., Mol. Environ. Aspects Mutagenesis Proc. Publ., Rochester Int. Conf.
Environ. Toxic. 6th, 1973, 223-252, 1974

OTHER
•
•

Last changed (administrative field for updating) : September 2001
Order number for sorting (administrative field)

UNEP PUBLICATIONS

83

OECD SIDSDISODIUM DISULPHITE
15-1) GENETIC TOXICITY IN VITRO (GENE MUTATIONS)TEST SUBSTANCE• Identity : Disodium disulphite (CAS No. 7681-57-4)⇒ Remarks : Source : BASF Aktiengesellschaft, Purity : 98 %METHOD•

Method/guideline followed : OECD TG 471•

Type : Reverse mutation assay (standard plate test & preincubation test)•

System of testing : bacterial•

GLP (Y/N) : No•

Year (study performed) : 1983•

Species/Strain : Salmonella typhimurium TA 1535, 1537, 98, 100•

Metabolic activation– Species and cell type : sprague-Dawley rats
– Induced or not induced : Aroclor-1254-induced•

Concentrations tested : 0, 20, 100, 500, 2500, 5000 ? /plate•

Statistical Methods : Not mentioned

REMARKS FIELD FOR TEST CONDITIONS– Test Design· Number of replicates : 2· Number of plate : 3 plate/dose (and /control)· Positive and negative control groups and treatment :negative control ; solvent control, sterility control
positive control ; -S9 mix : 10 ? 2-aminoantharcene(dissolved in DMSO) for all strains+S9 mix : 5 ? N-methyl-N’-nitro-N-nitrosoguanidine for TA 100, 1535
10 ? 4-nitro-o-phenylendiamine for TA 98
100 ? 9-aminoacridine chloride monohydrate for TA 1537
– Solvent : DMSO (dimethylsulfoxide)– Description of follow up repeat study
1st experiment : standard plate test with and without S-9 mix
2nd experiment : preincubation test with and without S-9 mix– Criteria for evaluating results : doubling of the spontaneous mutation rate (control), dose-response
relationship, reproducibility of the results

RESULTS•

Cytotoxic concentration : No bacteriotoxic effect•

Genotoxic effects– With metabolic activation : negative– Without metabolic activation : negative•

Statistical results: Not mentioned

REMARKS FIELD FOR RESULTS

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CONCLUSIONS
An increase in the number of his+ revertants was not observed both in the standard plate test and in thepreincubation test either without or with S-9 mix.

DATA QUALITY•

Reliabilities : Reliable without restrictions

Remarks fields of reliability
Well conducted, followed GLP-like requirement.

REFERENCES
BASF AG, Dept. of Toxicology, Unpublished study (89/380), 09.Oct.1989

OTHER
•
•

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OECD SIDSDISODIUM DISULPHITE
15-2) GENETIC TOXICITY IN VITRO (GENE MUTATIONS)TEST SUBSTANCE• Identity : disodium disulphite (CAS No. 7681-57-4)⇒Remarks : Source : Sigma Chemical Co., St. Louis, MO.

METHOD•

Method/guideline followed : Other•

Type : reverse mutation assay (preincubation)•

System of testing : bacterial•

GLP (Y/N) : Not details•

Year (Paper received) : 1986•

Species/Strain : Salmonella typhimurium TA 92, 1535, 100, 88, 110, 90, 97, 1538, 98, SB 2802, 2061•

Metabolic activation : Not applied•

Concentrations tested : 0.01-0.64 M•

Statistical Methods : No stated

REMARKS FIELD FOR TEST CONDITIONS– Test Design· Number of replicates : 3-4· Positive and negative control groups and treatment : Only negative control used
· Number of metaphases analysed : Not applicable– Solvent : 0.1 M sodium phosphate buffer– Criteria for evaluating results : The level of toxicity seen on the nutrient plates after 24 h incubation
was compared to toxicity seen in the background lawns of the mutation
plates scored after 48 h incubation at 37ºC

RESULTS•••

Cytotoxic concentration :No significant effects on mutagenicity of any strains at concentration up to 0.32 M
Genotoxic effects : slightly positive
Statistical results: Not mentioned

REMARKS FIELD FOR RESULTS– Mutagenic response strains : G 46, TR 3243 (only the strain carrying the his D6610 or his G46)
– Condition affecting mutagenicity : bisulfit-induced mutation appear to be the result of two different
mechanisms which may be a function of the repair capacity of the strains. It suggests that thedeamination of cytosine may be responsible for base pair substitution mutagenesis and the deaminationof cytosine may be the result of oxidative damage rather than through the direct formation of a cytosinebisulfite adduct because the rate of bisulfite autooxidation appears to play a role in the mutagenic
process.

· Plasmid : pKM101 slightly enhanced the level of base-pair substitutions· Genotype : his O1242 mutation, uvrB and rfa mutations affected the mutagencity· pH range : In the pH range of 4.4 - 5.6, the mutagenic response was maximized for TA97. The pH of
the bisulfite solution has an effect on bisulfite mutagenesis and aut ooxidation. If a lower pH slows therate of autooxidation allowing more unoxidized product to be taken up by the cell, then the enhanced

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mutagenicity seen after increasing the exposure length suggests that alterations in the rate of bisulfite
autooxidation should have effects on the level of mutagenicity.
· Preincubation time : 60 - 120 min of Preincubation time increased the No. of revertants– Statistical results : Not mentioned

CONCLUSIONSThis chemical is a weak mutagen at pH 5 and 6 in S. typhimurium strains carrying the his G46 and his D6610
mutations.

DATA QUALITY•

Reliabilities : Reliable with restrictions

REFERENCES
Pagano DG und Zeiger E, Conducting affecting the mutagenicity of sodium bisulfite in Salmonella
typhimurium , Mutation Research, 179, 159-166 (1987)

GENRERAL REMARKS
The dose levels in this study are not clear. This could make it difficult to compare to other studies.

OTHER
•
•

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OECD SIDSDISODIUM DISULPHITE
16) REPEATED DOSE TOXICITYTEST SUBSTANCE• Identity : Disodium disulphite (CAS No. 7681-57-4)⇒Remarks : Source : Amsterdamsche Chinine Fabriek (ACF)- purity 95~99 % (as calculated from SO2
determinations)

METHOD•

Method/guideline followed : Other•

Test type : Long-term feeding study•

GLP : No•Year : 1971•

Species : Rat•

Strain : Wistar•

Route of administration : oral (feed)•

Duration of test : about 2 year•

Doses/concentration levels : 0, 0.125, 0.25, 0.5, 1.0, 2.0 %•Sex : male & female•

Exposure period : 104 weeks(F0 and F1 generations), 30 weeks(F2 generations)•

Frequency of treatment : 7 d/ week•

Control group and treatment : basal diet containing 0 % Na2S2O 5•

Post exposure observation period : None•

Statistical methods : Student’s t test and chi-square test

REMARKS FIELD FOR TEST CONDITIONS– Test Subjects· Age at study initiation : Newly weaned rats
· No. of animals per sex per dose : 20 animals/dose/sex– Study Design· Vehicle : none (stock diet containing the test substance)· Satellite groups and reasons they were added : none
· Clinical observations performed and frequency : Changes of body weight were recorded weekly for the
1st 12wk and once every 4 wk thereafter. The food consumption of each diet group was measured atintervals during 1 wk periods. Hematological investigations were performed from control, 1, and 2 %dose groups of F0 at wk 52, 78, 100, at 52, 102 wk in the F1a generation and at wk 20 of F2 generation.
At week 32, 64, and 100 all rats of the F0 and F1a generation and at wk 28 those of the F2a generations
were examined for occult blood in feaces. Serum activities of glutamic-oxalacetic and glutamic-pyruvic
transaminases were estimated at wk 52, 104 in the F0 generation rats. Kidney function was examined in
the urine from controls, 1, and 2 % dose groups, at wk 13, 28, 52, 78 and 101 in F0, at wk 28, 52, 100 in
the F1 and wk 28 in the F2. Concurrently pooled urine analysis was performed for appearance, pH,
glucose, albumin, occult blood, ketones and microscopy of the sediment.

· Organs examined at necropsy (macroscopic and microscopic)
Interim observation on organ weight and pathological changes.
Mircoscopic: heart, kidneys, liver, spleen, brain, testes, ovaries, pituitary, thyroid, parathyroids,
adrenals, thymus, lungs, trachea, salivary glands, gastro-intestinal tract, pancreas, urinary bladder,88

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skeletal muscle, spinal cord, femoral nerve, skin, bone marrow(sternum), axillary and mesenteric lymph
nodes, exorbital lachrymal gland, aorta, mammary glands, uterus, prostate, seminal vesicle andcoagulating gland.

RESULTS••NOAEL(NOEL)– local toxicity (presence of occult blood and changes in gastric morphology) : 0.215 % Na2S2O 5 as actual
dose(72 mg SO 2/kg b.w. day or 106 mg Na2S2O5 /kg b.w/day) or 0.25 % (in the diet)– system toxicity : 1.91 % as actual dose (942 Na2S2O5 mg /kg b.w./day) or
Actual dose received by dose level: The SO2 determinations on the diets showed considerable losses ofsulphite. Proportionally the losses of sulphite decreased with increasing dietary levels of sulphite as tableshown below
Level of Na2S2O 5 added todiet (%)
0.125
0.25
0.5
1.0
2.0

•

Loss of Na2S2O5 after storagefor 1 week at –18ºC(%)
22
14
12
8
5

Actual dose level of Na2S2O5
(%)
0.098
0.215
0.44
0.92
1.91

Toxic response/effects by dose levelOccult blood was present in the faeces in groups given 1 % sulphite or more. Relative weights of the kidneys
were increased by the 2 % sulphite level in the F2-generation females only, but this increase wasaccompanied by neither functional nor histological changes. Pathological examination revealed hyperplasticchanges in both the fore- and glandular stomach with level of 1 and 2 % sulphite in each of the three
generation. Some slight alterations were found also with 0.5 % in the stomach of the F2-generation rats. No
carcinogenic effect was shown.

REMARKS FIELD FOR RESULTS–

Body weight : There was a marginal reduction in body -weight gain in both sexes of the F1 and F2generation given 2 % sulphite, also in females F1 given 0.125, 0.25, 0.5 % sulphite and those given 0.25,
0.5 % in the F2 generation. But there was no dose-relationship and the differences could partly be
explained by the higher initial body weights of controls.

–

Food consumption : There was no distinct differences in food consumption.

–

Thiamine content of urine and liver : The group given 2 % sulphite showed no distinct changes in thethiamine status when compared with control rats on the stock diet without extra thiamine. This indicatesthat thiamine added to the sulphited diets prevented thiamine deficiency even at a dietary level of 2 %sulphite–

General condition, mortality and growth : The general condition of the rats remained good during thefirst 72 week in the F0-generation as well as in the two descendant generations. After this, aging
symptoms developed in many rats and mortality increased rapidly in nearly all group. The survival in thesulphite groups was generally higher than in the controls, except in the case of males of the F1generation given 2 % sulphite. No deaths occurred in the females of the same group.
– Hematological findings incidence and severity: A marginally reduced haemoglobin content, haematocrit
value and erythrocyte count occurred in the F0-generation females fed on 2 % sulphite at week 52, 78
and 100, while the F1 generation males at 2 % showed an increase in leucocyte count at week 102. All
haematological values for test and control animals in all successive generations were within normal
ranges at all stages.
– Description, severity and duration of clinical signs
All rats in the highest dose group showed indications of occult blood in the faeces of all generations,while this effect occurred in only 13 - 60 % of the animals on diets containing 1 % sulphite. In 10 % of
the females given 0.25 % and in 10 % of the males given 0.5 % sulphite slight indications of intestinal
blood loss were observed in the F0-generation rats at week 32 only.
· Occult blood in the faeces

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DISODIUM DISULPHITE

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91

OECD SIDSDISODIUM DISULPHITE17) TOXICITY TO REPRODUCTIONTEST SUBSTANCE• Identity: Disodium disulphite (CAS No. 7681-57-4)⇒ Remarks : Source : Amsterdamsche Chinine Fabriek (ACF)- purity 95~99 %(as calculated from SO 2
determinations)

METHOD•

Method/guideline followed : Other•

Type : multigeneration study•

GLP (Y/N) : No details•

Year : 1971•

Species : Rat•

Strain : Wistar•

Route of administration : oral (feed)•

Doses/concentration levels : 0, 0.125, 0.25, 0.5, 1.0, 2.0 %•Sex : male/female•

Control group and treatment : basal diet containing 0 % Na2S2O 5•Frequency of treatment : 7 d/ week•

Duration of test : 2 yr•

Premating exposure period for males and female (P and F1) as appropriate : F0 : 21 weeks•

Statistical methods : Student’s t test and chi-square test

REMARKS FIELD FOR TEST CONDITIONS– Test animals· Number, age, sex per dose for P : Newly weaned rats, 20 animals/dose/sex· Number, age, sex per dose for F1a, F2a : 10 animals/dose/sex selected at weaning (F1-gen.) for
produce F2a, F2b and 10 males, 15 females of the F2a litters were selected for producing the next
generation.
– Test design· Vehicle : none (stock diet containing the substance)·

Dosing schedules and pre and post dosing observati ons periods for P, F1 and F2,: All rats of the F0generation were mated within their diet group at about week 21 and half of them also at week 34. 10
animals/dose/sex from the first litters were selected at weaning for rearing further generations. The F0generation rats as well as the selected F1a-generation rats were maintained on their diet for a period of
104 weeks. Rats of the F1a-generation were mated at week 12 and 30 to produce the F2a and the F2bgenerations. 10 males and 15 females form the F2a litters were mated to produce an F3a-, F3bgeneration by pairing them on week 14 and 22. These litters were discarded after weaning, and theparents were kept on their diets for about 30 weeks.

· Mating proceduresGroup mating was used throughout and lasted for a period of 2 week. At day 20 after the beginning of
the mating period, the females were individually housed until the litters had been weaned. Records weremade of the number of pups in each litter, and of the total weight of the litter at days 1, 8 and 21. On the
1st day, the litters containing more than 8 pups were reduced to that number to equalize the stress oflactation on the dams.
· Clinical observations performed and frequency

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All changes of body weight were recorded weekly for the 1st 12 wk and once every 4 wk thereafter.
The food consumption of each diet group was measured weekly. Hematological investigations were
performed with control, 1, 2 % dose groups of F0 at wk 52, 78, 100 in F1a at 52, 102 wk and at week
20 in the F2 generation. F0-, F1a- and F2-generation were examined for occult blood in feaces at week
32, 64 and 100. Serum activities of glutamic-oxalacetic and glutamic-pyruvic transaminases were
estimated at week 52, 104 in F0. Kidney function was examined for the controls, 1 and 2 % dosegroups, at week 13, 28, 52, 78 and 101 in F0, at week 28, 52, 100 in the F1 and week 28 in the F2.
Concurrently urine analysis was performed.
· Organs examined at necropsy (macroscopic and microscopic)
Interim observation on organ weight and pathological changes .
Mircoscopic : heart, kidneys, liver, spleen, brain, testes, ovaries, pituitary, thyroid, parathyroids,
adrenals, thymus, lungs, trachea, salivary glands, gastro-intestinal tract, pancreas, urinary bladder,skeletal muscle, spinal cord, femoral nerve, skin, bone marrow (sternum), axillary and mesentericlymph nodes, exorbital lachrymal gland, aorta, mammary glands, uterus, prostate, seminal vesicle andcoagulating gland.
– Parameters assessed during study
Female fertility, the number of young per litter, the birth weight, mortality of the young.
RESULTS•NOAEL (NOEL) and LOAEL (LOEL) for P, F1, F2 and F3
NOAEL : 2 % in the diet (actual dose 1.91 %) which is equivalent to 942 mg of Na2S2O 5 /kg b.w/day•

Actual dose received by dose level : 0, 0.098, 0.213, 0.440, 0.920, 1.91 % doses result from stock diet loss.

•

Parental data and F1 as appropriate : No consistent differences between groups in female fertility, thenumber of young per litter•

Offspring toxicity: No consistent differences between groups in birth weight or mortality of the young. Body
weight changes were seen in the offspring (F1, F2, F3). A signification reduction in the number of F2ageneration young was observed with 0.5, 1, and 2 % sulphite. During the lactation period the body weights of
the young in the 2 % group were generally lower than those of the controls and significantly decreased bodyweights at day 8 and 21, but there was no distinct dose-related response.

