O,O'-dioctadecylpentaerythritol bis(phosphite)

Endpoint summary

Description of key information

Oral; LD50 > 10,000 mg/kg bw; male/female rat; equivalent to OECD 401; Widersich (1971)
Inhalation; LC50 =  > 2 mg/L;  male/female rat; equivalent to OECD 403; Levi (1977)
Dermal; LD50 = > 2000 mg/kg bw; male/female rat; OECD 402, US EPA OPP 81-2, US EPA OPPTS 798.1100; Kiplinger (1994)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A non-GLP study conducted to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sherman

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200 - 220 g
- Fasting period before study: 16 hours prior to dose administration
- Housing: individually
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Animals were kept in a conditioned animal room

Route of administration:

oral: gavage

Vehicle:

vegetable oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2 g test material in 5 mL of vegetable oil

Doses:

10,000 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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No effects were observed at this dose level.

Mortality:

None of the animals died during the study.

Clinical signs:

other: None of the animals showed any signs of toxicity during the study.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

None of the animals showed any signs of toxicity at the maximum dose that could be given at a single administration. The acute oral LD50 in the rat was therefore determined to be > 10000 mg/kg.

Executive summary:

The acute oral toxicity of the test material was investigated by dosing 5 male and 5 female rats with a single dose of test material by gavage. Following exposure, animals were observed for 14 days. Under the conditions of the study, none of the animals showed any signs of toxicity at the maximum dose that could be given at a single administration. The acute oral LD50 in the rat was therefore determined to be > 10000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Quality of whole database:

Two non-GLP studies are available. Both were performed to sound scientific principles with a sufficient level of detail to assess the quality of the presented results. Both studies were assigned a reliability score of 2 according to the criteria of Klimisch (1977) and considered suitable as an accurate reflection of the test material.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

10 November 1977 to 24 November 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A non-GLP study performed to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

(exposure duration 1 hour rather than 4 hours)

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult
- Weight at study initiation: 225 g (average)
- Housing: individually
- Diet: ad libitum (except during exposure period)
- Water: ad libitum (except during exposure period)
- Acclimation period: 3 days

IN-LIFE DATES: From 10 November 1977 to 24 November 1977

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: specially constructed, all plexiglas inhalation chambers
- Exposure chamber volume: 355 cubic litres
- Method of holding animals in test chamber: Each animal was placed in a separate wire cage during exposure to prevent filtration of inspired air by animals fur
- System of generating test atmosphere: The chamber was equipped with blowers so that after the test material was introduced into the chamber's atmosphere the air was continually recirculating during the test period

TEST ATMOSPHERE
The average nominal test material concentration was calculated by dividing the total amount of test material used by the total volume of the chamber

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

1 h

Concentrations:

2 mg/L

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 weighing: all animals were weighed at study initiation and then again on day 14
- Necropsy of survivors performed: yes
- Other examinations performed: a gross pathological autopsy was conducted on all animals found dead during the study as well as on all surviving animals

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2 mg/L air

Based on:

test mat.

Exp. duration:

1 h

Mortality:

None of the animals died during the study.

Clinical signs:

other: All animals appeared normal during the 14 day period.

Body weight:

All of the animals gained weight during the study.

Gross pathology:

The organs of the thorax and abdomen appeared normal at gross pathology.

Table 1: Results

Animal no. and sex	Initial bodyweight (g)	Dose (mg/L)	Weight gain in 14 days (g)	Days to death
1F	204	2	46	survived
2F	201	2	78	survived
3F	210	2	60	survived
4F	202	2	70	survived
5F	206	2	60	survived
6M	228	2	102	survived
7M	242	2	106	survived
8M	232	2	130	survived
9M	236	2	112	survived
10M	254	2	136	survived

Interpretation of results:

other: LC50 in excess of 2 mg/L (1 h) (highest dose level tested), the classification of the test material cannot be interpreted based on the results of the study

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute inhalation LC50 was determined to be greater than 2 mg/L of atmosphere for a one hour exposure period to the test material.

