Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
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
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF guidelines 2000 (incl. most recent revisions)
Deviations:
no
Principles of method if other than guideline:
Deviations from the minimum level of relative humidity occurred. Evaluation: Laboratory historical data do not indicate an effect of the deviations.
The study integrity was not adversely affected by the deviation.
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Silver docosanoate
EC Number:
219-641-4
EC Name:
Silver docosanoate
Cas Number:
2489-05-6
Molecular formula:
C22H44O2.Ag
IUPAC Name:
silver(1+) docosanoate
Constituent 2
Reference substance name:
CH03220
IUPAC Name:
CH03220
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): CH03220
- Molecular formula (if other than submission substance): C22H4402.Ag
- Molecular weight (if other than submission substance):447.44
- Physical state: white powder
- Analytical purity: 100 wt % silver docosanoate
- Lot/batch No.: CH03220/AJ
- Storage condition of test material: at room temperature, protected from light
- Stability under storage conditions: stable
- Expiry date: 25 nov 2012 (1 year after receipt of the test substance)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Charles RIver Deutschalnd, Sulzfeld, Germany
- Females are nulliparous and non-pregnant
- Age: approx 10 weeks
- Body weight: variation did not exceed +/- 20% of the sex mean
- Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0oC (actual range: 19.8 – 23.5oC), a relative humidity of 40-70% (actual range: 36 - 66%) and 12 hours artificial fluorescent light and 12 hours darkness per day.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
corn oil
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
The test substance formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm2 for males and 18 cm2 for females. The test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, * successively covered with aluminum foil and Coban elastic bandage . A piece of Micropore tape* was additionally used for fixation of the bandages in females only.
Duration of exposure:
24h
Doses:
2000 mg/kg (10 mL/kg)
single dosage on day 1
No. of animals per sex per dose:
5 (5 males and 5 females)
Details on study design:
- Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm).
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany). Free access to tap water.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
dissolved
Mortality:
No mortality occurred.
Clinical signs:
Chromodacryorrhoea was noted in two males and two females on Day 1.
Scales were seen in the treated skin-area of one male in the second week of the study.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats
used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of CH03220 in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Assessment of acute dermal toxicity with CH03220 in the rat.

The study was carried out based on the guidelines described in:
OECD No.402 (1987) "Acute Dermal Toxicity"
Commission Regulation (EC) No 440/2008, B3: "Acute Toxicity (Dermal)" EPA, OPPTS 870.1200 (1998), "Acute Dermal Toxicity"

JMAFF Guidelines (2000), including the most recent revisions.

CH03220 was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Chromodacryorrhoea was noted in two males and two females on Day 1.

Scales were seen in the treated skin-area of one male in the second week of the study.

The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of CH03220 in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, CH03220 does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United

Nations (2011),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and

mixtures.