REMARKS FIELD FOR RESULTS–

Fertility and offspring toxi city : During lactation the body weight of the young in the 2 % group was
generally lower than the controls and the lower-dosed groups. In the F1a- and the F1b-generation
offspring (F2a and F2b pups) dietary levels of 1 and 2 % disodium disulfite were associated withdecreased body weight on days 8 and 21. This effect was primarily transient for the F2a pups, sinceanimals of the 1 % group recovered their body weight after weaning and the 2% group nearly recovered
their body weight as compared to the control. This reduced body weight was probably not a true
substance-related effect since it could be due to a higher initial body weight in the control groups.
Furthermore, these body weight changes were within or were not dramatically different from the control
values of the F1 pubs. A reduction in the number of F2a-generation offspring (F3a pups) was observedin the 0.5, 1.0 and 2.0 % dose groups, but it was not dose-dependent and did not occur in the F2bgeneration offspring (F3b pups).

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Dose (%)

No. of femaleswith litters

0
0.125
0.25
0.5
1.0
2.0

90
90
75
85
90
85

0
0.125
0.25
0.5
1.0
2.0

80
90
80
100
90
90

0
0.125
0.25
0.5
1.0
2.0

90
90
80
90
70
90

0
0.125
0.25
0.5
1.0
2.0

100
80
80
100
100
90

0
0.125
0.25
0.5
1.0
2.0

100
100
100
87
100
100

0
0.125
0.25
0.5
1.0
2.0

100
100
100
93
100
100

–

Mean no. of
Mean b.w. of young at day
rats/litters at birth
18
21
F0 -generation- 1st mating
8.7
5.9
15.7
44.5
9.1
5.9
15.0
42.5
9.8
5.9
14.3
40.0
9.5
6.1
15.1
42.3
10.6
6.1
15.6
43.2
9.8
5.9
13.8
3801
F 0-generation- 2nd mating
9.5
6.0
14.6
38.9
8.6
6.8
14.4
39.4
9.3
6.2
17.5
44.7
10.7
6.4
15.7
40.2
7.8
6.4
15.8
41.3
8.9
5.9
14.4
37.6
1
F -generation- 1st mating
10.4
6.2
17.9
45.6
10.7
5.9
14.8
40.6
10.0
5.7
16.2
40.9
8.8
6.0
15.6
43.2
9.1
6.0
15.0
38.6
9.7
6.2
14.7
37.7
F 1-generation- 2nd mating
10.4
6.7
18.3
49.4
11.0
6.2
16.0
45.9
10.9
5.9
16.9
44.8
8.7
6.1
19.4
51.9
9.4
6.5
15.9
45.1
10.8
6.2
15.9
42.9
F2 -generation- 1st mating
11.7
6.2
17.3
47.1
10.5
5.6
15.8
42.2
11.2
5.5
14.6
40.2
8.9
6.1
16.8
41.9
8.9
6.0
15.5
41.1
8.8
5.9
15.2
38.8
F 2-generation- 2nd mating
10.2
6.4
17.2
44.3
11.4
6.0
16.8
45.9
11.3
5.8
15.3
40.4
9.9
6.2
16.4
44.4
9.8
6.3
14.3
44.0
10.5
6.2
15.5
41.2

Mortality (%)
At birth
At weaning
9
1
9
1
5
8

13
23
25
1
9
14

8
26
8
0
0
13

0
0
17
5
4
8

0
1
0
1
0
2

16
11
5
15
15
10

0
1
3
3
5
4

11
8
3
4
7
3

5
1
0
3
0
3

2
14
0
10
1
2

3
2
0
1
2
0

8
13
4
7
21
7

Body weight : There was a marginal reduction in both sexes of the F1 and F2-generation given 2 %sulphite, 0.125, 0.25, 0.5 % sulphite in the female F1 and 0.25, 0.5% in the F2 generation. But there was
no dose- relationship.

– Food consumption : There was no distinct differences in food consumption.
– General condition, mortality and growth : The general condition of the rats remained good during the first72 week in the two descendant generations. After this, aging symptoms developed in many rats andmortality increased rapidly in nearly all group. The survival in the sulphite groups was generally higher
than in the controls, except in the case of males of the F1-generation given 2 % sulphite. No deaths
occurred in the females of the same group.
– Precoital interval : not stated–

Duration of gestation : not stated–

Gestation index (live litters/pregnancies) : no details––

Changes in lactation : not stated
Changes in estrus cycles : not stated–Effects on sperm : unknown–

Hematological findings incidence and severity: A marginally reduced haemoglobin content, haematocrit
value and erythrocyte count occurred in the F0-generation females fed on 2 % sulphite at week 57, 78
and 100, while the F1 generation males at 2 % showed an increase in leucocyte count at week 102. All
haematological values for test and control animals in all successive generations were within normal
ranges at all stages.

–

Kidney function and enzyme activity : Phenol-red excretion, specific gravity and glutamic-oxalacetictransaminase activity in the urine were not adversely affected by the feeding of sulphite. Urine analysis
values were essentially normal. Significant (p< 0.05) decreases in serum glutamic-pyruvic- transaminase
values occurred at week 104 in male rats of the F0-generation receiving 0.125 % sulphite. There were nodifferences in transaminase between the test and control animals of this generation activities either atweek 52 or at week 104.
Number of implantations : not stated–

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UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE
18-1) DEVELOPMENTAL TOXICITY/TERATOGENICITYTEST SUBSTANCE• Identity : Disodium disulphite⇒ Remarks : White crystalline material (FDA 71-22)

