Nickel, 5-[2-(2-hydroxy-3,7-disulfo-1-naphthalenyl)diazenyl]-1H-1,2,4-triazole-3-carboxylate sodium complexes

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 2002-11-25 and 2002-12-09. Report signed off 2003-01-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Meets the criteria for classification as Reliable without restriction according to Klimisch et al (1997)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

443-510-2

EC Name:

-

Cas Number:

738587-10-5

Molecular formula:

C26H14N10Ni2O18S4 as free acid

IUPAC Name:

dinickel(2+) sodium 3-carboxy-5-[(1E)-2-(7-oxido-2,6-disulfonaphthalen-1-yl)diazen-1-yl]-1H-1,2,4-triazol-1-ide 3-carboxy-5-[(1E)-2-(7-oxido-2-sulfo-6-sulfonatonaphthalen-1-yl)diazen-1-yl]-1H-1,2,4-triazol-1-ide

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Five male and five female Sprague-Dawley CD (Cd: CD® (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals weighed at least 200g, and were eight to twelve weeks of age. The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

The test concentration was 2000 mg/kg bodyweight of test substance. The appropriate amount of test material, moistened with distilled water, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area). A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive. Any other skin reactions, if present were also recorded. The animals were caged individually for the 24-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place. After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with moistened cotton wool to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

Duration of exposure:

24 hours

Doses:

2000 mg/kg/bodyweight

No. of animals per sex per dose:

5 male, 5 female

Control animals:

not required

Details on study design:

A group of ten animals (five males and five females) was given a single, 24-hour, semi-occluded dermal application of test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

The animals were observed for deaths or overt signs of toxicity at 0.5, 1, 2 and 4h after dosing and susequently once daily for fourteen days.

After removal of the dressings and subsequently once daily for fourteen days the test sites were examined for evidence of primary irritation.

Statistics:

None used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

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: 0

Clinical signs:

other: Signs of toxicity related to dose levels: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Dermal reactions: Red coloured staining which prevented evaluation of erythema was noted at the treatment sites of all animals up to six days after treatment.

There were no signs of dermal irritation.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

After a single application of the test substance the acute dermal median lethal dose (LD50) of the test substance in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. There were no deaths during the study, no signs of systemic toxicity, no signs of dermal irritation, all animals showed expected gains in bodyweight and there were no abnormalities noted at necropsy.

The test substance does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with EU labelling regulations Commision Directive 93/21/EEC for classification and labelling of dangerous substances and preparations and in accordance with Regulation (EC) No. 1272/2008.

Executive summary:

Introduction

The study was performed to assess the acute dermal toxicity of the test material in the Sprague Dawley CD strain rat. The method was designed to be compatible with:

OECD Guidelines for the Testing of Chemicals No. 42 'Acute Dermal Toxicity' (adopted 24 February 1987)

Method B3 Acute Toxicity (Dermal) of Commision Directive 92/69/EEC

Result

After a single application of the test substance the acute dermal median lethal dose (LD50) of the test substance in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. There were no deaths during the study, no signs of systemic toxicity, no signs of dermal irritation, all animals showed expected gains in bodyweight and there were no abnormalities noted at necropsy.

The test substance does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with EU labelling regulations Commision Directive 93/21/EEC for classification and labelling of dangerous substances and preparations and in accordance with Regulation (EC) No. 1272/2008.