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

Due to the similar chemical structure of C.I. Direct Blue 264 and Orasol Blue 825 a read-across between both compounds was initially suggested and experimentally verified. Toxicological investigations indicate that both compounds are not bioavailable and, consequently, not toxic even at the limit dose of 1000 mg/kg bw/day in repeated dose toxicity experiments. Based on the blue color of the substances, a coloration of feces and potential coloration of carcass, organs and urine is particularly valuable for the evaluation of bioavailability in repeated dose toxicity experiments.

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.

Study results on Orasol Blue 825:

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422) with Orasol Blue 825 in Wistar rats with oral administration by gavage is available. The rats were administered doses of 0, 100, 300 or 1000 mg/kg bw/day. Parameters indicative for systemic availability were examined. A detailed clinical examination of the animals was conducted including pathology (weight parameters, gross lesions, histopathology) and clinical pathology (hematology, clinical chemistry and urinalyses). For the toxicokinetic evaluation, the colors of feces and urine are evaluated. Regarding clinical examination, no signs of general systemic toxicity were observed up to an oral dose level of 1000 mg/kg bw/day (highest applied dose). A blue discoloration of feces in females of test group 2 (300 mg/kg bw/day), as well as in males and females of test group 3 (1000 mg/kg bw/day) was observed. During necropsy blue discoloration of contents was seen only throughout the gastro-intestinal system in many animals of both sexes of the mid and high dose group and in one female of the low dose group. No systemic organ was discolored indicating that the compound is not bioavailable to systemic organs. No discoloration in the urine was reported in any animal investigated, again, indicating that the compound is not bioavailable.

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 or Orasol Blue 825.

Acute toxicity:

Study results:

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

The acute oral toxicity of Orasol Blue 825 is higher than 10000 mg/kg bw in male and female rats.

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.

In a skin irritation/corrosion study and an eye irritation study Orasol Blue 825 was not irritating.

Conclusion:

With both substances 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.

An Ames test, a HPRT test and a mammalian erythrocyte micronucleus test with Orasol Blue 825 were negative.

Conclusion:

With both substances 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 a repeated dose gavage study with Orasol Blue 825 according to OECD TG 422 (Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test) no treatment-related adverse effects were observed. A NOAEL >1000 mg/kg bw/day was found.

General conclusion on read-across:

In all toxicological studies, similar results were obtained with both substances and it can be concluded that both compounds are not toxic in any test. Based on the animal experiments no bioavailability is assumed for both compounds. Therefore a read-across for toxicological endpoints is justified.

 

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

Due to the similar chemical structure of C.I. Direct Blue 264 and Orasol Blue 825 a read-across between both compounds was initially suggested and experimentally verified. Toxicological investigations indicate that both compounds are not bioavailable and, consequently, not toxic even at the limit dose of 1000 mg/kg bw/day in repeated dose toxicity experiments. Based on the blue color of the substances, a coloration of feces and potential coloration of carcass, organs and urine is particularly valuable for the evaluation of bioavailability in repeated dose toxicity experiments.

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.

Study results on Orasol Blue 825:

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422) with Orasol Blue 825 in Wistar rats with oral administration by gavage is available. The rats were administered doses of 0, 100, 300 or 1000 mg/kg bw/day. Parameters indicative for systemic availability were examined. A detailed clinical examination of the animals was conducted including pathology (weight parameters, gross lesions, histopathology) and clinical pathology (hematology, clinical chemistry and urinalyses). For the toxicokinetic evaluation, the colors of feces and urine are evaluated. Regarding clinical examination, no signs of general systemic toxicity were observed up to an oral dose level of 1000 mg/kg bw/day (highest applied dose). A blue discoloration of feces in females of test group 2 (300 mg/kg bw/day), as well as in males and females of test group 3 (1000 mg/kg bw/day) was observed. During necropsy blue discoloration of contents was seen only throughout the gastro-intestinal system in many animals of both sexes of the mid and high dose group and in one female of the low dose group. No systemic organ was discolored indicating that the compound is not bioavailable to systemic organs. No discoloration in the urine was reported in any animal investigated, again, indicating that the compound is not bioavailable.

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 or Orasol Blue 825.

Acute toxicity:

Study results:

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

The acute oral toxicity of Orasol Blue 825 is higher than 10000 mg/kg bw in male and female rats.

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.

In a skin irritation/corrosion study and an eye irritation study Orasol Blue 825 was not irritating.

Conclusion:

With both substances 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.

An Ames test, a HPRT test and a mammalian erythrocyte micronucleus test with Orasol Blue 825 were negative.

Conclusion:

With both substances 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 a repeated dose gavage study with Orasol Blue 825 according to OECD TG 422 (Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test) no treatment-related adverse effects were observed. A NOAEL >1000 mg/kg bw/day was found.

General conclusion on read-across:

In all toxicological studies, similar results were obtained with both substances and it can be concluded that both compounds are not toxic in any test. Based on the animal experiments no bioavailability is assumed for both compounds. Therefore a read-across for toxicological endpoints is justified.