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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Based on the analogy approach, Sulfates of potassium, sodium and calcium, by-product from fermentation is not considered to be hazardous for reproductive toxicity. A conservative NOAEL of 790 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.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
790 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
GLP compliant read across studies performed according to current guidelines (reliability 1 or 2)
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Quality of whole database:
GLP compliant read across studies performed according to current guidelines (reliability 1 or 2)
Additional information

No reproduction toxicity study 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 (OECD 422, NIER, 2002; OECD 421, Harlan laboratories; OECD 422, 2010; Product Safety Laboratories, OECD 422, 2002 respectively). Rats were exposed via the oral route 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). At the end of each study, no adverse effect related to treatment was observed on parental animals or reproductive function. All the NOAEL values for reproductive toxicity were found to be greater than the highest dose levels tested: 790 (converted for Calcium sulfate), 1000 (Sodium sulfate) and 1500 mg/kg bw/day (Potassium sulfate).

Based on the available data, the three Sulfates salts (source substances) have also the same pattern of toxicological behavior regarding the reproductive 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 reproductive toxicity. A conservative NOAEL of 790 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.

Effects on developmental toxicity

Description of key information

Based on the analogy approach, Sulfates of potassium, sodium and calcium, by-product from fermentation is not considered to be hazardous for developmental toxicity. A conservative NOAEL of 1500 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.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 500 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Read across studies performed according or similar to current guidelines (reliability 1 or 2)
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

No developmental toxicity test 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.

A study was conducted (equivalent to OECD 414, Food and Drug Research laboratories, 1974) to evaluate the teratogenicity potential of Calcium sulfate (CAS 7778-18-9). Pregnant rats, mice and rabbits were orally (gavage) exposed to a dose of 1600 mg/kg bw/day for 10 (rats and mice) or 13 (rabbits) consecutive days. The results showed no clearly discernable effects on nidation, or on maternal or fetal survival. The NOAEL for both maternal and developmental toxicity was determined to be 1600 mg/kg bw/day for the three species. A non-guideline study (Seidenberg et al, 1987) was performed on Sodium sulfate (CAS 7757-82-6). Pregnant mice were orally (gavage) exposed to Sodium sulfate at 2800 mg/kg bw/day from day 8 to 12 of gestation. No materno- or embryo-teratogenic toxicity was observed. The NOAEL for both maternal and developmental toxicity was determined to be 2800 mg/kg bw/day. A combined repeated dose toxicity study with the Reproduction/Developmental Toxicity Screening Test (OECD 422, Product Safety Laboratories, 2002) is available for Potassium sulfate (CAS 7778-80-5). Rats were exposed via the oral route (gavage) for 28 days (males) or 53 days (females). Concentrations used were up to 1500 mg/kg bw/day. No treatment-related maternal toxic effects were observed (no deaths, no signs of overt clinical toxicity, no effects on body weight, food consumption, or food efficiency). Additionally, no treatment related effects on gestation length, gestation index, litter size, offspring survival indices, sex ratio, offspring bodyweight, or macropathology for offspring was observed. Based on these results, the NOAEL for both maternal and developmental toxicity was defined to be equal or greater than 1500 mg/kg bw/day.

Based on the available data, the three Sulfates salts (source substances) have also the same pattern of toxicological behavior regarding the developmental 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 developmental toxicity. A conservative NOAEL of 1500 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 for both maternal and developmental toxicity.

Justification for classification or non-classification

Reproduction toxicity by oral route: While no information on the reproduction toxicity is available for the target substance, the available data on the three read-across substances showed no adverse effect for reproduction 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.

Developmental toxicity by oral route: While no information on the developmental toxicity is available for the target substance, the available data on the three read-across substances showed no adverse effect for development 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.

Additional information