Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 Feb - 18 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), November 2000, including most recent partial revisions
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): AF-654
- Physical state: white powder
- Lot/batch No.: #CE-201
- Expiration date of the lot/batch: 01 Jan 2005
- Storage condition of test material: at room temperature in the dark

Test animals

Species:
rat
Strain:
other: Wistar strain Crl:(WI) BR (outbred, SPF-Quality)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 9 weeks
- Weight at study initiation: male (mean) 306 ± 14 g; female (mean) 216 ± 14 g
- Housing: individually in labelled Makrolon type III cages containing purified sawdust as bedding material
- Diet: standard pelleted laboratory animal diet (Altromin, code VRF1), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.4 - 22.9
- Humidity (%): 29 - 80
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: 25 cm² for males and 18 cm² for females
- % coverage: 10
- Type of wrap if used: surgical gauze patch, successively covered with aluminium foil and Coban elastic bandage, for females bandages were fixed using a piece of micropore tape

REMOVAL OF TEST SUBSTANCE
- Washing: The skin was cleaned of residual test substance using water.
- Time after start of exposure: 24 hours

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

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: checks were done twice daily for mortalities, clinical signs were recorded at periodic intervals on the day of dosing and once daily thereafter, body weights were determined before dosing (day 1) and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed during the study
Mortality:
No mortality occurred.
Clinical signs:
Flat/hunched posture and/or chromodacryorrhoea were noted among all animals between days 1 and 5.
Body weight:
Body weight gain was within the normal range during the study.
Gross pathology:
No toxicologically relevant abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
White staining of the treated skin area was noted among most animals between days 2 and 9. In addition, erythema (days 2 and/or 3) or scales (between days 3 and 12) of grade 1 were noted on the treated skin area of some females (table 2).

Any other information on results incl. tables

Table 1. Table for acute dermal toxicity

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

2000

0/5/5

Day1 – Day5

---

0

Females

2000

0/5/5

Day1 – Day5

---

0

LD50 > 2000 mg/kg bw

 Day 1 refers to the day of test substance administration.                                                                                         

* first number = number of dead animals                                 

 second number = number of animals with clinical signs         

  third number = number of animals used                                                              

Table 2. Presence of skin effects

 

Female rats

Male rats

Animal no.

1

2

3

4

5

1 - 5

White staining

Day2 – Day8

Day2

Day2 – Day8

Day2 – Day9

---

Day2 - Day8

Day2 - Day8

Day2 - Day8

Day2 - Day8

Day2 - Day8

Erythema

(grade

1 - 4)

---

---

Day2 – Day3

(grade1)

---

Day2 (grade 1)

 ---

 ---

 ---

 ---

 ---

Scales (grade

1 - 3)

Day3 – Day12 (grade 1)

---

---

---

---

---

---

---

---

---

Day 1 refers to the day of test substance administration.     

---: sign not observed

Applicant's summary and conclusion

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