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Administrative data

Description of key information

No classified for STOT-RE.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
79 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP compliant read across studies performed according to current guidelines (Reliability 1 and 2).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No repeated dose toxicity data is available for Sulfates of potassium, sodium and calcium, by-product from fermentation. However, data are available on the three sulfate salts: Sodium sulfate (CAS 7757-82-6), Potassium sulfate (CAS 7778-80-5) and Calcium Sulfate (CAS7778-18-9) and a read across approach was used to fulfill data requirement for this endpoint.

The read across approach is based on the results of the transformation/dissolution study performed on the registered substance (Envigo Research Limited, 2016). This study demonstrated that Sulfates of potassium sodium and calcium, by-product from fermentation is completely transformed/dissolved (98.1%) within 30 minutes at pH 2 and at 37 °C. Hence, upon systemic uptake into the body, the registered substance will be present in dissolved form as sulfate anions and potassium, sodium and calcium cations. Furthermore, the three salts Sodium sulfate, Potassium sulfate and Calcium Sulfate are also completely dissociated in aqueous media in Sulfate anions and the respective cations, then this justifies that toxicity data can be read across from the three salts Sulfates of potassium, Sulfates of sodium and Sulfates of calcium to the target substance for systemic toxicity endpoints.

Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening or Reproduction/Developmental Toxicity Screening Tests were performed on Calcium sulfate (Calcium Sulfate dehydrate (CAS 10101-41-4) was tested), Sodium sulfate and Potassium sulfate (CAS 7778-80-5) (OECD 422, NIER, 2002; OECD 421, Harlan laboratories; OECD 422, 2010; Product Safety Laboratories, OECD 422, 2002 respectively). Rats were exposed to concentrations up to 1000 mg/kg (except for Potassium sulfate where the high dose used was 1500 mg/kg bw/day) for 2 weeks (Calcium sulfate) or 4 weeks for females and 7 weeks for males (Sodium and Potassium sulfate). No adverse effect related to treatment was observed for Potassium sulfate and Sodium sulfate and NOAEL values for general toxicity were found to be greater than the highest dose levels tested: 1000 (Sodium sulfate) and 1500 mg/kg bw/day (Potassium sulfate). The NOAEL for Calcium sulfate anhydrous was 79 mg/kg/day (100 mg/kg bw for calcium sulfate dihydrate) for males based on a significant decrease in TP (Total Protein), ALB (Albumin), BUN (Blood Urea Nitrogen), and CREA (Creatinine) at the 300 mg/kg b.w./day and 1,000 mg/kg b.w./day groups. No effects were observed in females.

Two chronic toxicity studies are also available on the analogues Potassium sulfate and Sodium sulfate. For Potassium sulfate (read across from Ammonium sulfate), in a combined chronic / carcinogenicity study (Similar to OECD 453, published data 2006), rats were fed a diet containing the test substance at concentrations of 0, 0.1, 0.6, or 3% (average daily intakes of 0, 42, 256, and 1527 mg/kg bw/d for males and 0, 48, 284, and 1490 mg/kg bw/d for females) for 1 year. Absolute and relative kidney weights were increased at the high dose level for both sexes. Absolute spleen weights were decreased and relative liver weights were increased in high dose males. No macroscopic changes were recorded by gross pathology, except for massive nodular or focal lesions suggesting neoplastic changes. At histopathological examination, non-neoplastic and neoplastic lesions were noted in the control and treatment groups, with no significant inter-group difference in their incidences or severity. The NOAEL of Ammonium sulfate was determined to be 0.6% diet (equivalent to 256 and 284 mg/kg bw/d in males and females, respectively) and the compound is non-carcinogenic under the conditions of the study. For Sodium sulfate, a non guideline chronic toxicity study (published data 1975) is available (the carcinogenicity part of the study is not reliable). Male rats were fed 0.84 % sodium sulfate (corresponding to approx. 320 -400 mg/kg bw) in the diet for 27 and 44 weeks respectively. No adverse effects were detected and a NOAEL of ≥ 320 mg/ kg bw was deduced.

Based on the available data, the three Sulfates salts (source substances) have also the same pattern of toxicological behavior regarding the repeated dose toxicity endpoint and are not considered to represent any hazard. Based on the analogy approach, Sulfates of potassium, sodium and calcium, by-product from fermentation is not considered to be hazardous for repeated dose toxicity. A conservative NOAEL-subacute of 79 mg/kg bw/day (lowest NOAEL amongst the three source substances) is attributed to the registered substance Sulfates of potassium, sodium and calcium, by-product from fermentation.

Justification for classification or non-classification

Repeated dose toxicity by oral route: While no information on repeated dose toxicity is available for the target substance, the available data on the three read-across substances showed no adverse effect upon repeated exposure by the oral route. Based on the read-across rationale and the weight of evidence, the substance is not considered to meet the criteria for classification according to Regulation (EC) No 1272/2008.

Specific Target Organ Toxicity– Repeated Exposure: Based on the data available on the read-across substances and on the read across approach, the target substance is not likely to exhibit significant toxic effects arising from a repeated exposure. As a result, the substance is not considered to meet the criteria for classification according to Regulation (EC) No 1272/2008.

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