Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Potential absorption and bioavailability:

Study results on C.I. Direct Blue 264:

No adverse effects were reported in a non-guideline pilot study where the C.I. Direct Blue 264 was administered orally by gavage to 3 male and 3 female rats per group, in daily doses of 0, 100, 500 or 1000 mg/kg bw/day for 14 days. There were no toxicologically significant effects on survival, clinical examinations, body weight, food intake and water intake. The only finding at clinical examinations was blue feces color, which was observed for all treated animals and is due to the color of the test substance. Findings clearly related to the oral administration of the test compound were noticed at necropsy only in the intestinal tract in males starting at 100 mg/kg bw/day and in females starting at 500 mg/kg bw/day. Changes in content, blue, was observed in small intestine, cecum and large intestine. No other organ was colored. Single males of this study displayed pale discoloration of the kidney. These observations are not necessarily indicative for a systemic effect on the kidneys induced by a test compound because they could have developed perimortally as a consequence of interindividual differences in the grade/status of exsanguination. Occasionally these gross observations do not have any histopathologic correlate at all or may show an equivocal histopathologic finding of the kidneys. To investigate potential uptake and excretion of the compound the color of the urine was investigated photometrically in this study. Urine has be collected during a period of about 16 hours at room temperature from all animals of the control and high dose groups near the end of the study. The color of the urine did not differ between these groups. Furthermore, photometry of urinary samples gave no evidence that the test substance was excreted with the urine. Based on the photometric urine analysis and the necropsy findings in this 14 day pilot study specifically designed to investigate potential compound uptake, distribution and excretion, no systemic absorption was observed.

Conclusion:

Overall, from the data of these repeated dose studies, there is no evidence of a toxicological relevant absorption of C.I. Direct Blue 264.

Acute toxicity:

Study results:

In an acute oral toxicity study in female rats a LD50 > 5000 mg/kg bw and a LD50 > 2000 mg/kg bw for acute dermal toxicity in male and female rats was found for C.I. Direct Blue 264.

Skin irritation/corrosion and eye irritation:

Study results:

In a skin irritation/corrosion study and an eye irritation study C.I. Direct Blue 264 was not irritating.

Conclusion:

No skin and eye irritation was observed.

Genotoxicity:

Study results:

An Ames test, an in-vitro MNT and a HPRT test with C.I. Direct Blue 264 were negative.

Conclusion:

All available genotoxicity tests were negative.

Subacute and reproductive toxicity:

Study results:

In a pilot 14 day oral gavage study with C.I. Direct Blue 264 in rats a NOAEL >1000 mg/kg bw/day was found. No toxicological relevant findings were observed on the following parameters: survival, clinical examination, body weight, food and water intake and necropsy.

In an OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents) the test item Direct Blue 264 (CAS 68411-04-1) was administered daily in graduated doses to 3 groups of test animals, one dose level per group for a treatment period of 90 days. The following doses were evaluated: 0 (control), 250, 500, or 1000 mg/kg body weight.

No test-item related mortality was observed and no adverse effects of the test item were found for male and female clinical observations, functional observations, body weight development, food consumption, hormone analysis, sperm parameters, haematology and coagulation, clinical biochemistry, urinalysis, gross macroscopic findings at necropsy, organ weights and histopathology in all treated dose groups.

The no observed adverse effect level (NOAEL) of Direct Blue 264 in this study is considered to be 1000 mg/kg body weight/day.

In an OECD TG 414 study no effects of Direct Blue 264 on pregnant females and foetuses were found at dose levels up to 1000 mg/kg body weight/day. The NOAEL (No Observed Adverse Effect Level) for both maternal toxicity and foetal toxicity of Direct Blue 264 in this study is considered to be 1000 mg/kg body weight/day (the highest dose tested).

Note:

The national Occupational Exposure Limit in Germany for chemically and biologically inert dust is 10 mg/m3 for inhalable and 2.5 mg/m3 for respirable dust (TRGS900).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Potential absorption and bioavailability:

Study results on C.I. Direct Blue 264:

No adverse effects were reported in a non-guideline pilot study where the C.I. Direct Blue 264 was administered orally by gavage to 3 male and 3 female rats per group, in daily doses of 0, 100, 500 or 1000 mg/kg bw/day for 14 days. There were no toxicologically significant effects on survival, clinical examinations, body weight, food intake and water intake. The only finding at clinical examinations was blue feces color, which was observed for all treated animals and is due to the color of the test substance. Findings clearly related to the oral administration of the test compound were noticed at necropsy only in the intestinal tract in males starting at 100 mg/kg bw/day and in females starting at 500 mg/kg bw/day. Changes in content, blue, was observed in small intestine, cecum and large intestine. No other organ was colored. Single males of this study displayed pale discoloration of the kidney. These observations are not necessarily indicative for a systemic effect on the kidneys induced by a test compound because they could have developed perimortally as a consequence of interindividual differences in the grade/status of exsanguination. Occasionally these gross observations do not have any histopathologic correlate at all or may show an equivocal histopathologic finding of the kidneys. To investigate potential uptake and excretion of the compound the color of the urine was investigated photometrically in this study. Urine has be collected during a period of about 16 hours at room temperature from all animals of the control and high dose groups near the end of the study. The color of the urine did not differ between these groups. Furthermore, photometry of urinary samples gave no evidence that the test substance was excreted with the urine. Based on the photometric urine analysis and the necropsy findings in this 14 day pilot study specifically designed to investigate potential compound uptake, distribution and excretion, no systemic absorption was observed.

Conclusion:

Overall, from the data of these repeated dose studies, there is no evidence of a toxicological relevant absorption of C.I. Direct Blue 264.

Acute toxicity:

Study results:

In an acute oral toxicity study in female rats a LD50 > 5000 mg/kg bw and a LD50 > 2000 mg/kg bw for acute dermal toxicity in male and female rats was found for C.I. Direct Blue 264.

Skin irritation/corrosion and eye irritation:

Study results:

In a skin irritation/corrosion study and an eye irritation study C.I. Direct Blue 264 was not irritating.

Conclusion:

No skin and eye irritation was observed.

Genotoxicity:

Study results:

An Ames test, an in-vitro MNT and a HPRT test with C.I. Direct Blue 264 were negative.

Conclusion:

All available genotoxicity tests were negative.

Subacute and reproductive toxicity:

Study results:

In a pilot 14 day oral gavage study with C.I. Direct Blue 264 in rats a NOAEL >1000 mg/kg bw/day was found. No toxicological relevant findings were observed on the following parameters: survival, clinical examination, body weight, food and water intake and necropsy.

In an OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents) the test item Direct Blue 264 (CAS 68411-04-1) was administered daily in graduated doses to 3 groups of test animals, one dose level per group for a treatment period of 90 days. The following doses were evaluated: 0 (control), 250, 500, or 1000 mg/kg body weight.

No test-item related mortality was observed and no adverse effects of the test item were found for male and female clinical observations, functional observations, body weight development, food consumption, hormone analysis, sperm parameters, haematology and coagulation, clinical biochemistry, urinalysis, gross macroscopic findings at necropsy, organ weights and histopathology in all treated dose groups.

The no observed adverse effect level (NOAEL) of Direct Blue 264 in this study is considered to be 1000 mg/kg body weight/day.

In an OECD TG 414 study no effects of Direct Blue 264 on pregnant females and foetuses were found at dose levels up to 1000 mg/kg body weight/day. The NOAEL (No Observed Adverse Effect Level) for both maternal toxicity and foetal toxicity of Direct Blue 264 in this study is considered to be 1000 mg/kg body weight/day (the highest dose tested).