SIAM 25, 17-18 October 2007

US/ICCASIDS INITIAL ASSESSMENT PROFILE
17855-14-0
7778-80-5
7778-18-9

CAS Nos.

Sulfate category:potassium magnesium sulfate
calcium sulfate
potassium sulfate

Chemical Names

K 2 Mg(SO 4 ) 2
K 2 SO 4
CaSO 4Structural Formula

SUMMARY CONCLUSIONS OF THE SIAR
Category/Analogue Rationale
The sulfate category consists of the inorganic salts; potassium magnesium sulfate, potassium sulfate andcalcium sulfate. In biological fluids and aquatic environments, the soluble portion of each category
member completely dissociates into the sulfate ion (SO 4 2- ) and the corresponding cations; potassium(K + ), magnesium (Mg 2+ ) and calcium (Ca 2+ ) at neutral pH. Based on similar physicochemical,
ecotoxicological and toxicological properties, these sulfate compounds can be considered part of thesame category. Available data for calcium sulfate, dihydrate (CAS No. 10101 -41-4), the hydrated formof the category member, and previously presented in the OECD HPV program, is used as read -across tofill data gaps for the category members.
Human HealthUpon uptake into biological systems the inorganic salts in the sulfate category will dissociate into thesulfate ion and the corresponding cations. Potassium, magnesium and calcium will enter the bodyelectrolyte pool, and are not expected to play a significant toxicological role except at extremely highdoses. Sulfate is an important macronutrient for the normal function of cells and is the fourth mostabundant anion in human plasma (300 µM). Sulfate is absorbed from the intestine by an active t ransportsystem. All cells have sulfate transporters for the influx/efflux of sulfate. Sulfate is also used fordetoxification of compounds to sulfate esters, which can be excreted in the urine. Sulfate is eliminatedby the kidney and levels are regulated by the kidney through a reabsorption mechanism.
The acute oral LD 50 values for potassium magnesium sulfate is>2,000 mg/kg bw (OECD TG 423/425).No
adverse clinical signs were observed. Although only reliability 4 studies were available for calcium
sulfate and potassium sulfate, reported LD 50 s for these substances were consistent with that reported forpotassium magnesium sulfate. No reliable acute dermal or inhalation toxicity data in animals areavailable. There are no reliable skin/eye irritation or sen sitization studies for the sulfates. T he
category/analogue, calcium sulfate dihydrate is not a skin irritant or a skin sensiti zer in experiments
performed to OECD TG 404 and 406, respectively. Dust of anhydrous calcium sulfate has an irritanteffect on the respiratory tract and eyes in humans in occupational settings, which may be related to its
dessicant properties. The irritating effects of anhydrous calcium sulfate cannot be applied to the category
as a whole.
This document may only be reproduced integrally. The conclusions and recommendations (and their rationale) in thisdocument are intended to be mutually supportive, and should be understood and interpreted together.

