Why the safety approval was withdrawn
JECFA, the joint FAO/WHO expert committee on food additives, evaluated indanthrene blue RS multiple times between 1959 and 1974. A temporary acceptable daily intake of 0-1 mg per kilogram of body weight was set in 1969, conditional on additional data being provided. The required information, covering how the dye is metabolised in the body and its effects on reproduction, embryonic development, and foetal harm, was never submitted by the 1974 deadline. JECFA consequently withdrew the temporary ADI. The JECFA specifications for the substance were formally withdrawn in 1984.
JECFA set a temporary ADI of 0-1 mg/kg body weight in 1969 and required data on metabolism and reproductive toxicity to be submitted by 1974. No data was provided and the temporary ADI was withdrawn.
1974Regulatory reviewJECFA evaluation, WHO Food Additives Series 6 and JECFA 28th meeting (NMRS 54/TRS 557)
The available long-term rat studies were judged inadequate because only selected parameters were examined. There was no information on metabolism, reproductive toxicity, embryotoxicity, or teratogenicity.
1966Regulatory reviewJECFA monograph 374, WHO Food Additives Series 6
JECFA specifications for indanthrene blue RS were formally withdrawn in 1984.
1984RegulatoryWHO/FAO JECFA database, EEC Serial No. E130, apps.who.int
Animal studies conducted before withdrawal
Rat studies lasting up to two years at dietary concentrations of 0.1% and 1% of feed found no increased tumour incidence and no changes attributed to the test diet. Acute oral toxicity in rats showed an LD50 of 2000 mg/kg. Guinea pig sensitisation tests found no sensitising activity. These results were not sufficient to establish a permanent ADI because metabolism data and reproductive toxicity studies were absent entirely.
Rats fed indanthrene blue RS at 0.1% and 1% of diet for up to two years showed no increased tumour incidence and no changes attributable to the test diet. The studies were judged inadequate due to limited parameters examined.
1966AnimalJECFA monograph 374, WHO Food Additives Series 6
Oral LD50 in rats was 2000 mg/kg body weight. No sensitising activity was found in guinea pigs.
1966AnimalJECFA monograph 374, WHO Food Additives Series 6
Removed from the EU food colours positive list
When the European Union replaced its 1962 food colours directive with Directive 94/36/EC, Anthraquinone Blue (another name for this substance) was among seven artificial colours explicitly deleted from the permitted list. The deletion was based on the Scientific Committee on Food's ongoing evaluation of toxicological data. E130 has not appeared in any subsequent EU food additives legislation, including Regulation (EC) 1333/2008, which is the current framework retained in UK law as assimilated legislation.
Seven artificial colours including Anthraquinone Blue were deleted from the EU food colours positive list when Directive 94/36/EC replaced the 1962 directive, based on SCF toxicological evaluations.
1994RegulatoryNATCOL Foods Colors Legislation review; EU Directive 94/36/EC
E130 does not appear in Annex II of EU Regulation (EC) 1333/2008 or in the UK FSA approved additives list. The sequence in the FSA list runs directly from E129 to E131 with no E130 entry.
2008RegulatoryUK Food Standards Agency approved additives list, food.gov.uk; EU Regulation (EC) 1333/2008
Anthraquinone dyes as a class: variable genotoxicity profile
Indanthrene blue RS belongs to the anthraquinone family of dyes, some members of which have shown genotoxic and mutagenic activity in laboratory tests. However, indanthrene blue RS itself (Vat Blue 4) could not be evaluated for genotoxicity in a key mouse lymphoma assay study because it is insoluble in cell culture medium. No IARC carcinogen classification exists for indanthrene blue RS specifically. The class-level concern is real but the compound-specific evidence for this particular dye is absent rather than negative.
In a mouse lymphoma assay of 16 anthraquinone dyes, Vat Blue 4 (indanthrene blue RS) could not be evaluated due to insolubility in the culture medium. Several other anthraquinone dyes in the same study showed mutagenic activity.
1991LabZeiger et al., analysis of genotoxicity of anthraquinone dyes in the mouse lymphoma assay, PubMed PMID 2038271