Registration Dossier

Administrative data

Description of key information

The test material D and C orange no 5 is not likely to classify as a toxicant upon repeated dosing by the oral and dermal route of exposure.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
The supporting QMRF report has been attached
Qualifier:
according to
Guideline:
other: Prediction is done using QSAR Toolbox version 3.3
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material: D & C Orange no. 5- Molecular formula: C20H10Br2O5- Molecular weight: 490.10 g/mol- Substance type: Organic
Species:
rat
Strain:
Crj: CD(SD)
Details on species / strain selection:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: gavage
Details on route of administration:
not specified
Vehicle:
not specified
Details on oral exposure:
not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
not specified
Frequency of treatment:
not specified
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
not specified
Positive control:
not specified
Observations and examinations performed and frequency:
not specified
Sacrifice and pathology:
not specified
Other examinations:
not specified
Statistics:
not specified
Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
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:
not specified
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
Dose descriptor:
NOEL
Effect level:
555.737 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: not specified
Critical effects observed:
not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

The prediction was based on dataset comprised from the following descriptors: NOEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((("a" or "b" or "c" or "d" or "e") and("f" and(not "g")) ) and("h" and(not "i")) ) and("j" and(not "k")) ) and("l" and(not "m")) ) and("n" and(not "o")) ) and("p" and "q") )

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Aryl AND Aryl halide AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Heterocyclic spiro rings AND Isobenzofuran AND Lactone AND Phenol AND Xanthene by Organic Functional groups

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Aryl halide AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Heterocyclic spiro rings AND Isobenzofuran AND Lactone AND Overlapping groups AND Phenol AND Xanthene by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Aromatic compound AND Aryl bromide AND Aryl halide AND Carbonic acid derivative AND Carboxylic acid derivative AND Diarylether AND Ether AND Halogen derivative AND Heterocyclic compound AND Hydroxy compound AND Lactone AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Aromatic compound AND Aryl bromide AND Aryl halide AND Carbonic acid derivative AND Carboxylic acid derivative AND Diarylether AND Ether AND Halogen derivative AND Heterocyclic compound AND Hydroxy compound AND Lactone AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as Phenolphthaleins OR Phenols (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "i"

Referential boundary:The target chemical should be classified as AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Hydroxylated Phenols OR AN2 >> Michael addition to the quinoid type structures >> Substituted Phenols by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "j"

Referential boundary:The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "k"

Referential boundary:The target chemical should be classified as Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "l"

Referential boundary:The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O AND Group 17 - Halogens Br AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "m"

Referential boundary:The target chemical should be classified as Group 15 - Nitrogen N OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as Aromatic compound AND Aryl bromide AND Aryl halide AND Carbonic acid derivative AND Carboxylic acid derivative AND Diarylether AND Ether AND Halogen derivative AND Heterocyclic compound AND Hydroxy compound AND Lactone AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "o"

Referential boundary:The target chemical should be classified as Carboxylic acid by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 4.52

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.52

Conclusions:
The No observed adverse effect level (NOAEL) for the test compound D and C Orange No. 5 is found to be 555.736877441 mg/Kg bw/day.
Executive summary:

Repeated dose oral toxicity study was estimated for the test compound D and C Orange No. 5 using SSS QSAR prediction database. The study aasumed the use of Sprague Dawley male and female rats during the subacute study. The No observed adverse effect level (NOAEL) for the test compound D and C Orange No. 5 is found to be 555.736877441 mg/Kg bw/day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
555.737 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Data is from K2 prediction database

