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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 14 day pilot study specifically designed to investigate potential compound uptake, distribution and excretion based on the intensive blue color of C.I. Direct Blue 264.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Objective of study:
other: 14 day pilot study specifically designed to investigate potential compound uptake, distribution and excretion based on the intensive blue color of the compound.
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
14 day oral gavage pilot study. The aim of the study was to investigate if there is evidence that C.I. Direct Blue 264 is absorbed after oral dosing and to investigate potential toxicity after repeated oral dosing.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
Purity: Approx. 98%
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Cremophor El (2% in tapwater; v/v)
Duration and frequency of treatment / exposure:
14 days; once per day
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 300, 1000 mg/kg bw/day
No. of animals per sex per dose:
3 males and 3 females
Control animals:
yes, concurrent vehicle

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
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.
Details on distribution in tissues:
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.
Details on excretion:
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.

Metabolite characterisation studies

Metabolites identified:
no

Any other information on results incl. tables

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.

Applicant's summary and conclusion

Executive summary:

A 14 day oral gavage pilot study was performed to investigate potential compound uptake, distribution and excretion based on the intensive blue color of C.I. Direct Blue 264.

In this study no adverse effects were observed at the limit dose 1000 mg/kg bw/day.

Compound related blue color was seen only in the intestinal tract.No other organ was colored blue. 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 systemic absorption of C.I. Direct Blue 264 is unlikely.