Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From October 20, 1999 to November 3, 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
OECD guideline 402 and EU guideline B.3. GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name: NINOX HCDO
- Purity: 92.32%
- Lot/batch No.: 876 TK
- Sample number: VI
- Physical state: off white paste
- Storage condition of test material: room temperature, in the dark.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK)
- Age at study initiation: eight to twelve weeks old
- Weight at study initiation: males 206 to 232 g, and the females 214 to 225 g.
- Housing: in suspended polypropylene cages furnished with wood flakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ºC
- Humidity (%): 30-70 %
- Air changes (per hr): approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light and twelve hours darkness

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approximating to 10% of the total body surface area.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: After the 24-hour contact period

TEST MATERIAL
- Concentration (if solution): 2174 mg/kg (equivalent to 2000 mg/kg bodyweight of pure test material).
Duration of exposure:
24-hours
Doses:
2174 mg/kg (equivalent to 2000 mg/kg bodyweight of pure test material).
No. of animals per sex per dose:
Ten animals (five males and five females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 174 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The dose 2174 mg/kg is equivalent to 2000 mg/kg bodyweight of pure test material
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study. Very slight to well-defined erythema was noted at the treatment sites of all animals one and two days after dosing and very slight oedema was noted at the treatment sites of eight animals one day after dosing. On the treated site of some animals a slight brown discoloration of the epidermis (in four animals) bleeding (in one animal), desquamation (in four animals) and crust formation (in five female animals) was noted.
Body weight:
All animals showed expected gain in bodyweight during the study except for one female animal which showed bodyweight loss during the first week and expected gain in bodyweight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual bodyweight and weekly changes

 

Doselevel

mg/kg

Animal Number and Sex

Bodyweight

(g) atDay

Bodyweight Gain (g)

During Week

 

 

0

7

14

1

2

2174

1-0 Male

206

238

286

32

48

1-1 Male

228

285

336

57

51

1-2 Male

232

280

345

48

65

1-3Male

220

257

312

37

55

1-4 Male

215

201

322

46

61

2-0 Female

214

215

234

1

19

2-1 Female

220

225

236

5

11

2-2 Female

225

220

245

-5

25

2-3 Female

224

235

265

11

30

2-4 Female

225

226

250

1

24

 

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Conclusions:
The acute dermal median lethal dose (LD50) of the test substance in the Sprague-Dawley rat was found to be greater than 2174 mg/kg bodyweight (equivalent to 2000 mg/kg bodyweight of pure test material). The test substance is not to be classified as acute dermal toxicant according to CLP Regulation.
Executive summary:

The Acute Dermal Toxicity assay for the test substance was performed in Sprague-Dawley rats. One female group and one male group, of 5 animals each one, were treated with a single dose of 2174 mg/kg bodyweight, equivalent to 2000 mg/kg bodyweight of pure test material (Limit test). The test material was applied uniformly to an area of shorn skin (approximating to 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 bandage. After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water. Clinical observation was conducted at 1/2,1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Body weight was controlled before the administration, on day 0 and on days 7 and 14 after the administration. All animals were subjected to gross necropsy. No test substance related effects were noted from clinical observations or post-mortem examination. The acute dermal median lethal dose (LD50) of the test substance in the Sprague-Dawley rat was found to be greater than 2174 mg/kg bodyweight (equivalent to 2000 mg/kg bodyweight of pure test material).