Aluminum, benzoate C16-18 fatty acids complexes - high aluminium

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

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other: GLP compliant, guideline study, available as an unpublished report.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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Aluminum, benzoate C16-18-fatty acids complexes

EC Number:

303-385-6

EC Name:

Aluminum, benzoate C16-18-fatty acids complexes

Cas Number:

94166-87-7

Molecular formula:

C23H37AlO5, C25H41AlO5

IUPAC Name:

Aluminum, benzoate C16-18-fatty acids complexes

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

Specific details on test material used for the study:

The substance is the source of the read-across.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system 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:

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.