METHOD•

Method/guideline followed : Other•

GLP : No details•

Year : 1972•

Species : Rat•

Strain : Wistar•

Route of administration : oral (gavage)•

Doses/concentration levels : 0, 1, 5, 24, 110 mg/kg bw•

Sex : Female•

Exposure period : day of 6-15 of gestation•

Frequency of treatment : daily•

Control group and treatment : Negative control : sham treated controls
Positive control : Asprin 250 mg/kg bw•

Duration of test : day of 20 gestation•

Statistical methods : Not described•

Statistical methods : Not described– Age at study initiation : Not stated– Number of animals per dose per sex : Not stated– Vehicle : water– Clinical observations performed and frequency:
Body weights : on days 0, 6, 11, 15 and 20 of gestation
Appearance, behaviour and food consumption : daily– Mating procedures : Not stated–Parameters assessed during study(maternal and fetal) : Average body weight, pregnancy data, skeletal
abnormality, soft tissue abnormality– Organs examined at necropsy : The numbers of implantation site, resorptions and live/dead fetuses wererecorded. Fetuses were examined for the presence of external congenital abnormality, visceralexamination(1/3 of fetuses) and skeletal defect( remaining 2/3 of the fetuses)

RESULTS••••NOAEL maternal toxicity : 110 mg/kg bw/day
NOAEL teratgenicity : 110 mg/kg bw/day
Maternal data with dose level : No clear effect on maternal toxicity
Fetal data with dose level : No clear effect on fetal survival

REMARKS FIELD FOR RESULTS– Reproduction data
The administration of the disodium disulphite to pregnant rats had no clear effect on nidation, or on
maternal or fetal survival.

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Dose (mg/kg)
Pregnancies
Total No.
Died or Aborted(before day 20)
To term(on day 20)
Corpora Lutea
Total No.
Average/dam matedLive Litters
Total No.
Implant sites
Total No.
Average/dam
Resorptions
Total No.
Dams with 1 or more sites resorbed
Dams with all sites resorptions% partial resorptions% comlete resorptions
Live Fetuses
Total No.
Average/dam
Sex ratio(M/F)
Dead Fetuses
Total No.
Dams with 1 or more deadDams with all dead% partial dead% all deadAverage Fetuses Weight g

Sham

Positive

1.0

5.0

24.0

110.0

21
0
21

23
0
23

24
0
24

23
0
23

24
0
24

24
0
24

236
9.83

266
11.1

274
11.4

266
11.1

282
11.8

270
11.3

21

23

24

23

24

24

232
11.0

265
11.5

266
11.4

265
11.5

274
11.4

266
11.1

4
3
0

9
7
0

8
6
0
26.1
-

10
6
0
25.0
-

8
6
0
25.0
-

-

-

4
4
0
16.7
-

227
10.8
0.86

256
11.1
0.91

261
10.9
0.63

257
11.2
0.67

264
11.0
0.87

258
10.8
0.73

1
1
0

0
-

1
1
0
4.17
3.80

0
3.81

0
3.87

0
3.86

14.3

4.76
-

30.4

3.67

2.53

– Body weight
No significant differences were found between treatment and negative control group.
Average body weight of pregnant dams
Dose
(mg/kg)day 0

Average Body wt(g)day 6
day 11day 150positive control

209
216

227
237

252
257

276
279

346
342

1.0
5.0

209
209

232
229

253
250

278
272

343
337

24.0
110.0

211
213

231
233

253
253

277
274

348
345

day 20– Food/water consumption
No significant difference is found in comparison with to control.
– Description, severity, time of onset and duration of clinical signs : Not described– Gross pathology incidence and severity :No clear effect on nidation, or on maternal or fetal survival– Fetal data·. Grossly visible abnormalities
The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ fromthe number occurring spontaneously in the sham-treated controls.

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Summary of skeletal findings
findings
Sternebrae
Incompletd oss.
Bipartite
Missing
Ribs
Wavy
Less than 12
Vertebrae
Incompletd oss.
Skull
Incompletd oss.
Miscellaneous
Hyoid;missing
Hyoid;reduced

0

1.0

31/14

12/7

3/1

1/1

6/5

8/7

2/1

Dose (mg/kg)
5.0
24.0

110.0

Positive

13/10

16/12

1/1

1/1

163/23
2/1
105/22

4/4
1/1

9/7

3/3

84/21
3/3

1/1

1/1

2/2

1/1

127/23

16/10

11/8

16/11

35/13

23/9

149/23

19/11

8/6
2/2

6/5

18/8
1/1

17/7
4/3

120-23

14/11
1/1

Numerator=Number of fetuses affected; Denominator= Number of litters affected

CONCLUSIONSNo teratological or other developmental effects were indicated in fetues at any dose level.

DATA QUALITY•

Reliabilities : Reliable with restriction

REFERENCES (Free Text)
National Technical Information Service (NTIS) U.S. Department of Commerce, Teratologic Evaluation ofCompound FDA 71-22 (Sodium Meta-Bisulfite), Prepared for the FDA, PB-221 795, Sept. 1972

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18-2) DEVELOPMENTAL TOXICITY/TERATOGENICITYTEST SUBSTANCE• Identity : Disodium disulphite⇒ Remarks : White crystalline material (FDA 71-22)

METHOD•

Method/guideline followed : Other•

GLP : No details•

Year : 1972•

Species : Rabbit•

Strain : Dutch•

Route of administration : oral (gavage)•

Doses/concentration levels : 1.23, 5.71, 26.5, 123 mg/kg bw•

Sex : Female•

Exposure period : day 6 - 18 of gestation•

Frequency of treatment : daily•

Control group and treatment : Negative control : sham treated controls
Positive control : 2.5 mg/kg of 6-aminonicotinamide dosed on day 9•

Duration of test : 29 days of gestation•

Statistical methods : Not described•

Statistical methods : Not described– Age at study initiation : Not stated– Number of animals per dose per sex : 20 - 14 animals/dose– Vehicle : water– Clinical observations performed and frequency : Body weights were recorded on days 0, 6, 12, 18 and
29 of gestation, and were observed daily for appearance, behavior and food consumption.
– Mating procedures : Not specified– Parameters assessed during study(maternal and fetal) : Average body weight, survival data, pregnancy
data, skeletal abnormality, soft tissue abnormality– Organs examined at necropsy : The numbers of corpora lutea, implantation site, resorptions andlive/dead fetuses were recorded. Fetuses were examined for the visceral abnormalities by dissection. All
fetuses were processed for staining with Alizarin Red S dye and examined for skeletal defects.

