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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2009-12-17 to 2010-02-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

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

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))
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Quaternary ammonium compounds, benzylbis(hydrogenated tallow alkyl)methyl, chlorides
EC Number:
263-082-9
EC Name:
Quaternary ammonium compounds, benzylbis(hydrogenated tallow alkyl)methyl, chlorides
Cas Number:
61789-73-9
IUPAC Name:
61789-73-9
Constituent 2
Reference substance name:
Quaternary ammoniums compounds, benzylbis (hydrogenated tallow alkyl) methyl, chlorides
IUPAC Name:
Quaternary ammoniums compounds, benzylbis (hydrogenated tallow alkyl) methyl, chlorides

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Approximately 10 weeks old
- Weight at study initiation: Males: 388 ± 9 g and Females: 263 ± 12 g
- Fasting period before study: Not applicable
- Housing: The rats were housed individually in polycarbonate cages with stainless steel lid
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: At least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): Approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light

IN-LIFE DATES: From: 17 December 2009 To: 10 February 2010

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal area
- % coverage: 10% of the total body surface of the animals
- Type of wrap if used: Hydrophilic gauze pad held in contact with skin by an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage. The gauze pad was moistened with 2 mL purified water prior to applying the test material

REMOVAL OF TEST SUBSTANCE
- Washing : No
-Time after start of exposure: 24 hours after application, the dressing was removed and any residual test item was removed using a dry cotton pad.

TEST MATERIAL
- Amount(s) applied : 200, 1000 and 2000 mg/kg bw
- Concentration (if solution): Not applicable, the test material was a paste.
- Constant volume or concentration used: yes. Constant concentration - dose volume adjusted for bodyweight on day of treatment
Duration of exposure:
24 hours
Doses:
200, 1000 and 2000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex at 2000 mg/kg bw, 1 female at 1000 mg/kg bw and 1 female at 200 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed after dose administration at least once during the first 30 minutes, periodically during the first 24 hours, then daily for a period of 14 days. Dermal reactions were scored using a standard Draize assessment. Bodyweights were recorded at weekly intervals from Day 1.
- Necropsy of survivors performed: yes
Statistics:
none

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was reported at any of the tested dose levels.
Clinical signs:
other: No clinical signs were reported except some local dermal reactions observed in all dose groups (see other findings).
Gross pathology:
No macroscopic changes were noted at necropsy.
Other findings:
Local reactions such as erythema and oedema were reported during the course of the study.

At the dose-levels of 200 and 1000 mg/kg bw, well-defined to severe erythema, scabs, dryness and discoloration area (greenish, brownish or blackish) and/or oedema were observed with a similar severity.

Local reactions (erythema, dryness, oedema, discoloration area and scabs) observed at 2000 mg/kg bw were similar in severity to those recorded at 1000 mg/kg bw.

Any other information on results incl. tables

In the first step, no mortality and systemic clinical signs were noted in the one female treated at the dose-level of 200 mg/kg bw and in the other one treated at the dose-level of 1000 mg/kg bw. The local reactions were observed with a similar severity whatever the dose. According to these results, a highest dose-level of 2000 mg/kg bw was tested in one female and then confirmed in four additionnal females and five males.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (Reg. 1272/2008/EC) and Directive 67/548/EEC
Conclusions:
Under the experimental conditions of this study and according to the criteria laid down in CLP (Reg 1272/2008/EC) and directive 67/548/EEC, the test material (Quaternary ammoniums compounds, benzylbis (hydrogenated tallow alkyl) methyl, chlorides ) is not classified.
Executive summary:

The objective of this study was to evaluate the toxicity of the substance following a single dermal application to rats according to the OECD guideline 402 and to the EU Method B.3. The study was conducted in compliance with the principles of Good Laboratory Practice regulations.

The test item in its original form was applied to the skin of Sprague-Dawley rats. The treated area was then covered by a semi-occlusive dressing for 24 hours. In first instance, the test item was administered sequentially at dose-levels of 200, 1000 then 2000 mg/kg to one female per dose-level, in order to evaluate the potential toxicity and local tolerance of the test item. According to the results obtained at each dose-level, a highest dose-level was tested or the dose-level was confirmed in four other females and tested in five males.

Mortality and clinical signs were checked daily for a period of 14 days following the single application of the test item. Body weight was recorded on days 1, 8 and 15. At the end of the 14-day observation period all animals were sacrificed and subjected to necropsy.

In the first step, at the dose-level of 200 and 1000 mg/kg, no mortality and systemic clinical signs were noted. The local reactions, as erythema (well-defined to severe), scabs, dryness and discoloration area (greenish, brownish or blackish) and/or oedema were observed with a similar severity.

According to these results, a highest dose-level of 2000 mg/kg was tested in one other female and then confirmed in four additionnal females and five males.No deaths and no relevant systemic clinical signs were observed during the study at the dose-level of 2000 mg/kg. Local reactions (erythema, dryness, edema, discoloration area and scabs) observed at 2000 mg/kg were similar in severity to those recorded at 1000 mg/kg. The body weight was not affected by the test item treatment. No abnormalities were observed at macroscopic examination.

Under these experimental conditions, the dermal LD0 of the test substance was higher than or equal to 2000 mg/kg in rats.