3-phenyl-7-[4-(tetrahydrofurfuryloxy)phenyl]-1,5-dioxa-s-indacen-2,6-dione

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Part of the SNIF file, which was accepted by the Belgian national authority for NONS

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))

Version / remarks:

84/449/EWG, B.7

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-phenyl-7-[4-(tetrahydrofurfuryloxy)phenyl]-1,5-dioxa-s-indacen-2,6-dione

EC Number:

413-330-9

EC Name:

3-phenyl-7-[4-(tetrahydrofurfuryloxy)phenyl]-1,5-dioxa-s-indacen-2,6-dione

Cas Number:

134724-55-3

Molecular formula:

Hill formula: C27H20O6 CAS formula: C27H20O6

IUPAC Name:

6-{4-[(oxolan-2-yl)methoxy]phenyl}-12-phenyl-4,10-dioxatricyclo[7.3.0.0³,⁷]dodeca-1(12),2,6,8-tetraene-5,11-dione

Details on test material:

Not reported within the SNIF file

Test animals

Species:

rat

Strain:

other: CD (SD)BR VAF

Sex:

not specified

Details on test animals or test system and environmental conditions:

Not reported within the SNIF file

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

Not reported within the SNIF file

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Not reported within the SNIF file

Duration of treatment / exposure:

28 days (recovery group (14d), control and highest dose)

Frequency of treatment:

7 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 10, 100 or 1000 mg/kg bw/ day
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

Not reported within the SNIF file

Positive control:

Not reported within the SNIF file

Examinations

Observations and examinations performed and frequency:

Not reported within the SNIF file

Sacrifice and pathology:

Not reported within the SNIF file

Other examinations:

Not reported within the SNIF file

Statistics:

Not reported within the SNIF file

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

effects observed, treatment-related

Behaviour (functional findings):

not specified

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:

not specified

Details on results:

Clinical observations:
One male rat of the high dose group displayed pink fur and diarrhea, the animal died at day 10 p.a. presumptaly due to misapplication
Ppink fur was evident in all high dose animals. miscoloured caudal region in medium and high dose male and female and low dose female rats

Haematology:
male rats (all dose groups): doseindependent decrease in leukocyte count and neutrophil granulocytes within biological variation
in high dose males of the recovery group increased number of monocytes was evident, the females displaed increased MCHC and MCV values,.

Clinical chemistry:
Some variation without dose correlation were noticed. the alkaline phosphatase activity was reduced dose dependently in all treatment groups but without being statistical significant. High dose males of the recovery group displayed reduction of glucose, protein globulin, and potassium levels and increase of ALAT-activity and the albumin-globulin-ratio.

Urinalysis:
doseindependent increase of pH in medium and high dose groups. male of the high dose recovery group displayed increased protein excretion into the urine.


Effects in organs:
no treatment related effects

Effect levels

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.

Target system / organ toxicity

Critical effects observed:

not specified