Registration Dossier

Administrative data

Description of key information

Subacute NOAEL (rat): 1000mg/kg bw (Annex V; GLP)

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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Annex V guideline study with GLP compliance
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: Annex V
GLP compliance:
yes
Limit test:
no
Test material information:
Composition 1
Species:
other: Rat (Crj: CD(SD))
Route of administration:
oral: unspecified
Vehicle:
olive oil
Details on oral exposure:
Method administration:
gavage
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 6 animals at 0 mg/kg bw/day
Male: 6 animals at 8 mg/kg bw/day
Male: 6 animals at 40 mg/kg bw/day
Male: 6 animals at 200 mg/kg bw/day
Male: 6 animals at 1000 mg/kg bw/day

Female: 6 animals at 0 mg/kg bw/day
Female: 6 animals at 8 mg/kg bw/day
Female: 6 animals at 40 mg/kg bw/day
Female: 6 animals at 200 mg/kg bw/day
Female: 6 animals at 1000 mg/kg bw/day

Details on results:
CLINICAL OBSERVATIONS:
MORTALITY DATA:
There were no deaths during the study.

CLINICAL OBSERVATIONS:
No treatment-related observations.


BODY WEIGHT:
No abnormalities were noted in the dosing period

FOOD CONSUMPTION:
No abnormalities were noted during the dosing period


LABORATORY FINDINGS:
HAEMATOLOGY:
No abnormalities were noted at the end of the study period

BLOOD CHEMISTRY:
No abnormalities were noted at the end of the study period


EFECTS IN ORGANS:
NECROPSY:
No abnormalities were noted at necropsy at the end of the study period


ORGAN WEIGHTS:
Increased absolute and relative liver weights were noted in males at 1000 mg/kg bw/day dose group. No other related changes were noted.


HISTOPATHOLOGY:
No treatment-related effects were observed.

Cyst formation in the kidney was noted in both sexes of the 1000 mg/kg bw/day dose groups. This was not considered to be due to the test substance as this observation is common in this strain of rat and was also noted in control group animals.

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day
Dose descriptor:
NOEL
Effect level:
200 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day
Critical effects observed:
not specified
Conclusions:
Classified as: Not classified
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:
Information from migrated NONS file, as per inquiry number 06-0000020961-70-0000, permission to refer granted by ECHA

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

Additional information

One 28 day repeated dose toxicity study in rats was available. In the subacute toxicity key study (Annex V/GLP) the substance was administered to Crj: CD(SD) rats (6/sex) by gavage in olive oil (7 days/week for 28 days) at dose levels of 0, 8, 40, 200, 1000 mg/kg bw/day.

There were no deaths during the study. There were no treatment-related effects in clinical signs, body weight, food consumption, hematology or clinical chemistry. Increased absolute and relative liver weights were noted in males at 1000 mg/kg bw/day dose group. No other related changes in organ weights were noted. No abnormalities were noted at necropsy at the end of the study period and no treatment-related histopathological findings were observed.

The NOEL was 200 mg/kg bw/day and the NOAEL was 1000 mg/kg/ bw/day.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Only 1 key study available

Justification for classification or non-classification

Based on the available information in the dossier, the substance Flyadd-3 (CAS No. 135861-56-2) does not need to be classified as specific target organ toxicity (repeated) when considering the criteria outlined in Annex I of 1272/2008/EC.