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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Endpoint:
repeated dose toxicity: oral
Adequacy of study:
other information

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Annex V
GLP compliance:
yes
Limit test:
yes

Test animals

Species:
other: Rat (Wistar)

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: Water (Milli-U)
Details on oral exposure:
Method of administration:
Daily 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: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
50 mg/kg/day: No treatment-related findings noted.


150 mg/kg/day: No treatment-related findings noted.


1000 mg/kg/day:


- Unscheduled death of 4 males and 2 females.

- Lethargy, muscle twitching, hunched posture, piloerection,
emaciated appearance, calm behaviour, and uncoordinated
movements (males), hunched and/or cramped posture and
emaciated appearance (females).

- Slightly low motor activity of the sole surviving group 4
male.

- Reduced body weight (gain) (males/females).

- Reduced (relative) food consumption (males).

Laboratory findings:
50 mg/kg/day: No treatment-related findings noted.


150 mg/kg/day: No treatment-related findings noted.


1000 mg/kg/day:


- Decreased white blood cell and lymphocyte counts,
prothrombin time and potassium values, increased neutrophil
counts, mean corpuscular haemoglobin concentration values,
bilirubin, cholesterol, total protein, sodium and albumin
levels in the one male which survived to study termination.
Alanine aminotransferase activitiys (by 64%) and bilirubin
levels (by 46%) were statistically significantly increased
in females.

Effects in organs:
50 mg/kg/day: No treatment-related findings noted.


150 mg/kg/day: No treatment-related findings noted.


1000 mg/kg/day:


-Apparently treatment-related findings observed at
necroscopy were thickened stomach (3/5 males) and
discoloured thymus in 4/5 males. Isolated instances of other
findings were observed but these were not considered to be
treatment-related.

-No clear treatment-related effect on organ weights were
noted in males. In females, absolute and relative liver
weights were increased by 22% and 38% respectively.

-The following findings were observed following a
histopathological assessment: atrophy of the testes (4/5),
lymphoid atrophy of the spleen in males (4/5), myleoid
hyperplasta at the sternum in 5/10 animals and lymphoid
atrophy of the thymus (5/5 males). All these findings were
reported at 1000 mg/kg/day.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
150 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
150 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Classified as: Not classified