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

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Data source

Reference

Reference Type:

secondary source

Title:

A Multigeneration Study in Rats of D&C Red 33 in the Diet

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 -19

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: Multigeneration Study

Principles of method if other than guideline:

Multigeneration Study 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): No data available

Test animals

Species:

rat

Strain:

Sprague-Dawley

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: No data available - Diet (e.g. ad libitum): Purina Rodent Chow 5002, ad libitum- Water (e.g. ad libitum): No data available - Acclimation period: No data available ENVIRONMENTAL CONDITIONS- Temperature (°C): No data available - Humidity (%):No data available - Air changes (per hr): No data available - Photoperiod (hrs dark / hrs light): No data available

Administration / exposure

Route of administration:

oral: feed

Type of inhalation exposure (if applicable):

not specified

Vehicle:

other: Purina Rodent Chow 5002

Details on 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): Purina Rodent Chow 5002 - Storage temperature of food: No data available VEHICLE- Justification for use and choice of vehicle (if other than water): Purina Rodent Chow 5002 - Concentration in vehicle: 0, 0.25, 2.5; 7.5 and 25 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

Details on mating procedure:

- M/F ratio per cage:: No data available- Length of cohabitation:: No data available- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancyNo data available- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.: No data available- Further matings after two unsuccessful attempts: [no / yes (explain)]: No data available- After successful mating each pregnant female was caged (how):: No data available- Any other deviations from standard protocol:F0: 20 animals per sex per dose levelF1a: mating on day 100F1b and F1c: mating at least 10 day laterF2a: mating of 20 F1 animals randomly selectedF3: mating of 20 F2b littersF0 parental animals were mated twice (each group 20 males and 20 females), to produce two litters and the F1 parents were mated to produce three litters and the F2 parents were mated once to produce the F3a litters.

Duration of treatment / exposure:

110 days

Frequency of treatment:

Daily

Duration of test:

More than 110 days

No. of animals per sex per dose:

Total: 600F0 generation 0 mg/kg bw/day: 20 male, 20 female 0.25 mg/kg bw/day: 20 male, 20 female2.5 mg/kg bw/day: 20 male, 20 female7.5 mg/kg bw/day: 20 male, 20 female25.0 mg/kg bw/day: 20 male, 20 femaleF1 generation 0 mg/kg bw/day: 20 male, 20 female 0.25 mg/kg bw/day: 20 male, 20 female2.5 mg/kg bw/day: 20 male, 20 female7.5 mg/kg bw/day: 20 male, 20 female25.0 mg/kg bw/day: 20 male, 20 femaleF2 generation 0 mg/kg bw/day: 20 male, 20 female 0.25 mg/kg bw/day: 20 male, 20 female2.5 mg/kg bw/day: 20 male, 20 female7.5 mg/kg bw/day: 20 male, 20 female25.0 mg/kg bw/day: 20 male, 20 female

Control animals:

yes, concurrent vehicle

Examinations

Maternal examinations:

Survival, clinical sign, Body weight and food consumption and Histopathology were examined.

Ovaries and uterine content:

No data available

Fetal examinations:

Survival, clinical sign, Body weight and food consumption were examined.

Statistics:

No data available

Indices:

Fertility indices, gestation anomalies, viability and survival of the pups were examined.

Historical control data:

No data available

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effectsDetails on maternal toxic effects:Mortality:No effect on survival of treated rats were observed as compared to control. Clinical signs: When treated with 25 mg/kg bw/day, discoloration (pink or reddish) of the urine were observed in treated male and female rats as compared to control.Body weight:No effect on body weight of treated rats was observed as compared to control. Food consumption:No effect on food consumption of treated rats was observed as compared to control. Reproductive performance:No effect on fertility indices, gestation anomalies, viability and survival of the pups were observed in treated rats as compared to control.Histopathology:No histopathological changes were observed intreated rats as compared to control.

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

25 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

25 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effectsDetails on embryotoxic / teratogenic effects:Mortality:No effect on survival of treated F1 and F2 pups were observed as compared to control. Clinical signs: When treated with 25 mg/kg bw/day, discoloration (pink or reddish) of the urine were observed in F1 and F2 treated male and female pups as compared to control.Body weight: No effect on body weight of F1 and F2 treated male and female pups were observed as compared to control.Food consumption:No effect on food consumption of treated F1 and F2 rats were observed as compared to control. Reproductive performance: No effect on fertility indices, gestation anomalies, viability and survival of the pups were observed in treated rats as compared to control.Histopathology:In F2a generation, 1 pup had exencephaly, spina bifida and great vessel anomalies which was considered an incidental finding.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

25 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: fetotoxicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL was considered to be 25 mg/kg bw/day for F0, F1 and F2 generation when Charles River COBS CD (Sprague Dawley) male and female rats were treated wtih D&C Red 33.

Executive summary:

In a Multigeneration Study,Charles River COBS CD (Sprague Dawley) male and female rats were treated wtih D&C Red 33 in the concentration of 0, 0.25, 2.5, 7.5 and 25.0 mg/kg bw/day orally in deit. No effect on survival of F0, F1 and F2 generation were observed. Discoloration (pink or reddish) of the urine were observed in F0, F1 and F2 treated male and female rats as compared to control. Similaly, no effect on body weight and food consumption of treated F0, F1 and F2 rats were observed as compared to control.No effect on fertility indices, gestation anomalies, viability and survival of the pups were observed in F0, F1 and F2 treated rats as compared to control. In addition no effect on histopathology of F0 and F1 treated rats were observed. In F2a generation, 1 pup had exencephaly, spina bifida and great vessel anomalies which was considered an incidental finding.Therefore,NOAEL was considered to be 25 mg/kg bw/day for F0, F1 and F2 generation when Charles River COBS CD (Sprague Dawley) male and female rats were treated wtih D&C Red 33.