Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from Scientific Opinion document on the re-evaluation of Patent Blue V as a food additive, published by the European Food Safety Authority

Data source

Reference

Reference Type:

secondary source

Title:

Scientific Opinion on the re-evaluation of Patent Blue V (E 131) as a food additive, EFSA Panel on Food Additives and Nutrient Sources added to Food

Author:

European Food Safety Authority (EFSA), Parma, Italy

Year:

2015

Bibliographic source:

Scientific Opinion on the re-evaluation of Patent Blue V (E 131) as a food additive, EFSA Panel on Food Additives and Nutrient Sources added to Food, European Food Safety Authority (EFSA), Parma, Italy, EFSA Journal 2013;11(3):2818, April’ 2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Guideline details not available

Principles of method if other than guideline:

Absorption, distribution, metabolism and excretion of the chemical hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt (Synonym: Patent Blue V) as a food additive was investigated

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt

EC Number:

204-934-1

EC Name:

Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt

Cas Number:

129-17-9

Molecular formula:

C27H32N2O6S2.Na

IUPAC Name:

hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt

Constituent 2

Reference substance name:

hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt (Synonym: Patent Blue V)

IUPAC Name:

hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt (Synonym: Patent Blue V)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

CAS No: 129-17-9Name in test report: (14C) Patent Blue VType of chemical: Organic

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on exposure:

Groups of male and female Sprague-Dawley rats were given oral doses between 1.6 and 3.2 mg (14C) Patent Blue V/kg bw, and then killed at intervals of up to 48 hours.

Duration and frequency of treatment / exposure:

Duration of study – 72 to 120 hours

Doses / concentrations

Remarks:

Doses / Concentrations:1.6 and 3.2 mg (14C) Patent Blue V/kg bw

No. of animals per sex per dose / concentration:

6

Control animals:

not specified

Positive control reference chemical:

Details not available

Details on study design:

Details not available

Details on dosing and sampling:

Details not available

Statistics:

Details not available

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Low absorption observed after oral administration from the gastrointestinal (GI)tract of the rats

Main ADME results 2

Type:

distribution

Results:

Wide tissue distribution was observed. Small amounts of the dose were present in the carcass at 72 hours and less than 0.1 % of the dose was present at 120 hours.

Main ADME results 3

Type:

metabolism

Results:

2 substances representing 30-32 % and 12-14 % of the urinary radioactivity and 3 minor components were detected but not identified.

Main ADME results 4

Type:

excretion

Results:

In 6 male rats given oral doses of 1 to 1.5 mg (14C) Patent Blue V/kg bw, a total of 93 % of the dose appeared in the faeces within 24 hours. Radioactivity extracted from the faeces in these studies was in the form of unchanged colour.

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

2 substances representing 30-32 % and 12-14 % of the urinary radioactivity and 3 minor components were detected but not identified.

Any other information on results incl. tables

There was some evidence for preferential accumulation of radioactivity in the thyroid.

The early rapid elimination of the majority of the radioactivity was followed by a much slower excretion of the remainder (possibly as a result of coprophagy).

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study resultsIn an in-vivo study carried out on Sprague-Dawley male rats, upon oral administration, a total of 93 % of the dose appeared in the faeces within 24 hours. Less than 0.5 % of the radioactivity was excreted in the urine (most within the first 4 hours). There was low absorption of the administered chemicals. There was some evidence for preferential accumulation of radioactivity in the thyroid. However, since the majority of the adminstered chemical was eliminated out of the body of the rats, the bio-accumulation potential of the chemical hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt Synonym: (14C) Patent Blue V appears to be low.

Executive summary:

In an in-vivo study carried out onSprague-Dawley male rats, upon oral administration, a total of 93 % of the dose appeared in the faeces within 24 hours. Less than 0.5 % of the radioactivity was excreted in the urine (most within the first 4 hours). There was low absorption of the administered chemicals. There was some evidence for preferential accumulation of radioactivity in the thyroid. However, since the majority of the adminstered chemical was eliminated out of the body of the rats, the bio-accumulation potential of the chemicalhydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt Synonym: (¹⁴C) Patent Blue V appears to be low.