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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Principles of method if other than guideline:
European Community (EC) Council Directive 96/54/EC, Annex
IV.D, replacing EC Directive 67/548/EEC, Part B : Methods
for the Determination of Toxicity and other Health Effects;
B.7: "Repeated Dose (28 days) Toxicity (oral)". Official
Journal of the European Communities No. L248, September
1996.


Organisation for Economic Co-operation and Development
(OECD), OECD Guidelines for Testing of Chemicals, Section 4,
Health Effects, No. 407: "Repeated Dose 28-day Oral
Toxicity Study in Rodents", Paris Cedex, 27 July 1995.


Japanese Chemical Substances Control Law 1987 according to
the notification of November 21, 2003 by Ministry of Health,
Labor and Welfare (No. 1121002), Ministry of Economy, Trade
and Industry (No. 2) and Ministry of Environment (No.
031121002).


United States Environmental Protection Agency (EPA). Health
Effects Test Guidelines, OPPTS 870.3050, Repeated dose 28-
day oral toxicity study in rodents. Office of Prevention,
Pesticides and Toxic Substances (7101), EPA 712-C-00-366,
July 2000.
GLP compliance:
yes (incl. certificate)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): TC4ASO2
- Substance type: multi-constituent
- Physical state: white powder
- Analytical purity: 97.8%
- Composition of test material, percentage of components: 92.9% 4-tert-Butylsulfonylcalix(4)arene (CAS 204190-49-8)
4.9% 4-tert-Butylsulfonylcalix(8)arene
- Lot/batch No.: AYUI-1Y
- Expiration date of the lot/batch: 07 October 2007
- Stability under storage conditions: Stable
- Storage condition of test material: At room temperature in the dark

Test animals

Species:
other: Rat: Wistar Crl:(WI) BR
Sex:
male/female

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: Propylene glycol. Accuracy, homogeneity and stability over 5 hours of formulations of test substance in propylene glycol were demonstrated by analyses.
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 60 mg/kg bw/day
Male: 5 animals at 250 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 60 mg/kg bw/day
Female: 5 animals at 250 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
Mortality:

No mortality occured during the study period.


Clinical signs:

No clinical signs of toxicity were noted during the
observation period.


Functional observations:

Hearing ability, pupillary reflex, static righting reflex
and grip strength were normal in all animals.

Laboratory findings:
Haematology:

Haematological parameters of treated rats were considered
not to have been affected by treatment.


Clinical Biochemistry:

No toxicologically significant changes in clinical
biochemistry parameters were observed.

Effects in organs:
Macroscopic:

Macroscopic observations at necropsy did not reveal any
alterations that were considered to have arisen as a result
of treatment with the test substance.


Organ weights:

Organ weights and organ to body weight were considered to
have been unaffected by treatment.


Microscopic:

There were no microscopic findings recorded which could be
attributed to treatment with the test substance.

Effect levels

open allclose all
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

Any other information on results incl. tables

Comments:
An extra 5 animals per sex in the control and high dose
group (1000 mg/kg/day) were allowed 14 days of recovery.


No toxicologically significant changes in body weights and
body weight gain were recorded.


Food consumption before or after allowance for body weight
was similar between treated and control animals.

Applicant's summary and conclusion

Conclusions:
Classified as: Not classified