Phthalocyanine Blue


CAS No. 147-14-8

Copper, [29H, 31H-Phthalocyanate(2-)] / Pigment Blue-15


Phthalocyanine blue was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 40, 200 and 1000 mg/kg/day and in an OECD preliminary reproductive/developmental toxicity screening test at doses of 0, 40, 200 and 1000 mg/kg/day. Phthalocyanine Blue was also tested for mutagenicity with assays for reverse mutation in bacteria and chromosomal aberrations in cultured Chinese hamster (CHL) cells.

In the repeat dose toxicity study, significant decrease in red blood cell counts and tendencies for reduction in hemoglobin and packed cell volume were detected dose-dependently in the 200 and 1000 mg/kg males. A significant increase in erythroblasts was detected in the 1000 mg/kg females after the recovery period. Additionally, the 1000 mg/kg males showed increases in absolute and relative spleen weights. No histopathological changes due to the test chemical were detected. These findings suggest that phthalocyanine blue at 200 and 1000 mg/kg slightly affects the red blood cells of both sexes. The NOEL for the 28-day repeat dose case was 40 mg/kg/day. No toxicity regarding reproduction and development was observed, with a NOEL of 1000 mg/kg/day.

The mutagenicity tests were all negative. Phthalocyanine blue was not mutagenic for bacteria either with or without exogenous metabolic activation up to 5000 μg/plate. Neither chromosomal aberrations nor polyploidy were induced in CHL cells given up to 3 mg/ml with or without exogenous metabolic activation.

Phthalocyanine Blue[147-14-8]

1. Repeat Dose Toxicity 1)

Purity:Technical grade
Test species/strain:Rat/Slc:Wistar
Test method:Guidelines for 28-Day Repeat Dose Toxicity Test of Chemicals (Japan)
 Route:Oral (gavage)
 Number of animals:Male, 10; Female,10/group
 Doses:0 (Vehicle), 40, 200, 1,000 mg/kg/day
 Vehicle:Corn oil
 Administration period:Male and Female, 28 days
 Terminal kill:Day 29 or 43

 Test results:

No changes in general condition, body weight gain or food consumption were detected in any of the groups. After the 28 days of administration, a significant decrease in red blood cell count (RBC) and decrease of hemoglobin (Hb) and packed cell volume (PCV) were detected in the 200 and 1000mg/kg male groups. These slight changes were dose dependent. After the recovery period, significant increase of erythroblasts was detected in the 1000 mg/kg female group. Additionally, increases of absolute organ weights of lung, spleen, adrenal and salivary gland and a tendency for increased relative organ weights of the spleen were evident in the 1000 mg/kg male group were detected. No histopathological changes due to administration of phthalocyanine blue were detected. These findings suggest that phthalocyanine blue slightly affects red blood cells in rats at 200 and 1000 mg/kg.
NOEL: 40 mg/kg/day

2. Preliminary Reproductive/Developmental Toxicity 2)

Test species/strain:Rat/Crj:CD (SD)
Test method:OECD Preliminary Reproduction Toxicity Screening Test
 Route:Oral (gavage)
 Doses:0 (vehicle), 40, 200,1000 mg/kg/day
 Number of animals:Male,12; Female,12/group
 Administration period:Male, 42 days
Female, from 14 days before mating to day 3 of lactation
 Terminal kill:Male, days 28, 47
Female, day 28, day 4 of lactation

 Test results:

No effects were noted in reproductive ability of either sex, or in delivery and maternal behavior, viability, clinical signs, body weight change or autopsy findings of pups.

NOEL for P generation: 1000 mg/kg/day
NOEL for F1 generation: 1000 mg/kg/day

<Maternal and paternal general toxicity>
Regarding clinical sign and autopsy, blue discoloration of feces was noted in all animals of the groups receiving 40 mg/kg or more; moreover blue-green or grayish blue discolorations of the contents of the stomach and intestines were noted in a few animals of the 200 mg/kg group and in almost all animals of both sexes in the 1000 mg/kg group. These changes were due to the color of the test substance. In terms of body weight change, food consumption, organ weight and histopathological examination, no effects of the test substance were noted.

3. Genetic Toxicity

3-1 Bacterial test 1)

Purity:Technical grade
Test species/strains:S.typhimurium TA100, TA98, TA102,TA97
Test method:Maron & Ames (1983)
 Procedure:Preincubation assay
 Positive controls:-S9, AF-2 (TA100, TA98) Mitomycin C (TA102) ICR-191 (TA97)
+S9, 2-Aminoanthracene (all strains)
 Doses:0, 25, 50, 100, 250, 500, 1000, 2500, 5000 μg/plate
 S-9:Rat liver, induced with KC-400 (equivalent to PCB)
 No. of replicate:1
 Test results:
Minimum concentration of test substance at which toxicity to bacteria was observed:
No toxicity was observed at a concentration of 5000μg/plate with or without metabolic activation.

Genotoxic effects:
TA100, TA98, TA102, TA97
with metabolic activation:[ ][ ][*]
without metabolic activation:[ ][ ][*]

3-2 Non-bacterial in vitro test (Chromosomal aberration test) 1)

Purity:Technical grade
Type of cell used:Chinese hamster CHL cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
 Positive controls:Benzopyrene
 Doses:-S9: 0, 0.75, 1.5, 3 mg/ml
+S9: 0, 0.75, 1.5, 3 mg/ml
 S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone

 Test results:
None of dose groups induced any choromosomal aberrations or polyploidy in CHL cells with and without S9 mix.
Lowest concentration producing cytogenetic effects in vitro:
without metabolic activation: > 1.3 mg/ml
with metabolic activation: > 3 mg/ml
without metabolic activation: > 3 mg/ml

Genotoxic effects:
with metabolic activation:[ ][ ][*]
without metabolic activation:[ ][ ][*]

1)The tests were performed by Biological Safety Research Center, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158, Japan. Tel 81-3-3700-1141 Fax 81-3-3700-2348
2)he test was performed by Safety Research Institute for Chemical Compounds Co., Ltd., 363-24 Shinei, Toyohira-ku, Sapporo, Hokkaido, 004, Japan. Tel 81-11-885-5031 Fax 81-11-885-5313