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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Data is from study report
Justification for type of information:
Data is from study report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: as below
Principles of method if other than guideline:
Combined repeated dose carcinogeniecity was conducted for the test material D & C Orange no. 5 to determine the toxic nature of the test compound upon repeated application by the oral route of administration.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4',5'-dibromo-3',6'-dihydroxyspiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one
EC Number:
209-876-0
EC Name:
4',5'-dibromo-3',6'-dihydroxyspiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one
Cas Number:
596-03-2
Molecular formula:
C20H10Br2O5
IUPAC Name:
4',5'-dibromo-3',6'-dihydroxyspiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one
Details on test material:
- Name of test material: D & C Orange no. 5- Molecular formula: C20H10Br2O5- Molecular weight: 490.10 g/mol- Substance type: Organic

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS- Source: no data available- Age at study initiation: No data available- Weight at study initiation: No data available- Fasting period before study: No data available- Housing: Premating: individually Mating: Female housed with males on 1:1 ratio Gestation/lactation: individually- Diet (e.g. ad libitum): No data available- Water (e.g. ad libitum): No data available - Acclimation period: 15 daysENVIRONMENTAL CONDITIONS- Temperature (°C): No data available- Humidity (%): No data available- Air changes (per hr): No data available- Photoperiod (hrs dark / hrs light): No data availableIN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: No data DIET PREPARATION- Rate of preparation of diet (frequency): No data- Mixing appropriate amounts with (Type of food): No data- Storage temperature of food: No dataVEHICLE- Justification for use and choice of vehicle (if other than water): feed- Concentration in vehicle: No data- Amount of vehicle (if gavage): No data- Lot/batch no. (if required): No data- Purity: No data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
17 weeks
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:0, 0.2, 0.5, 1 % (0, 100, 250, 500 mg/kg)Basis:no data
No. of animals per sex per dose:
60
Control animals:
yes
Details on study design:
No data available
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes - Time schedule: No data available - Cage side observations checked in table [No.?] were included.DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: No data available DERMAL IRRITATION (if dermal study): not applicable- Time schedule for examinations: not applicableBODY WEIGHT: Yes - Time schedule for examinations:F0 generation: Males- Twice pretest & weekly during the premating & mating periods. Females- Twice pretest, weekly during the premating, mating & gestation PeriodsF1 generation: Day 0, 4, 14 and 21 (pups were weighted individually on day 21) FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes F0 generation: Males-pretest and weekly during the pre mating period. Females-pretest weekly during the premating period & for the first 2 week of Gestation.- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No dataFOOD EFFICIENCY: no data- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No dataWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data- Time schedule for examinations: no dataOPHTHALMOSCOPIC EXAMINATION: Yes- Time schedule for examinations: F0 generation: Pretest- Dose groups that were examined:HAEMATOLOGY: Yes- Time schedule for collection of blood: No data- Anaesthetic used for blood collection: No data- Animals fasted: No data- How many animals: No data- Parameters checked in table [No.?] were examined.CLINICAL CHEMISTRY: Yes - Time schedule for collection of blood: No data- Animals fasted: No data available - How many animals: No data- Parameters checked in table [No.?] were examined.URINALYSIS: Yes - Time schedule for collection of urine: No data available- Metabolism cages used for collection of urine: No data - Animals fasted: No data- Parameters checked in table [No.?] were examined.NEUROBEHAVIOURAL EXAMINATION: No data- Time schedule for examinations: No data- Dose groups that were examined: No data- Battery of functions tested: sensory activity / grip strength / motor activity / other: No dataOTHER:
Sacrifice and pathology:
GROSS PATHOLOGY: Yes HISTOPATHOLOGY: Yes
Other examinations:
No data
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
There were no remarkable observation (clinical sign & mortality) noted in any animals for the F0 generation
Mortality:
no mortality observed
Description (incidence):
There were no remarkable observation (clinical sign & mortality) noted in any animals for the F0 generation
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
decrease in body weight
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Significant changes in food consumption observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
Food consumption and compound intake: Male rat: Significant increase in food consumption observed than control (p ≤0.05: p ≤0.01) at dose level 0.2 on 8th week, 0.5% (250mg) on 4 & 8th week and 1% (500mg/kg) on 4th week.Female rat: Significant difference observed than control (p ≤0.05: p ≤0.01) at dose level 0.2%(100mg/kg), 0.5% (250 mg/kg) and 1% (500mg/kg) on 4, 8, 11, 12th week

Effect levels

Dose descriptor:
LOEL
Effect level:
100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Decrease in body weight

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Body weight and weight gain:

Mean body weight value grams (Male):

Dose %

 

Premating

Week

0

4

8

9

0

Mean

118

313

424

442

0

Mean

119

314

422

439

0.2

Mean

117

306

407

431

0.5

Mean

117

235**

364**

393**

1

Mean

116

199**

273**

313**

Significant difference observed than control (*p ≤0.05: **p ≤0.01)

Mean body weight value grams (Female):

Dose %

 

Premating

Mating

Gestation

Week

-1

0

1

4

8

9

11

12

0

Mean

73

114

156

217

264

272

317**

385*

0

Mean

73

115

157

223

272

282

335**

407*

0.2

Mean

73

113

149

219

270

279

333*

406*

0.5

Mean

74

114

128

207**

262

271*

316**

363*

1

Mean

74

114

122

199**

259**

265**

307**

348**

Significant difference observed than control (*p ≤0.05: **p ≤0.01)

Applicant's summary and conclusion

Conclusions:
The LOEL value for D & C Orange no. 5 is 100mg/kg based on decresed in body weight of male and female rat.
Executive summary:

Repeated dose toxicity test is carried out with rats. Diet containing (0, 0.2, 0.5, 1%) 0, 100, 250 and 500mg/kg) D & C Orange no.5 were fed to groups of 60 male and 60 female rat for 12 week. Mortality checks were made twice daily and animals were weighed weekly. Food consumption and compound intake are also observed.There were no remarkable clinical sign & mortality noted in any animals for the F0 generation. Body weight of male rats were decreased than control at 0.5(250mg/kg) and 1%(500mg/kg) dose level and female body weight significantly decrease than control at 0.2 (100mg/kg), 0.5(250mg/kg) and 1%(500mg/kg). In male rat: Significant increase in food consumption was observed than control (p ≤0.05: p ≤0.01) at dose level 0.2 on 8thweek, 0.5% (250mg) on 4 & 8thweek and 1% (500mg/kg) on 4thweek. In female rat: Significant difference was observed than control (p ≤0.05: p ≤0.01) at dose level 0.2%(100mg/kg), 0.5% (250 mg/kg) and 1% (500mg/kg) on 4, 8, 11, 12thweek. Based on the results noted the LOEL value is 0.2% (100mg/kg) for D & C Orange no. 5.