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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
19 May - 2 Jun 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study. The test substance was applied with an occlusive dressing.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
the test substance was applied with an occlusive dressing
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
the test substance was applied with an occlusive dressing
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
the test substance was applied with an occlusive dressing
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:
yes
Remarks:
the test substance was applied with an occlusive dressing
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): only trade name given
- Substance type: clear, colourless liquid
- Physical state: liquid
- Analytical purity: 100%
- Lot/batch No.: CB 00390004
- Expiration date of the lot/batch: 31 Mar 2011
- Storage condition of test material: at room temperature in the dark
- Density: 0.87 g/mL

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 10 weeks
- Weight at study initiation: 269-284 g (males), 181-194 g (females)
- Housing: animals were housed individually in labelled Makrolon cages (MIII 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, UK). During the acclimation period the animals were housed in groups in Macrolon cages (MIV type).
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6-21.2
- Humidity (%): 39-62
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the back of the animals; 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 and Coben elastic bandage, respectively. A piece of Micropore tape was used to fix the bandage in females only.

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes, the dose volume was calculated as dose level (g/kg) / density (g/mL)
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: an untreated, adjacent skin area served as the control
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed twice daily for mortality; the body weight was recorded on Day 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: yes, on Day 15 the animals were subjected to necropsy and all gross macroscopical abnormalities were recorded
- Other examinations performed: clinical signs were observed at periodic intervals on the day of dosing (day 1) and once daily thereafter, until sacrifice. The time of onset, degree and duration were recorded and the symptoms graded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study period (see Table 1).
Clinical signs:
Piloerection was observed from 4 h - day 2 after dosing in 2/5 males (see Table 2). Chromodacryorrhoea (excessive secretion of a reddish-brown liquid from the eyes) (grade 1) was observed in 3/5 males 2-4 hours after dosing. No systemic clinical signs of toxicity were observed during the study period in females.
Body weight:
The body weight gains of males and females were within the normal ranges during the study period.
Gross pathology:
The necropsy and histopathological examination did not reveal substance-related findings.
Other findings:
- Other observations: On the treated skin area, erythema was observed for up to 4 days during Day 3-7 in 3/5 females. Scales or scabs (grade 1) were noted on the treated skin area in 5/5 females and 3/5 males for up to 9 days during Day 7-15 of the observation period.

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

0/3/5

4 h – day 2 

Day 1-3

0

Females

2000

0/0/5

-

Day 1

0

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: Clinical signs, systemic/local

Effect*

Max grade

Male No./duration (hours or day after dosing)

Female No./duration (hours or day after dosing)

 

 

1

2

3

4

5

6

7

8

9

10

Systemic

 

 

 

 

 

 

 

 

 

 

 

Piloerection

 1

4 h - 2 d

 

 

 

4 h - 2 d

 

 

 

 

 

Chromoda-cryorrhoea

 3

 

2 - 4 h

2 - 4 h

4 h

 

 

 

 

 

 

Local

 

 

 

 

 

 

 

 

 

 

 

Erythema, focal

 4

 

 

 

 

 

7 d

 

7 d

3 – 7 d

7 d

Scales

 3

 

 

8 – 10 d

7 – 15 d

 

7 – 8 d, 14 d

8 – 11 d

7 – 9 d

7 – 8 d

7 – 9 d

Scabs

 3

 

7 - 11 d

 

9 - 15 d

 

8 – 13 d

 

 

 

 

* all 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