Reaction mass of calcium sulfate and potassium sulfate and sodium sulphate

Endpoint summary

Description of key information

Oral:
- Calcium sulfate, dihydrate, LD50 > 2000 mg/kg bw (according to OECD Guideline 420).
- Potassium magnesium sulfate, LD50>2000 mg/kg bw (according to OECD Guideline 425).
Dermal:
Potassium sulphate, LD50 > 2000 mg/kgbw (according to OECD Guideline 402). 
Inhalation:
Calcium sulfate, LC50 > 3.26 mg/L (3260 mg/m3) (according to OECD Guideline 403)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

3 260 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity:

Studies in Animals

No reliable acute oral toxicity study is available for potassic extracts. However, data on some of the individual salts present in the potassic extracts or on structurally similar salts are available. Moreover, the possibility to apply the results obtained on the mono-constituents to the multiconstituent substance, is supported in the ECHA Guidance on QSAR and grouping of chemicals (2008). Several second source publications show a high oral LD50 value for potassium sulphate. Indeed, a summary report from Henkel (Henkel, unpublished) stated oral administration of 2 - 5 ml of a solution in water of sodium sulfate (concentration not given) to 10 rats (mean body weight 270 gram), with an observation period of 8 days. No symptoms were observed and the LD50 was given as > 10 g/kg. This is confirmed by reliable acute oral toxicity studies performed in rats according to OECD 425 with potassium magnesium sulfate (and ammonium phosphate sulfate) (LD50 > 2000 mg/kg bw). Moreover, in an acute oral toxicity following OECD Guideline 420, calcium sulfate, dihydrate was administered to rats. The LD50 was given as > 2000 mg/kg bw. No mortality was observed within every dose level. There were no specific clinical signs during test period. Rats showed normal body weight gain during test period. No abnormal necropsy observations in relation to administration of calcium sulfate, dihydrate were observed.

Studies in Human

There is one fully controlled study on the effects of sodium sulfate in humans (Heizer et al., 1997). In a range-finding study, four healthy volunteers received controlled amounts of drinking water with stepwise increasing concentrations of sulfate, up to 1200 mg/l of sulfate, over six consecutive two-day periods. The calculated dose of sodium sulfate was 0, 21, 31.5, 42, 52.5 and 63 mg/kg/day. Apar from a faster stoll passage, no abnormalities were found. In a subsequent two-day study volunteers received 0 mg on the first day and 63 mg sodium sulfate on the second day. A clinically insignificant increase in stool volume, decrease in stool consistency and passage time was noted, but no change in stool frequency or diarrhea.

In clinical practice sodium sulfate, alone or with magnesium sulfate, was used as a laxative to induce rapid emptying of the gut, in doses of 300 mg/kg up to 20 grams maximum for an adult. The laxative action is ascribed to fecal fluid retention caused by the hygroscopic action of unresorbed sodium sulfate in the large intestine (Gilman et al., 1980). Use of sodium sulfate has been gradually abandoned and the substance has been replaced by other laxatives because of the uncontrollable watery diarrhea and accompanying abdominal cramping it tends to produce.

Conclusion

Animal data on the acute oral toxicity of the individual salts in the potassic extracts or analogue of the sulfate category show no deleterious effects and, taken together with the human data, this do not support classification. Then, in view of the large body pool of sulfate anions and the high body turnover, the acute oral toxicity of sulfate must be low, as long as the counter-ion is not toxic.

Acute dermal toxicity:

For acute dermal toxicity a reliable OECD 402, EC B.3, EPA and JMAFF guideline study in rats with potassium sulfate is available, showing an LD50 > 2000 mg/kg bw. No mortality, effects on body weight and gross pathology were observed. However, some effects on the skin were: Chromodacryorrhoea was noted in two males and one female on Day 1. Scales and scabs were noted in one male and one female between Day 5 and 11. No valid data are available on the acute dermal toxicity for sodium sulfate and calcium sulfate. Then, the data with potassic sulfate is used in a read-across approach to assess the acute dermal toxicity of sodium and calcium sulfate and therefore to assess the toxicity of the potassic extracts. Based on these results, Potassic extracts do not have to be classified for acute dermal toxicity.

Acute inhalation toxicity:

In an acute inhalation toxicity study (nose only), rats were exposed to Calcium sulfate, dihydrate at 3.26 mg/l during 4h. No deaths occurred. Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection and wet fur. Animals recovered quickly to appear normal from Day 2 post-exposure. One male animal exhibited a reduced body weight gain during week 1 but recovered to show normal development during week 2. Normal body weight development was noted for all other animals during the course of the study. With the exception of one instance of dark patches on the lungs, no macroscopic abnormalities were detected at necropsy. The LC50 is greater than 3.26 mg/l (3260 mg/m³). In addition, there is one study (Last et al., 1980) in which rats were exposed to 10 mg/m³ of sodium sulfate as a dry particle aerosol in air with 50% humidity (particle size 1.15 µm Mean Mass Aerodynamic Diameter) for 72 hours. These six male rats served as negative controls for rats exposed to various concentrations of sodium sulfite and sodium hydroxymethane sulfonate. Clinical effects were not reported. Compared to the filtered-air control group, no significant changes in various inflammation-related lung tissue parameters, determined post-mortem, were found (DNA, RNA, protein, wet-to-dry weight ratio, glycoprotein secretion in trachea explants). Moreover, mucociliary clearance was investigated with ammonium sulfate and appeared not to have been significantly affected in male rats exposed to 3.6 mg/m³ (0.4 µm) for 4 h. In conclusion, there were no deaths or signs of overt toxicity in animals exposed to individual salts present in the potassic extracts or analogue by inhalation and therefore, the available data do not support classification.

Gilman A.G., Goodman L.S. and Gilman A. (eds). (1980). Goodman and Gilman's the Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co. Inc. p.1005.

Heizer W.D., Sandler R.S., Seal E. Jr., Murray S.C., Busby M.G., Schliebe B.G. and Pusek S.N. (1997). Intestinal effects of sulfate on drinking water on normal human subjects. Dig. Dis. Sci. 42 (5): 239 -246.

Henkel, KGgA, unpublished data, Archive-No. TBD 710056.

Justification for classification or non-classification

Studies with the individual salts present in the potassic extracts or analogue show that potassic extracts do not have to be classified for acute toxicity according to Directive 67/548/EC and the CLP regulation.