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: dermal
Remarks:
combined repeated dose and carcinogenicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed journal
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Repeated dose toxicity/ carcinogenicity study was performed to determine the toxicity of the test compound D & C Orange no. 5.
GLP compliance:
not specified
Limit test:
no
Species:
mouse
Strain:
ICR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Strain details: 100 ICR (Swiss Webster derived)- Source: No data- Age at study initiation: No data- Weight at study initiation: No data- Fasting period before study: No data available- Housing: Each animal was assigned an identification number and individually housed in a supported wire cage.- Diet (e.g. ad libitum): No data available- Water (e.g. ad libitum): No data available - Acclimation period: No data availableENVIRONMENTAL 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
Type of coverage:
open
Vehicle:
water
Details on exposure:
TEST SITE- Area of exposure: 6 cm²- % coverage: No data available- Type of wrap if used: No data available- Time intervals for shavings or clipplings: according to the rate of hair growthREMOVAL OF TEST SUBSTANCE- Washing (if done): No data available- Time after start of exposure: No data availableTEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.1 ml of the vehicle containing 133.4 mg test material- Concentration (if solution): 0.1ml- Constant volume or concentration used: yes- For solids, paste formed: no data availableVEHICLE- Justification for use and choice of vehicle (if other than water): No data available- Amount(s) applied (volume or weight with unit): no data- Concentration (if solution):0.1 ml- Lot/batch no. (if required): Not data- Purity: no data availableUSE OF RESTRAINERS FOR PREVENTING INGESTION: no data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
492 days
Frequency of treatment:
Twice weekly
Remarks:
Doses / Concentrations:1 mg (mean dose-136.5 mg)Basis:no data
No. of animals per sex per dose:
50
Control animals:
yes
Details on study design:
No data available
Positive control:
The positive control (3, 4-benzpyrene), the observed effects in rodents were as expected for this known dermal carcinogen. Ninety-four percent of the mice in the positive control group developed typical gross skin lesions associated with the area of treatment in an average latent period of 245 days.
Observations and examinations performed and frequency:
Observations and examinations performed & frequencyCAGE SIDE OBSERVATIONS: Yes - Time schedule: daily- Cage side observations checked in table [No.?] were included.DETAILED CLINICAL OBSERVATIONS: no data- Time schedule: no dataBODY WEIGHT: no data- Time schedule for examinations: no dataFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): no data- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data- 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: No data - Time schedule for examinations:- Dose groups that were examined: No dataHAEMATOLOGY: No data- 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.DERMAL IRRITATION (if dermal study): No data- Time schedule for examinations: No dataCLINICAL CHEMISTRY: No data- Time schedule for collection of blood: No data- Animals fasted: No data - How many animals: No data- Parameters checked in table [No.?] were examined.URINALYSIS: No data- Time schedule for collection of urine: No data- 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:- Dose groups that were examined:- Battery of functions tested: No data sensory activity / grip strength / motor activity / other: No dataOTHER:
Sacrifice and pathology:
GROSS PATHOLOGY: Yes HISTOPATHOLOGY: Yes
Other examinations:
No data
Statistics:
No data
Clinical signs:
no effects observed
Dermal irritation:
not specified
Mortality:
no mortality observed
Body weight and weight changes:
not specified
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:
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:
no effects observed
Histopathological findings: neoplastic:
not specified
Details on results:
Effect- Spleen: Extramedullary HematopoiesisVehicle control: 5/50 female mice, 8/50 male miceTest material: 6/50 female mice, 4/50 male mice
Dose descriptor:
NOAEL
Effect level:
136.5 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No observed incidence of neoplasia
Critical effects observed:
not specified
Conclusions:
The dermal application of 1 mg (136.5 mg/Kg bw) of D & C Orange no. 5 failed to increase the incidence of neoplasia. Hence the No Observed Adverse Effect Level (NOAEL) was assessed to be 1mg (136.5 mg/Kg bw).
Executive summary:

Repeated dose toxicity/ carcinogenicity study is carried out to find toxicity of D & C Orange no. 5. 100 ICR (Swiss Webster derived) mice, 50 males and 50 females treated with 0.1 ml dose containing 1mg of D & C Orange no. 5. An additional three groups of 100 mice were treated with the vehicle (distilled water), and another group of 100 mice was treated with 3, 4-benzpyrene (positive control) dissolved in acetone. Initially, the hair on the dorsal area of each animal was clipped with an animal clipper free of lubricating oil. Subsequent periodic clipping was performed according to the rate of hair growth. This area of approximately 6 cm² was treated twice weekly. Observation were made daily for mortality and gross toxicity. No adverse effect were observed related to D & C Orange no. 5. The dermal application of 1 mg (136.5 mg/Kg bw) of D & C Orange no. 5 failed to increase the incidence of neoplasia. Hence the No Observed Adverse Effect Level (NOAEL) was assessed to be 1mg (136.5 mg/Kg bw).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
136.5 mg/kg bw/day
Study duration:
chronic
Species:
mouse
Quality of whole database:
Data is from K2 publication

