Reaction product of {mixture of [poly(1~4)chlorosulfonylphthalocyaninato-N29,N30,N31,N32]copper(Ⅱ) and [poly(1~3) chlorosulfonyl (tribenzo[b,g,l]pyrido[2,3-q]-5,10,15,20-tetraazaporphyrinato-N21,N22,N23,N24)] copper(Ⅱ) and [poly(1~2) chlorosulfonyl (dibenzo[b,g(or b,l)]dipyrido [2,3(or 3,2)-l,q(or g,q)]-5,10,15,20-tetraazaporphyrinato-N21,N22,N23,N24)] copper(Ⅱ) and [monochlorosulfonyl (benzo[b]tripyrido [2,3(or 3,2)-g,l,q]-5,10,15,20-tetraazaporphyrinato-N21,N22,N23,N24)]copper(Ⅱ) }and 2-[4-(2-aminoethylamino)-6-(benzylamino)-1,3,5-triazin-2-ylamino]benzene-1,4-disulfonic acid, and ammonia water and sodium chloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 20 - February 15, 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to current OECD test guidelines and GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

E-C104

IUPAC Name:

E-C104

Details on test material:

- Name of test material (as cited in study report): E-C104
- Physical state: Blue powder, solid
- Lot/batch No.: MB-1
- Expiration date of the lot/batch: Five years from shipment day (November 4, 2010)
- Storage condition of test material: Room temperature, in an air tight container in a dark place

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc. (Hino breeding center)
- Age at study initiation: 7 week old males and 10 week old females
- Weight at study initiation: 201.5 to 219.4 g for males and 218.2 to 240.3 g for females
- Fasting period before study: not applicable
- Housing: Stainless steel cages (WxDxH: 226x346x198mm), stainless steel cage racks and feeders, one animal per cage.
- Diet (ad libitum): Autoclave-sterilised pellet diet (CRF-1, Oriental Yeast Co., Ltd.). Each lot has been analysed: contaminants confirmed to be within acceptable limits established by the test facility.
- Water (ad libitum): Well water admixed with NaClO (about 2 ppm). Analysed twice a year: contaminants confirmed to be within acceptable limits establised by the test facility.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.9-23.8
- Humidity (%): 48.4-57.0
- Air changes (per hr): 10 to 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Remarks:

moistened with water (1 ml)

Details on dermal exposure:

TEST SITE
- Area of exposure: 4 x 5 cm
- % coverage: within 10% of total body surface
- Type of wrap if used: After hair clipping animals were fitted with a neck collar. The test substance was applied on a lint cloth lined with an impermeable sheet (Blenderm, 3M Health Care). This was covered with an elastic adhesive bandage (SILKYTEX white No.5, Alcare Co. Ltd.)

REMOVAL OF TEST SUBSTANCE
- Washing: wiped with a gauze sheet immersed in lukewarm water and water was removed with dry tissue paper. Animals were fitted with neck collars during dosing and the recovery period.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Required amount, calculated based on body weight on day of dosing. The lint cloth, where the substance was applied to, was moistened with an appropriate amount of water (1 ml).

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for their mortality and clinical signs before the dosing and at 30 min, 1, 3 and 6 hours postdose on the day of dosing (Day 1) and once daily for 14 days thereafter. All animals were subjected to body weight measurement before the dosing (Day 1) and on Days 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: no

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No death occured in either sex.

Clinical signs:

other: No substance related changes were seen in clinical signs.

Gross pathology:

No abnormalities were seen in either sexe.

Other findings:

No skin irritaion was observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of E-C104 in rats was considered to be more than 2000 mg/kg under the conditions of this study (OECD 402).

Executive summary:

E-C104 was administered once percutaneously to five male and five female Crl:CD(SD) rats at a dose of 2000 mg/kg to evaluate its acute dermal toxicity in accordance with OECD test guideline 402. The dose was appllied for 24 hours occlusively after which the application site was wiped. As a result, no mortality occurred in either sex and no test substance related change was seen in clinical signs, body weight or necropsy. Therefore, the LD50 value of E-C104 in rats was considered to be more than 2000 mg/kg under the conditions of this study.