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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
sub-chronic toxicity: oral
Type of information:
other: SNIF
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)

Data source

Referenceopen allclose all

Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
2008
Reference Type:
other: SNIF#001-4.2.10-01
Title:
Unnamed
Year:
2008

Materials and methods

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

Test material

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Method of administration:
Dietary admixture
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
100 mg/kg bw/day
Basis:
no data
Remarks:
Doses / Concentrations:
300 mg/kg bw/day
Basis:
no data
Remarks:
Doses / Concentrations:
1000 mg/kg bw/day
Basis:
no data
No. of animals per sex per dose:
Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 100 mg/kg bw/day
Male: 5 animals at 300 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 100 mg/kg bw/day
Female: 5 animals at 300 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day
Control animals:
yes, plain diet

Results and discussion

Results of examinations

Details on results:
Clinical observations:
Achieved dosage

The mean achieved dosages corresponded to approximately 9,
27 and 90 mg/kg/day at 100, 300 and 1000 ppm respectively.


Mortality

No unscheduled deaths occurred during the study.


Clinical signs

Bright yellow urine was noted in all test item-treated
animals. At 1000 ppm, all the animals showed yellowish coat.
In absence of other observations (at clinical pathology and
histopathology), this variation was most probably related
to the test item/metabolite excretion.


Functional Observation Battery

Except for the yellowish coat and bright yellow urine
already noted during the weekly clinical signs session, no
test item treatment-related changes were noted in the
autonomy, physiology or neurotoxicology parameters. No
differences of toxicological significance were seen in motor
activity.


Body weight

At 1000 ppm, during the first week of dosing, males gained
18% and females 36% less weight than controls. This resulted
in a slightly lower female mean body weight gain over the
whole dosing period (-18%), which was most probably related
to the slightly low food consumption.


Food consumption

At 1000 ppm, from days 1 to 4, males ate 11%, p < 0.01 and
females 16%, p < 0.01 less food than controls. After this
transient observation, food consumption was comparable to
control values.

Laboratory findings:
Hematology and blood biochemistry

No test item treatment-related effects were noted at any
concentration tested.

Effects in organs:
Organ weights

At 1000 ppm, when compared to controls, statistically
significant higher relative liver weight (+16%) was noted in
males. This difference did not correlate with any
macroscopic and microscopic findings or blood biochemical
changes, and thus was considered to be of minor
toxicological importance.


Macroscopic post-mortem examination

At 1000 ppm, yellow hair was noted in all rats.


Microscopic examination

3/5 and 2/5 males, respectively treated at 300 and 1000 ppm
showed sporadic necrotic germ cells in the testes; another
(1/5) male at 1000 ppm had vacuolated Sertoli cells together
with a few sloughed in epididymis. Although the severity of
these changes, which can be found sporadically in untreated
rats, was minimal to slight and poorly dose-related, a
relationship to treatment with the test item could not be
excluded.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
100 ppm
Based on:
test mat.
Sex:
male
Basis for effect level:
other: The NOAEL (No Observed Adverse Effect Level) was identified at 100 ppm (equivalent to 9 mg/kg/day) in the males.
Dose descriptor:
NOAEL
Effect level:
1 000 ppm
Based on:
test mat.
Sex:
female
Basis for effect level:
other: The NOAEL (No Observed Adverse Effect Level) was identified at 1000 ppm (equivalent to 90 mg/kg/day) in females.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

EU guidelines indicating that R48 should be applied cite 'severe organ damage' such as 'widespread or severe necrosis' (Directive 2001/59/EC, Annex 6, page 276). As the effects seen in this study were neither severe nor widespread, in isolation they were considered insufficient to justify assignment of R48.

Applicant's summary and conclusion

Conclusions:
Classified as: Not classified