Dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt

Carcinogenicity

Description of key information

From the data available on the carcinogenecity of Fast Green FCF (chemical name: dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt) & using the weight of evidence appraoch, it can be concluded that the chemical is not likely to be carcinogenic within the dose levels mentioned in the studies since the tumors and adenomas were not attributed to the test chemical and were not differnt from those observed in the control. Hence, it is concluded that the chemical is not likely to be carcinogenic.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from authoritative source of scientific information

Qualifier:

according to guideline

Guideline:

other: Carcinogenicity test was performed on male and female Charles-River CD-1 mice treated with fast green FCF with different concentrations.

Principles of method if other than guideline:

Fast Green FCF was studied in a carcinogenicity study to evaluate its toxic nature in mice

GLP compliance:

no

Species:

mouse

Strain:

other: Charles-River CD-1

Sex:

male/female

Route of administration:

oral: feed

Type of inhalation exposure (if applicable):

not specified

Vehicle:

other: Diet

Details on exposure:

No data available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

2 Yrs

Frequency of treatment:

Daily

Remarks:

Doses / Concentrations:0, 0.5, 1.5, or 5.0% (0,714.28,2142.85,7142.857 mg/kg/day)Basis:nominal in diet

No. of animals per sex per dose:

60 animals/sex/dose

Control animals:

yes

Details on study design:

No data available

Positive control:

No data available

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: YesHAEMATOLOGY: Yes - Time schedule for collection of blood: No data available- Anaesthetic used for blood collection: 3, 6, 12, and 18 months- Animals fasted: No data- How many animals: Ten animals/sex/group- Parameters examined. Haemoglobin, haematocrit, and erythrocyte counts were measured.

Sacrifice and pathology:

GROSS PATHOLOGY:Yes, gross changes/tissue masses were examined.HISTOPATHOLOGY: Yes, The following tissues were examined histologically from all survivors from the control and 5%-dose groups as well as all animals dying or killed in extremis from these groups: adrenals, aorta, bone and marrow (femur), brain (3 sections), eyes (with optic nerve), gall bladder, gastrointestinal tract (oesophagus, stomach, duodenum, ileum, caecum, colon), heart, kidneys, liver, lung, lymph nodes (mesenteric and mediastinal), mammary gland, nerve (sciatic), ovaries, pancreas, pituitary, prostate, salivary gland, seminal vesicles, skeletal muscle, skin, spinal cord, spleen, testes with epididymides, thymus, thyroid/parathyroid, trachea, urinary bladder, uterus, and gross lesions/tissue masses. In addition, gross changes/tissue masses were examined histologically from all animals in the lower-dose groups.

Other examinations:

No data available

Statistics:

No data available

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, 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:

effects observed, treatment-related

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Description (incidence and severity):

No treatment related neoplasm observed

Details on results:

CLINICAL SIGNS AND MORTALITY: No dose related effect on mortality of animals was notedBODY WEIGHT AND WEIGHT GAIN: Body weight of 5%-dose group female was lower than control and the mean body weight for male 5%-dose group was lower than controls at weeks 52 and 78.FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):No data availableFOOD EFFICIENCY: No data availableWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data availableOPHTHALMOSCOPIC EXAMINATION: No data availableHAEMATOLOGYNo dose related effects was observed but slight reduction in haemoglobin, haematocrit, and erythrocyte counts were observedCLINICAL CHEMISTRY: No data availableURINALYSIS: No data availableNEUROBEHAVIOUR: No data availableORGAN WEIGHTS: No data availableGROSS PATHOLOGY: YesHISTOPATHOLOGY: NON-NEOPLASTIC: No data availableHISTOPATHOLOGY: NEOPLASTIC (if applicable): No treatment related lesions were observed, benign and malignant neoplasms did not differ significantly between controls and treated animals

Relevance of carcinogenic effects / potential:

No treatment related lesions were observed, benign and malignant neoplasms did not differ significantly between controls and treated animals. Thus, Fast green FCF (2353-45-9) is found to be non-carcinogenic with a No Observed Adverse Effect level at 7142.857 mg/kg/day in male/female Charles CD-1 mice.

Dose descriptor:

NOAEL

Effect level:

7 142.857 mg/kg diet

Based on:

test mat.

Sex:

male/female

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

Conclusions:

The Carcinogenic Low Observed adverse effect level (LOAEL) for the test compound Fast Green FCF is 625 mg/kg bw in male and female Charles Albino rats.

Executive summary:

Carcinogenicity test was performed on male and female Charles-River CD-1 mice mice by a daily intake of at 0,714.28, 2142.85, 7142.857 mg/kg/day concentrations for 2 years. All animals dying or killed in a moribund condition and organ histopathology was observed for all animals. No treatment-related effects on mortality were observed. No dose-related haematological changes were observed and no dose related a benign and malignant neoplasm was observed in treated animals.

 

Fast green FCF (2353-45-9) is found to be non-carcinogenic with a No Observed Adverse Effect level at 7142.857 mg/kg/day in male/female Charles CD-1 mice.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

7 142.857 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Quality of whole database:

Weight of evidence using data is from peer reviewed journals and authoritative source of scientific information

Justification for classification or non-classification

The chemical is not likely to be carcinogenic within the dose levels mentioned in the studies since the tumors and adenomas were not attributed to the test chemical and were not differnt from those observed in the control. Hence, based upon the weight of evidence approach it is concluded that the chemical is not likely to be carcinogenic.

Additional information

Studies of Fast Green FCF were reviewed for carcinogenicity from reliable sources having Klimisch rating 2

The summary of the weight of evidence studies is furnished below

Sr. No	End Point	Value	Species	Route	Effects	Remarks
1.	LOAEL	625 mg/kg bw	Rat	Oral : feed	Observation made indicate an increased incidence of urothelial hyperplasia in treated males and of urinary bladder transitional cell/urothelial neoplasms in males of the 5%-dose group	Experimental data for target chemical
2.	NOEL	1 mg/kg bw	Hamster	Subcutaneously (SC) or intraperitoneally	No effect	Experimental data for target chemical
3.	NOAEL	7142.857 mg/kg bw	Mouse	Oral : feed	No effect	Experimental data for target chemical
4.	NOAEL	2500 mg/kg bw	Rat	Oral : Unspecified	No effect	Experimental data for target chemical

 

Thus, it can be concluded that the chemical is not likely to be carcinogenic within the dose levels mentioned in the studies since the tumors and adenomas were not attributed to the test chemical and were not differnt from those observed in the control. Hence, it is concluded that the chemical is not likely to be carcinogenic.

               

Justification for selection of carcinogenicity via oral route endpoint:
Data is from authoritative source of scientific information