1-Octadecanaminium,N,N-Dimethyl-N-Octadecyl-,(Sp-4-2)-[29h,31h-Phthalocyanine2-Sulfonato(3-)-N 29,N 30,N 31,N 32]Cuprate(1-)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study; well documented study report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

In the report the first day of the treatment is noted as day 1 instead of day 0 due to changed procedures; all animals were provided with tap-water and not with tap-water diluted with decalcified water as per protocol

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

yes

Remarks:

In the report the first day of the treatment is noted as day 1 instead of day 0 due to changed procedures; all animals were provided with tap-water and not with tap-water diluted with decalcified water as per protocol

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Physical state: Blue powder
- Purity: 100% - moisture
- Lot/batch No.: Ref Mix 51785
- Stability under test conditions: Stable under storage conditions
- Storage condition of test material: At room temperature in the dark
- Other: Disposal category III

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Source: Charles River Wiga. Sulzfeld, West-Germany
-Age at study initiation: approx. 7 weeks
-Weight at study initiation: males: 253~276 g; females: 167~192 g.
-Fasting period before study: Feed was withheld overnight prior to dosing until approximately 3-4 h after administration of the test article.
-Housing: housed in groups of 5 per sex in polycarbonate cages containing purified sawdust as bedding material.
-Diet: free access to standard pelleted laboratory animal diet (RMH-B from Hope Farms, The Netherlannds)
-Water: free access to tap-water.
-Acclimation period: at least 5 days under laboratory conditions.

ENVIRONMENTAL CONDITIONS
-Temperature (°C): 21± 3 oC
-Humidity (%): 30-70%
-Air changes: 7.5 – 15 air changes per hr
-Photoperiod (12 hrs dark /12 hrs light)

IN-LIFE DATES: From: Jan 5th 1989 To: Jan 19th 1989

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: male (5 x 5 cm); female (3.5 x 5 cm)
- Type of wrap if used: using a gauze patch fixed successively to aluminum foil and flexible bandage, with drops of petrolatum
TEST SITE
- Area of exposure: male (5 x 5 cm); female (3.5 x 5 cm)
- Type of wrap if used: using a gauze patch fixed successively to aluminum foil and flexible bandage, with drops of petrolatum.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with tissue moistened with tap water.
- Time after start of exposure: 24 h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ml/kg body weight
- Concentration (if solution): 200 mg/kg body weight
- Constant volume or concentration used: no
- For solids, paste formed: no

Duration of exposure:

24 h

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 male; 5 female

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations at periodic intervals on the day of dosing (day 1) and twice daily thereafter for at least 14 days; Bodyweight measurements taken on days 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: body weight, clinical signs, skin irritation, skin fur, eyes and mucous membrane, and behavior pattern, tremors, convulsion, salivations, diarrhea, lethargy, sleep and coma.

Statistics:

Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 1

Clinical signs:

other: On day 1, lethargy and dyspnea was noted in one male and one female, respectively. There were no other clinical signs of toxicity or behavioral changes over the 15 day observation period

Gross pathology:

Effects on organs:
No treatment-related macroscopic findings were observed.

Other findings:

- Other observations: The treated skin surface of animals showed no irritation.

Any other information on results incl. tables

Albino rats, Wistar (outbred, SPF-quality), were treated with a single dose of the test material (2000 mg/kg bw) to the dorsal skin, the following results were obtained:

Table 1. Body Weights

Sex	Mean Body Weight (g) on (Mean ± SD)			Mean Body Weight (g) Gain Day 1-15
	Day 1*	Day 8	Day 15
Male	265 ± 10.3 (N = 5)	289 ±15.5 (N = 5)	336 ± 32.3 (N = 5)	93 ± 11.1 (N = 5)
Female	181 ± 10.1 (N = 5)	199 ±10.9 (N = 4)	212 ± 19.5 (N = 4)	57 ± 11.1 (N = 4)

Day 1: Day of dosing.

 

Table 2. Incidence of treated skin abnormalities

OBSERVATION	DAY OF EVALUATION
	2*		5		8		15
# of Animals Examined	M	F	M	F	M	F	M	F
No Abnormalities	0	0	0	0	0	0	0	0
Blue Discoloration	5	4	5	4	5	4	5	4

*: following bandage removal;

M: Male;

F: Female.

Table 3. Macroscopic Founding 

Day 1 Female	Found dead No. 7: No abnormalities detected.
Day 15 Male Female	Sacrificed at termination. No. 1, 2, 3, 4, 5: No abnormalities detected. No. 6, 8, 9, 10: No abnormalities detected.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: other: EEC Directive 83/467/EEC, Annex VI of the EEC Directive 67/548/EEC

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Albino rats, Wistar (outbred, SPF-quality) strain, was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

In an acute dermal toxicity study, a group of ~ 7 week old Wistar strain rats (five male and five female) were dermally exposed to the test material dissolved in water for 24 hours to approximately 5 x 5 cm (male), or 3.5 x 5 cm (female) body surface areas at a dose level of  2000  mg/kg bw.  Animals then were observed for 14 days.

Combined dermal LD₅₀wad estimated to exceed 2000 mg/kg bw.

On day 1, lethargy anddyspneawas noted in one male and one female, respectively. There were no other clinical signs of toxicity or behavioral changes over the 15 day observation period. The treated skin surface of animals showed no irritation. Macroscopic examination of all animals at the end of the study did not reveal any changes that were considered to have arisen as a result of treatment.