Black HM 2482

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February 5th to February 26th, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted MAy 12, 1981

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EWG Directive 84/449/ EWG, Amtsblatt der Europaeischen Gemein-schaften L 251, Jahrgang 27, 19. 9. 84. B.3. Akute Toxizitaet - dermal/ 103

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

400-920-6

EC Name:

-

Cas Number:

89857-06-7

Molecular formula:

C50 H53 N11 O14 S

IUPAC Name:

5'-[2-(7-{2-[4-(2-{1'-[3-(dimethylazaniumyl)propyl]-6'-hydroxy-4'-methyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium-5'-yl}diazen-1-yl)phenyl]diazen-1-yl}-8-hydroxy-6-sulfonatonaphthalen-2-yl)diazen-1-yl]-6'-hydroxy-3,4'-dimethyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium bis(2-hydroxypropanoate)

Test animals

Species:

rat

Strain:

Wistar

Remarks:

KFM-Han

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable)
- Source: Kleintier farm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland
- Age at study initiation: 9 - 11 weeks
- Weight at study initiation: 228 - 252 g males; 180 - 198 g females
- Housing: individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, Switzerland)
- Diet: pelleted standard Kliba 343, Batch 15/84 rat maintenance diet ("Kliba", Klingentalmuehle AG, Switzerland), ad libitum
- Water: community tap water from Itingen, ad libitum
- Acclimation period: one week under laboratory conditions, after veterinary examination
- Method of randomisation in assigning animals to test and control groups: computer-generated random algorithm

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Air changes: 10 -15 per hour
- Photoperiod: 12 hours artificial fluorescent light / 12 hours dark, at least 8 hours music/light period

Administration / exposure

Type of coverage:

occlusive

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2% solution of CMC, carboxymethyl cellulose natrium salt purum, visc. 100 CPS

Details on dermal exposure:

VEHICLE
- Concentration: 2% solution of CMC, Carboxymethylcellulose natriumsalt purum, visc. 100 CPS, Fluka AG 9470 Buchs/Switzerland in distilled water

MAXIMUM DOSE VOLUME APPLIED: Group 1: 4 ml at 2000 mg/kg

DOSE PREPARATION
Test article was placed into a glass beaker on a tared Mettler PK 4800 balance and the vehicle was added. A weight/volume dilution was prepared using a homogenizer. Homogeneity of the test article was maintained during treatment using a magnetic stirrer. The preparations were made immediately prior to each dosing.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

Approximately 24 hours before treatment, the backs of the animals were shaved with an electric clipper, exposing an area of approximately 20 square centimeters.
0n test day 1 the test article was applied evenly on the skin and covered with an occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.
Twenty-four hours after the application, the dressing was removed and the skin reaction was assessed according to the method of Noaks and Sanderson (Noaks, D.N. and Sanderson, 0.11. "A Method for Determining the Dermal Toxicity of Pesticides". Brit. J. Industr. Med., 26, 59-64, 1969).

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: 4 times during test day 1 and daily during days 2 - 15 for mortality/viability. Test days 1 (pre-administration), 8 and 15 for body weights. Each animal was examined for changes in appearance and behaviour 4 times during day 1, and daily during days 2 - 15.
- Necropsy of survivors performed: yes. Necropsies were performed by experienced prosectors. AII animals were necropsied. AII animals surviving to the end of the observation period were anesthetized by intraperitoneal injection of sodium pentobarbital and killed by exsanguination.
- Clinical signs including body weight
- Examinations performed: clinical signs, body weight, pathology,: Observations included general behavior, nose, respiration, eye, motility, body position, motor susceptibility, skin...

Statistics:

The LOGIT-Model could not be applied to the observed rates of death. The LD50 was estimated without use of a statistical model.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

No changes were observed.

Gross pathology:

No gross pathological changes were observed in any of the animals.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified according to CLP Regulation (EC no. 1272/2008)

Conclusions:

LD50 (male/female rats) > 2000 mg/kg

Executive summary:

The test item was evaluated for acute dermal toxicity when administered to Wistar rats by a single occlusive dermal application, followed by an observation period of 15 days. The study was performed fallowing the OECD Guideline No. 402.
The test item was administered to rats of both sexes at a dose of 2000 mg/kg. The following death rate was observed: 0% at 2000 mg/kg. No local or systemic symptoms were observed in any treated animal. No macroscopic organ changes were observed.

The LD50 of the test item was estimated to be greater than 2000 mg/kg.