Butyltris[(2-ethyl-1-oxohexyl)oxy]stannane

Endpoint summary

Description of key information

Acute Oral Toxicity: Auletta (1989)

Under the conditions of the study the acute oral LD50 was greater than 5000 mg/kg in males and 3200 mg/kg in females.

Acute Dermal Toxicity

Under the conditions of the study the acute dermal LD50 of the test material was greater than 8000 mg/kg.

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:

key study

Study period:

19 July 1988 to 04 October 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: CD (Sprague-Dawley derived)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately 9 - 12 weeks old
- Weight at study initiation: Males: 289 - 351 g; Females: 214 - 260 g
- Fasting period before study: Animals were fasted overnight (for approximately 18 hours) prior to dosing
- Housing: Group-housed (six/cage) during equilibration and individually housed during study in suspended, stainless steel cages with wire mesh bottoms
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 21 or 22 days

ENVIRONMENTAL CONDITIONS
- Temperature: 67 - 76°F
- Humidity: 30 - 70%
- Photoperiod: 12 hours light, 12 hours dark (controlled by an automatic timer)

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 4.6 mL/kg

Doses:

Range-finding study: 100, 500, 1000, 2500 and 5000 mg/kg
LD50 determination study: 2500, 3000, 3500 and 5000 mg/kg (3000 mk/kg: females only and 5000 mg/kg: males only)

No. of animals per sex per dose:

Range-finding study: 1 animal per sex per dose
LD50 determination study: 5 animals per sex per dose (3000 mk/kg: females only and 5000 mg/kg: males only)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Viability Check: twice daily
Observations of Pharmacologic and Toxicological Signs: approximately 1, 2 and 4 hours after dosing and daily thereafter for fourteen days.
Body Weights: pre-fast (weights used for calculation of doses), day 7 and 14 and terminal: any animals which did not survive for 14 days were weighed at the time of death or at the time they were found dead.
- Necropsy of survivors performed: yes, gross post-mortem examinations were performed on all animals which died or were found dead during the study. At termination of the observation period (Day 14), all surviving animals were killed by carbon dioxide inhalation and examined grossly. All abnormalities
were recorded but no tissues were saved.
- Animals used for range-finding screens were observed for viability twice daily for seven days and deaths were recorded. No post-mortem examinations were made on animals used for range-finding screens.

Preliminary study:

In the range-finding study, there were no deaths at 100, 500, 1000 or 2500 mg/kg but 2/2 animals died at 5000 mg/kg.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

3 200 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 871 - <= 3 529

Mortality:

- A sex-related difference was apparent, with females more affected than males. In males no mortality was seen at doses of up to 5000 mg/kg, while the LD50 in females was 3200 mg/kg.
- Mortality is summarised in Table 1.

Clinical signs:

other: - Signs seen on the day of dosing in most or all groups included ataxia, nasal, oral and ocular discharge, hypopnea, hypoactivity, wet rales, faecal and urinary staining, irregular breathing and prostration. - On the day after dosing, unthrifty coat, hypo

Gross pathology:

- Gross post-mortem observations were generally unremarkable.
- Post-mortem examinations of animals which were found dead revealed changes which generally appeared to represent autolytic changes or normal variability.
- Changes in animals killed after 14 days were similar to those seen in control animals in this laboratory killed by carbon dioxide inhalation or were considered to represent normal physiological variation.

Table 1: Summary of Mortality During the Study

Dose Level (mg/kg)	Mortality		Time of Death
	Male	Female
2500	0/5	1/5	Day 1
3000	-	0/5	-
3500	0/5	4/5	22 hrs - Day 2
5000	0/5	-	-

Interpretation of results:

other: Not classified in accordance with EU Criteria

Conclusions:

Under the conditions of this study the male LD50 was greater than 5000 mg/kg and the female LD50 was 3200 mg/kg.

Executive summary:

The acute oral toxicity of the test material was investigated in a study similar to OECD 401.

During the study, male and female CD (Sprague-Dawley derived) rats were dosed with a single oral dose of the test material and observed for 14 days. The doses were chosen based on the results of a range finding study. For the definitive test males were dosed at 2500, 3500 and 5000 mg/kg and females were dosed at 2500, 3000 and 3500 mg/kg.

A sex-related difference was apparent, with females more affected than males. In males no mortality was seen at doses of up to 5000 mg/kg, while the LD50 in females was 3200 mg/kg.

Signs seen on the day of dosing in most or all groups included ataxia, nasal, oral and ocular discharge, hypopnea, hypoactivity, wet rales, faecal and urinary staining, irregular breathing and prostration. On the day after dosing, unthrifty coat, hypothermia, abdominal griping, soft stool and/or decreased food consumption were evident in some animals in all groups. Abnormalities continued in some animals for several days after dosing, but all animals were free of significant abnormalities at study termination (one male in the 5000 mg/kg group continued to exhibit an unthrifty coat).

