Reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate

Endpoint summary

Description of key information

Based on read-across following an analogue approach:
Oral:
In an oral chronic toxicity study the NOAEL of ammonium sulphate was 256 and 284 mg/kg bw/day in males and females, respectively. Except for changes in organ weights, no treatment-related effects were noted.
Inhalation:
In the available studies, neither local effects in the respiratory tract nor signs of systemic toxicity were observed after repeated subacute exposure of rats to 300 mg/m³ of ammonium sulphate aerosol.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

256 mg/kg bw/day

Study duration:

chronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

300 mg/m³

Study duration:

subacute

Species:

rat

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:

 

Oral

Oral repeated dose toxicity was evaluated in a study equivalent to OECD guideline 453 (Ota et al., 2006). Groups of 10 male and female Fischer 344 rats were fed with a diet containing 0.1, 0.6, or 3% ammonium sulphate for 52 weeks, while 50 animals per group were fed with a diet containing 1.5 and 3 % ammonium sulphate for 2 years, respectively. While no mortality was observed during and after the 52 week dosing period, the survival rate during the 2 year study for control, 1.5% and 3.0% groups were 88%, 78% and 76% for males, respectively, and 76%, 80% and 80% for females, respectively. At the high dose level, the absolute and relative kidney weights were increased in both sexes, while absolute spleen weights were decreased. The relative liver weights were slightly increased only in the high dose males. No substance-related changes were found in all groups regarding body weight and weight-gain, haematological and clinical parameters, respectively. Gross pathology revealed no macroscopic changes different from that found in controls. The non-neoplastic and neoplastic lesions noted in the control and treatment groups were with no significant inter-group difference in their incidences or severity. Based on the result the NOAEL was estimated to be 0.6% ammonium sulphate in diet, corresponding to 256 mg/kg bw/d for males and 284 mg/kg bw/d for females, respectively.

In a subchronic study, groups of 10 male and female Fischer 344/DuCrj rats were fed with a diet containing 0.38, 0.75, 1.5, 3% ammonium sulphate for 13 weeks (Takagi et al., 1999). No substance-related effects were observed on body and organ weights as well as on haematological, serum biochemical, or histopathological examinations. However, diarrhoea was noted during the observation period in males of the 3% dose group. Based on these results, the NOAEL was set at 3% corresponding to 1792 mg/kg bw/day for males and 1975 mg/kg bw/day for females, respectively.

 

Inhalation

Groups of ten male rats were whole body exposed to an aerosol-concentration of 300 mg/m³ ammonium sulphate 8 h daily for 3, 7, or 14 days, respectively (Pepelko et al., 1980). The treatment did not alter arterial blood gases, pH, and bicarbonate. When body weights, vital capacity, respiratory volume and wet lung weights of rats exposed for 14 day were compared to controls, none of these parameters were significantly affected by the exposure. Histological examination of the trachea, bronchial lymph nodes and lungs also revealed no changes that could be definitely attributed to exposure. Thus, the NOAEC was set at 300 mg/m³air, the highest dose tested. In a pre-study, six male rats were exposed to an ammonium sulphate aerosol (1000 -1200 mg/m³) for three consecutive days (Pepelko et al., 1980). No gross toxicological effects were noted, so that a NOAEC of 1000 mg/m³ was defined.

Justification for classification or non-classification

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