SIAM 25, 17-18 October 2007

US/ICCAIn a combined repeated-dose/reproductive/developmental toxicity screening study (OECD TG 422) rats
were treated with 0, 50, 750 and 1,500 mg/kg bw/day potassium sulfate by oral gavage for 28 days. TheNOAEL was 1,500 mg/kg bw/day based on the absence of treatment related adverse effects at the hig hest
dose tested. In a combined repeated -dose/reproductive/developmental screening study (OECD TG 422),
rats were treated by oral gavage with 0, 100, 300 and 1000 mg/kg bw/day of the category analogue
calcium sulfate, dihydrate. Male rats showed changes in clinical chemistry (decreased levels of total
protein, albumin, blood urea nitrogen, and creatinine) at 300 mg/kg bw/day. Female rats showed notreatment related effects at the highest dose tested. The overall NOAEL was 100 mg/kg bw/day. As theclinical chemistry effects observed were only seen for calcium sulfate and not for potassium sulfate theeffects can be ascribed to the calcium ion. No repeated-dose studies for calcium sulphate and potassium
magnesium sulphate are available.
Potassium sulfate and calcium sulfate were negative with and without metabolic activation in Ames tests(OECD TG 471) and in vitro chromosomal aberrations tests (OECD TG 473). No in vitro genotoxicity
studies were available for potassium magnesium sulphate. Calcium sulfate dihydrate tested negative inthe micronucleus test in vivo up to the test concentration of 5000 mg/kg bw (OECD TG 474). The
members of the sulfate category are not considered to be mutagenic or genotoxic. No reliable data areavailable for carcinogenicity.
In a reproductive/developmental toxicity screening study (OECD TG 422), rats were treated with 0, 50,750 and 1500 mg/kg bw/day potassium sulfate by oral gavage. The NOAEL for reproduction anddevelopmental toxicity was 1,500 mg/kg bw/day based on the ab sence of treatment related adverse
effects at the highest dose tested. In a reproductive/developmental toxicity screening study (OECD TG422) with calcium sulfate dihydrate, rats treated up to 1000 mg/kg bw/day by oral gavage showed notreatment-related effects on reproduction and development. The NOAEL for reproductive anddevelopmental toxicity was 1000 mg/kg bw/day. Based on the available data, members of the sulfatescategory are not expected to be reproductive or developmental toxicants.
Environment
The sulfate category members are solid compounds with melting points ranging from 972 to 1450ºC anda relative density ranging from 2.31 to 2.97. Physico -chemical properties such as partition coefficientare not applicable for inorganic salts. Vapor pres sure for these inorganic salts is expected to benegligible. All substances from the sulfate category are soluble in water (2.09 -240 g/L) and dissociate
upon release into aqueous environments. The pKa of sulfuric acid describes the behavior of the sulfate
ion in aqueous solution; the equilibrium hydrogen sulfate/sulfate is 1.92 at 25 o C, which indicates that thesulfate dianion is present at pH 7. The cations are not expected to play a significant toxicological role at
low doses.
Any sulfate released into the environment will be distributed between water and soil. Sulfate isconstantly replenished by means of the sulfur cycle (sulfate/sulfide oxidation and reduction), and is
ubiquitous in the environment because of the abundance of sulfur on earth. Terrestr ial evaporite minerals
and the ocean are the largest reservoirs of planetary sulfate. The fate and behavior of sulfates, such asbioaccumulation, are also closely related to the sulfur cycle in air, soil and water. Living organisms
assimilate sulfate and reduce it to organic sulfur, an essential constituent of some amino acids andpolysaccharides. The reduction of sulfate by sulfate -reducing bacteria may produce hydrogen sulfide
under anaerobic conditions.
LC 50 values for the sulfate salts ranged from >63. 6 mg/L for potassium magnesium sulfate to 3,550 mg/L
for potassium sulfate for fish toxicity ( Oncorhynchus mykiss, Pimephales promelas and Lepomismacrochirus) and >100 mg/L for calcium sulfate dihydrate to >1970 mg/L for calcium sulfate for aquatic
invertebrates (Daphnia magna and Ceriodaphnia dubia). For calcium sulfate dihydrate a growth rateEC 50 for algae (Pseudokirchneriella subcapitata) of >100 mg/L was reported.
Exposure
This document may only be reproduced integrally. The conclusions and recommendations (and their rationale) in thisdocument are intended to be mutually supportive, and should be understood and interpreted together.

SIAM 25, 17-18 October 2007

US/ICCA

According to the latest figures (2004) the production volume for the sulfate category was estimated to beapproximately 6,100 ktonnes for Japan and the Nordic countries. Worldwide production of potassium
sulfate in 2006 was 5.12 Mtonnes. Potassium magnesium sulfate and potassium sulfate are mainly usedas fertilizers. In 2005-2006, 149,892 tonnes of potassium magnesium sulfate were consumed in theUnited States. Calcium sulfate (identified as phosphogypsum) is used as a fertilizer. Purified calcium
sulfate is also used in construction materials, as filler in paint, paper and too thpaste, and as a foodadditive (to coagulate soy milk, production of tofu, as a nutrient, dietary supplement, yeast food, doughconditioner, firming agent, and sequestrant).
Occupational exposure may occur in general during production, transport and proc essing of thesubstances. Field exposure of workers is possible during use as a fertilizer. The dermal and inhalationroutes will be the most important routes of exposure. In the United States, the Occupational Safety andHealth Administration has set permissible exposure limits (PEL) of 15 mg/m 3 (as total dust) and 5 mg/m 3PEL (as respirable fraction) (8 hour Time Weighted Average). Consumer exposure may occur whenusing fertilizers. In the Sponsor country, calcium sulfate and potassium sulfate are used as foodadditives and are generally recognized as safe (GRAS) by the Food and Drug Administration.
Environmental exposure is mainly limited to soil and water after use as a fertilizer.

RECOMMENDATIONS AND RATIONALE FOR THE RECOMMENDATION AND NATURE
OF FURTHER WORK RECOMMENDED
Human health: The chemicals are currently of low priority for further work. The chemicals do
not possess hazards for human health with the exception of irritation caused by anhydrous
calcium sulfate. This hazard does not warrant further work as it is related to transient effects. It
should nevertheless be noted by chemical safety professionals and users.
Environment: The chemicals are currently of low priority for further work for the environment
due to their low hazard profile.
It is recommended that the use of the chemicals as fertilizers be taken into account whenassessing environmental exposure.

This document may only be reproduced integrally. The conclusions and recommendations (and their rationale) in thisdocument are intended to be mutually supportive, and should be understood and interpreted together.