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Administrative data

Description of key information

A repeated toxicity oral study with the test item SIKA Hardener LI was performed according to OECD guideline 408. The derived no observed adverse effect level (NOAEL) was 300 mg/kg bw/day. 
Testing via inhalation and dermal routes was waived, according to the REACH Regulation (EC) No 1907/2006/EEC, Annex VIII, 8.6.1.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
GLP and OECD Guideline study

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose toxicity: oral

A 90-day oral (gavage) toxicity study was performed with SIKA Hardener LI in male and female Hsd.Brl.Han: Wistar according to OECD Gudeline 408. The test item was administered orally to the test animals (n=15 animals/sex in the control and high dose groups, n= 10 animals/sex in the low and middle dose groups) once a day at 0 (vehicle control), 1000, 300 and 100 mg/kg bw/day doses corresponding to concentrations of 200 mg/mL, 60 mg/mL and 20 mg/mL, applied in a dose volume of 5 mL/kg bw for 90 days. 5 animals/sex in the control and high dose groups were observed without administration for four weeks (recovery observations). Polyethylene glycol 400 was used as vehicle. Animals were observed for mortality twice a day in the course of the study. Daily general clinical observations and weekly detailed clinical observations were performed. A functional observation battery was conducted in the last week of treatment. The body weight and food consumption were measured and evaluated weekly. Clinical pathology examinations (including hematology and clinical chemistry) and gross pathology were conducted one day after the last treatment and at the end of the recovery period. The absolute and relative weights of selected organs were determined. Full histopathology was performed on the preserved organs or tissues of the animals of the control and high dose groups including recovery groups. Thymus showing macroscopic changes was examined histologically in one male animal of 300 mg/kg bw/day group. SIKA Hardener LI caused salivation (male and female), changes in white blood cell count (females) and in spleen weight (females) at 1000 mg/kg bw/day in Hsd.Brl.Han: Wistar rats after the consecutive 90-day oral (gavage) administration. At 300 mg/kg bw/day, salivation was observed in some male and female animals during the treatment period. Slight changes in the white blood cell count and spleen weight relative to body weight in female animals were judged to be toxicologically not relevant. At 100 mg/kg bw/day, there was no test item related effect. Based on these observations the No Observed Adverse Effect Level (NOAEL) was determined as follows: NOAEL: 1000 mg/kg bw/day for male animals; NOAEL: 300 mg/kg bw/day for female animals.

Additionally, a second repeated dose toxicity study (supporting study) is available: A 28-day oral (gavage) toxicity study was performed with SIKA Hardener LI in male and female CRL:(WI) BR Wistar rats according to EC method B.7 and OECD guideline 407. Dose levels administered in this study were selected based on data obtained during a 14-day dose-range-finding toxicity study. The test item was administered to control and treatment groups (n= 5 animals per group and sex) at doses of 0, 50, 350 and 1000 mg/kg bw/day doses levels, at a 4 mL/kg bw in PEG 400. Stability and homogeneity of test item in the vehicle was confirmed. Administration of SIKA Hardener LI did not lead to any toxicologically adverse effects at dose levels of 50, 350 or 1000 mg/kg bw/day. There were no changes in the animal clinical condition, body weight or food consumption. No treatment related effects noted in clinical pathology (haematology, coagulation and clinical chemistry). There were no macroscopic or microscopic findings, or changes in the organ weights. In conclusion, under the conditions of this study, the no observed effect level (NOEL) for SIKA Hardener LI was 1000 mg/kg bw/day (limit dose).

Repeated dose toxicity: dermal

Repeated dose toxicity testing via the dermal route was waived, according to the REACH Regulation (EC) No 1907/2006, Annex VIII, 8.6.1.

Repeated dose toxicity: inhalation

Repeated dose toxicity testing via inhalation was waived, according to the REACH Regulation (EC) No 1907/2006, Annex VIII, 8.6.1.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
only one subchronic study available

Justification for classification or non-classification

Based on a chronic repeated oral toxicity study, test item SIKA Hardener LI was not classified and labelled according to Directive 67/548/EEC (DSD) and to Regulation (EC) No 1272/2008 (CLP).