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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:
09 to 23 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OCED, EU & US EPA test guidelines in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
156559-00-1
Cas Number:
156559-00-1
IUPAC Name:
156559-00-1
Constituent 2
Reference substance name:
Hatcol 3344
IUPAC Name:
Hatcol 3344
Test material form:
other: clear colourless liquid
Details on test material:
Identification: Hatcol 3344
CAS Number: 156559-00-1
Description: Clear colourless liquid
Batch: H102-01 -28
Purity: 96.9%
Composition: Pentaeryhritol mixed tetraesters with 2-ethylhexanoic acid, nonanoic acid, and pentanoic acid
Test substance storage: At room temperature in the dark
Stability under storage conditions: Stable
Expiry date: 31 October 2003
Specific gravity (15.5°C): 0.99

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 5 males and 5 females (females were nullparous and nonpregnant).
Age and body weight: Young adult animals (approx. 8 weeks old) were selected. Bodyweight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark

Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 18.1-23.7°C), a relative humidity of 30-70% (actual range: 44-78%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures In the room might have caused the fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually housed In labelled Macrolon cages (type III height 15 cm.) containing purified sawdust as bedding material (SAWI, Jetu Werk. Rosenberg, Germany).
Acclimatisation: period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from A1tromin (code VRF i), Lage, Germany).
Water: Free access to tap-water.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
A health Inspection was performed prior to commencement of treatment to ensure that the animals were In a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.
Method: Dermal application.
Clipping: One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
Application: The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm2 for males and 18 cm2 for females. The test substance was held in contact with the skin with a dressing consisting of a surgical gauze patch (Surgy 1 D) successively covered with aluminium foil and Coban flexible bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Frequency: Single dosage. on day 1.
Dose level (volume): 2000 mg/kg (2.02 ml/kg) body weight. Dose volume calculated as follows: dose level: specific gravity.
Application period: 24 hours, after which dressings were removed and the skin cleaned of residual test substance using water.
Duration of exposure:
24 hours
Doses:
Single dosage, on day 1.
No. of animals per sex per dose:
5 males & 5 females - all dosed
Control animals:
not required
Details on study design:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
All females and some males showed scales, scabs and/or general/maculate erythema on the treated skin site during the observation period from day 3 onwards. In addition chromodacryorrhoea was noted among some animals on days 1 and/or 2, with diarrhoea in one male between days 2 and 4.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
No further findings noted in the study report.

Any other information on results incl. tables

TABLE 1: CLINICAL SIGNS

TEST DAY

 

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

MAX

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

GRADE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

MALES 2000 MG/KG

ANIMAL 1

NO CLINICAL SIGNS NOTED

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 2

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Scales (Treated Skin)

(3)

-

-

-

-

-

-

-

-

1

1

1

1

1

1

1

1

1

Scabs (Treated Skin)

(3)

-

-

-

-

-

-

-

-

1

1

1

1

1

2

2

1

1

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromadacryorrhoea (Nose)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 3

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Diarrhoea

(1)

-

-

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

Chromodacryorrhoea (Snout)

(3)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 4

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Nose)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 5

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

General Erythema (Treated Skin)

(4)

-

-

-

-

1

1

1

-

-

-

-

-

-

-

-

-

-

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Snout)

(3)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

FEMALES 2000 MG/KG

ANIMAL 6

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Erythema Maculate (Treated Skin)

(4)

-

-

-

-

2

2

1

1

1

1

1

1

1

1

-

-

-

Scales (Treated Skin)

(3)

-

-

-

-

-

-

-

-

1

1

1

1

1

1

1

1

1

Scabs (Treated Skin)

(3)

-

-

-

-

-

-

-

1

1

1

1

1

1

1

1

1

1

ANIMAL 7

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Erythema Maculate (Treated Skin)

(4)

-

-

-

-

1

1

1

1

1

-

-

-

-

-

-

-

-

Scales (Treated Skin)

(3)

-

-

-

-

-

-

-

-

1

-

-

-

-

-

-

-

-

Scabs (Treated Skin)

(3)

-

-

-

-

-

-

-

1

1

1

1

1

1

1

1

1

1

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Snout)

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 8

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Scales (Treated Skin)

(3)

-

-

-

-

-

-

-

-

1

1

-

-

-

-

-

-

-

ANIMAL 9

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Scales (Treated Skin)

(3)

-

-

-

-

-

-

-

-

1

1

-

-

-

-

-

-

-

ANIMAL 10

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Scales (Treated Skin)

(3)

-

-

-

-

1

1

1

1

1

1

1

1

1

-

-

-

-

Scabs (Treated Skin)

(3)

-

-

-

-

-

-

-

-

-

-

-

-

-

1

1

1

1

-=SIGN NOT OBSERVED/ .=OBSERVATION NOT PERFORMED/ +=ANIMAL DEAD

 

TABLE 2: BODYWEIGHTS (GRAMS)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

MALES 2000 MG/KG

 

1

285

334

390

 

2

266

303

352

 

3

273

303

336

 

4

283

322

372

 

5

247

280

311

 

MEAN

271

308

352

 

ST.DEV.

15

21

31

 

N

5

5

5

FEMALES 2000 MG/KG

 

6

191

214

233

 

7

192

212

236

 

8

204

227

245

 

9

186

224

268

 

10

198

218

235

 

MEAN

194

219

243

 

ST.DEV.

7

6

15

 

N

5

5

5

 

TABLE 3: MACROSCOPIC FINDINGS

ANIMAL ORGAN

FINDINGS

DAY OF DEATH

MALES 2000 MG/KG

1

No findings noted

Schedule necropsy Day 15 after treatment

2

No findings noted

Schedule necropsy Day 15 after treatment

3

No findings noted

Schedule necropsy Day 15 after treatment

4

No findings noted

Schedule necropsy Day 15 after treatment

5

No findings noted

Schedule necropsy Day 15 after treatment

FEMALES 2000 MG/KG

6

No findings noted

Schedule necropsy Day 15 after treatment

7

No findings noted

Schedule necropsy Day 15 after treatment

8

No findings noted

Schedule necropsy Day 15 after treatment

9

No findings noted

Schedule necropsy Day 15 after treatment

10

No findings noted

Schedule necropsy Day 15 after treatment

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of HATCOL 3344 in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Assessment of acute dermal toxicity with HATCOL 3344 in the rat.

The study was carried out based on the guidelines described in: Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1200. "Acute Dermal Toxicity, ECCommission Directive 92169/EEC, Part B.3, "Acute Toxicity-Dermal", OECD No102, "AcuteDermal Toxicity" and JMAFF: Japanese Test Guidelines.

HATCOL 3344 was administered to five Wistar rats of each sex by dermal application at 2000mg/kg body weight for 24 hours. Animals were subjected to daily observations and weeklydetermination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

All females and some males showed scales, scabs and/or general/maculate erythema on the treated skin site during the observation period from day 3 onwards. In addition chromodacryorrhoea was noted among some animals on days 1 and/or 2, with diarrhoea in one male between days 2 and 4.

The body weight gain during the observation period was within the range expected for rats used in this type of study.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 3344 in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3344 does not have to be classified and has no obligatory labelling requirement for dermal toxicity.