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Administrative data

Description of key information

Repeated dose toxicity: oral
NOAEL was considered to be 30mg/kg bw/day when male and female rats were exposed to FD&C Red No. 32 repeatedly by oral (feed).

Repeated dose toxicity: inhalation

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol, which is reported as 0.000001559 Pa. Thus, exposure to inhalable dust, mist and vapour of the chemical 1 -[(2,4 -dimethyl phenyl)diazenyl]-2 -naphthol is highly unlikely. Therefore this study is considered for waiver.

Repeated dose toxicity: dermal

The acute toxicity value for substance 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely. Thus, it is expected that substance 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no dermal absorption data as well as no data available that suggests that substance 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic 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 publication.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: As mention below
Principles of method if other than guideline:
Repeated dose oral toxicity study was conducted on male and female rats for a period of 44 weeks by oral feed for FD&C Red No. 32.
GLP compliance:
not specified
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material (as cited in study report):FD&C Red No. 32.
- Molecular formula: C18H16N2O
- Molecular weight : 276.337 g/mol
- Substance type: Organic
- Physical state: Solid
- Smiles : Cc1ccc(N=Nc2c(O)ccc3ccccc23)c(C)c1
- InChI: 1S/C18H16N2O/c1-12-7-9-16(13(2)11-12)19-20-18-15-6-4-3-5-14(15)8-10-17(18)21/h3-11,21H,1-2H3/b20-19+
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data available
- Age at study initiation: 5 to 6 weeks old
- Weight at study initiation: 40-360g
- Fasting period before study: No data available
- Housing: The animals were kept in groups of two to a cage.
- Diet (e.g. ad libitum): Diet ad libitum
- Water (e.g. ad libitum): Water ad libitum
- Acclimation period: No data available
Route of administration:
oral: feed
Vehicle:
other: rodent Diet
Details on oral exposure:
VEHICLE
- Justification for use and choice of vehicle (if other than water): No data available
- Concentration in vehicle: 0,0.03,0.75and 1.5% (0,30,75and 1500mg/kgbw/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:
44 weeks
Frequency of treatment:
Daily
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
30 mg/kg bw/day (nominal)
Dose / conc.:
75 mg/kg bw/day (nominal)
Dose / conc.:
1 500 mg/kg bw/day (nominal)
Remarks:
0,0.03,0.75and 1.5%
No. of animals per sex per dose:
Total number-120
0 mg/kgbw/day 20 male and female rats
30 mg/kgbw/day 20 male and female rats
75 mg/kgbw/day 20 male and female rats
1500mg/kgbw/day 20 male and female rats
Control animals:
yes, concurrent vehicle
Details on study design:
No data available
Positive control:
Not specified.
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included:
Mortality was observed.

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

BODY WEIGHT: Yes
- Time schedule for examinations: Body weight of the test animal was recorded weekly.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, food consumption of the test animal was recorded weekly.
- 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: No data available

FOOD EFFICIENCY: Yes
- 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: Yes

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: Yes, haematology determinations were made for 20 weeks on groups of male and female rats at the dose level of 30mg/kg bw/day.
A slight modification of the pyridine-haemochromogen method of Rimington was used and the mean values of the final determinations were made.
- 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: Blood haemoglobin parameter was examined.

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: No data available
- Time schedule for collection of urine: No data available
- 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-In the study exposure period was 65 weeks for control animals while it was 44 weeks for treatment group.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, A complete necropsy was done on all 44-week exposure groups animals. All abnormalities were recorded on the individual animal necropsy forms. Heart, liver, kidney, Spleen, adrenal and testes. from all scheduled sacrifice animals were weighed. The mean weight in mg/g of body weight was calculated for male and female rats at he dose levl of 30mg/kg bw/day for treated group compare to control.


HISTOPATHOLOGY: A detailed examination was made of the haematoxylin-eosin stained paraffin sections of a number of organs including heart, liver, kidney, Spleen, adrenal and testes in male and female rats at he dose levl of 30mg/kg bw/day for treated group compare to control.
Statistics:
Standard deviation was observed.
Clinical signs:
not specified
Mortality:
mortality observed, treatment-related
Description (incidence):
Mortality; No mortality was obserserved at the dose level of 30 mg/kg bw/day in treated group compared to control.

Mortality was observed ,by the end of 20 weeks in all the rats on the 1500 mg/kg bw/day level .
Mortality was also observed ,by the end of 40 weeks in all the rats on the 75 mg/kg bw/day level .
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No significant change was observed at the dose level of 30 mg/kg bw/day in treated group compared to control.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No significant change was observed at the dose level of 30 mg/kg bw/day in treated group compared to control.

