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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

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

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): RPA 405217, product : Dimethyl Benzylidène Cyclo Pentanone
- Substance type: yellowish powder
- Analytical purity: 96.5 %
- Purity test date: 13.01.1992
- Lot/batch No.: 07/W
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Sprague-Dawley rats
- Source: Iffa Crédo, 69210 L'Arbresle, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 277 ± 6 g for the males und 231 ± 12 g for the females
- Housing: animals were kept in a conventional air-conditioned animal room ; animals were housed in groups of 4 to 7 animals of the same sex during the acclimatisation period and groups of 5 animals of the same sex during the study , they were housed in sterilizable polycarbonate cages (48 x 27 x 20 cm) during the acclimatization period, and (35.5 x 23.5 x 19.3 cm) throughout the study covered with a stainless steel lid containing food and a water bottle
- Diet (ad libitum): yes, with a certified pellet diet "Rats - Mice sustenance ref. A04 C" (U.A.R. 91360 Villemoisson-sur-Orge, France). An analysis of the quality of the food und the major contaminants (pesticides, heavy metals, mycotoxins, etc.) was performed by the supplier und given for each batch.
- Water (ad libitum): free access to tap water filtered by a 0.22 micron filter membrane, chemical analyses were made periodically
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity: 50 ± 20 % relative humidity
- Air : The air was non-recycled and filtered by absolute filters.
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal, 5 x 6 cm for the females and 5 x 7 cm for the males (appr. 10 % of the body surface)
- % coverage: semiocclusive
- Type of wrap if used: adhesive hypoallergic aerated semiocclusive dressing (Laboratoires de Pansements et d'Hygibne, 21300 Chenove, France) attached to a restraining bandage (Laboratoire 3M Santö, 92245 Malakoff, France).
- the test substance and the gauze patch were held in contact with the skin for 24 hours

REMOVAL OF TEST SUBSTANCE
- Washing : Residual test substance was removed by a gauze patch saturated with water for injections batch No. 1332 (Biosédra, 92240 Malakoff, France)

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): a single dose of 2000 mg/kg bw of the test substance in its original form was prepared on a hydrophilic gauze patch (Semes France, 54183 Heillecourt, France) pre-moistened with 2 ml of water for injections

VEHICLE
- Water for injections batch No. 1332 (Biosédra, 92240 Malakoff, France) was used in order to disperse the test substance for coetaneous application
Duration of exposure:
The single application was performed on the 22.11.91 In the morning (day 1), und was followed by a 14-day observation period until the 6.12.91
(day 15).
The test substance and the gauze patch were held in contact with the skin for 24 hours
Doses:
- a single dose of 2000 mg/kg bw
No. of animals per sex per dose:
- 5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Mortality was checked frequently just after application of the test substance and then at least twice a day during the 14-day observation
period
- Frequency of observations and weighing: The animals were observed frequently after administration of the test substance and at least once a day tor 14 days in order to determine the reversibility or irreversibility of any clinical signs. The animals were individually weighed just before administration of the test substance und then on days 5, 8 und 15. The body weight gain of the treated animals was compared to a reference curve of the C .I.T. control animals with the same initial weight.
- Necropsy of survivors performed: yes
On the 15th day, the surviving animals were sacrificed after CO2 inhalation in excess and a necropsy was performed. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs was performed: digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organ with obvious abnormalities.
- Due to the absence of macroscopic lesions no organ samples were taken and no histological examination was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the observation period.
Clinical signs:
No clinical signs vere observed during the study.
Body weight:
The body weight gain of the animals was normal.
Gross pathology:
The macroscopic examination of the main organs of the animals sacrificed at the end of the study revealed no apparent abnormality.
Due to the absence of macroscopic lesions, no samples were talcen for histological examinations.

Applicant's summary and conclusion

Executive summary:

In an acute dermal toxicity study according to OECD Guideline 402 (E)-5[(4 - chlorophenyl)methylene]-2,2 - dimethylcyclopentanone

(95.6 %) was administered to a group of 10 Sprague-Dawley rats (5 males and 5 females). The test substance was prepared in its original form on a moistened compress at a dose level of 2000 mg/kg bw and then applied to the clipped skin (Rhone-Poulenc, 1992). After 24 hours with a semiocclusive dressing, residual test substance was removed using a compress saturated with water. The mortality, general behaviour end body weight gain of the animals were observed for a period of 14 days after the single application of the test substance. A necropsy was performed on each animal sacrificed at the end of the study.

The general behaviour and body weight gain of the animals were not influenced by the treatment. No deaths occurred at tbe dose level of 2000 mg/kg bw. The macroscopic examination revealed no abnormalities in the animals sacrificed at the end of the study.

Thus, the LD 0 of the test substance administered by oral route in rats was higher than or equal to 2000 mg/kg.

No signs of toxicity were observed at this dose level.