RESULTS••••NOAEL maternal toxicity : 123 mg/kg bw/day
NOAEL teratogenicity : 123 mg/kg bw/day
Maternal data with dose level : No clear effect on maternal toxicity
Fetal data with dose level : No clear effect on fetal survival

REMARKS FIELD FOR RESULTS– Reproduction data
The administration of the disodium disulphite to pregnant rats had no clearly discernible effect on
nidation, or on maternal or fetal survival.
– Body weight

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No significant differences were found between treatment and negative control group.
– Food/water consumption
No significant difference is found in comparison with to control.
– Description, severity, time of onset and duration of clinical signs: Not described– Fetal data·. Grossly visible abnormalities
The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ fromthe number occurring spontaneously in the sham-treated controls.

CONCLUSIONSNo teratological or other developmental effects were indicated in fetues at any dose level.

DATA QUALITY•

Reliabilities : Valid with restriction

REFERENCES (Free Text)
National Technical Information Service (NTIS) U.S. Department of Commerce, Teratologic Evaluation ofCompound FDA 71-22. Sodium Metabisulfite in Rabbit, PB -267 194, July 1974

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OECD SIDSDISODIUM DISULPHITE
BEYOND S IDS ELEMENTS
1) CHRONIC TOXICITY TO AQUATIC INVERTEBRATES (DAPHNIA)TEST SUBSTANCE
Ÿ Identity : Disodium disulphite (CAS NO. 7681-57-4)⇒ Remarks : Source : disodium disulphite, > 98 % (w/w), (BASF sulfite - factory RCA B 306)

METHODŸ Method : OECD TG202
Ÿ Test type : 21 days reproduction test
Ÿ GLP : YES
Ÿ Year : 1993
Ÿ Analytical monitoring : not statedŸ Species/Strain/Supplier : Daphnia magna
Ÿ Test details : semi-static
Ÿ Statistical methods : Duncan’s multiple range test
⇒ Remarks:– Test organism :·Source, Supplier, any pretreatment, breeding method : The clone of Daphnia straus used was supplied by
Institut National de Recherche Climique Appliquee, France, in 1978. The Daphnids are cultured understandard conditions in the laboratory· Age at study initiation : 2 - 24 hrs– Test condition :· Stock solution preparation : a defined amount of the test substance was weighed out and suspended directlyin the test medium by stirring. The nominal concentration of the stock solutions were 100 mg/L
· Test temperature range : 20 ±2?
· Exposure vessel type : numbered glass beakers nominal volume 100 mL, covered with numbered caps
· Dilution water source : the synthetic medium M4· Dilution water chemistry : hardness = 2.20-3.20 [m mol/L ];Ca: Mg = approx. 4:1; alkalinity up to pH 4.3 = 0.80-1.00 [m mol/L ]· Lighting- Day : Night rhythm 16:8 hours
Density of light : 5-6 µE/(m*m*s) in the range of 400-700 nm· Water chemistry in test : Oxygen content : 8.0 - 15.5 mg/L; pH=7.5 - 8.0· Feeding : Green algae ( Scenedesmus subspicatus)– Element (unit) basis : reproduction– Test design : number of animals/vessel : 1, total number of animals/concentration : 10
– Method of calculating mean measured concentrations : Not stated– Exposure period : 21 days
– Analytical monitoring : Not stated

RESULTSŸ Nominal concentration (as mg/L) : 1.0, 5.0, 10.0
Ÿ Measured concentration (as mg/L) : not determinedŸ Units (results expressed in what unit) : mg/L
Ÿ Reproduction LC0 (21days) > 10.0 mg/L, NOEC (21days) > 10.0 mg/L
Ÿ Statistical results, as appropriate : by Duncan’s multiple range test , NOEC is >10.0 mg/L
⇒ Remarks:

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UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE• Biological observations· summary of the effect of the test substance on the reproduction of Daphnia magna. The values given are
the mean, cumulative values for parent animals which survived the exposure for 21 days
Conc.
(mg/L)

0.0
1.0
5.0
10.0

Survivalof parent
animals

Live young per live
parental animal

%

n

100
100
100
90

108.3
105.0
119.2
107.7

±1 SD *
21.2
17.9
19.1
9.1

Dead young per live
parental animal
n

0.0
0.0
0.0
0.0

±1 SD *
0.0
0.0
0.0
0.0

Aborted eggs per live
parent animal
n

0.0
0.0
0.0
0.0

±1 SD *
0.0
0.0
0.0
0.0

1SD *: 1 standard deviation·Was control response satisfactory? : Yes

CONCLUSIONSFor Disodium disulphite, LC0 is 10.0 mg/L and NOEC is >10.0 mg/L. Experimental designs and results were
well documented and prescribed conditions in the guideline were well satisfied.
⇒ Remarks :DATA QUALITY
Ÿ Reliabilities : Reliable without restrictions.
⇒ Remarks :REFERENCES (Free Text)
BASF AG, Dept. of ecology, unpublished data (2057/93) 10, December, 1993.

