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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 Jan - 04 Feb 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted June 1996
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), adopted Nov 2000 including the most recent revisions
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): UM-235
- Physical state: white powder
- Lot/batch No.: #SI-1
- Expiration date of the lot/batch: 01 Jan 2005
- Storage condition of test material: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany (strain: Crl:(WI) BR (outbred, SPF-Quality))
- Age at study initiation: 8 weeks
- Weight at study initiation: male (mean) 307 ± 15g, female (mean) 228 ± 15g (did not exceed ±20 % of the sex mean)
- Housing: individually in Makrolon cages (type III) containing purified sawdust as bedding material
- Diet: standard pelleted laboratory animal diet (Altromin (code VRF 1)), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.6 - 22.9 (actual range)
- Humidity (%): 38 - 80 (actual range)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: 25 cm² for males, 18 cm² for females
- % coverage: 10
- Type of wrap if used: surgical gauze patch, successively covered with aluminium foil and Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: using water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 10 mL/kg bw
- Concentration (if solution): 200 mg/mL (w/w) (calculated from 10 mL/kg bw amount and 2000 mg/kg bw)
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and viability: twice daily; clinical signs: at periodic intervals on the day of dosing and once daily thereafter (see Table 1 under "any other information on material and methods including tables")
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities were observed.
Clinical signs:
5/5 males showed flat or hunched posture starting 2 hours after dsoing until 1 day after dosing in 4/5 animals and 2 days after dosing in 1/5 males. Chromodacryorrhoea (Snout) was seen in 5/5 males starting 2 hours after dosing and was completely reversed in all males 2 days after dosing. 1/5 male animals showed diarrhoea 1 day post dosing. Additionally, 1/5 males and 1/5 females showed ptosis 4 h after dosing.
5/5 females showed flat posture 2 and 4 hours after dsoing, 4/5 females showed hunched posture thereafter, until 2 days post dosing. Chromodacryorrhoea (Snout) was seen starting 2 hours after dosing until 1 day after dosing in 5/5 females. 4/5 females showed general erythema starting 1-2 days after dosing at the treated skin site, erythema was visible until the third day post dosing in 3/5 females and 1/5 females still had erythema visible 5 days after dosing. Scales were visible on the treated skin site of 2/5 females. 1/5 showed scales only 5 days after dosing. For the other female scales were visible starting 4 days post dosing until the end of the observation period and additionally, scabs were seen from day 6 post dosing until the end of the observation period (see Table 2).
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

Table 2. Table for acute oral toxicity. 

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

2000

0/5/5

2 h - Day3

---

0

Females

2000

0/5/5

2 h – Day15

---

0

LD50 > 2000 mg/kg bw

* first number = number of dead animals                                 

 second number = number of animals with clinical signs         

 third number = number of animals used           

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified