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Administrative data

Description of key information

In an OECD TG 416, 10 male and 10 females from each dose group were evaluated for functional, behavioural and sensory observations.  There were no treatment-related changes.

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Link to relevant study records
Reference
Endpoint:
neurotoxicity: oral
Remarks:
developmental
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD Guideline under GLP conditions - satellite group as part of two generation reproduction study in the rat.
Qualifier:
according to
Guideline:
other: OECD TG 416 - satellite group
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The concentration of the test substance in the dietary admixtures was determined by high performance liquid chromatography mass selective (HPLC/MS) using an external standard technique.
Frequency of treatment:
Daily in diet
Remarks:
Doses / Concentrations:
3000, 6000 and 12000 ppp (250, 500 and 1000 mg/kg, respectively)
Basis:
nominal in diet
No. of animals per sex per dose:
10 animals of either sex per dose
Control animals:
yes, plain diet
Details on study design:
During week 10, extensive functional observations and opthalmoscopic examinations were performed on ten selected animals of either sex from each dose group, together with haematology and blood chemistry assessment. The animals were not fasted before sampling.

The ten selected F0 males and ten F0 females from each treatment and control group were observed for signs of functional/behavioural toxicity once weekly.

During week 10, the ten F0 selected animals were assessed for sensory reactivity to auditory, visual and proprioceptive stimuli, grip strength and motor activity.

See reproductive toxicity summary for additional details on reproductive parameters.
Neurobehavioural examinations performed and frequency:
Once weekly
Behaviour (functional findings):
no effects observed
Details on results:
There were no treatment related effects in the functional performance parameters measured for the F0 generation animals. There were no treatment related effects in behavioural parameters measured for the F0 generation. There were no treatment related effects in the sensory reactivity parameters measured for the selected F0 generation animals.

Behavioural assessment: All inter and intra group differences in urination, defection and transfer arousal scores were considered to be a result of normal variation for rats of the strain and age used and were of no toxicological importance.
Hunched posture was evident in 12000 ppm (1000 mg/kg) females during Weeks 4, 5 and 6 assessments, however in isolation this finding was considered of no toxicological importance.
Dose descriptor:
NOEL
Effect level:
12 000 ppm (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Highest dose tested (1000 mg/kg)
Remarks on result:
other: Generation: maternal (migrated information)
Conclusions:
In an OECD TG 416, 10 male and 10 females from each dose group were evaluated for functional, behavioural and sensory observations. No treatment-related changes were observed.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
chronic
Species:
rat

Additional information

Neurotoxicity:

Key study

In an OECD 416 study conducted under GLP conditions, on male and female Sprague-Dawley rats, the NOEL for neurotoxicity related effects of Molyvan 855 is 1000 mg/kg b. w.


Justification for selection of effect on neurotoxicity via oral route endpoint:
Well conducted study in accordance with OECD Guideline and GLP.

Justification for classification or non-classification

Neurotoxicity:

According to Regulation EC No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, Molyvan 855 is not classified for Neurotoxicity.