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Administrative data

Description of key information

OECD 422: NOAEL = 1000 mg/kg bw/day (WIL Research Europe, 2013)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

A combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test of N,Nā€-Hexane-1,6-diylbis[Nā€™-benzylurea] was conducted in rats by oral gavage according to OECD 422 guideline and GLP (WIL Research Europe, 2013).

 

Rationale for dose levels

Based on the results of a dose range finding study, the dose levels for this combined 28-day oral gavage study with reproduction/developmental toxicity screening test were selected to be 100, 300 and 1000 mg/kg bw/day.

 

Study outline

After acclimatization, four groups of ten male and ten female Wistar Han rats were exposed by oral gavage to the test substance at 0, 100, 300 and 1000 mg/kg bw/day.

Males were exposed for 29 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females were exposed for 42 -53 days, i.e. during 2 weeks prior to mating, during mating, duringpost-coitum, and during at least 4 days of lactation.

 

Evaluated parameters

The following observations and examinations were evaluated: mortality / viability, clinical signs (daily), functional observations and locomotor activity (Week 4 (males); end of lactation (females)),  body weight and food consumption (at least at weekly intervals), clinical pathology (Week 4 (males); end of lactation (females)), macroscopy at termination, organ weights and histopathology on a selection of tissues, and reproduction/developmental parameters, consisting of mating, fertility and conception indices, precoital time, number of corpora lutea and implantation sites, gestation index and duration, parturition, maternal care, sex ratio and early postnatal pup development (mortality, clinical signs, body weights and macroscopy).Formulations were analyzed once during the study to assess accuracy, homogeneity and stability.

Results/discussion

Accuracy, homogeneity and stability of formulations were demonstrated by analyses.

 

No parental, reproduction or developmental toxicity was observed up to the highest dose level tested (1000 mg/kgbw/day).

 

Conclusion

Based on these results, a parental, reproduction and developmental No Observed Adverse Effect Level (NOAEL) of at least 1000 mg/kg bw/day was derived.

Justification for classification or non-classification

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