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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: GLP study

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
1997

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Method B7 of directive 92/69/EEC and Japanese Ministry of Health and Welfare (MHW) and Ministry of International Trade and Industry (MITI) Guideline 1986.
Principles of method if other than guideline:
Specifically designed to meet MITI guidelines
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
425-220-8
EC Name:
-
Cas Number:
5945-33-5
Molecular formula:
C39H34O8P2
IUPAC Name:
4-(2-{4-[(diphenoxyphosphoryl)oxy]phenyl}propan-2-yl)phenyl diphenyl phosphate; 4-{2-[4-({[4-(2-{4-[(diphenoxyphosphoryl)oxy]phenyl}propan-2-yl)phenoxy](phenoxy)phosphoryl}oxy)phenyl]propan-2-yl}phenyl diphenyl phosphate

Test animals

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Polyethylene glycol 400
Details on oral exposure:
Oral gavage, once daily, for 28 consecutive days


Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 10 animals at 0 mg/kg bw/day
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 10 animals at 1000 mg/kg bw/day
Female: 10 animals at 0 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 10 animals at 1000 mg/kg bw/day
Details on study design:
The test material was adminstered to 3 groups, each of five male and five female rats, by gavage, for twenty eight consecutive days. A control of five male and five female rats was dosed with vehicle alone. Two recovery groups, each of five male and five females, were treated with the high dose (1000mg/kg/day) or the vehicle for twenty eight consecutive daysand then maintained without treatment for further forteen days.


Clinical signs, body weight development, food and water consumption were monitored during the study. Haematology, blood Chemistry and urinalysis were evaluated for all non-recovery group animals at the end of the treatment period and for recovery group animals at the end of the treatment-free period.
All animals were subjected to gross necropsy examination and histopathological evaluation of selected tissus from non-recovery high dose and control animals.

Examinations

Observations and examinations performed and frequency:
Mortality, clinical observations, body weight, food and water consumption, Haematology, blood chemistry, urinalysis, pathology, histopathology.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
No mortalities. No treatment related indications of toxicity were observed
Parameters tested: Mortality, clinical observations, body weight, food and water consumption, Haematology, blood chemistry, urinalysis,
pathology, histopathology.

Effect levels

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Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day (nominal)
Sex:
male/female
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

No mortalities. No treatment related indications of toxicity were observed

Applicant's summary and conclusion

Conclusions:
NOEL after 28 days exposure is 1000 mg/kg/day, Classified as: Not classified
Executive summary:

A robust summary is attached.

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