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Administrative data

Description of key information

The potential toxicity of post crystallization of ammonium sulphate aqueous phase products resulting from ammoniac neutralisation of sulphuric acid waste waters formed during methylmethacrylate synthesis, following daily oral administration (gavage) to rats was evaluated in a 4-weeks repeated dose toxicity study. The No Observable Effect Level (NOEL) was established at 250 mg/kg/day and the No Adverse Observable Effect Level (NOAEL) was established at 1000 mg/kg/day, based on a slight gastric irritation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

The potential toxicity of the test item following daily oral administration (gavage) to rats for 4 weeks, was evaluated according to OECD (No. 407, 03 October 2008) and Commission Regulation (EC) (No. 440/2008, B.7, 30 May 2008) guidelines (Rokh, 2010c). The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. The test item was administered daily by oral route for 29 days to 3 groups of five male and five female Sprague-Dawley rats at the dose-levels of 62.5, 250 and 1000 mg/kg/day under a dosage‑volume of 5 mL/kg/day. Another group of five males and five females received the vehicle, purified water, under the same experimental conditions and acted as control group. The test item was administered as a solution in the vehicle and the dosage form preparations were made extemporaneously before each administration. Each control and test item dosage form preparation was analysed for concentration of the test item in weeks 1 and 4. Animals were checked at least twice a day for mortality and at least once a day for clinical signs. A detailed clinical examination was performed once a week. A Functional Observation Battery (FOB), including detailed clinical examination, assessment of reactivity to manipulation and different stimuli and motor activity, was evaluated in each animal once at the end of the treatment period. Body weight was recorded once before group allocation, on the first day of treatment, and then once a week until the end of the study. Food consumption was recorded once a week during the study. Hematology, blood biochemistry and urinalysis investigations were performed on all animals at the end of the treatment period. On completion of the treatment period, the animals were sacrificed and a complete macroscopic post‑mortem examination was performed on all animals. Selected organs were weighed and designated tissues specimens were preserved. A microscopic examination was performed on designated tissues from control and high-dose animals and on all macroscopic lesions and on stomach with forestomach from low- and intermediate-dose animals.

The test item concentrations in administered dosage forms remained within an acceptable range of variation when compared to the nominal values. No unscheduled mortality occurred during the study. No relevant clinical signs related to treatment with the test item were noted. There were no signs of disturbance of neurobehaviour in any of the test item-treated animals. Body weight and food consumption were not affected by the treatment with the test item. Hematology, blood biochemistry and urinalysis parameters did not reveal any toxicologically significant effect of the test item. No important or statistically significant changes in organ weights or organ-to-body weight ratios and no treatment-related necropsy findings were noted in any of the treated animals. A minimal acanthosis was noted in the limiting ridge of the forestomach, extending into the forestomach, in 4/5 males and 1/5 females treated at 1000 mg/kg/day with occasional increase in exocytosis of small mononuclear cells. No such change was noted inforestomachof animals treated at 62.5 or 250 mg/kg/day. This finding may be related to a local effect of the test item. Due to the very limited magnitude of this change, it was not considered to be adverse to the health of the affected animals.

The test item was administered daily by oral route for 29 days to Sprague-Dawley rats at the dose‑levels of 62.5, 250 and 1000 mg/kg/day under a dosage-volume of 5 mL/kg/day. No relevantin vivofindings were noted in any of the test item-treated animals. Hematology, blood biochemistry and urinalysis parameters were not considered to be affected by the treatment with the test item. There were no treatment-related organ weights and macroscopic changes. At the high-dose, microscopic findings related to local effect of test item were observed in the forestomach and consisted of minim epithelial acanthosis in most males and one female. At the intermediate- and low-dose, no treatment-related microscopic changes were observed. The No Observable Effect Level (NOEL) was established at 250 mg/kg/day and the No Adverse Observable Effect Level (NOAEL) was established at 1000 mg/kg/day, based on a slight gastric irritation.

Justification for classification or non-classification

No classification is warranted for repeated dose toxicity under EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008.