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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10.06. - 04.09.1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline study, GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted on 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Remarks:
NOTOX B.V., Hambakenwetering 7, 5231 DD ‘s-Hertogenbosch, The Netherlands
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
431-770-1
EC Name:
-
Cas Number:
216698-07-6
Molecular formula:
C32 H44 O4
IUPAC Name:
2-[2-oxo-5-(2,4,4-trimethylpentan-2-yl)-2,3-dihydro-1-benzofuran-3-yl]-4-(2,4,4-trimethylpentan-2-yl)phenyl acetate
Details on test material:
- Description: White solid
- Purity: 98.7%
- Storage condition of test material: At room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Germany.
- Age at study initiation: approx. 8 weeks old
- Housing: Individually housed in labelled polycarbonate cages containing purified sawdust as bedding material (Woody SPF, supplied by B.M.I., Helmond, The Netherlands).
- Diet: standard pelleted laboratory animal diet, ad libitum
- Water: tap-water, ad libitum
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: 5x7 cm on the back
- % coverage: 10% of the total body surface, i.e. 25 cm² for males and 18 cm² for females.
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminum foil and Coban flexible bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
-24 hours, after which dressings were removed and the skin cleaned of residual test substance using water.

TEST MATERIAL
- Concentration (if solution): 2000 mg/kg bw
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
Duration of exposure:
24 hrs
Doses:
2000 mg/kg bw
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: twice daily
- Necropsy of survivors performed: yes
- Other examinations performed:
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.


Statistics:
No statistical analysis was performed.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Red staining of the nose, neck and head (considered an indicator of generalized stress and derived from chromodacryorrhea) was noted on day 2 in two females. The animals had recovered from the symptoms between days 3 and 7. Scales were seen in the treated skin-area of one female between days 3 and 7.
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.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
Not applicable.

Applicant's summary and conclusion

Conclusions:
The dermal LD50 value of the test article in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

The acute dermal toxicity of the test substance was assessed in a toxicity study following OECD guideline 402 and in compliance with GLP. The test article was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. Red staining of the nose, neck and head (considered an indicator of generalized stress and derived from chromodacryorrhea) was noted on day 2 in two females. The animals had recovered from the symptoms between days 3 and 7. Scales were seen in the treated skin-area of one female between days 3 and 7. The mean 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 the test substance in Wistar rats was established to exceed 2000 mg/kg body weight