Morpholinium, 4-[2-[2-[(2-hydroxyphenyl)methylene]hydrazinyl]-2-oxoethyl]-4-methyl-, chloride (1:1)

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Additional information

A GLP compliant Combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test was performed according to guideline OECD 422 (WIL Research Europe B.V. 2013). After acclimatization, four groups of ten male and ten female Wistar Han rats were exposed daily by oral gavage to the test substance, Tinocat ES 96000, at 0, 80, 250 and 800 mg/kg bw/day (dose level selection based on the results of a 14-day dose range finding study). Males were exposed for 29 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females were exposed for 43- 54 days, i.e. during 2 weeks prior to mating, during mating, during post-coitum, and during at least 4 days of lactation. Formulation analysis showed that the formulations were prepared accurately, were homogenous, and were stable for at least 5 hours at room temperature.Parental results:Females at 800 mg/kg bw/day had higher absolute and relative spleen weights. Microscopic alterations associated with treatment were present in the spleen and sternal bone marrow of females. These were characterized by an increased severity of primarily erythroid hemopoeitic foci in the spleen of treated animals and a parallel increase in the incidence of minimal erythroid hyperplasia in the bone marrow. However, this alteration may have reflected a slightly increased erythrocyte turnover in treated animals, which remained within physiological limits. Taken together, the changes noted for females at 800 mg/kg bw/day were considered to be treatment related but not adverse.Reproductive results:No reproductive toxicity was observed up to the highest dose level tested (800 mg/kg bw/day). Eight pregnant females is normally the minimum accepted number per group recommended by the OECD 422 guideline, though there were only seven pregnant females and litters available for evaluation in the control group. A thorough assessment was still possible because all litters were in good condition and an extensive historical control database is also available to support evaluation of treated groups with the concurrent controls.Developmental results:No developmental toxicity was observed up to the highest dose level tested (800 mg/kg bw/day). In conclusion, treatment with Tinocat ES 96000 by oral gavage in male and female Wistar Han rats at dose levels of 80, 250 and 800 mg/kg bw/day revealed no parental, developmental or reproductive toxicity up to 800 mg/kg bw/day. Based on these results, a parental, reproduction and developmental No Observed Adverse Effect Level (NOAEL) of 800 mg/kg bw/day was derived.

Short description of key information:
Based on the results of a combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test of TINOCAT ES 96000 in rats by oral gavage, no reproductive and developmental effects were observed. Therefore, a NOAEL of 800 mg/kg bw/day was derived.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

Based on the available data, the test substance is not classified with regard to toxicity to reproduction according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP), respectively.