Reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate

Endpoint summary

Description of key information

Ammonium sulphate is of relatively low acute toxicity (LD50, oral, rat: 2000 - 4250 mg/kg bw; LD50 dermal, rat/mouse > 2000 mg/kg bw; 8-h LC50, inhalation, rat > 800 mg/m³). Clinical signs after oral exposure included staggering, prostration, apathy, and laboured and irregular breathing immediately after dosing at doses near to or exceeding the LD50 value. In humans, inhalation exposure to 0.1 - 0.5 mg ammonium sulphate/m³ aerosol for two to four hours produced no pulmonary effects. At 1 mg ammonium sulphate/m³ very slight pulmonary effects in the form of a decrease in expiratory flow, in pulmonary flow resistance and dynamic lung compliance were found in healthy volunteers after acute exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

4 250 mg/kg bw

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

Acute oral toxicity was evaluated in a reliable study similar to OECD 401 with rats, in which the oral LD50 was determined to be 4250 mg/kg bw (95% confidence limits: 3788 – 4769; BASF, 1969). At doses near to or exceeding the LD50 value, staggering, prostration, apathy, and laboured and irregular breathing were observed immediately after dosing. On the next day, secretion out of eyes and mouth, and reddened eyes and nose were seen. In the post-exposure observation days the surviving animals were without clinical symptoms. No clinical signs were noted at doses up to and including 2500 mg/kg bw, respectively.

In another study conducted according to OECD guideline 423, LD50 values >2000 mg/kg bw were reported for rats and mice, respectively (Yamanaka et al., 1990).

In addition, a case of a fatal poisoning with ammonium sulphate was reported from an 85-year-old woman after drinking an unspecified amount of ammonium sulphate dissolved in beer in a suicidal attempt (Sato et al., 1999). Heart, lung, liver and kidney did not show any pathological findings on macro- and microscopic examination. There was mild petechial haemorrhage in the gastric fundic mucosa without any erosion or corrosion. In serum, ammonium and sulphate ions were significantly increased (25 000 µg/dL and 12.35 mEq/L, resp.; normal range 30 - 80 µg/dL and 0.25 - 0.35 mEq/L, resp.).

 

Inhalation

Regarding acute inhalation toxicity, no study conducted according to current guidelines and/or standard procedure is available. However, several studies can be used for assessment since they were well conducted and documented and do provide essential data. Moreover, several studies providing human data are available, and are therefore used as key studies while the animal data are used as supporting studies to evaluate acute inhalation toxicity.

In a study with human volunteers, exposure of 13 healthy male subjects to an ammonium sulphate aerosol for four hours at a concentration of 0.133 mg/m³ (MMAD 0.55 µm) produced no significant effects related to 19 measured pulmonary parameters, including specific airway resistance, forced vital capacity, and forced expiratory flow (Stacy et al., 1983).

No significant changes in pulmonary parameters were reported from five healthy and six asthmatic volunteers exposed for 2 h to ammonium sulphate (0.1 - 0.3 mg/m³; MMAD 0.3 - 0.6 µm) (Avol et al., 1979).

At 1 mg sulphate/m³ (MMAD 1 µm) ammonium sulphate inhaled for 16 min produced a small but significant decrease in expiratory flow in sixteen healthy subjects (Utell et al., 1982).

Pulmonary function (measured by body plethysmography and spirometry), and bronchial reactivity to metacholine were not affected in 20 non-smoking volunteers after a 4-hour exposure to 0.5 mg/m³ ammonium sulphate (Kulle et al., 1984). Exposure included two 15-minute light to moderate exercise stints per day in the exposure chamber.

In summary the given human data show, that except for some minor but non-significant changes in pulmonary parameters, no adverse effects were described.

Besides the studies providing data on acute inhalation toxicity in humans, following studies with animals are used for hazard assessment:

The acute inhalation toxicity of ammonium sulphate aerosols (average diameter 1 - 3 µm) was examined in guinea pigs (Pepelko et al., 1980). Groups of six animals were exposed to an aerosol concentration of 500 - 600 or 600 – 700 mg/m³, while a group of 20 animals was exposed to an aerosol concentration of 800 – 900 mg/m³, respectively. One animal in the mid dose group and 8 animals of the high dose group died as a result of acute shock and airway constriction after 8 hours exposure. Based on these results, the LC50 is estimated to be > 800 mg/m³.

In an inhalation risk test, 12 rats were exposed to a saturated atmosphere of ammonium sulphate, which was generated by blowing air through a layer (5 cm) of substance (BASF, 1969). After an exposure period of 8 hours, no mortality, no abnormal clinical signs and no pathological findings were reported.

Acute inhalation toxicity of ammonium sulphate was also analyzed in a study with 10 – 12 male Wistar rats nose only exposed to an aerosol with a concentration of 3.6 mg/m³ and a MMAD of 0.4 µm for 4 hours (Phalen et al., 1980). As a result, mucociliary clearance was found to be not significantly affected by ammonium sulphate exposure.

 

Dermal

Acute dermal toxicity of ammonium sulphate was evaluated in a limit test performed according to OECD 434, where groups of three male and female Wistar rats and ddY mice received dermal applications of 2000 mg/kg bw, respectively (Yamanaka et al., 1990). As result, a LD50 value of > 2000 mg/kg bw is reported for both rats and mice, respectively, while details on clinical signs and necropsy findings were not given.

Justification for classification or non-classification

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