O,O'-dioctadecylpentaerythritol bis(phosphite)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 August 1993 to 9 September 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

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. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

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:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

O,O'-dioctadecylpentaerythritol bis(phosphite)

EC Number:

223-276-6

EC Name:

O,O'-dioctadecylpentaerythritol bis(phosphite)

Cas Number:

3806-34-6

Molecular formula:

C41H82O6P2

IUPAC Name:

3,9-bis(octadecyloxy)-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane

Test material form:

solid: flakes

Details on test material:

- Name of test material (as cited in study report): Distearyl pentaerythritol diphosphite
- Physical state: solid (white flakes)
- Storage condition of test material: away from heat and ignition sources in a dry place at room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazletown Research Products, Inc., Denver, Pennsylvania
- Age at study initiation: approximately 11 weeks
- Weight at study initiation: 2098 - 2240 g
- Housing: individually
- Diet: Purina® Certified Rabbit Chow® #5322 (ad libitum)
- Water: tap water (ad libitum)
- Acclimation period: 6 days (minimum)

ENVIRONMENTAL CONDITIONS
- Temperature: 65 - 72 °F
- Humidity: 60 - 82 %
- Photoperiod: 12 hours light / 12 hours dark

IN-LIFE DATES: From 26 August 1993 to 9 September 1993

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: on the day before dosing, hair from the back of the rabbits was removed using animals clippers. The animals were also shaved, to aid dermal observations, on study days 3, 7, 10 and 14.
- % coverage: 13 - 15 % of total body surface
- Type of wrap if used: doses were applied under gauze binders and secured with Dermiform® tape

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- For solids, paste formed: no

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and clinical signs were observed at approximately 1.0, 3.0 and 4.0 hours post-dose and on day 0 and twice daily thereafter for 14 days. Dermal observations were made 30-60 minutes after bandage removal and daily thereafter for 13 days. Bodyweights were recorded on study days 0, 7 and 14.
- Necropsy of survivors performed: yes (examination of major organ systems of the cranial, thoracic and abdominal cavities)

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: No signs of toxicity were observed at this dose level.

Mortality:

None of the animals died during the study.

Clinical signs:

other: 2 females had a soft stool on day 1. 2 animals had their collars caught in their mouth during test material exposure and one of these animals had wet red material around the mouth. There were no other clinical findings.

Gross pathology:

Accessory splenic tissue, a common congenital abnormality in this strain of rabbit, was noted for 5 animals. No other gross necropsy findings were recorded.

Other findings:

The test material induced very slight to moderate erythema on all rabbits and very slight oedema on 8 rabbits. Desquamation was present on eight sites by day 7 and one site by day 14. There were no other dermal findings. Three sites had very slight erythema and/or desquamation at study termination on day 14.

Any other information on results incl. tables

Table 1: Bodyweights and Mortality

Day	Males		Females
	Bodyweight (g) (mean)	Mortality	Bodyweight (g) (mean)	Mortality
0	2170	0/5	2165	0/5
7	2505	0/5	2420	0/5
14	2739	0/5	2640	0/5

Table 2: Individual dermal observations

		Day
		1	2	3	4	5	6	7	8	9	10	11	12	13	14
16496 Male	Erythema	1	1	1	1	1	1	1	1	1	1	1	SNR	SNR	1
	Oedema	1	0	0	0	0	0	0	0	0	0	0			0
	Other findings	-	-	-	-	-	-	d	-	-	-	-			-
16498 Male	Erythema	2	1	1	1	1	1	1	1	SNR	1	1	SNR	SNR	SNR
	Oedema	1	0	0	0	0	0	0	0		0	0
	Other findings	-	-	-	-	-	d	d	-		-	-
16503 Male	Erythema	3	1	1	1	1	1	0	0	SNR	SNR	SNR	SNR	SNR	SNR
	Oedema	1	0	0	0	0	0	0	0
	Other findings	-	-	-	d	d	d	d	d
16507 Male	Erythema	2	1	1	1	1	1	1	1	1	1	1	1	1	1
	Oedema	1	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other findings	-	-	-	d	d	d	d	d	-	-	-	-	-	d
16508 Male	Erythema	2	1	1	1	1	1	1	1	1	1	1	1	SNR	SNR
	Oedema	1	0	0	0	0	0	0	0	0	0	0	0
	Other findings	-	-	-	d	d	d	d	d	-	-	-	-
16523 Female	Erythema	2	SNR	1	1	1	1	1	1	1	SNR	SNR	SNR	SNR	SNR
	Oedema	1		0	0	0	0	0	0	0
	Other findings	-		-	-	-	d	d	-	-
16524 Female	Erythema	3	1	1	1	1	1	0	SNR	SNR	SNR	SNR	SNR	SNR	SNR
	Oedema	1	0	0	0	0	0	0
	Other findings	-	-	-	-	-	d	d
16530 Female	Erythema	1	SNR	1	1	1	1	0	0	0	SNR	SNR	SNR	SNR	SNR
	Oedema	0		0	0	0	0	0	0	0
	Other findings	-		-	-	-	-	d	d	d
16533 Female	Erythema	1	SNR	1	1	1	1	1	1	1	1	SNR	SNR	SNR	0
	Oedema	0		0	0	0	0	0	0	0	0				0
	Other findings	-		-	-	-	-	-	-	-	-				d
16536 Female	Erythema	1	SNR	1	1	1	1	1	1	1	1	SNR	SNR	SNR	SNR
	Oedema	1		0	0	0	0	0	0	0	0
	Other findings	-		-	-	-	-	-	-	-	-
d = Desquamation SNR = Scored, not remarkable

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, there were no deaths, clinical signs of toxicity, remarkable bodyweight changes of test material related gross necropsy findings.The test material induced very slight to moderate erythema on all rabbits and very slight oedema on 8 rabbits. Nine sites had desquamation within 2 weeks after dosing. Dermal irritation decreased over the period with three rabbits having very slight erythema and/or desquamation at study termination on day 14. There was no sign of systemic toxicity among the rabbits. based on the data obtained, the acute dermal LD50 of the test material in the albino rabbit was determined to be in excess of 2000 mg/kg.

Executive summary:

The acute dermal toxicity of the test material was determined in accordance with standardised guidelines OECD 402, US EPA OPP 81 -2 and US EPA OPPTS 798.1100. During the study rabbits were administered with a single dermal dose of test material which was held in place, under a semi-occlusive dressing, for a period of 24 hours. Following exposure to the test material, animals were observed for 14 days for mortality and clinical signs. All surviving animals were necropsied on day 14. Under the conditions of the study, there were no deaths, clinical signs of toxicity, remarkable bodyweight changes of test material related gross necropsy findings.The test material induced very slight to moderate erythema on all rabbits and very slight oedema on 8 rabbits. Nine sites had desquamation within 2 weeks after dosing. Dermal irritation decreased over the period with three rabbits having very slight erythema and/or desquamation at study termination on day 14. There was no sign of systemic toxicity among the rabbits. based on the data obtained, the LD50 of the test material was determined to be in excess of 2000 mg/kg.