Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002-07-09 to 2002-08-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
(1992)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
GLP compliance:
yes
Remarks:
statement
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid, fine scales

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, D-97633 Sulzfeld
- Age at study initiation: About 8 weeks (males) and 12 weeks (females)
- Weight at study initiation: females (mean) = 243 g; males (mean) = 271 g
- Housing: Single caging in Makrolon cages type III (39 cm x 23 cm x 15 cm). Wire mesh lids. Sanitation of the cages once a week.
- Diet: Altromin 1324 forte, gamma irradiated with 25 kGy 60Co, ad libitum (Altromin GmbH, D-32791 Lage).
Exception: The feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.
- Water: Tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: average 23 °C
- Humidity: average 69 %
- Air changes: 12 per hour
- Photoperiod: Artificial light from 6 a.m. to 6 p.m.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal thoracal region. The hair of the dorsal trunk was clipped with an electrical hair clipper (Aesculap GH, 0.1 mm cutterhead) one day before the application of the test substance. The individual amounts of the test substance were calculated using the body weights determined on the day of the administration.
- % coverage: 10 % of estimated body surface (6.5 x 8 cm = 52 cm2)
- Type of wrap if used: A cellulose patch (Pur-Zellin, Hartmann AG) with the calculated amount of the test substance overlying soaked with deionised water to get optimal contact with the skin, was applied to the test site and held in place by fixing marginally with non irritating tape (Blenderm Wundpflaster, 3M). Patch and tape were covered semi-occlusively by a dressing (Fixomull Stretch, Fa. Beiersdorf).

REMOVAL OF TEST SUBSTANCE
After 24 hours of exposure the dressing was removed and the test substance was wiped off using wet cellulose tissue.

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg bw were applied using a water soaked cellulose patch to guarantee optimal skin contact.
Duration of exposure:
24 h
Doses:
dose range finding study (400, 894 and 2000 mg/kg bw/ day)
main study (2000 mg/kg bw/ day)
No. of animals per sex per dose:
3 males and 3 females for dose range finding study (1 animal /sex/ dose)
5 male and 5 females for main study (2000 mg/kg bw)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 0, 0.5, 1, 2, 4 and 6 hours after administration of the test substance and once a day for a total of 14 days
- Frequency of observations and weighing: observation of systemic signs of toxicity was performed every day. Body weight was measured at day 0, 7 and 14. Body weight gain was calculated for each week.
- Necropsy of survivors performed: Yes. The animals were killed by 80 % CO2+ 20 % air 14 days post application and subjected to a necropsy including a gross pathological examination.

Results and discussion

Preliminary study:
No mortality was observed for any tested dose of the preliminary dose range finding study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Low signs of discomfort (chromodacryorrhoea) was found in 1 female after 1-2 days post application.
Body weight:
Slight body weight decrease was observed in females after 14 days.
Gross pathology:
No effects of organ toxicity were observed during necroscopy.
Other findings:
Local irritations were found in 1 female 1 to 7 days post application.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No mortality or toxic effects of the test item were observed at maximal tested dose of 2000 mg/kg bw. The test item is therefore not classified for acute dermal toxicity according to the Directive 93/21/EEC (DSD) and Regulation (EC) No. 1272/2008 (CLP).
Executive summary:

The aim of the study was to investigate acute toxic effects of the test item after a single dermal administration to rats according to the OECD 402. Administration of 2000 mg/kg bw were performed once under semi- occlusive conditions to 5 males and 5 females, respectively. No mortality and no signs of clinical toxicity were observed within the observation period of 14 days. The LD50 was estimated to be > 2000 mg/kg bw.