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Administrative data

Description of key information

A 28-day and 90-day oral toxicity study in rats identified a NOAEL of 1000 mg/kg bw/day, the highest dose tested.  The substance has not been tested for repeat-dose toxicity via dermal or inhalation exposure.

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:
subchronic
Species:
rat

Additional information

OECD 407 - 28 Day Repeated Dose Toxicity Study

The test substance was studied for oral toxicity potential in a 28-day gavage study in Crl:CD(SD) rats. The study was performed to GLP and in accordance with OECD Test Guideline 407. Dosage levels were 0, 100, 300 and 1000 mg/kg/day. The low- and mid-dose groups comprised five male and five female rats each, while the control and high-dose groups each comprised 10 animals of each sex. Following the 28 days of dosing, five animals per sex per group were euthanised; the remaining five animals per sex from the control and high-dose groups were maintained for a 14-day recovery period before sacrifice. Parameters evaluated included mortality, clinical observations, body weight, food consumption, locomotor activity, functional observational battery of assessments for neurotoxicity, haematology, serum chemistry, urinalysis, organ weights, gross pathology and histopathology. No test substance-related adverse effects on any of the evaluated parameters were reported. The no-observed effect level (NOEL) and no-observed adverse effect level (NOAEL) for this study is 1000 mg/kg/day, the highest dose tested.

OECD 408 - 90 Day Repeated Dose Toxicity Study

The potential toxicity of EC 294-705-2 was evaluated after daily administration by oral gavage to Sprague Dawley rats (10/sex/dose) for a minimum of 90 consecutive days according to OECD guideline 408, including evaluation of potential neurotoxicity by functional observation battery (FOB) and motor activity (MA) assessment. Dosage levels were 0,100,300, and 1000 mg/kg bw/day. A concurrent control group received the vehicle (PATG [50% polyethylene glycol (PEG) 400, 20% Akoline MCM, 20% Tetraglycol, and 10% Gelucire 44/14]).

Test substance related effects were limited to clinical observations of red, clear, yellow or brown material findings on various body surfaces and non-adverse microscopic findings of minimal to moderate nodularmacrophage hyperplasia and macrophage necrosis in the mesenteric lymph nodes. Based on the absence of adverse effects up to and including the highest dose tested, the NOAEL in this study is 1000 mg/kg bw/day.

Chronic Toxicity

It is proposed that further oral toxicity testing (chronic toxicity study identified in REACH Annex X) of the test substance is not appropriate, in view of the absence of toxicity in the 28-day and 90 day oral toxicity study in rats despite the administration of doses of up to 1000 mg/kg/day. This proposal is made in accordance with Rules 8.6.3 and 8.6.4 of Annex X of the REACH Regulation.

Justification for classification or non-classification

A 28-day and 90-day oral toxicity study in rats identified a NOAEL of 1000 mg/kg bw/day, the highest dose tested. Therefore, no repeat-dose specific target organ toxicity was seen and no classifications under CLP are required based on the results of the study. The substance has not been tested for repeat-dose toxicity via dermal or inhalation exposure.