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OECD SIDSDISODIUM DISULPHITE
2) SKIN IRRITATIONTEST SUBSTANCE• Identity : Disodium disulphite –powder (CAS No. 7681-57-4)• pH : 4.4 – 4.9 in a 20 % solution of water⇒ Remarks : Source : Hoechst AG purity : > 96 %METHOD• Method/guideline followed : OECD TG 404• Type : in vivo semiocclusive study• GLP : yes• Year (study performed) : 1981
• Species/Strain : Rabbit / Albino New zealand• Sex : not specified• No. of animals: 3• Total dose : 500 mg of disodium disulphite• Vehicle : 0.1 mL saline solution (NaCl 0.9 %)• Exposure time : 4 hours• Grading scale : Draize

REMARKS FIELD FOR TEST CONDITIONS_ Controls : none
_ Area of exposure : about 24 h before treatment the dorsal surface (ca. 25 cm 2) was shaved with electronic
clippers. Only animals with intact skin were used.

RESULTS
Not irritating•

Cumulative total and percent responders : all 3 animals responded with slight erythema with an averagescore of 0.4. No edema was observed.

REMARKS FIELD FOR RESULTS• Numerical skin grades at 1, 24, 48 and 72 hours :Individual Animal Grades for erythema and eschar
1 h after patch removal (animal No. 1,2,3)0, 0, 024 h after patch removal (animal No. 1,2,3)
1, 1, 148 h after patch removal (animal No. 1,2,3)0, 0, 172 h after patch removal (animal No. 1,2,3)0, 0, 0No edema was observed.
• Delayed grading scores at 7 to 14 days : not necessary to perform– Reversible effects : all effects were reversible by 72 hours.
– Erythema/edema findings : only erythema was observed

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UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE– Other dermal lesion including systemic effects : none

CONCLUSIONS
The disodium disulphite was not irritating to the skin of the rabbit.

DATA QUALITY• Reliabilities : Reliable without restriction

REFERENCES (Free Text)
Hoechst AG, Unpublished studies (87.1241), 11.Aug.1987

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OECD SIDSDISODIUM DISULPHITE
3) EYE IRRITATIONTEST SUBSTANCE• Identity : Disodium disulphite –fine crystal powder (CAS No. 7681-57-4)• pH : 4.4 – 4.9 in a 20 % solution of water⇒Remarks : Source : Hoechst AG, Purity : > 96 %, impurities : Na2SO3 (2 %), N a2SO4(2 %)METHOD• Method/guideline followed : OECD TG 405• Type : in vivo study• GLP : yes• Year (study performed) : 1987
• Species/Strain : Rabbit / Albino New zealand• Sex : not specified• No. of animals per dose : 3• Dose : 100 mg/eye•

Observation period (list the time points at which grading/scoring took place) : 1, 24, 48, and 72 hours after
application of the test substance, as well as 7 days after application.

• Exposure time : 24 hours• Scoring method used : Draize

REMARKS FIELD FOR TEST CONDITIONS_ Anesthetics :_ Vehicles :_ Eye washed : rinsed after 24 hr exposure

RESULTS• Corrosive (yes or no) : no
• Individual scores : 1 h, 24 h, 48 h, 72 h, and 7 d for animals 1, 2, 3
- Conjunctiva chemosis 1 h : 3, 3, 3; 24 h : 2, 2, 3; 48 h : 1, 1, 2; 72 h : 1, 2, 2; 7 d : 1, 1, 3
- Conjunctiva redness : 1 h : 2, 3, 3; 24 h : 3, 3, 3; 48 h : 3, 2, 3; 72 h : 3, 3, 3; 7 d : 2, 3, 3
- Iris : 1 h : 1, 0, 1; 24 h : 1, 1, 1; 48 h : 1, 1, 1; 72 h : 1, 1, 1; 7 d : 1, 1, 1
- Corneal opacity : 1 h : 1, 1, 1; 24 h : 2, 2, 2; 48 h : 2, 2, 2; 72 h : 1, 2, 2; 7 d : 2, 3, 3
- Corneal opacity fluor : 24 h : 3, 1, 2; 72 h : 2, 4, 4; 7 d : 2, 3, 2
In addition, on day 7 corneal vascularization was slightly noticeable in two animals and clearly noticeable in one
animal.
• Overall irritation score : not specified• Tool used to assess score : additional evaluation of corneal opacity under UV light after fluorescein
installation at the 24 and 72 hour time points, as well as after 7 days.
• Description of lesions : corneal opacity and vascularization of the cornea

REMARKS FIELD FOR RESULTS
•
•
•

106

Number of affected : all animals
Score reduced time (up to 21 days) :Reversible effect : based on the effects seen after 7 days (corneal opacity and vascularization of the

UNEP PUBLICATIONSOECD SIDSDISODIUM DISULPHITE

cornea) the effects were probably not reversible.

CONCLUSIONS
The disodium disulphite was irritating to the eye in rabbit.

