2-({2-[4-(dimethylamino)benzoyloxy]ethyl}(methyl)amino)ethyl 4-(dimethylamino)benzoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 October 2006 to 06 November 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

466-080-8

EC Name:

-

Molecular formula:

C23H31N3O4

IUPAC Name:

466-080-8

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Identification: LFC 2098.
Manufactured on: 05/29/2006.
Common name : Aminoester
CAS RN: Not assigned.
Declared concentration: 100%.
Analysed concentration: 100%
Class: Chemical speciality for industrial uses.
Homogeneity: Not applicable.
Stability: Stable under normal conditions.
Formulation: Not applicable.
Physical state: Solid.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Species: Rattus norvegicus (Albinos Rats).
Strain: Wistar.
Source: Tecam (Sao Roque, SP).
Sex and number: 10 animals (5 males and 5 females).
Body weight range and age: Healthy young adult rats 11 weeks old at treatment; the weight variation of animals was not greater than 20 percent of the mean weight for each sex.

ENVIRONMENTAL CONDITIONS
Acclimatization: Animals were acclimatized for 5 days prior to dosing in a controlled room; all the animals were inspected during this period and animals exhibiting abnormal signs were not used for the study.
Housing: Animals were housed using suitable rodent cages with 5 animals per cage.
Feeding: Filtered water and pelleted commercial diet for the species (Biobase Biotec) were provided ad libitum throughout acclimatization and test periods; food and water were analysed and monitored by TECAM/SP throughout the year for environmental contaminants.
Temperature: 19 to 22°C.
Average relative humidity: 68%.
Light cycles: 12 hours/day.

Administration / exposure

Type of coverage:

other: Porous

Vehicle:

water

Details on dermal exposure:

Volume of test substance to be applied to the skin was calculated according to individual body weight.
Test substance was then applied uniformly over an area of approximately 10% of the total body surface area and was held in contact with the skin with a porous gauze dressing and non-irritant tape throughout a 24-hour exposure period.
At the end of this period, residual test substance was removed using water.
Each animal received the test substance diluted with deionized water.

Duration of exposure:

24 h

Doses:

2000mg/kg bw

No. of animals per sex per dose:

5 male
5 female

Control animals:

no

Details on study design:

In the present test, one group of 10 rats (5 males and 5 females) was treated with LFC 2098 by the dermal route at 2000mg/kg bw. Test substance was applied diluted in deionized water (333.76mg/mL). Approximately 24 hours prior to the application of the test substance, each rat was identified and prepared by clipping the fur from the dorsal area using an electric clipper. Immediately before exposure, each animal was weighed and identified. Volume of test substance to be applied to the skin was calculated according to individual body weight. Test substance was then applied uniformly over an area of approximately 10% of the total body surface area and was held in contact with the skin with a porous gauze dressing and non-irritant tape throughout a 24-hour exposure period. At the end of this period, residual test substance was removed using water. A concurrent control was not tested.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No

Clinical signs:

No clinical signs were observed on the treated animals following treatment with LFC 2098.

Body weight:

All tested animals showed body weight gain after 14 days. Body weight gain was higher in males than in females.

Gross pathology:

No macroscopic alterations were observed in major organs of the examined animals.

Any other information on results incl. tables

Animals	Mean body weight (g)
	Day 1	Day 7	Day 14	body weight changes
Male	348.4 ± 29.9	365.6 ± 30.6	397.0 ± 28.7	48.6 ± 5.0
Female	214.0 ± 11.0	221.6 ± 10.9	235.1 ± 13.9	21.1 ± 4.8

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

According to the results test substance, dermal LD50 of test substance LFC 2098 was considered higher than 2000 mg/kg bw.

Executive summary:

This study was carried out to provide information on health hazards likely to arise from acute exposure by the dermal route to the test substance LFC 2098 to rats (Rattus norvegicus). Wistar rats of both sexes (5 males and 5 females) were selected and maintained under controlled environmental conditions. Based on individual body weight, dosing of the test substance was calculated in 2000mg/kg body weight (bw).

Each animal received the test substance diluted with deionized water and applied uniformly over an area approximately 10% of the total body surface area throughout a 24-hour exposure period.

Residual test substance was removed after 24 hours and animals were observed for 14 days. At the end of the period, gross pathology examination was performed. No macroscopic alterations were observed in any of the major organs of the examined animals. According to the results dermal LDSO was considered higher than 2000mg/kg bw.