Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991-01-17 to 1991-01-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
For logistic reasons (application as paste) and the short period between preparation and application no analytical examination of the stability of the sample in the formulation was conducted.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
4,7-methanooctahydro-1H-indene-diyldimethyl bis(2-carboxybenzoate)
EC Number:
407-410-2
EC Name:
4,7-methanooctahydro-1H-indene-diyldimethyl bis(2-carboxybenzoate)
Molecular formula:
C28H40O8
IUPAC Name:
2-[({5-[(2-carboxycyclohexanecarbonyloxy)methyl]tricyclo[5.2.1.0²,⁶]decan-8-yl}methoxy)carbonyl]cyclohexane-1-carboxylic acid; 2-[({8-[(2-carboxycyclohexanecarbonyloxy)methyl]tricyclo[5.2.1.0²,⁶]decan-4-yl}methoxy)carbonyl]cyclohexane-1-carboxylic acid
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): TCD-Emulgator (Tricyclodecandioldihexahydrophthalatdicarbonsäure)
- Substance type: White crystals
- Physical state: Solid
- Lot No.: 90003
- Expiration date of the lot/batch: 1992-01-08
- Stability under test conditions: Stable at room temperature (SOP HXX 0031202)
- Storage condition of test material: Room temperature, tightly closed

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen (Germany)
- Age at study initiation: 9 weeks (m); 13 week (f)
- Weight at study initiation: 230 g (m); 204 g (f)
- Housing: Makrolon cages Type II on non-dusty wood pellets
- Diet (e.g. ad libitum): Fixed-formula standard diet, Altromin 1324 pellets (Altromin GmbH und Co KG, Lage) ad libitum
- Water (e.g. ad libitum): Potable water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 50 ± 10 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
castor oil
Remarks:
Cremophor EL
Details on dermal exposure:
TEST SITE
- Area of exposure: Back and flanks
- % coverage: 10 %
- Type of wrap if used: Fermoflexband, Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washing with lukewarm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): Not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): No data
- Concentration (if solution): No data
- Lot/batch no. (if required): No data
- Purity: No data
Duration of exposure:
24 h
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weekly (day 1, 8 and 15)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Preliminary study:
During the observation period none of the animals died. The growth of male animals was not affected. The females' body weight slightly decreased in the first week of observation. At the end of the experiment none of the killed animals showed pathological-anatomical findings.
Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
During the testing no mortalities occurred.
Clinical signs:
No systemic symptoms of poisoning were observed.
No local skin alterations that could be attributed to the test sample were observed.
From the beginning of the experiment, crystallised residues of the substance were partly sticking to the skin, causing skin lesions at the time the bandage was removed. The effect occurred in 4 of 5 male and 5 of 5 female animals and continued until day 12.
Body weight:
The body weight of female animals slightly decreased during the first week of observation.
Gross pathology:
No apparent pathological findings were observed during the experimental period.
Other findings:
No other findings.

Any other information on results incl. tables

Bodyweights of male and femal rats:

Male

Female

Animal

Day

Animal

Day

1

8

15

1

8

15

1

233 g

248 g

276 g

1

206 g

197 g

202 g

2

225 g

234 g

259 g

2

207 g

202 g

209 g

3

231 g

244 g

262 g

3

203 g

199 g

204 g

4

234 g

243 g

276 g

4

200 g

196 g

202 g

5

229 g

240 g

266 g

5

205 g

199 g

204 g

Av.

230 g

242 g

268 g

Av.

204 g

199 g

204 g

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study in rat according to EU method B.3, no mortality or clinical signs were reported up to a limit dose of 2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study, groups of young adult Wistar rats (5 male and 5 female) were dermally exposed to the test item (95.7 %) in Cremophor EL paste for 24 hours applied on 10 % of body surface area at a dose of 2000 mg/kg bw. Animals were then observed for 14 days.

No mortality occurred in limit the test at a concentration of > 2000 mg/kg bw both in male and female rats.

The test item is not classified following CLP Annex I based on the exceeded limit dose of 2000 mg/kg bw for male and female rats.  

Systemic poisoning was not observed. Local skin alterations did not appear. When removing the coverage, skin lesions occurred. The lesions were not considered substance related. The growth of male and female rats was not affected. Female animals slightly lost weight during the first week of observation. No mortalities occurred. At the end of the 14 days of observation all of the killed animals were without pathological findings.