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose toxicity: Oral

Various peer reviewed publications for the target chemical and its read across have been summarized below to determine the toxic nature of the test compound D and C orange no 5:

Repeated dose oral toxicity study was estimated for the test compound D and C Orange No. 5 using SSS QSAR prediction database. The study aasumed the use of Sprague Dawley male and female rats during the subacute study. The No observed adverse effect level (NOAEL) for the test compound D and C Orange No. 5 is found to be 555.736877441 mg/Kg bw/day.

Repeated dose toxicity test (Procter and Gamble, 1992) is carried out with rats for the test compound D & C Orange no. 5 (CAS no 596-03-2). 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.

In a Teratogenic toxicity study (Burneti et al, 1986), CD Sprague-Dawley female rats were treated with D&C YELLOW NO. 8 (RA CAS no 518-47-8) at a concentration of 0, 100, 500 and 1500 mg/kg body weight/ day by oral gavage. Six rats died during the dosing period at 1500 mg/kg bw/day and Orange discoloration of the urine was observed in all the treated rats as compared to control. Similarly, green discoloration of the amniotic fluid and green colored small intestines were observed at 1500 mg/kg bw/day and green discoloration of the amniotic fluid was observed at 100 and 500 mg/kg bw/day treated rats as compared to control. In addition, slight increase in the number of litters with unossified sternebrae (sternebrae nos 1-6) and rudimentary 14th rib(s) were observed as compared to control. However, these values fell within the ranges of historical control data. There were no biologically meaningful or statistically significant differences in the number of litters and number of fetuses with malformations,number of foetuses or litters with developmental variations in any of the treated groups. Therefore, the No Observed Adverse Effect Level (NOAEL) was considered to be 500 mg/kg body weight /day when CD Sprague-Dawley female rats were treated with D&C YELLOW NO. 8 orally by gavage from day 6 to 19 of gestation.

In the same study (Burneti et al, 1986), Dutch Belted female Rabbits were treated with D&C YELLOW NO. 8 (RA CAS no 518-47-8) at a concentration of 0, 30, 100 and 250 mg/kg body weight/ day by oral gavage. One rabbits died each in 30 and 250 mg/kg bw/day including control. One rabbit was aborted on day 28 of gestation at 250 mg/kg bw/day as compared to control. Pneumonia was observed in three rabbit which were died. Orange discoloration of the urine was observed in all the treated rabbits between days 7 and 28 of gestation as compared to control. In addition, no effects were observed on body weight and body weight gain and gross pathology of treated rabbits as compared to control. There were no biologically meaningful or statistically significant differences in the mean numbers of corpora lutea, total implantations+ early or late resorptions, viable foetuses, foetal sex distribution or mean foetal body weight in any of the treated groups as compared to the control group. At 30 and 100 mg/kg bw/day, malformations were observed in two foetuses from two litters. However, these values fell within the ranges of historical control data. Therefore, the No Observed Adverse Effect Level (NOAEL) was considered to be 250 mg/kg body weight /day when Dutch Belted female Rabbits were treated with D&C YELLOW NO. 8 orally by gavage from day 6 to 27 of gestation.

In a repeated dose oral toxicity study by Sweeta et al (2004), Fischer-344 (F-344) male rats were treated with D&C Red No. 28 (RA CAS no 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, the No Observed Adverse Effect Level (NOAEL) was considered to be 500 mg/kg/day when Fischer-344 (F-344) male rats were treated with D&C Red No. 28 for 14 days.