Food consumption was affected by the test substance at the dose level of 75and 1500 mg/kg bw/day.
Food efficiency:
no effects observed
Description (incidence and severity):
No significant change was observed at the dose level of 30 mg/kg bw/day in treated group compared to control.

Food efficiency was affected by the test substance at the dose level of 75and 1500 mg/kg bw/day.
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
No significant change was observed at the dose level of 30 mg/kg bw/day in treated group compared to control.
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:
no effects observed
Description (incidence and severity):
No significant changes was observed in mean and final organ weight of male animals Heart, liver, spleen, kidneys and testes at the dose level of 30 mg/kg bw/day in treated group compared to control.
Except in mean organ weight of liver in female rats of 30 mg/kg bw/day significant change was observed.No significant changes was observed in mean organ weight of female animals Heart, spleen, kidneys and testes at the dose level of 30 mg/kg bw/day in treated group compared to control.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No significant changes was observed in male animals Heart, liver, spleen, kidneys and testes at the dose level of 30 mg/kg bw/day in treated group compared to control.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No consistent histopathological changes were observed in the tissues or organs of the male and femalerats at the dose level of 30 mg/kg bw/day.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
Other-In the study exposure period was 65 weeks for control animals while it was 44 weeks for treatment group.
Key result
Dose descriptor:
NOAEL
Effect level:
ca. 30 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant mortality occurred in the study. Exposure-related adverse clinical signs were absent. No significant change were observed in body weight, food consumption , food efficiency, hematology, gross pathology and histopathology.
Critical effects observed:
not specified

CUMULATIVE NUMBER OF DEATHS

Concentration of the colour in diet

Sex

No.of rats

Time in week on test

 

2

4

8

12

16

20

24

28

32

36

40

44

FD&C Red No. 32

 

control

M

20

0

2

3

4

5

7

10

11

11

12

13

13

F

20

0

0

2

2

3

6

7

7

7

7

7

7

30 mg/kgbw/day

M

20

0

0

2

3

3

7

9

9

9

9

16

18

F

20

0

0

1

1

5

5

6

6

6

6

8

9

75 mg/kgbw/day

M

20

2

3

4

11

15

15

15

16

17

19

20

 

F

20

0

0

0

9

11

13

15

15

15

16

20

 

1500mg/kgbw/day

M

20

2

8

11

17

19

20

 

 

 

 

 

 

F

20

0

2

 

10

18

19

20

 

 

 

 

 

 

Conclusions:
NOAEL was considered to be 30mg/kg bw/day when male and female rats were exposed to FD&C Red No. 32 repeatedly by oral (feed).
Executive summary:

A study was designed to investigate the chronic repeated dose toxicity effects of FD&C Red No. 32in young male and female rats by an oral route for 44 weeks. The rats were exposed by oral feed for 44 week to the concentrations of 0, 30,75and 1500mg/kgbw/day.No mortality was observed at the dose level of 30mg/kg bw/day in treated group compared to control.Mortality was observed ,by the end of 20 weeks in all the treated rats on the dose level of 1500 mg/kg bw/day .Mortality was also observed ,by the end of 40 weeks in all the rats on the concentration of 75 mg/kg bw/day .No significant change were observed in clinical sign,body weight, food consumption , food efficiency, hematology, gross pathology and histopathology of male and female rats obserserved at the dose level of 30mg/kg bw/day in treated group compared to control. Therefore NOAEL was considered to be 30mg/kg bw/day for FD&C Red No. 32in male and female rats by an oral route for 44 weeks.

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

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
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:
short-term repeated dose toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Mode of Action Analysis / Human Relevance Framework

Additional information

Repeated dose toxicity: oral

Various experimental studies were reviewed to determine the toxic nature of FD&C Red No. 32 (3118-97-6)(IUPAC name: 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol )upon repeated exposure by oral route. The studies are as mentioned below:

 

Chronic oral toxicity study was performed by M. G. ALLMARK et.al (J. Pharma. Pharmacology, 1956) to determine the oral toxic nature of FD&C Red No. 32 upon repeated exposure for 44 weeks. A study was designed to investigate the chronic repeated dose toxicity effects of FD&C Red No. 32in young male and female rats by an oral route for 44 weeks. The rats were exposed to test chemical by oral feed for 44 week to the concentrations of 0, 30,75and 1500mg/kgbw/day. No mortality was observed at the dose level of 30mg/kg bw/day in treated group compared to control. Mortality was observed ,by the end of 20 weeks in all the treated rats on the dose level of 1500 mg/kg bw/day .Mortality was also observed ,by the end of 40 weeks in all the rats on the concentration of 75 mg/kg bw/day .No significant change were observed in clinical sign,body weight, food consumption , food efficiency, hematology, gross pathology and histopathology of male and female rats observed at the dose level of30mg/kg bw/day in treated group compared to control. Therefore NOAEL was considered to be 30mg/kg bw/day for FD&C Red No. 32 in male and female rats by an oral route for 44 weeks.