DATA QUALITY• Reliabilities : Reliable without restriction

REFERENCES (Free Text)
Hoechst AG, Unpublished studies (87.1293), 21.Aug. 1987

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OECD SIDSDISODIUM DISULPHITE
4)

CARCINOGENICITYTEST SUBSTANCE• Identity : Disodium disulphite (CAS No 7681-57-4)⇒ Remarks : Source : Amsterdamsche Chinine Fabriek (ACF)- purity 95 ~ 99 % (as calculated from SO 2
determinations)

METHOD•

Method/guideline followed : Other•

Test type : Long-term feeding study•

GLP : No•Year : 1971•

Species : Rat•

Strain : Wistar•

Route of administration : oral (feed)•

Duration of test : about 2 year•

Doses/concentration levels : 0, 0.125, 0.25, 0.5, 1.0, 2.0 %•Sex : male & female•

Exposure period : 104 weeks(F0 and F1 generations), 30 weeks(F2 generations)•

Frequency of treatment : 7 days/ week•

Control group and treatment : basal diet containing 0 % Na2S2O 5•

Post exposure observation period : None•

Statistical methods : Student’s t test and chi-square test

REMARKS FIELD FOR TEST CONDITIONS–Test Subjects· Age at study initiation : Newly weaned rats
· No. of animals per sex per dose : 20 animals/dose/sex– Study Design
6 experimental groups were maintained on a diet containing 0, 0.125, 0.25, 0.5, 1.0 and 2.0 % of disodium
disulfite. 20 animals/dose/sex were used. All rats (F0-generation) were mated at wk 21 of treatment within
their dose group. Half of them were mated again at wk 34. 10 males and 10 females were selected atweaning from the 1st litters of each group to become the F1a-generation. The F0-generation rats, as well as
selected F1a-generation rats were maintained on their diets for a period of 104 wk. Rats of the F1ageneration were mated at wk 12 and 30 to produce the F2a and F2b generations. 10 males and 15 females
from the F2a litters were mated to produce an F3a- and F3b-generation by pairing them on wk 14 and 22.
The resulting litters were discarded after weaning, and the parents were kept on their diets for about 30 wk.
The number of animals used for histological examinations after 1 year was 4-5 from the F0 animals; after
104 weeks of treatment was 19-24/dose/sex from the F0-gen. and the F1-gen. together; and after 30 wk oftreatment, 10-15/dose/sex were used from the F2-generation. An extensive set of tissues from each rat of theF0-, F1a- and F2a-gen. were examined microscopically. Several special stains were also employed. For
more details of the method used see section 16.
· Vehicle : none(stock diet containing the test substance)· Satellite groups and reasons they were added : none
· Organs examined at necropsy (macroscopic and microscopic)
Interim observation on organ weight and pathological changes.
Mircoscopic : heart, kidneys, liver, spleen, brain, testes, ovaries, pituitary, thyroid, parathyroids,
adrenals, thymus, lungs, trachea, salivary glands, gastro-intestinal tract, pancreas, urinary bladder,skeletal muscle, spinal cord, femoral nerve, skin, bone marrow(sternum), axillary and mesenteric lymph
nodes, exorbital lachrymal gland, aorta, mammary glands, uterus, prostate, seminal vesicle and

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coagulating gland.

RESULTS•NOAEL(NOEL)
1.91 % as actual dose (942 Na2S2O5 mg /kg bw/day)•

Actual dose received by dose level : The SO 2 determinations on the diets showed considerable losses ofsulphite. Proportionally the losses of sulphite decreased with increasing dietary levels of sulphite as shown
below table.
Level of Na2S2O5 added todiet(%)
0.125
0.25
0.5
1.0
2.0

Loss of Na2S2O 5 after storagefor 1 week at –18 °C (%)
22
14
12
8
5

Actual dose level of Na2S2O 5
(%)
0.098
0.215
0.44
0.92
1.91

REMARKS FIELD FOR RESULTS–

General condition, mortality and growth : The general condition of the rats remained good during thefirst 72 week in the F0-generation as well as in the two descendant generations. After this, aging
symptoms developed in many rats and mortality increased rapidly in nearly all group. The survival in thesulphite groups was generally higher than in the controls, except in the case of males of the F1generation given 2 % sulphite. No deaths occurred in the females of the same group.

–

Type and incidence of tumours
The number of lymphoreticular pulmonary tumours in males decreased with increasing levels of sulphite
in the diet. The incidence of thyroid and pituitary tumours in the control group of the male rats was
exceptionally low, whereas those noted in the various test groups represented numbers normally found in
the strain of rats used. All other neoplasms occurred in a random manner with no apparent er lationshipbetween number, location or type of tumours and the treatment.

Dietary level (%)
No.of rats examined
Total no. of rats with tumors
Lung:
Malignant lymphoreticular tumor
Thyroid:
Light-cell tumor: adenoma
Pituitary
Adenoma
Carcinoma
AdrenalPhaeochromocytoma
Benign :Malignant :Cortical adenoma
Cortical carcinoma
Ovary granulose cell tumor
Uterus Polyp
Leukemia

0
24
17

0.125
24
22

Males
0.25
0.5
25
25
21
18

1
25
17

2
25
18

0
25
20

0.125
25
12

Females
0.25
0.5
25
25
16
15

1
25
17

2
25
14

10

10

8

6

6

3

2

5

4

5

2

4

1

8

6

4

8

5

4

5

5

4

3

7

0
0

5
2

5
1

1
2

4
2

4
2

8
0

2
1

4
1

3
1

4
0

0
0

6
1
0
0

4
2
0
1

8
1
0
0

5
4
1
0

1
1
0
0

7
0
0
0

0

0

1
0
0
0
1
3
2

0
0
0
0
0
3
0

4
0
0
0
0
4
1

1
0
0
0
0
3
0

2
0
0
0
0
3
2

2
0
0
0
1
3
0

3

1

2

0

CONCLUSIONS
Non-neoplastic observations were found in this study.
DATA QUALITY•

Reliabilities : Reliable with restrictions

REFERENCES (Free Text)

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DISODIUM DISULPHITE

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