In Combined repeated dose & carcinogenicity study by Borzelleca et al (1987), Charles River CD-1 COBS male and female mice were exposed to FD & C Red No. 3 (Erythrosine, RA CAS no 16423-68-0) in the concentration of 0.0, 0.3, 1.0 and 3.0 % orally. The result shows that FD & C Red No. 3 (Erythrosine) was toxic. Toxic changes were observed on decreased body weight in male and female at 3.0 %, decreased in lymphocyte level in female at 1.0 % and increase in food consumption of 1.0 and 3.0 % treated mice as compared to controls. In addition, microscopic changes were observed as Red/pink discoloration of the gastro-intestinal tract and statistically significant increase in lymphocytic lymphoma in 3.0 % treated male and female but not differs from controls. Therefore, No Observed Adverse Effect Level (NOAEL) was considered to be4759 mg/kg/day (3.0%) for male and 1834 mg/kg/day (1.0 %) for female when Charles River CD-1 COBS male and female mice were exposed to FD & C Red No. 3 (Erythrosine) orally for 104 weeks. 

In the study Borzelleca et al (1987), Charles River CD male and female rats were exposed to FD & C Red No. 3 (Erythrosine,RA CAS no 16423-68-0) in the concentration of 0.0, 0.1, 0.5, 1.0 and 4.0 % in original study and in chronic study orally. The results shows that FD & C Red No. 3 (Erythrosine) was toxic, toxic changes were observed as increase in body weight of male rats and decrease in body weight of female rat, increase in food consumption and increased in thyroid weight of 1.0 and 4.0 % treated male and female rat as compared to control. In addition, in male rats increase in the incidence of thyroid follicular cell hyperplasia follicular cysts, follicular adenomas and carcinomas were observed in 4.0 % treated rats of original study and in chronic study.Therefore, No Observed Adverse Effect Level (NOAEL) was considered to be 0.5 % (251 mg/kg/day) for male rats and 1.0 % (641 mg/kg/day) for female rats when Charles River CD male and female rats treated with F & C Red No. 3 (Erythrosine) orally for 30 months or more.

 

Repeated dose toxicity: Dermal

Peer reviewed publications for the target chemical and its read across were reviewed to determine the toxic nature of the test compound D and C orange no 5:

Repeated dose toxicity/ carcinogenicity study was carried out by Carson (1984) to find toxicity of D & C Orange no. 5. 100 ICR (Swiss Webster derived) mice, 50 males and 50 females treated with 0.1 ml dose containing 1mg of D & C Orange no. 5. An additional three groups of 100 mice were treated with the vehicle (distilled water), and another group of 100 mice was treated with 3, 4-benzpyrene (positive control) dissolved in acetone. Initially, the hair on the dorsal area of each animal was clipped with an animal clipper free of lubricating oil. Subsequent periodic clipping was performed according to the rate of hair growth. This area of approximately 6 cm² was treated twice weekly. Observation were made daily for mortality and gross toxicity. No adverse effect were observed related to D & C Orange no. 5. The dermal application of 1 mg (136.5 mg/Kg bw) of D & C Orange no. 5 failed to increase the incidence of neoplasia. Hence the No Observed Adverse Effect Level (NOAEL) was assessed to be 1mg (136.5 mg/Kg bw).

In the same study, ICR (Swiss Webster derived) white male and female were exposed to FD & C Red No. 3 (Erythrosine, RA CAS no 16423-03-2) in the concentration of 0 and 1 mg/kg/day and 10 mg of 3, 4-benzpyrene as positive control. The results show that FD & C Red No. 3 (Erythrosine) was not toxic, no toxic changes were observed on survival and clinical sign. In addition, gross pathological changes such as swelling in left ear, swelling in neck and nodule in liver was observed in treated female mice and histopathological changes such as inflammatory cyst lined by fibrous tissue capsule, reticulum cell sarcoma and mammary gland adenocarcinoma were observed in female mice but the effect is not significant as compared to control.  Therefore, the No Observed Adverse Effect Level (NOAEL) was considered to be 1 mg/kg (133.0 mg) when ICR (Swiss Webster derived) white male and female mice treated with FD & C Red 3. (Erythrosine) for 525 days dermally.

Based on the available data, the test material D and C orange no 5 is not likely to classify as a toxicant upon repeated dosing by the oral and dermal route of exposure.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

Data is from predicted database

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

Data is from peer reviewed publication

Justification for classification or non-classification

Based on the available data, the test material D and C orange no 5 is not likely to classify as a toxicant upon repeated dosing by the oral and dermal route of exposure.