Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

No adverse effects observed in a 28-day repeated dose toxicity test in rats at doses up to 1000 mg/kg bw/d.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
Preliminary study to guideline study, in the spirit of GLP
Qualifier:
no guideline available
Version / remarks:
14-day dose range finding study for OECD 422
Principles of method if other than guideline:
14-day dose-range finding study for the OECD 422 study
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 20.8 - 26.0°C (target: 22 ± 3 °C)
Relative humidity: 35 - 70% (target: 30 - 70%)
Ventilation: 15-20 air exchanges/hour
Housing/Enrichment: Rodents were housed up to 5 animals of the same sex per cage
Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice
Water was provided ad libitum
Route of administration:
oral: gavage
Vehicle:
olive oil
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
14 days
Frequency of treatment:
Daily
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
300 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
5 males and 5 females per group were tested at each dose concentration
Control animals:
yes, concurrent vehicle
Observations and examinations performed and frequency:
Animals were inspected for signs of morbidity and mortality twice daily (at the beginning and end of each working day). Clinical observations were made twice daily, before and after treatment, at the beginning and towards the end of the working day as practical.
Sacrifice and pathology:
On Day 14, after an overnight period of food deprivation of the surviving animals, blood samples were collected from all animals immediately prior to the scheduled necropsy by heart puncture under pentobarbital anaesthesia.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Immunological findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects
Remarks:
NOAEL > 1000 mg/kg bw/d
Key result
Critical effects observed:
no
No test item related systemic effects were seen in any of the dose groups
Conclusions:
ZEF 6099/100 administered by oral gavage to Wistar rats for 14 consecutive days at dose levels of 100, 300 or 1000 mg/kg bwt/day in olive oil had no adverse effects. The NOAEL was greater than 1000 mg/kg bw/d.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
adequate

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

Mode of Action Analysis / Human Relevance Framework

Not applicable; no significant toxicity observed.

Additional information

In an OECD 422 guideline study of ZEF 6099/100 in the Wistar rat at oral doses of 100, 300 and 1000 mg/kg bw/d, the test material did not result in adverse effects in clinical signs, body weight, organ weights, food consumption, neurological assessment, haematology, coagulation, clinical chemistry, urinalysis, or gross/histopathology.  There were no effects in reproductive parameters nor in F1 offspring viability, clinical signs, development or macroscopic examination.  The NOAEL is greater than 1000 mg/kg bw/d.

Justification for classification or non-classification

In repeated oral (gavage) dose toxicity testing in the rat for 28 days according to the OECD 422 method, no significant toxicity was observed. The NOAEL is greater than the highest dose tested, 1000 mg/kg bw/d. The criteria for Regulation EC No. 1272/2008 for classification for specific organ toxicity, repeated exposure, or for other hazards not included in the STOT-RE classification scheme, are not met. The substance is not classified.