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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral
Remarks:
other: not provided by SNIF#001-4.2.10-01
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Experimental work carried out by a trusted and reliable laboratory.

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: ANNEX V
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
other: Rat (CD-derived)

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: distilled water. Solutions adjusted to pH 5.2 with phosphoric acid
Details on oral exposure:
Method of 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: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 10 mg/kg bw/day
Male: 5 animals at 100 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 10 mg/kg bw/day
Female: 5 animals at 100 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
There were no deaths and no clinical signs of toxicity were observed.

Laboratory findings:

The following haematological and biochemical changes were generally within the historical control range nad thus of doubtful toxicological significance /the test laboratory discounted the findings)

In the top dose males, statistically significant decreases were seen in neutrophils and platelets, with a dose dependent trend at other doses. Cholesterol levels, were lower in top dose males and females, and in intermediate dose males, compared to concurrent controls, reaching statistical significance in male of both dose groups. Decreased ALT in top dose females ans decreased phosphorus in top dose males was also noted.

Effects in organs:
At the top dose, slight increases inrelative organ weights (<20%) were noted for the liver and kidney in both sexes. Minimal centrilobular hepatocyte vacuolation was noted in two to dose males, but this was not considered to be of toxicological signifcance.

Effect levels

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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:
1 000 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:
Classifies as: Not classified
Executive summary:

Data for this end point has been supplied by ECHA. Ref SNIF#001 -4.2.10.1, ECHA letter dated 04/09/2013