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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:
July 23, 2014 - August 22, 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 402.
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay, Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515-519, 69120 Heidelberg
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): Dichlone
- Physical state: Solid/ yellow
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: mean weights males: 230.8 g, females: 207.8g
- Housing: Single housing in Makrolon cages type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 - 70 %
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: August 04, 2014 To: August 22, 2014

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: About 40 cm² (corresponds to at least 10% of the body surface)
- Type of wrap if used: The test item was covered with an 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 (if done): rinsing of the application site with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Constant concentration used: yes
- For solids, paste formed: no, suspension

VEHICLE
- Amount(s) applied (volume or weight with unit): 3.08 ml/kg bw
- Concentration (if solution): 65g/100 ml
Duration of exposure:
24 h
Doses:
2000 mg/kg bodyweight
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 weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Frequency of observation: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: scoring of skin findings

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
Clinical signs:
No systemic clinical signs were observed during clinical examination with one exception in the male group. One male revealed impaired general state and piloerection on study day 1.
Body weight:
The mean body weight of the animals increased within the normal range throughout the study period with one exception in the female group. One female revealed stagnation of body weight during the first week, but the body weight was within the normal range during the second week.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Any other information on results incl. tables

Local effects:

All male animals revealed severe erythema (grade 4) from day 1 until day 3. In one animal severe erythema persisted until day 7. In this animal the finding decreased to moderate erythema (grade 3) on day 8, to well-defined erythema (grade 2) from day 9 until day 10 and to very slight erythema (grade 1) on day 13. The other four animals showed well-defined erythema from day 6 until day 7 and very slight erythema from day 8 until day 10. All animals revealed slight edema (grade 2) on day 1, which increased to moderate edema (grade 3) on day 2 and 3. From day 6 until day 7 slight edema was noted again in all animals. Edema decreased to very slight edema (grade 1) in four out of five males from day 8 until day 10. Black discolored scaling and incrustations were noted additionally in three out of five males from day 6 until day 14. The two other males revealed black discolored scaling and incrustations from day 6 until day 7 or 8 and again from day 13 until day 14.

Four out of five females revealed moderate erythema from day 1 until day 3. The fifth female showed moderate erythema on day 1 and 3, but severe erythema (grade 4) on day 2. The findings decreased to well-defined erythema in 2 females from day 6 until day 7 or 10, respectively. In one of these females very slight erythema was seen from day 8 until day 10. In the other three animals very slight erythema was seen from day 6 until day 10. Four out of five females revealed slight edema from day 1 until day 3, while from day 6 until day 10 very slight edema was noted in these animals. The fifth female revealed slight edema on day 1 and 3 and moderate edema on day 2. From day 6 until day 10 very slight edema was observed in this animal. In three animals black discolored scaling was seen from day 6 until day 14, in another animal this finding was noted from day 13 until day 14 only.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the median lethal dose (LD50) of Dichlone after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.
Executive summary:

In an GLP-compliant acute dermal toxicity study (Limit Test) following OECD guideline 402, young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of Dichlone (as suspension in corn oil Ph.Eur.) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. Impaired general state and piloerection were recorded in one male on teh first day of the study only. No signs of systemic toxicity were observed in the other animals (four males, five females). No mortality occurred. The following test item-related local effects were recorded during the course of the study: very slight to severe erythema (grade 1 to 4), very slight to moderate edema (grade 1 to 3), black discolored scaling and black discolored incrustations. The local effects occurred during the whole study period (14 days). No macroscopic pathologic abnormalities were noted in all animals examined at the end of the study. The mean body weight of the animals increased within the normal range throughout the study period with one exception in the female group. One female revealed stagnation of body weight during the first week, but the body weight was within the normal range during the second week. No mortality occurred. Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw