Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 April 2008 to 30 April 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Date of inspection: 21 August 2007 Date of Signature: 15 October 2007
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): 3-Octadecyloxypropyl-N,N,N-trimethylammonium chloride
- Molecular formula (if other than submission substance): Not applicable
- Molecular weight (if other than submission substance): Not applicable
- Smiles notation (if other than submission substance): Not applicable
- InChl (if other than submission substance): Not applicable
- Structural formula attached as image file (if other than submission substance): Not applicable
- Substance type: white solid
- Physical state: solid
- Analytical purity: Not reported
- Impurities (identity and concentrations): Not reported
- Composition of test material, percentage of components: Not reported
- Isomers composition: Not reported
- Purity test date: Not reported
- Lot/batch No.: Exp. I-070518
- Expiration date of the lot/batch: Not reported
- Radiochemical purity (if radiolabelling): Not applicable
- Specific activity (if radiolabelling): Not applicable
- Locations of the label (if radiolabelling): Not applicable
- Expiration date of radiochemical substance (if radiolabelling): Not applicable
- Stability under test conditions: Not reported.
- Storage condition of test material: room temperature in the dark
- Other: Not reported.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK.
- Age at study initiation: 8 to 12 weeks of age.
- Weight at study initiation: At least 200 g. The weight variation did not exceed ± 20% of the mean weight for each sex.
- Fasting period before study: Not reported.
- Housing: . The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Certified Rat and Mouse Diet ad libitum. The diet was routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
- Water (e.g. ad libitum): Mains drinking water ad libitum. The water was routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 19 to 25ºC.
- Humidity (%): Set to achieve limits of 30 to 70%.
- Air changes (per hr): At least 15 changes per hour.
- Photoperiod (hrs dark / hrs light): Twelve hours continuous light (06:00 to 18:00) and 12 hours darkness.

IN-LIFE DATES: From: Day 0 To: Day 14

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: Water to moisture the test substance.
Details on dermal exposure:
TEST SITE
- Area of exposure: Back and flanks.
- % coverage: Approximately 10% of the total body surface area.
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.- Time after start of exposure: Twenty-four hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The appropriate amount of the test material, moistured with distilled water. No more details were reported.
- For solids, paste formed: No.

VEHICLE
- Amount(s) applied (volume or weight with unit): Not reported.
Duration of exposure:
Twenty-four hours.
Doses:
2000 mg/kg.
No. of animals per sex per dose:
Five males and 5 females.
Control animals:
no
Details on study design:
- Duration of observation period following administration: Fourteen days.
- Frequency of observations and weighing: Observation - ½, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days for deaths or overt signs.
Body weight - prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: Mortality, clinical signs, body weight and gross necropsy.
Statistics:
Not reported.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Dermal Reactions
Individual dermal reactions are given in Table 1 and Table 2.
Well-defined erythema was noted at the treatment sites of all animals one day after dosing with very slight or well-defined erythema noted in all females two days after dosing. Very slight erythema was noted at the treatment sites of four females three and four days after dosing. Other signs of dermal irritation noted were crust formation, small superficial scattered scabs and superficial cracking of the epidermis.
Treatment sites appeared normal two to thirteen days after dosing.

Any other information on results incl. tables

Table 1 Individual Dermal Reactions - Males

Dose Level mg/kg

Animal Number and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Male

Erythema

2

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-1

Male

Erythema

2

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-2

Male

Erythema

2

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-3

Male

Erythema

2

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

Cf

Cf

Cf

Cf

Cf

Cf

Cf

0

0

0

0

0

0

1-4

Male

Erythema

2

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

Cf

Cf

Cf

Cf

Cf

Cf

Cf

0

0

0

0

0

0

0= No reactions 

Cf = Crust formation  

Table 2 Individual Dermal Reactions - Females

Dose Level mg/kg

Animal Number and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0

Female

Erythema

2

2

1

1

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

Cr

Cr

Cf

Cf

Cf

Cf

0

0

0

0

0

0

2-1

Female

Erythema

2

1

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2

Female

Erythema

2

1

1

1

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

Cr

Cr

0

0

0

0

0

0

0

0

0

0

2-3

Female

Erythema

2

1

1

1

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

CrSs

CrSs

CfSs

Cf

Cf

Cf

0

0

0

0

0

0

2-4

Female

Erythema

2

1

1

1

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

Ss

CrSs

CfSs

Cf

Cf

Cf

Cf

Cf

Cf

Cf

0

0

0= No reactions 

Cf = Crust formation                          

Cr = Superficial cracking of the epidermis                      

Ss = Small superficial scattered scabs

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in the Sprague Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. The test material does not meet the criteria for classification according to EU classification system.
Executive summary:

Introduction. The study was performed to assess the acute dermal toxicity of the test material in the Sprague‑Dawley CD strain rat. The method was designed to meet the requirements of the following:

§        OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted)

§        Method B3 Acute Toxicity (Dermal) of Commission Directive 92/69/EEC

Method. A group of ten animals (five males and five females) was given a single, 24-hour, semi‑occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation. Well-defined erythema was noted at the treatment sites of all animals. Other signs of dermal irritation noted were crust formation, small superficial scattered scabs and superficial cracking of the epidermis. Treatment sites appeared normal two to thirteen days after dosing. 

Bodyweight. All animals showed expected gains in bodyweight over the study period.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute dermal median lethal dose (LD50) of the test material in the Sprague‑Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. The test material does not meet the criteria for classification according to EU classification system.