Executive summary:

The acute inhalation toxicity of the test material was determined following a methodology similar to that outlined in the standard guideline OECD 403. During the study, 5 male and 5 female rats were exposed to atmospheres containing test material at 2 mg/L for 1 hour. During the exposure period, mortality and signs of reaction to the test material were assessed. Following exposure the animals were returned to their cages where they were observed for 14 days. At the end of the 14 day exposure period all animals were subject to a gross pathological examination.

Under the conditions of the study, none of the animals died. All animals appeared normal during the 14 day observation period and gross necropsy revealed that the organs of the thorax and abdomen appeared normal. The acute inhalation LC50 was therefore determined to be greater than 2 mg/L of atmosphere for a one hour exposure period to the test material.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

One non-GLP study performed to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data. The study was assigned a reliability score of 2 according to the criteria of Klimisch (1977).

Acute toxicity: via dermal route

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

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

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

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)

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.

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study was performed to GLP and was conducted in accordance with standardised guidelines. The two supporting studies were non-GLP studies conducted to sound scientific principles with a sufficient level of reporting to assess the quality of the presented results. The overall quality of the dataset is good.

Additional information

Oral

In the key study, the acute oral toxicity of the test material was investigated by dosing 5 male and 5 female rats with a single dose of test material by gavage. Following exposure, animals were observed for 14 days. Under the conditions of the study, none of the animals showed any signs of toxicity at the maximum dose that could be given at a single administration. The LD50 was subsequently determined to be in excess of 10,000 mg/kg bw.

 

Supporting information is available in the form of a study in which the acute oral toxicity of the test material was determined following a methodology similar to that of standard guideline OECD 401. During the study groups of 2 male and 2 female rats received single oral doses of undiluted test material at 1350, 4556 and 15380 mg/kg. Animals were observed for mortality and clinical signs for 14 days following dose administration. Under the conditions of the study, none of the animals died. Symptoms exhibited by the animals were limited to hypoactivity and ruffed fur one day post-oral administration. The duration of these reactions was one day. Necropsy examination of the animals at sacrifice revealed solidified test material in 3 animals at the 15380 mg/kg dose level and in 1 animal at the 4556 mg/kg dose level. No other gross pathologic alterations were noted. Under the conditions of the study, no animals died when dosed up to 15,380 mg/kg. The LD50 was reported to be > 15,380 mg/kg.

 

Dermal
In the key study, 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.

 

Supporting information is available in the form of two studies which were conducted in accordance with Section 191.10 of the Final Order, Enforcement Regulations, Federal Register (1961), Vol. 26, No. 155 p. 7336. During the studies 800 mg/kg test material was applied to the skin of six rabbits, three with intact skin and three with abraded skin. In one study (Moldovan 1972), mortality was recorded up to 14 days following dose administration. Under the conditions of the study, none of the animals died. The LD50 was therefore reported to be in excess of 800 mg/kg. In the other supporting study (Moldovan 1971) mortality, following test material administration was recorded. Under the conditions of the study, one of three animals died in both the group of animals with intact skin and in the group of animals with abraded skin. The LD50 was reported to be in excess of 800 mg/kg.

 

Inhalation
The acute inhalation toxicity of the test material was determined following a methodology similar to that outlined in the standard guideline OECD 403. During the study, 5 male and 5 female rats were exposed to atmospheres containing test material at 2 mg/L for 1 hour. During the exposure period, mortality and signs of reaction to the test material were assessed. Following exposure the animals were returned to their cages where they were observed for 14 days. At the end of the 14 day exposure period all animals were subject to a gross pathological examination. Under the conditions of the study, none of the animals died. All animals appeared normal during the 14 day observation period and gross necropsy revealed that the organs of the thorax and abdomen appeared normal. The acute inhalation LC50 was therefore determined to be greater than 2 mg/L of atmosphere for a one hour exposure period to the test material. 

Justification for selection of acute toxicity – oral endpoint
The study with the lowest LC50 value is selected.

Justification for selection of acute toxicity – inhalation endpoint
Only one study is available. LC50 in excess of 2 mg/L (1 h) (highest dose level tested), the classification of the test material cannot be interpreted based on the results of the study.

Justification for selection of acute toxicity – dermal endpoint
Klimisch 1 study

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification as no signs of toxicity were noted during the course of any of the acute toxicity studies.