The majority of surviving animals in the 2500 and 3000 mg/kg dose groups gained weight both 7 and 14 days after dosing. Several surviving animals in the 3500 and 5000 mg/kg dose groups exhibited weight losses at Day 7 but gained weight between Days 7 and 14. Gross post-mortem observations were generally unremarkable.

Under the conditions of this study the male LD50 was greater than 5000 mg/kg and the female LD50 was 3200 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 200 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

17 May 1979 to 20 June 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

The test material was applied once dermally to the prepared sites under gauze patches. The patches were secured with adhesive tape and the trunks were wrapped with impervious material. Dermal reactions were scored at 24 hours, days 3, 7 & 14 by the Draize scoring system. The rabbits were observed daily for 14 days for signs of toxicity, pharmacological effects and mortality.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 9 weeks old
- Weight at study initiation: 2.2 - 2.8 kg
- Housing: The animals were housed 2/cage in suspended wire mesh cages (30 x 18 x 18 ").
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 21 °C

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Immediately prior to dosing, the fur was clipped from the abdomen of the animals. The clipped area was 200 cm².
- % coverage: 10% of the body surface
- Type of wrap if used: The test material was applied once dermally to the prepared sites under gauze patches. The patches were secured with adhesive tape and the trunks were wrapped with impervious material.

REMOVAL OF TEST SUBSTANCE
- The test material was kept in contact with the skin for 24 hours, at which time the wrappings were removed. An estimate of the amount of material remaining was recorded.
- The exposure site was wiped, but not washed, to remove excess material.

TEST MATERIAL
- Amount(s) applied: 2.0, 4.0, 8.0 and 16.0 g/kg.

Duration of exposure:

24 hours

Doses:

2.0, 4.0, 8.0 and 16.0 g/kg.

No. of animals per sex per dose:

- 2.0 and 4.0 g/kg: 2 animals per sex
- 8.0 g/kg: 3 males and 1 female
- 16.0 g/kg: 1 male

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Dermal reactions were scored at 24 hours and on days 3, 7 and 14 according to the Draize scoring system.
- The rabbits were observed daily for 14 days for signs of toxicity, pharmacological effects and mortality.
- Body weights were recorded pre-test and in the survivors at 14 days.
- The rabbits were not examined for gross pathology.

Statistics:

The LD50, if possible, was calculated according to the method of Litchfield & Wilcoxon.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 8 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the testing.

Clinical signs:

other: Isolated instances of lethargy, ptosis, few faeces in pan, and yellow nasal discharge were sporadically noted in 3 animals. Eight out of thirteen animals appeared normal at all times. Lethargy was noted in two animals on day 0, but had cleared by day 1 an

Gross pathology:

Not performed.

Table 1: Individual Bodyweights

Dose level (g/kg)	Animal No. and sex	Bodyweight (kg)
		Day 0	Day 14
2.0	1-F	2.7	2.9
	2-F	2.5	2.7
	3-M	2.8	2.9
	4-M	2.8	3.0
4.0	5-M	2.2	2.5
	6-M	2.4	2.5
	7-F	2.5	2.5
	8-F	2.4	2.5
8.0	9-M	2.7	2.6
	10-M	2.8	2.8
	11-F	2.5	2.4
	12-M	2.5	2.7
16.0	13-M	2.6	2.5

 

Table 2: Dermal Scores

Dose level (g/kg)	Animal No. and sex	Dermal Scores
		Day 0		Day 3		Day 7		Day 14
		E	O	E	O	E	O	E	O
2.0	1-F	2	2	2	2	1f	0	0	0
	2-F	2	1	2	1	1f	1	0	0
	3-M	1	1	1	1	1f	0	1	0
	4-M	1	1	2	2	1	1	1	0
4.0	5-M	2	2	2	2	1f	2	0f	0
	6-M	1	2	2	2	1f	2	0f	0
	7-F	2	2	2	2	1f	1	1f	0
	8-F	3	1	3	2	2f	1	1f	0
8.0	9-M	2	2	3	3	4f	2	4fe	2
	10-M	3	2	3	2	2	2	4fe	2
	11-F	2	2	2	3	3	2	4fe	2
	12-M	3	2	2	2	2	2	4fe	2
16.0	13-M	2	2	2	2	3f	2	4fe	2

E = erythema

O = oedema

e = slight eschar

f = skin flaking

Interpretation of results:

other: Not classified in accordance with EU Criteria

Conclusions:

Under the conditions of this study the acute dermal LD50 of the test material was determined to be greater than 8000 mg/kg.

Executive summary:

The acute dermal toxicity of the test material was determined in a study using New Zealand White rabbits.

