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Description of key information

Summary of 28-day repeated dose toxicity study

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
62.5 mg/kg bw/day
Study duration:

Additional information

Testing for subacute oral toxicity (28 applications within 29 days) found the following; slight decreases in erythrocyte counts, hemoglobin and hematocrit values were observed in females after repeated oral administration of the test substance at the daily dose of 1000 mg/kg body weight. Males showed slightly increased liver weights. Slight decreases in erythrocyte counts (females) and slightly increased liver weights (males) were also observed at the daily dose of 250 mg/kg body weight. A compound-related effect cannot be excluded. However, the changes were minor and there were no histopathological correlates for anemia or liver damage. Likewise, clinical chemistry parameters were inconspicuous, and histopathological examination did not reveal any compound-related effect.No compound-related adverse effects were observed at the dose level of 62.5 mg/kg body weight per day.The discoloration of adipose tissue observed at all dose levels is considered not to be of toxicological relevance.With regard to the present study the 'No Observed Adverse Effect Level" (NOAEL) is 62.5 mg/kg body weight per day. However, no clear toxic effects were observed at the dose levels of 250 and 1000 mg/kg per day.


Furthermore, it is considered that the substance is unlikely to be inhaled and the physicochemical and toxicological properties suggest low potential for significant rate of absorption through the skin. In addition the results of laboratory animal studies show negligible acute dermal toxicity. In the 28 - days repeated dose study via oral gavage, administration does not exacerbate systemic toxicity effects which suggest bioavailability is low, thereby there is low toxicity potential. This intrinsic property/toxicity potential can therefore be extrapolated to repeated dermal and inhalation routes of administration. Further studies for these endpoints are therefore not appropriate both on predictive toxicology and animal welfare grounds.

The test substance does seem be absorbed from the gastrointestinal tract as demonstrated by coloured urine; however based on additional bioaccumulation data, significant bioaccumulation potential can most probably be excluded, despite colouration of adipose fat cells being observed at all dose levels. From the mutagenicity assays it appears that the test substance is not metabolised toward genotoxic structures. Review of the available data indicates that the substance does not exhibit a conspicuous toxicokinetic behaviour. The results from all studies with dermal exposure indicate that the test substance has insignificant or no dermal absorptive potential. Bioaccumulation of the test substance can therefore most probably be excluded.

Due to this fact, and the fact that exposure to the test substance is expected to be very low, based on its granular form and its identified uses, further animal testing such as a 90-day sub-chronic toxicity study is considered not to be justified.

The following information is taken into account for any hazard / risk assessment:

Assessment of subacute exposure by oral route is discussed below.

Value used for CSA (route: oral):

NOAEL: 62.5 mg/kg bw/day (subacute; rat)

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimish et al system. This ranking was deemed appropriate because the studies were conducted to GLP an in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds. As the effects are considered adaptive rather than toxicological, no classification is proposed.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for prolonged effects is therefore required.

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