3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from peer reviewed journal

Data source

Reference

Reference Type:

publication

Title:

Absorption and elimination of D&C Red No. 28 in male F-344 rats

Author:

C.J. Sweeta, A.M. So´ lyoma, I.G. Sipesb,*

Year:

2004

Bibliographic source:

Food and Chemical Toxicology 42 (2004) 641–648

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Subacute repeated dose toxicity study of D&C Red No. 28 orally in rats was conducted.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid

EC Number:

242-355-6

EC Name:

3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid

Cas Number:

18472-87-2

Molecular formula:

C20H4Br4Cl4O5.2Na

IUPAC Name:

Sodium 2,3,4,5-tetrachloro-6-(2,4,5,7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)benzoate

Test material form:

solid: particulate/powder

Details on test material:

IUPAC name: 3,4,5,6-Tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid
Molecular weight: 829.6388
Molecular formula: C20-H2-Br4-Cl4-O5.2Na
Smiles: [Na+].[Na+].[O-]c1c(Br)cc2c(Oc3c(Br)c([O-])c(Br)cc3C24OC(=O)c5c(Cl)c(Cl)c(Cl)c(Cl)c45)c1Br
Inchl: InChI=1S/C20H4Br4Cl4O5.2Na/c21-5-1-3-17(9(23)15(5)29)32-18-4(2-6(22)16(30)10(18)24)20(3)8-7(19(31)33-20)11(25)13(27)14(28)12(8)26;;/h1-2,29-30H;;/q;2*+1/p-2

Specific details on test material used for the study:

- Name of test material: Acid Red 92
- Molecular formula: C20H2Br4Cl4O5Na2
- Molecular weight: 829.66 g/mol
- Substance type: Organic
- Physical state: Red powder
- Impurities (identity and concentrations):6-0.5 %

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague–Dawley Inc. (Indianapolis, IN).
- Age at study initiation: 7-weeks-old
- Weight at study initiation: 145g ± 8 g
- Fasting period before study: 12 hour
- Housing: Animals were housed in individual Nalgene metabolism cages or wire hanging cages.
- Diet (e.g. ad libitum): Teklad 4% Mouse-Rat Diet, ad libitum
- Water (e.g. ad libitum): Water, ad libitum
- Acclimation period: 5–7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 23.33 °C
- Humidity (%): 40-60%
- Air changes (per hr): 15 fresh filtered air changes per hour
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle

IN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: Blended rat chow (Teklad 4% Mouse-Rat Diet)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: Diet was prepared by blending rat chow (Teklad 4% Mouse-Rat Diet) mixed with Red 28 for 14 days such that their daily intake would be 500 mg/kg.

DIET PREPARATION
- Rate of preparation of diet (frequency): Every three days
- Mixing appropriate amounts with (Type of food): Blending rat chow (Teklad 4% Mouse-Rat Diet)
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): blending rat chow (Teklad 4% Mouse-Rat Diet)
- Concentration in vehicle: 500 mg/kg/day
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 days

Frequency of treatment:

Daily

Doses / concentrations

Dose / conc.:

500 mg/kg bw/day (nominal)

No. of animals per sex per dose:

500 mg/kg: 56 male rats

Control animals:

not specified

Details on study design:

No data available

Positive control:

No data available

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data available
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. No data available

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data available

BODY WEIGHT: Yes
- Time schedule for examinations: Every other day

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

FOOD EFFICIENCY: No data available
- 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 data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available

OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available

HAEMATOLOGY: No data available
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available

CLINICAL CHEMISTRY: No data available
- Time schedule for collection of blood: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available

URINALYSIS: Yes
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: Yes, for 24 hours
- Parameters checked in table [No.?] were examined. Presences of D&C Red No. 28 in urine were examined.

NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available

OTHER: No data available

Sacrifice and pathology:

No data available

Other examinations:

No data available

Statistics:

No data available

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Description (incidence and severity):

The animals gained weight over the 14-day feeding period on the Red 28 diet. As there is no control in the study the effect were not supposed to be treatment related.

Food consumption and compound intake (if feeding study):

not specified

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:

no effects observed

Description (incidence and severity):

No dye was detected in the urine or cage rinse of the animals pretreated with Red 28 in the diet.

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

body weight and weight gain

other: No effects was observed

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

NOAEL was considered to be 500 mg/kg/day when Fischer-344 (F-344) male rats were treated with 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydr oxy-3-oxoxanthen-9-yl)benzoic acid (D&C Red No. 28) (CAS Number: 18472-87-2).

Executive summary:

In a repeated dose oral toxicity study, Fischer-344 (F-344) male rats were treated with 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydr oxy-3-oxoxanthen-9-yl) benzoic acid (D&C Red No. 28) (CAS Number: 18472-87-2) orally in diet in the concentration of 500 mg/kg/day. Increase in body weight gain was observed in treated rats. As there is no control in the study the effect were not supposed to be treatment related. Daily intake would be 500 mg/kg for 14 days. Therefore, NOAEL was considered to be 500 mg/kg/day on the basis of body weight when Fischer-344 (F-344) male rats were treated with 3,4,5,6-tetrachloro-2-(1,4,5,8 -tetrabromo-6-hydr oxy-3-oxoxanthen-9-yl)benzoic acid (D&C Red No. 28) (CAS Number: 18472-87-2) for 14 days.