During the study, animals were treated with a dose of 2.0, 4.0, 8.0 or 16.0 g/kg of test material under an occlusive patch for 24 hours. The rabbits were observed daily for 14 days for signs of toxicity, pharmacological effects and mortality. Body weights were recorded pre-test and in the survivors on day 14. Dermal reactions were scored at 24 hours and on days 3, 7 and 14 according to the Draize scoring system.

Under the conditions of the study all animals survived. Isolated instances of lethargy, ptosis, few faeces in pan, and yellow nasal discharge were sporadically noted in 3 animals. Eight out of thirteen animals appeared normal at all times. Lethargy was noted in two animals on day 0, but had cleared by day 1 and both animals then remained normal throughout the test. Slight weight loss was noted in the higher dose animals and dermal reactions were moderate to severe at the higher dose levels.

The acute dermal LD50 of the test material was therefore determined to be in excess of 8000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

8 000 mg/kg bw

Additional information

Acute Oral Toxicity: Auletta (1989)

In the key study, the acute oral toxicity of the test material was investigated in a study similar to OECD 401. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study, male and female CD (Sprague-Dawley derived) rats were dosed with a single oral dose of the test material and observed for 14 days. The doses were chosen based on the results of a range finding study. For the definitive test males were dosed at 2500, 3500 and 5000 mg/kg and females were dosed at 2500, 3000 and 3500 mg/kg.

A sex-related difference was apparent, with females more affected than males. In males no mortality was seen at doses of up to 5000 mg/kg, while the LD50 in females was 3200 mg/kg.

Signs seen on the day of dosing in most or all groups included ataxia, nasal, oral and ocular discharge, hypopnea, hypoactivity, wet rales, faecal and urinary staining, irregular breathing and prostration. On the day after dosing, unthrifty coat, hypothermia, abdominal griping, soft stool and/or decreased food consumption were evident in some animals in all groups. Abnormalities continued in some animals for several days after dosing, but all animals were free of significant abnormalities at study termination (one male in the 5000 mg/kg group continued to exhibit an unthrifty coat).

The majority of surviving animals in the 2500 and 3000 mg/kg dose groups gained weight both 7 and 14 days after dosing. Several surviving animals in the 3500 and 5000 mg/kg dose groups exhibited weight losses at Day 7 but gained weight between Days 7 and 14. Gross post-mortem observations were generally unremarkable.

Under the conditions of this study the male LD50 was greater than 5000 mg/kg and the female LD50 was 3200 mg/kg.

Acute Oral Toxicity: Braun (1978)

In a supporting study, the acute oral toxicity of the test material was investigated in a study similar to OECD 401. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study, male and female Sprague-Dawley rats were dosed with a single oral dose of the test material and observed for 14 days. The doses were chosen based on the results of a range finding study. For the definitive test animals were dosed at 4.0, 5.6, 8.0 and 11.3 g/kg.

Under the conditions of the study 3/10 animals died at 4.0 g/kg, 7/10 animals died at 5.6 g/kg, 8/10 animals died at 8.0 g/kg and 8/10 animals died at 11.3 g/kg.

Common in-life signs of effect noted during the fourteen day study included: ataxia, tremors, red nasal and clear nasal discharge, oral discharge, chromodacryorrhea, lacrimation, urinary staining of the abdomen, motor activity decrease, motor activity increase, respiratory rate increase, faecal staining of the abdomen, alopecia, abdominal griping, and general poor condition. In-life signs of effect persisted throughout the study. A loss of weight or a failure to exhibit normal weight gain was noted in 4 of 7 surviving animals at 4.0 g/kg, 1 of 2 surviving animals at 8.0 g/kg, and all surviving animals, each at 5.6 g/kg and 11 .3 g/kg.

The LD50 was determined to be 5.3 g/kg, with 95 confidence limits of 4.1 to 6.5 g/kg.

Acute Dermal Toxicity

The acute dermal toxicity of the test material was determined in a study using New Zealand White rabbits. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study, animals were treated with a dose of 2.0, 4.0, 8.0 or 16.0 g/kg of test material under an occlusive patch for 24 hours. The rabbits were observed daily for 14 days for signs of toxicity, pharmacological effects and mortality. Body weights were recorded pre-test and in the survivors on day 14. Dermal reactions were scored at 24 hours and on days 3, 7 and 14 according to the Draize scoring system.

Under the conditions of the study all animals survived. Isolated instances of lethargy, ptosis, few faeces in pan, and yellow nasal discharge were sporadically noted in 3 animals. Eight out of thirteen animals appeared normal at all times. Lethargy was noted in two animals on day 0, but had cleared by day 1 and both animals then remained normal throughout the test. Slight weight loss was noted in the higher dose animals and dermal reactions were moderate to severe at the higher dose levels.

The acute dermal LD50 of the test material was therefore determined to be in excess of 8000 mg/kg.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute toxicity.