 

Supported by experimental study was performed by M. G. ALLMARK et.al (J. Pharma. Pharmacology, 1956) to determine the oral toxic nature of FD&C Red No. 32 upon repeated exposure for20 weeks by oral gavage. Repeated dose oral toxicity study was conducted on male and female rats by oral gavage for 20 weeks. By the end of 20 weeks, 6male rats receiving a dose of 200 mg/kg bw/day had died whereas all 10 female rats have survived for 20 weeks .However, 5 male and 3 female rats receiving a dose of 400 mg/kg bw/day had died by the end of the experiment. No significant change were observed in food consumption and food efficiency at the dose level of 200 mg/kg bw/day.A significant decline in blood haemoglobin values was found in all groups of both sex at the dose level of both 200 and 400 mg/kg bw/day. Statically Significant change in the mean organ weight was observed in male and female ,which includes Lung heart ,liver, spleen, kidney, adrenal and testes ,at the dose level of400 mg/kg bw/day. Altered spermatogenesis are observed in male test group receiving the dose 400mg/kgbw/day compare to control in histopathology . Therefore LOAEL was considered to be200 mg/kg bw/day in male and female rats for FD&C Red No. by oral gavage for 20 weeks study.

Supported by another experimental study performed by Philip Rofe (British journal of industrial medicine, 1957) to determine the oral toxic nature of Sudan II upon repeated exposure for 26 days. 32 (3118-97-6).Repeated dose oral toxicity study was conducted on male rats. When the test animal was fed with the test substance for 26 days, low observed effects were noted at a dose level of 552.674 mg/kg body weight/day.Heinz body level usually takes the following course: there is first a latent period between the beginning of ingestion of dye and the appearance of Heinz bodies in the blood, and this may last one or several days depending on the dye, its concentration, and the individual response of the animal; there follows a relatively rapid rise to a peak frequency of Heinz bodies and this is followed by a fall to a fluctuating lower level which is maintained so long as the dye is consumed. Test chemical induces the production of Heinz bodies in the test animal. The Heinz body induction index means (H) is 2.1. The peak Heinz body incidence (% RBC’s) was found to be 40.0 and the time required to reach peak incidence was 20.4 days. Therefore LOAEL was considered to be 552.674 mg/kg body weight/day in male rats.

Further supported by experimental study conducted by Government of Canada (Canadian Centre for Occupational Health and Safety, 2017) to determine the oral toxic nature of SUDAN II upon repeated exposure by oral feed. Repeated dose oral toxicity study was conducted on rats for estimating the adverse effect of the test substance SUDAN II in albino rats by oral feed. When the test animal was orally exposed to the test substance daily at a dose level of20000 mg/kg body weight/day, low adverse effects were observed. Harmful morphologic changes were observed in the kidney. Significant histopathological change was observed in the kidney. Therefore LOAEL was considered to be20000 mg/kg body weight/day for Sudan II in albino rats by oral feed.

 

The data available for the target chemical FD&C Red No. 32 (3118-97-6)(IUPAC name: 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol ) is insufficient to classify the chemical as toxic. Also the NOAEL value range can be close to30mg/kg bw/day . Based on the observations made, FD&C Red No. 32 does not exhibit toxicity upon repeated exposure by oral route. Hence the test chemical is not likely to classify as a toxicant upon repeated exposure by oral route. Further testing is required to clearly judge the test chemical as toxic upon repeated exposure.

Repeated dose toxicity: inhalation

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol, which is reported as 0.000001559 Pa. Thus, exposure to inhalable dust, mist and vapour of the chemical 1 -[(2,4 -dimethyl phenyl)diazenyl]-2 -naphthol is highly unlikely. Therefore this study is considered for waiver.

Repeated dose toxicity: dermal

The acute toxicity value for substance 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely. Thus, it is expected that substance 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no dermal absorption data as well as no data available that suggests that substance 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Justification for classification or non-classification

The data available for the target chemical FD&C Red No. 32 (3118-97-6)(IUPAC name: 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol ) is insufficient to classify the chemical as toxic. Also the NOAEL value range can be close to30mg/kg bw/day . Based on the observations made, FD&C Red No. 32 does not exhibit toxicity upon repeated exposure by oral route. Hence the test chemical is not likely to classify as a toxicant upon repeated exposure by oral route. Further testing is required to clearly judge the test chemical as toxic upon repeated exposure.