Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
24 October 2012 and 14 November 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as an unpublished report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

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)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
- Physical state: Pale Yellow Solid
- Purity: Not applicable - UVCB
- Substance identity: Aluminum, benzoate C16-18-fatty acids complexes
- Batch number: 11074091 + Benzoic acid
- Carbon Content: 65.1%
- Analysis code: A118
- Date recieved: 07 June 2012
- Expiration date: 01 July 2013
- Storage of test material: Room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:

TEST ANIMALS
- Source :Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: Eight to twelve weeks of age
- Weight at study initiation: At least 200g
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24 Hour exposure period and in groups of up to four, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK
- Water (e.g. ad libitum): Mains drinking water
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 ºC
- Humidity (%): Relative humidity 30 to 70%
- Air changes (per hr): At least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): The lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
TEST SITE
- Area of exposure: Back and flanks of each anomal
- % coverage: Approximately 10% of the total body surface
- Type of wrap if used: Surgical gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight
- For solids, paste formed: Yes

VEHICLE
- Amount(s) applied (volume or weight with unit): Not reported
- Concentration (if solution): Not reported
- Lot/batch no. (if required): Not reported
- Purity: Not reported
Duration of exposure:
24 hours contact period.
Doses:
2000 mg /kg body weight
No. of animals per sex per dose:
In the absence of data suggesting the test item was toxic, one male and one female rat were initially treated with the test item at a dose level of 2000 mg/kg. As no mortalities were noted a further group of animals (four males and four females) was similarly treated with the test item at a dose level of 2000 mg/kg bodyweight to give a total of five males and five females.
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days (or other?): The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Frequency of observations and weighing: Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31:
EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth) 4
Oedema Formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 95% confidence limits not reported
Mortality:
No deaths occurred during the study.


Clinical signs:
No clinical signs of systemic toxicity were observed during the course of the study.
Body weight:
Animals showed expected gains in bodyweight over the study period, except for three animals which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Other findings:
Individual dermal reactions are given in Table 2 and Table 3 in overall remarks section.
Very slight erythema was noted at the test site of three females up to two days after dosing. There were no signs of dermal irritation noted at the test sites of the remaining animals.

Any other information on results incl. tables

Table 1              Individual Clinical Observations and Mortality Data

Dose Level

mg/kg

Animal Number and Sex

Effects Noted After Initiation of Exposure (Hours)

Effects Noted After Initiation of Exposure (Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-0

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-1

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-2

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-3

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-1

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-2

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-3

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0


0 = No signs of systemic toxicity

See Overall remarks for Dermal Reactions Tables 2 and 3.

Table 4              Individual Bodyweights and Weekly Bodyweight Changes

Dose Level mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Change (g) During Week

0

7

14

1

2

2000

1-0 Male

412

403

419

-9

16

3-0 Male

253

271

291

18

20

3-1 Male

252

265

285

13

20

3-2 Male

260

274

296

14

24

3-3 Male

241

251

266

10

15

2-0 Female

252

245

260

-7

15

4-0 Female

203

206

209

3

3

4-1 Female

210

217

222

7

5

4-2 Female

219

217

229

-2

12

4-3 Female

208

209

218

1

9

Table 5              Individual Necropsy Findings

Dose Level

mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

2000

1-0

Male

Killed Day 14

No abnormalities detected

3-0

Male

Killed Day 14

No abnormalities detected

3-1

Male

Killed Day 14

No abnormalities detected

3-2

Male

Killed Day 14

No abnormalities detected

3-3

Male

Killed Day 14

No abnormalities detected

2-0

Female

Killed Day 14

No abnormalities detected

4-0

Female

Killed Day 14

No abnormalities detected

4-1

Female

Killed Day 14

No abnormalities detected

4-2

Female

Killed Day 14

No abnormalities detected

4-3

Female

Killed Day 14

No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: other: Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31
Conclusions:
The acute dermal median lethal dose (LD50) of aluminum, benzoate C16-18-fatty acids complexes in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

Introduction. 

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat.The acute oral toxicity of the test item to the Wistar strain rat was assessed in a GLP-compliant study following OECD guideline 402 (adopted 1987) and Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008 in a proprietary, experimental study (Harlan 2013). The study is considered reliable and relevant for use for this endpoint.

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.  Very slight erythema was noted at the test site of three females up to two days after dosing. There were no signs of dermal irritation noted at the test sites of the remaining animals.

Bodyweight.  Animals showed expected gains in bodyweight over the study period, except for three animals which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute dermal median lethal dose (LD50) of aluminum, benzoate C16-18-fatty acids complexess in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.