Reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

1 288 mg/kg bw/day

Additional information

Based on the available information on absorption, distribution, metabolism and excretion properties as well as the available toxicological data of all three components of the reaction mass, it can be concluded, that ammonium sulphate is the most critical substance within the reaction mass. Thus, available data on ammonium sulphate will be used for hazard assessment of the toxicological properties of the reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate. Furthermore, available information on sodium sulphate was taken into account:

Toxicity to reproduction was evaluated in a one-generation study which was performed similar to OECD 415 (Andres and Cline, 1989). Groups of 10 female ICR mice were given sodium sulphate in drinking water at levels of 625, 1250, 2500 and 5000 mg sulfate/L (ca. 250 - 850, 480 - 2040, 1270 - 4320, 1790 - 6560 mg sulfate/kg bw) beginning one week prior to breeding and up to 14 days during lactation. At day 21 after parturition, the pups were weaned and the dams were rebred at first oestrus immediately following weaning. The effective number of dams per group was low with 4 - 9 animals in the first parity, and 4 in the second parity since only animals that delivered during each parity were used in the analysis. It was found, that the control mice, receiving only distilled water, consumed significantly less water than mice receiving sulfate treatments while control mice treated with sodium carbonate drank significantly more water than mice treated with sulfate. However, no differences were found in litter size, litter weaning weights, or gestational or lactational weight gain of the dams after sodium sulphate treatment, respectively. Besides this, no toxicity to the dams was found. It is worth to mention that the study exhibit clear limitations, as the pretreatment period was short, only females were treated, the litters were not histopathologically examined and no fertility indices were calculated. However based on the given data, no indication of toxicity to reproduction was evident, so that a NOAEL of 5000 mg/L corresponding to 1790 - 6560 mg/kg bw/d was estimated which corresponds to the highest dose tested.

Moreover, supporting evidence for the absence of effects on reproduction by the reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate is available from two repeated dose toxicity studies with ammonium sulphate.

In a combined chronic oral / carcinogenicity study, similar to the requirements of OECD 453, groups of 50 Fischer 344 rats /sex were fed a diet containing ammonium sulphate at concentrations of 1.5, or 3% for 2 years (Ota et al. 2006). These concentrations corresponded to average daily intakes of 564.1, and 1288.2 mg/kg bw/d for males and 4649.9, and 1371.4 mg/kg bw/d for females, respectively. As part of the examinations, all gonads of the males and females were examined histopathologically. Since no substance-related changes were observed in all dose groups, the NOAEL for reproductive toxicity was found to be 1288.2 mg/kg bw/d for males and 1371.4 mg/kg bw/d for females, respectively, which is the highest dose tested.

In a subchronic repeated dose toxicity study with ammonium sulphate, groups of 10 male and female Fischer 344/DuCrj rats were fed a diet containing 0.38, 0.75, 1.5, 3% ammonium sulphate for 13 weeks (Takagi et al., 1999). Since no histological changes of testes were observed (ovaries were not examined), the NOAEL for toxicity on male reproduction was set as 1792 mg/kg bw.

Short description of key information:
Together the data on toxicity on reproduction by sodium sulphate and ammonium sulphate suggest that no effects on reproduction by the reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate are expected.

Effects on developmental toxicity

Description of key information

Based on the read-across data on sodium sulphate, developmental toxicity after exposure to the reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate is not expected.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

2 800 mg/kg bw/day

Additional information

There are no studies available in which the potential developmental toxicity of the reaction mass was investigated. Furthermore, there are no data available on ammonium sulphate, which is considered to be the most critical substance within the reaction mass. However, information is available for sodium sulphate. Thus, data on sodium sulphate are used for hazard assessment of the potential developmental effects of the reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate:

Developmental toxicity was evaluated in a study with 28 female ICR mice which received an oral dose of 2800 mg /kg bw sodium sulphate on days 8 through 12 of gestation (Seidenberg et al., 1986). No evidence of maternal toxicity based on mortality and body weight gain or increased resorption rates was found. While the birth weight of the neonates was significantly increased compared to vehicle controls, sodium sulphate had no effect on pup survival as well as no adverse developmental effects. Thus, a NOAEL of 2800 mg/kg bw/d was deduced for maternal toxicity as well as for developmental toxicity.

Information on developmental toxicity was also derived in a one-generation study described in detail under discussion for toxicity on reproduction. This study was performed similar to OECD 415 (Andres and Cline, 1989). Groups of 10 female ICR mice were given sodium sulphate in drinking water at levels of 625, 1250, 2500 and 5000 mg sulfate/L (ca. 250 - 850, 480 - 2040, 1270 - 4320, 1790 - 6560 mg sulfate/kg bw) beginning one week prior to breeding and up to 14 days during lactation. At day 21 after parturition, the pups were weaned. No differences were found in litter size and litter weaning weights after sodium sulphate treatment, respectively. Based on this study, a NOAEL of 5000 mg/L corresponding to 1790 - 6560 mg/kg bw/d can be estimated, which is the highest dose tested.

Justification for classification or non-classification

Based on read-across, the available data on toxicity to reproduction are conclusive but not sufficient for classification according to the criteria of Directives 67/548/EEC (DSD) and 1272/2008/EC (CLP).