Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Remarks:

combined repeated dose and reproduction / developmental screening

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Data source

Reference

Reference Type:

secondary source

Title:

Long term rat feeding study, exposure beginning in utero

Author:

International Research and Development Corporation

Year:

2007

Bibliographic source:

Scientific Committee on Consumer Products (SCCP), OPINION ON Acid Red 33, COLIPA n° C22, 2007 page no -12

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Principles of method if other than guideline:

Combined repeated dose repro-devp. Screen of D&C Red 33 in rats

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate

EC Number:

222-656-9

EC Name:

Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate

Cas Number:

3567-66-6

Molecular formula:

C16H13N3O7S2.2Na

IUPAC Name:

disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate

Constituent 2

Reference substance name:

D&C Red 33

IUPAC Name:

D&C Red 33

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): D&C Red 33 - Molecular formula (if other than submission substance): C16H11N3Na2O7S2- Molecular weight (if other than submission substance): 467 g/mole- Substance type: Organic - Physical state: Powder - Impurities (identity and concentrations): 4-Amino-5-hydroxy-2,7-naphthalenedisulfonic acid (disodium salt) < 0.3%, 4,5-Dihydroxy-3-(phenylazo)-2,7-naphthalenedisulfonic acid (disodium salt) < 3%, 4-Aminoazobenzene < 100 ppb, 4-Aminobiphenyl < 275 ppb, Aniline < 25 ppm, Azobenzene < 1 ppm, ,Benzidine < 20 ppb, 1,3-Diphenyltriazene < 125 ppb, Heavy Metal Content, Antimony, Arsenic, Mercury < 5 ppm, Cadmium < 10 ppm and Lead < 20 ppm

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: Diet

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: No data available DIET PREPARATION- Rate of preparation of diet (frequency): No data available - Mixing appropriate amounts with (Type of food): No data available - Storage temperature of food: No data available VEHICLE- Justification for use and choice of vehicle (if other than water): No data available - Concentration in vehicle: 0, 12, 25, and 102 mg/kg bw/day for male and 0, 15, 31, and 129 mg/kg bw/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:

24 months

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:0, 12, 25, and 102 mg/kg bw/day for male and 0, 15, 31, and 129 mg/kg bw/day for female Basis:actual ingested

No. of animals per sex per dose:

Total: 600 0 mg/kg bw/day: 120 male, 120 female 12 and 15 mg/kg bw/day: 60 male, 60 female25 and 31 mg/kg bw/day: 60 male, 60 female102 and 129 mg/kg bw/day: 60 male, 60 female

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Positive control:

No data available

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes - Cage side observations checked in table [No.?] were included: Morbidity and mortality were observed DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: Daily BODY WEIGHT: Yes - Time schedule for examinations: Weekly throughout the in utero segment weekly for the first 14 weeks, biweekly (the second7 days of every two weeks) the next 12 weeks and once monthly (7 days during the third week of each month) thereafter for the post-weaning segment of the study.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: No data available - Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available 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: Yes - Time schedule for examinations: At week 16 of the in utero segment, during week 1 and months 3, 6, 12, 18 and 24 of the post-weaning segment of the study. - Dose groups that were examined: All rats were examined. HAEMATOLOGY: Yes - Time schedule for collection of blood: At 3, 6, 12, 18 and 24 months of study - Anaesthetic used for blood collection: No data available - Animals fasted: No data available - How many animals: 10 rats/sex/group - Parameters checked in table [No.?] were examined. No data available CLINICAL CHEMISTRY: Yes - Time schedule for collection of blood: At 3, 6, 12, 18 and 24 months of study - Anaesthetic used for blood collection: No data available - Animals fasted: No data available - How many animals: 10 rats/sex/group - Parameters checked in table [No.?] were examined. No data available URINALYSIS: Yes - Time schedule for collection of urine: at3, 6 and 12 months- Metabolism cages used for collection of urine: No data available - Animals fasted: No data available - Parameters checked in table [No.?] were examined. No data available 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:

GROSS PATHOLOGY: Yes Interim sacrifice and necropsy of 10 rats/sex/group were conducted following 12 months of compound administration.HISTOPATHOLOGY: Yes

Other examinations:

No data available

Statistics:

No data available

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:

not specified

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:

effects observed, treatment-related

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Details on results:

Mortality: No effect on survival of treated rats were observed as compared to control. Clinical signs: Differences in the colour of urine, faeces, hair or exposed skin areas were observed in treated rats as compared to control. Body weight and weight gain: No effect on body weight were observed in treated rats as compared to control. Food consumption and compound intake: No effect on food comsumption were observed in treated rats as compared to control. Compound intake: : Dosage levels of 0.025, 0.05 and 0.2% is corresponded to 12, 25, and 102 mg/kg bw/d for males and 15, 31, and 129 mg/kg bw/d for females. Food efficiency: No data availableWater consumption and compound intake: No effect on water consumption were observed in treated rats as compared to control. Opthalmoscopic examinationNo effect on opthalmoscopic examination were observed in treated rats as compared to control. Haematology: No effect on hematological examination were observed in treated rats as compared to control. Clinical chemistry: No effect on Clinical chemistry of treated were observed as compared to control. Urinanalysis: When treated with 102 and 129 mg/kgbw/day, orange to red discoloration of the urine at 18 months and light-red colour of urine were observed other than colour, no differences were observed in treated rats as compared to control. Neurobehaviour: No data availableOrgan weightsNo data availableGross pathology: No effect on gross pathology of treated were observed as compared to control. Histopathology: No histopathological changes were observed in treated rats as compared to control.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No effect on survival, clinical sign, body weight, food consumption, Ophthalmoscopy, hematology, clinical chemistry, gross pathology and histopathology

2

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No effect on survival, clinical sign, body weight, food consumption, Ophthalmoscopy, hematology, clinical chemistry, gross pathology and histopathology

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL was considered to be 102 mg/kg bw/day for male and 129 mg/kg bw/day for female rats when male and female rats were treated with D&C Red 33.

Executive summary:

In a Combined repeated dose repro-devp. Screen,male and female rats were treated with D&C Red 33 in the concentration of 0, 12, 25, and 102 mg/kg bw/day for male and 0,15, 31, and 129 mg/kg bw/day for femaleorally in diet. No effect were observed on survival of treated rats. differences in thecolour of urine, faeces, hair or exposed skin areas were observed in treated rats as compared to control. No effect were observed on body weight, food consumption and water consumption of treated rats as compared to control. Similarly, No effect on opthalmoscopic examination, hematology and Clinical chemistry of treated rats were observed as compared to control. In addition, no gross pathological and histopathological changes were observed in treated rats as conpared to control. Therefore,NOAEL was considered to be 102 mg/kg bw/day for male and 129 mg/kg bw/day for female rats when male and female rats were treated with D&C Red 33 orally for 24 months.