Registration Dossier

Administrative data

Description of key information

The substance is classified for acute oral toxicity based on LD50 values ranging from 160 to 1300 mg/kg. Acute dermal toxicity, OECD 402, GLP: LD50 (rat) > 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Principles of method if other than guideline:
Guideline not specified
GLP compliance:
not specified
Species:
mouse
Sex:
not specified
Dose descriptor:
LD50
Effect level:
440 mg/kg bw
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Principles of method if other than guideline:
no guideline specified
GLP compliance:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
560 mg/kg bw
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Principles of method if other than guideline:
guideline not specified
GLP compliance:
not specified
Species:
rat
Sex:
not specified
Dose descriptor:
LD50
Effect level:
1 300 mg/kg bw
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Principles of method if other than guideline:
No guideline specified
GLP compliance:
no
Species:
mouse
Sex:
not specified
Dose descriptor:
LD50
Effect level:
440 mg/kg bw
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Principles of method if other than guideline:
no guideline specified
GLP compliance:
no
Species:
rat
Sex:
not specified
Dose descriptor:
LD50
Effect level:
160 mg/kg bw
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
160 mg/kg bw
Quality of whole database:
The reported LD50 values range from 160 mg/kg to 1300 mg/kg in the rat. The lowest value was chosen here as a worst case approach, although the real value is likely somewhere in between.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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
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
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
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
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.

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.

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

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Acute Oral Toxicity:

Several LD50 values are available in the literature, ranging from 160 mg/kg to 1300 mg/kg bw. As a result, evaluating all data available in a weight of evidence approach, the test article is considered to be of moderate toxicity after single ingestion resulting in classification with Cat 4.

Acute Dermal Toxicity:

In an GLP-compliant acute dermal toxicity study 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 animals were observed for 14 days. Impaired general state and piloerection were recorded in one male on the first day of the study only. No signs of systemic toxicity were observed in the other animals (four males, five females). No mortality occurred. Signs of local irritation were recorded. 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 except one female animal, which showed stagnation of body weight during the first week. No mortality occurred. Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw.

Justification for classification or non-classification

Classification,Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is considered to be classified with H302 for acute oral toxicity under Regulation (EC) No. 1272/2008.