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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 October 1992 to 10 November 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with OECD test guidelines in compliance with GLP and reported with a valid GLP certificate.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Lowinox 624-98,5
IUPAC Name:
Lowinox 624-98,5
Test material form:
liquid: viscous
Details on test material:
Name: Lowinox 624-98,5
Batch No.: 18.09.92
Supplied by: Chemische Werke LOWI GmbH & Co., W-8264 Waldkraiburg
Chemical name: 6-tert. Butyl 1-2,4-dimethylphenol
Physical state: clear liquid
Density: 0.96 g/ml (20°C) (as specified by sponsor)
Identification: labelled, where appropriate, with name of test article, batch no., name of sponsor, project no., date of receipt, storage conditions, handling precautions and expiry date
Storage: ambient
Stability: not specified

Test animals

Species:
rat
Strain:
other: Bor: WISW (SPF Cpb)
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: rat
Strain: Bor: WISW (SPF Cpb)
Source: Winkelmann Versuchstierzucht, Garenslr. 27, 4799 Borchen
Date of receipt: September 30 and October 7, 1992
Acclimation period: at least 15 days
Animal selection: random
Animal identification: with coloured markings; cage labelled with dosage, sex, date of study initiation, project no.
Weight range at study initiation: m: 235 - 282 g, f: 180 - 207 g
Housing: individual housing in cages (Makrolon type II)
Illumination: artificial lighting (120 lux) from7.00 a.m. -7.00 p.m.
Temperature: 22± 30 °C
Relative humidity: 30 - 70 %
Measurement: with thermohygrometer twice daily

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Prior to study initiation, the animals were acclimated to laboratory conditions for at least 5 days. Only healthy animals were used in the test.
24 h before treatment, the fur was removed with electric clippers from an area of roughly 5 x 10 cm on the back of each anima. The skin was subsequently examined for abrasions and animals with healthy, intact skin were then coloured for individual identification.

Preparation and application of the test article: A single dermal application of the test article was performed. The substance was held in contact with the skin with a porous gauze dressing and Elastoplast (Beiersdorf).
Duration of exposure:
The exposure period was 24 h.
Doses:
The test article was applied once
No. of animals per sex per dose:
Preliminary range finding test: 2 female animals
Main study - 5 males and 5 female animals
Control animals:
no
Details on study design:
Range finding: A preliminary range finding test with doses of 200, 500 and 2000 mg/kg body weight was conducted on two female rats, per dose.
On the basis of the range finding results, each animal was given a single dermal administration of "Lowinox 624-98,5" at a dose of 2000 mg/kg body weight. The skin was exposed to the test article for 24 h and signs of erythema and oedema were subsequently evaluated once daily for 14 days.
Clinical observations were conducted at regular intervals during the 14-day observation period. Body weights were measured at days 0, 7 and 14 p.a. Gross pathological examinations were performed on animals at termination.

Results and discussion

Preliminary study:
There were no deaths in the preliminary study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No anmals died during the course of the main study.
Clinical signs:
No abnormal clinical signs were observed.
Body weight:
Weight gains were reduced in most of the anmals at day 7 p.a. In one male and in one female the body weight was decreased at day 7 p.a. At day 14 p.a. weight gains were normal in the males but reduced in the females.
Gross pathology:
Gross pathological examinations at 14 days p. a. (terminal necropsy) revealed no test article-dependent findings. That macroscopic change observed was attibutable to the sacrificing procedure or to minor variations which can occur spontaneously in rats of this strain and age.
Other findings:
No signs of oedema were observed. At day 1 p.a. very slight to well-defined erythema were observed. At days 4 and 5 p.a. in two females very slight erytema and slight scale formation were observed.

Any other information on results incl. tables

APPENDIX 2 – CLINICAL OBSERVATIONS

Test article: Lowinox 624-98,5                    Project no.: 10-04-1635/00-92

Species: Rat                                                 Sex: m, f

Figures in parentheses indicate number of surviving animals

Dose mg/kg

Observation period p.a.

Findings

2000

10 min – day 14 (10/10)

No abnormal clinical signs

 

APPENDIX 3 – BODY WEIGHTS

INDIVIDUAL VALUES (g)

Dose: 2000 mg/kg

Anim. No.

Sex

Day 0

Day 7 p.a.

Day 14 p.a.

1

M

273

281

312

2

M

235

238

263

3

M

282

293

325

4

M

273

271

293

5

M

280

283

310

6

F

202

204

209

7

F

200

189

198

8

F

200

206

214

9

F

180

183

188

10

F

202

202

214

MEAN VALUES (g)

Sex

N

Day 0

Day 7 p.a.

Day 14 p.a.

Males

5

268.6±19.2

273.2±21.2

300.6±23.9

Females

5

196.8±9.4

196.8±10.2

204.6±11.3

 

APPENDIX 5 – INDIVIDUAL VALUES OF SKIN RECATION

Test article: Lowinox 624-98,5                    Project no.: 10-04-1635/00-92

Species: Rat                                                Dose: 2000 mg/kg

Sex: m, f

Anim. No.

Sex

Days p.a.

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Ery

Oed

Ery

Oed

Ery

Oed

Ery

Oed

Ery

Oed

Ery

Oed

Ery

Oed

Ery

Oed

Ery

Oed

Ery

Oed

Ery

Oed

Ery

Oed

Ery

Oed

Ery

Oed

1

M

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2

M

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3

M

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4

M

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

5

M

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

6

F

1

0

0

0

0

0

1

0*

1

0*

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

7

F

1

0

0

0

0

0

1

0*

1

0*

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

8

F

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

9

F

2

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

10

F

2

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Ery = Erythema

Oed = Oedema

* = slight scale formation

 

APPENDIX 6 – NECROPSY

Test article: Lowinox 624-98,5                  Project no.: 10-04-1635/00-92

Species: Rat                                              Animal no.: 1 – 10

Sex: m, f                                                   Dose: 2000 mg/kg

Terminal sacrifice: 14 days p.a.                  n = 10

Animal no.

Specific Findings

3, 5

Lung: hyperaemia

1, 2, 4, 6 – 10

No specific findings

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 > 2000 mg/kg
Executive summary:

The aim of the test was to determine the acute median lethal dose of "Lowinox 624-98,5". Information derived from the test serves to indicate the existence of possible hazards likely to arise from short-term exposure to the test article by the dermal route.

The test was conducted according to the OECD guideline for the testing of chemicals OECD 402 (February 24, 1987) and to the EEC directive 84/449/EEC (September 19,1984). The study was carried out as described in the corresponding protocol approved by the testing facility and the study sponsor on September 15 and 18, 1992. Theprinciples of Good Laboratory Practice for (he testing of chemicals as specified bynational (BGB1. I, no 13, § 19 a, March 22, 1990) and international (OECD, Paris,1982) legislation were followed during the performance of the study.

 

The acute dermal toxicity of "Lowinox 624-98,5" was investigated in 5 male and 5 female Wistar rats.

On the basis of the range finding results, each animal was given a single dermal administration of "Lowinox 624-98,5" at a dose of 2000 mg/kg body weight. Theskin was exposed to the test article for 24 h and signs of erythema and oedema were subsequently evaluated once daily for 14 days.

Clinical observations were conducted at regular intervals during the 14-day observation period. Body weights were measured at days 0, 7 and 14 p.a. Gross pathological examinations were performed on animals at termination.

The following results were obtained:

1. No abnormal clinical signs were observed.

2. No signs of oedema were observed. At day 1 p.a. very slight to well-defined erythema were observed. At days 4 and 5 p.a. in two females very slight erythema and slight scale formation were observed.

3. Weight gains were reduced in most ofthe animals at day 7 p.a. In one male and in one female the body weight was decreased at day 7 p.a. At day 14 p.a. weight gains were normal in the males but reduced in the females.

4. Gross pathological examinations at 14 days p.a. (terminal necropsy) revealed no test article-dependent findings.

5. According to the requirements of the limit test, the LD5O values after 24 h and 14 days were as follows:

male and female> 2000 mg/kg

The above value is higher than the limit specified as harmful by the EEC directive 91/32/EC and the Gefahstofferordnung (GefStoff), 1987(BGBL.I p. 2721). When applied to the skin, the test article "Lowinox 624-98,5" may therefore be classified as "non-toxic".

No classification and labelling is applicable.