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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:
From October 18, 2011 to November 15, 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted February 24, 1987
Deviations:
no
Qualifier:
according to
Guideline:
other: Commission Regulation (EC) No 440/2008 of 30 May 2008, PartB: Methods for the determination of toxicity and other health effects: Acute Toxicity (Dermal); Official Journal of the European Union, No. L 142
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted August 1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
30.03.2011
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Golpanol BEO
- Physical state: Liquid / yellow, clear
- Analytical purity: 99.4%
- Density: 1.156 g/mL
- Lot/batch No.: 92713124U0
- Storage condition of test material: Room temperature
- Storage stability: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Test species / strain / quality: Rat / Wistar / Crl:WI (Han) SPF
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: Young adult animals (male animals approx. 8 weeks, female animals approx. 12 weeks); female animals were nulliparous and non-pregnant
- Mean body weight (± SD) at study initiation: Males: 236.4 ± 8.85; Females : 202.8 ± 3.83
- Housing: single, Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, Altrip, Germany)
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Clipping of the fur: about 24 hours before administration
- Area of exposure: dorsal and dorsolateral parts of the trunk; about 40 cm²
- % coverage: at least 10% of the body surface
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4.33 mL/kg bw
- Concentration: undiluted
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
5000 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:
• Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
• Clinical observations: Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
• Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times until the last day of observation.
• Mortality: A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes
•Assessment of skin reactions
The evaluation of skin reactions was performed according to Draize, J.H. (1959): Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occured.
Mortality:
No mortality occurred.
Clinical signs:
No systemic clinical signs were observed during clinical examination.
Body weight:
Males: The mean body weight increased within the normal range throughout the study period.
Females: The mean body weight did not adequately increase during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
Other findings:
Local effects:
Males: In four male animals well-defined erythema (grade 2) was noted on study day 1 and 2, decreased to very slight erythema (grade 1) on study day 5 and persisted in these animals up to study day 9, 12 or 14.
In the fifth animal only very slight erythema (grade 1) was noted from study day 1 until study day 12.
Additionally, incrustations were observed in two animals from study day 8 until study day 14.
Orange discoloration of the fur was observed in two other males from study day 5 until study day 14.
Females: In three female animals well-defined erythema (grade 2) was observed on study day 1 and persisted in two of these animals until study day 9 or 13. Well-defined erythema decreased in these two animals to very slight (grade 1) and was seen until study day 14. In the third animal well-defined erythema increased to moderate erythema (grade 3) on study day 2, persisted until study day 9 and decreased to well-defined erythema again from day 12 to day 14.
The two other animals showed very slight erythema on study day 1 and 2, which increased to well-defined erythema from study day 5 until day 9. In two females very slight edema (grade 1) was noted on study day 1 or 2 only. In a further animal slight edema (grade 2) was noted on study day 2, decreased so very
slight (grade 1) on study day 5 and 6 but increased to slight again on study day 7 up to study day 9. On study day 12 very slight edema was noted again in this animal. Furthermore incrustations and scaling were noted in the three females which showed edema from study day 5 until study day 14. In two of these animals orange discoloration of the fur was noted from study day 5 until study day 14 also.

Any other information on results incl. tables

Table 1: Mean body weight

Mean

SD

Day 0

 

Males

236.4

8.85

Females

202.8

3.83

Day 7

 

Males

262.6

13.16

Females

206.0

3.32

Day 14

 

Males

291.8

17.50

Females

215.8

9.28

 

Applicant's summary and conclusion