Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 July 1987 to 28 July 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-isopropyl-9H-thioxanthen-9-one
EC Number:
226-827-9
EC Name:
2-isopropyl-9H-thioxanthen-9-one
Cas Number:
5495-84-1
Molecular formula:
C16H14OS
IUPAC Name:
2-isopropyl-9H-thioxanthen-9-one
Test material form:
solid
Details on test material:
- A mixture of 2-(1-methylethyl)-9H-thioxanthene-9-one and 4-(1-methylethyl).-9H-thioxanthene-9-one.
- Appearance: pale yellow solid

Test animals

Species:
rat
Strain:
other: Crl:COBS CD (SD) BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Seven to ten weeks of age.
- Weight at study initiation: 200 to 221 g
- Housing: Animals were housed individually in metal cages with wire mesh floors.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 to 22 °C
- Humidity: 69 % (mean daily relative value)
- Air changes: Approximately 15 per hour.
- Photoperiod: Lighting was controlled by means of a time switch to 12 hours artificial light in each 24 hour period.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Remarks:
Distilled
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorso-lumbar region. One day prior to treatment hair was removed from the dorso-lumbar region of each rat with electric clippers exposing an area equivalent to 10 % of the total body surface. No shaving or chemical depilation was used.
- % coverage: 10 % of the total body surface
- Type of wrap if used: The test material was applied by spreading it evenly over the prepared skin. The treated area was covered with gauze which was held in place with an impermeable dressing encircled firmly around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the 24-hour exposure period, the dressings were carefully removed and the treated area of skin decontaminated by washing in warm (30 to 40 °C) water and blotting dry with absorbent paper.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2.80 mL/kg
- Concentration: 71.4 % (w/v) in distilled water
- For solids, paste formed: Yes
Duration of exposure:
24 hours
Doses:
2.0 g/kg bodyweight
No. of animals per sex per dose:
Five animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed once in the morning and again at the end of the experimental day. This latter observation was at approximately 16.30 hours on weekdays or 11.30 hours on Saturday and Sunday. Clinical signs were recorded at each observation. The nature, severity, approximate time of onset and duration of each toxic sign were recorded. A separate record was kept of dermal changes other than erythema and oedema.
- Individual bodyweights of rats were recorded on Days 1 (day of dosing), 8 and 15.
- Necropsy of survivors performed: Yes - all animals on the study were killed on Day 15 by cervical dislocation and were subjected to a macroscopic post mortem examination, which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of abnormal organs when present was recorded.

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:
There were no deaths following a single dermal dose of the test material at 2.0 g/kg bodyweight.
Clinical signs:
There were no clinical signs of systemic reaction to treatment.
Body weight:
An unchanged bodyweight was recorded for a single female during the second week of the study. Otherwise anticipated bodyweight gains were recorded for all animals at Days 8 and 15.
Gross pathology:
Terminal autopsy findings were normal.
Other findings:
Sites of application of the test material developed no irritation responses or other dermal changes.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of the study, the LD50 has been determined to be greater than 2.0 g/kg bw.
Executive summary:

A study was conducted to investigate the acute dermal toxicity of the test material in accordance with the standardised guidelines OECD 402 and EU Method B.3.

A group of ten rats (five males and five females) was treated at 2.0 g/kg bodyweight. One day prior to treatment hair was removed from the dorso­lumbar region of each rat with electric clippers exposing an area equivalent to 10 % of the total body surface. The test material was applied by spreading it evenly over the prepared skin. The treated area was then promptly covered with gauze which was held in place with an impermeable dressing encircled firmly around the trunk. The skin was exposed to the test material for 24 hours before the patch was removed and the area washed. The animals were observed for 14 days before they were sacrificed and gross necropsy performed.

Sites of application of the test material developed no irritation responses or other dermal changes. There were no deaths following treatment and no clinical signs of systemic reaction were observed. Anticipated body weight gains were recorded for all animals except one female that had unchanged bodyweight in the second week of the study. Terminal autopsy findings were normal.

Under the conditions of the study, the LD50 has been determined to be greater than 2.0 g/kg bw.