Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 21 September 2007 to 25 February 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP compliance

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Remarks:
(21 July 2004)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
483-360-5
EC Name:
-
Cas Number:
114435-02-8
Molecular formula:
C3H3FO3
IUPAC Name:
483-360-5
Test material form:
other: Solid with a low melting point (i.e. liquefied solid)
Details on test material:
Name of the test susbtance: Monofluoroethylene carbonate

Test animals

Species:
rat
Strain:
other: HsdRccHan : WIST rats
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33178 Borchen.
- Females nulliparous and non-pregnant: no data
- Age at study initiation: Approximately 8 weeks for the male and 10 - 11 weeks for female animals
- Weight at study initiation: males: 215 - 233 g and females: 201 - 218 g
- Housing: The animals were kept in Macrolon cages on Altromin saw fiber bedding.
- Diet: Ad libitum, Altromin 1324 maintenance diet for rats and mice, totally-pathogen-free (TPF)
- Water: Free access to tap water (drinking water, municipal residue control, microbiol. controlled periodically)
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10 x I hour
- Photoperiod: Artificial light, sequence being 12 hours light, 12 hours dark

IN-LIFE DATES: From: 7 January 2008 To: 29 January 2008

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area
- % coverage: Approximately 10% of the total body surface
- Type of wrap if used: The occlusive dressing consisted of a gauze dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner.

REMOVAL OF TEST SUBSTANCE
At the end of the exposure, the residual test item was removed by using tap water.

TEST MATERIAL
The test item was applied uniformly over an area of approx. 10% of the total body surface at a single dose (2000 mg/kg bw).
Duration of exposure:
24 hours
Doses:
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
- Frequency of observations and weighing: Animals were observed for 14 days after dosing. A careful clinical examination was made at least twice on the day of dosing and once a day thereafter.
The animals were weighed prior to application and once a week thereafter.
- Necropsy of survivors performed: Yes
- Other examinations performed:
*Clinical signs: Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
*Pathology: All gross pathological changes were 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:
At 2000 mg/kg, 1 male wad found dead on day 2 post-dose.
Clinical signs:
Small wounds, unevenly spread on the application site (8 - 10 days post-dose); eschar formation, partial eschar ablation (11 days post-dose); eschar formation, eschar ablation (12 - 13 days post-dose); wounds on the application site partially healed, eschar formation (14 days post-dose) were observed for all female animals and for 3 male animals.

Slightly to moderately reduced spontaneous activity, piloerection, apathy, half eyelid-closure, bent back (1 - 2 days) were observed for 1 male animal. During 3 to 7 days post-dose, no treatment-related symptoms were observed. After, small wounds, unevenly spread on the application site (8 - 10 days post-dose); eschar formation, partial eschar ablation (11 days post-dose); eschar formation, eschar ablation (12 - 13 days post-dose); wounds on the application site partially healed, eschar formation (14 days post-dose) were observed for this animal.

Slightly to moderately reduced spontaneous activity, piloerection, apathy, half eyelid-closure, bent back (24 - 26 hours) were observed for 1 male animal. After, this animal was found dead in abdominal position; piloerection (2 days post-dose).

Body weight:
Weight gain of all animals was within the expected range (see Table 1 in "Any other information on result incl. tables"), although female animal no. 2 and male animal no. 1 lost weight during the first 7 days.
Gross pathology:
Beside acute injection of blood vessels in the abdominal region of the sacrificed animals, which is due to the euthanasia injection, no specific gross pathological changes were found in any animal of any step.
Other findings:
After removing the dressing, the skin of the dorsal area of the test animals showed an orange discoloration.

Any other information on results incl. tables

Table 1: Weight gain in g (Dose: 2000 mg/kg)

Animal No.

Sex

Day 0

Day 7

Day 14

1 - male

215

185

236

2 - male

232

251

284

3 – male

224

--

--

4 - male

233

247

289

5 - male

221

245

286

1 - female

212

220

231

2 - female

205

179

210

3 – female

201

205

211

4 – female

218

224

236

5 - female

208

208

220

-- : Dead animal

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Considering the reported data of this dermal toxicity test it can be stated that the test item Monofluoroethylene carbonate has acute dermal toxic potential and may be harmful in contact with skin.
The dermal LD50 was determined to be > 2000 mg/kg bw ≤ 5000 mg/kg bw.
Executive summary:

The acute dermal toxicity of Monofluoroethylene carbonate was evaluated in male and female rats when administered as a single topical application at level of 2000 mg/kg bw. The test item was held in contact with the skin by a semi-occlusive dressing throughout a 24 -hour period. Mortality, clinical signs and bodyweight changes were monitored throughout the study.

At the end of the observation period, all animals were sacrificed and were subjected to gross necropsy.

One male was found dead on Day 2 post-dose in abdominal position.

Two males showed reduced spontaneous activity, piloerection, half eyelid closure and bent back immediately after the termination the exposure.

The formation of small wounds on the application site were observed in all animals (except the dead animal) as from day 8 post-dose. Eschar formation was observed on days 11 - 13 post dose. At the end of the observation period the wounds were partially healed, although eschar formation was still observed.

After removing the dressing, the skin of the dorsal area of the test animals showed an orange discoloration.

Weight gain of all animals was within the excepted range.

Beside acute injection of blood vessels in the abdominal region of the sacrificed animals, which is due to the euthanasia injection, no specific gross pathological changes were found in any animal of any step.

Considering the reported data of this dermal toxicity test it can be stated that the test item Monofluoroethylene carbonate has acute dermal toxic potential and may be harmful in contact with skin.

The dermal LD50 was determined to be > 2000 mg/kg bw ≤ 5000 mg/kg bw.