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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5 - 19 Dec 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

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:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted 1992
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted 1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: powder aggregated into lumps
Details on test material:
- Name of test material (as cited in study report): SPM-N
- Physical state: white lumps with powder
- Lot/batch No.: T-9314
- Expiration date of the lot/batch: 29 Aug 2008
- Storage condition of test material: at room temperature in the dark
- Other: pH 7.6-7.5 (1% in water, indicative range)

Test animals

Species:
rat
Strain:
other: Wistar Crl:WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 263 ± 11 g (mean ± SD, males); 189 ± 5 g (mean ± SD, females)
- Housing: during the study period, animals were housed individually in labelled Macrolon cages (MII type; height 18 cm) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom). During the acclimatisation period, animals were housed in groups in Macrolon type MIV cages.
- Diet: pelleted rodent diet SM R/M-Z (SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0-21.7
- Humidity (%): 40-59
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 5 Dec 2007 To: 19 Dec 2007

Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: approximately 25 cm² for males and 18 cm² for females
- % coverage: 10
- Type of wrap if used: the test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), covered with aluminium foil, which was covered with Coban elastic bandage. A piece of Micropore tape was additionally used to fix the wrapping in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated site was cleaned of residual test substance using tap water
- Time after start of exposure: 24 h

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

VEHICLE
- Concentration (if solution): 10 mL/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for mortality and morbidity twice daily; the occurrence of clinical signs was recorded at periodic intervals on Day 1 (0, 2, 4 h after administration) and once daily thereafter until Day 15; body weight was recorded on Day 1 (prior to administration), 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.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Systemic effects were observed on Day 1 up to 4 h after administration. Flat posture was observed in 2/5 males 2 and 2-4 h after dosing on Day 1, respectively, while chromodacryorrhoea was noted in 4/5 males and 1/5 females 0, 2 or 4 h after administration (see Table 1 and 2).
Body weight:
The body weight gains were within the normal ranges in males and females during the whole study period.
Gross pathology:
No substance-related findings were noted at macroscopic post mortem examination of the animals..
Other findings:
- Other observations: Mild local effects on the treated skin were seen throughout the study period. White staining of the skin was noted in all animals for up to 4 consecutive days in the period Day 2-5. Scales or scabs were seen in 1/5 males and 3/5 females for 1-10 consecutive days in the period Day 4-15, while focal erythema was observed in 2/5 females on Day 3 or 3-4, respectively.

Any other information on results incl. tables

Table 1: Mortality and clinical signs

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

2000

0/5/5

0 h on Day 1 – Day 10 

-

0

Females

2000

0/5/5

0 h on Day 1 – Day 15 

-

0

Overall LD50 > 2000 mg/kg bw

* first number = number of dead animals                                 

 second number = number of animals with systemic clinical signs         

 third number = number of animals used                               

 

Table 2: Overview of clinical signs and duration

Observations

Males (time of observation)

Females (time of observation)

No.

1

2

3

4

5

1

2

3

4

5

Systemic

Flat posture

 

 

 

2-4 h, Day 1

2 h, Day 1

 

 

 

 

 

Chromodacryorrhoea (snout)

0 h, Day 1

2 h, Day 1

4 h, Day 1

4 h, Day 1

 

4 h, Day 1

 

 

 

 

Treated skin

Scales

grading slight (1) to severe (3)

 

 

Day 6-10

grade: 1

 

 

 

 

 

 

Day 12

grade: 1

White staining

Day 2-5

Day 2-4

Day 2-3

Day 2-3

Day 2

Day 2-4

Day 2-4

Day 2-4

Day 2

Day 2

Scabs

grading slight (1) to severe (3)

 

 

 

 

 

 

Day 4-15

grade: 1

Day 5-14

grade: 1

 

Day 8-11

grade: 1

Focal erythema

grading slight (1) to very severe (4)

 

 

 

 

 

Day 3

grade: 1

 

 

 

Day 3-4

grade: 1

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