Bis(neodecanoyloxy)dioctylstannane

Endpoint summary

Description of key information

one Guideline study on acute toxicity by the oral route available

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July - August 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
16JSVA015
- Expiration date of the lot/batch:
14. September 2018
- Purity test date:
not state

RADIOLABELLING INFORMATION (if applicable)
not applicable

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Room Temperature: (20 ± 5°C), keep container tightly closed, store under inert gas
- Stability under test conditions:
assumed stable


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
none

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dobrá Voda, Slovak Republic
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 190 - 200 g
- Fasting period before study: over night
- Housing: in gorups of 3
- Diet (e.g. ad libitum): The laboratory food ssniff (Spezialdiäten GmbH, Germany) was
offered at recommended doses each day approximately at the same
time.
- Water (e.g. ad libitum): Supply of
drinking was unlimited.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.7 ± 0.7° C,
- Humidity (%): 55.1 ± 3.1 %.
- Air changes (per hr): central air conditioning, no value given
- Photoperiod (hrs dark / hrs light): 12-hour light /12-hour dark

IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: not stated
- Amount of vehicle (if gavage): not stated
- Justification for choice of vehicle: Olive oil is a standard vehicle according to OECD TG 423
- Lot/batch no. (if required): L61067
- Purity: not applicable

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

DOSAGE PREPARATION (if unusual): not applicable

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Available information indicated that the test item is likely to be non-toxic; therefore, a limit dose of 2000 mg/kg body weight was used as a starting dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days ´
- Frequency of observations:
Animals were observed individually immediately after administration of the test item and 0.5, 1, 2, and 4 hours later. Each animal was inspected daily for the next 14 days.
Observations included: changes in skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity, and behavioural pattern. Particular attention was given to potential neurologic endpoints such as tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma
and weighing:
Individual weights of animals were measured immediately prior to test item was administered and
weekly thereafter. Weight differences after first and second weeks after administration were
calculated and recorded
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Statistics:

none applied

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Five of six females survived the limit dose of 2000 mg/kg body weight.
Female No 6 was
lethargic from Day 5 to Day 12 and died on Day 13 post-treatment.

Clinical signs:

other: Lethargy and sleepiness between 0.5 and 4 hours after treatment was observed in all animals. These observations in animals No 1, 2 and 3 were noticed on Day 1 post-treatment too. Female No 6 was lethargic from Day 5 to Day 12 and died on Day 13 post-treat

Gross pathology:

All animals were necropsied. During necropsy, no macroscopic findings were observed in females
No 1-5. Adrenomegaly, petechial haemorrhages on the gastric mucosa in female No 6 were registered.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item Bis(neodecanoyloxy)dioctylstannane is greater than 2000 mg/kg body
weight after single oral administration to Wistar rats.

Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item

Bis(neodecanoyloxy)dioctylstannane when administered as a single oral dose to Wistar rats. The

procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used.

Available information indicated that the test item is likely to be non-toxic; therefore, a limit dose of

2000 mg/kg body weight was used as a starting dose.

One group of 3 females was dosed. Due to lethargy of all animals, next step proceeded after 7 days.

Test item-related mortality was not observed during 7 days; another 3 females were treated with the

same dose.

Five females survived the limit dose. One female died on Day13 post-treatment. Lethargy and

sleepiness between 0.5 and 4 hours after treatment was observed in all animals. These observations

in animals No 1, 2 and 3 were noticed on Day 1 post-treatment too. From Day 5 to Day 12 female No

6 was lethargic and this animal died on Day 13 post-treatment.

During post-treatment time, the rest animals displayed neither signs of intoxication, change of health,

nor any other adverse reaction. Stagnation of the body weight in 4 animals, slight increase of the body

weight in 1 animal and decrease of the body weight in 1 animal between the first and second week

were observed.

During necropsy, no macroscopic findings were observed in 5 females. In died female adrenomegaly,

petechial haemorrhages on the gastric mucosa were registered.

The LD50 of the test item Bis(neodecanoyloxy)dioctylstannane is greater than 2000 mg/kg body

weight after single oral administration to Wistar rats.

Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD

Guideline 423 it can be concluded that the test item Bis(neodecanoyloxy)dioctylstannane is classified

in GHS Category 5 (> 2000 – 5000) with a LD50 cut off value equal to 2500 mg/kg body weight, after

single oral administration to Wistar rats.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 March 2013 to 11 April 2013

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

(On one occasion the relative humidity was recorded below the protocol range with a recording of 44 %. This study deviation neither affected the overall interpretation of study findings nor compromised the integrity of the study.)

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

(On one occasion the relative humidity was recorded below the protocol range with a recording of 44 %. This study deviation neither affected the overall interpretation of study findings nor compromised the integrity of the study.)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: HsdHan™:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Limited, Bicester, UK
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 179 - 196 g
- Fasting period before study: animals were fasted from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing
- Housing: animals were housed in groups of up to five during the acclimatisation period in cages that conform to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989). From the day prior to dosing (Day –1), the rats were housed in groups of three in similar cages.
- Diet: SQC(E) Rat and Mouse Maintenance Diet No 1, from Special Diets Services Ltd, Witham, UK, ad libitum
- Water: mains water, ad libitum
- Acclimation period: 7 - 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 45 - 65 %
- Air changes (per hr): 15 - 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

In order to enrich both the environment and the welfare of the animals, they were provided with wooden Aspen chew blocks, nesting materials and rodent retreats. Environmental enrichment materials were removed during the period of fasting from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- Individual doses
Individual doses (mL) were calculated using the fasted body weights of the rats on the morning of dosing (Day 1) and the specific gravity for the neat material.

- Dose volume
The test material was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.
During the study, the animals were treated with a dose volume of 1.87 mL/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 animals initially then a further 3 animals once the survival of the previously treated animals was confirmed.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: All animals were examined at the beginning and end of the working day throughout the acclimatisation and study periods to ensure they were in good health. Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded immediately post dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period.
- Frequency of weighing: Individual body weights were recorded on Day 1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes. A full macroscopic necropsy was performed and all lesions were recorded. The necropsy procedure included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines. No tissue preservation or histopathological assessment of tissues was undertaken.

- Other examinations performed: yes (gene analysis)
Blood samples for gene analysis (0.5 mL nominal) were taken from all animals on Day -1 and Day 1 (24 hours after dosing).
Samples were taken from jugular vein into into trisodium citrate anticoagulant. Samples were mixed gently by hand then continuously for at least 2 minutes on automatic mixer. Once mixed the 3 samples from each group, at each timepoint, were pooled together and placed in a cooled Kryorack. The resultant plasma was separated, transferred to uniquely labelled clear polypropylene tubes and frozen immediately at <–50 °C.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the study.

Clinical signs:

other: No clinical signs were seen during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Gene analysis findings were not reported.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the acute median dose level of the test material was found to exceed 2000 mg/kg.

Executive summary:

The acute oral toxicity of the test material was investigated in a GLP study which was conducted in accordance with the standardised guidelines OECD 423 and EU Method B.1 tris, following the Acute Toxic Class method.

During the study two groups of 3 female rats were sequentially treated with test material at dose level of 2000 mg/kg bw. The test material was administered orally, by gavage, without dilution. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths and no signs of toxicity. All rats achieved body weight gains during the first and second weeks of the study. No abnormalities were noted at necropsy. Therefore, under the conditions of the study, the acute median dose level of the test material was found to exceed 2000 mg/kg.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not reported

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The data are taken from an abstract of a journal with nlimited information regarding the methodology; it is not possible to assess the accuracy of the information.

Principles of method if other than guideline:

Limited information is mentioned in the literature regarding methods.

GLP compliance:

not specified

Test type:

other: unknown

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

- Fasting before administration.

Route of administration:

oral: gavage

Vehicle:

not specified

Doses:

- Single dose.

Details on study design:

- Observed for 21 days.

Sex:

male

Dose descriptor:

LD50

Effect level:

6 450 mg/kg bw

Based on:

test mat.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material was reported to have an LD50 of 6450 mg/kg which is above the limits of classification.

Executive summary:

The oral toxicity of the test material was determined to be LD₅₀ 6450 mg/kg. Male rats were exposed to a single dose of the test material and observed for 21 days. There is limited information available as the study is written in German. The LD₅₀ is above the limit of classification and so the substance is "not classified" according to Regulation 1272/2008.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

other: Handbook data

Adequacy of study:

supporting study

Study period:

not reported

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The data are taken from an abstract of an handbook with no reported methodology; it is not possible to assess the accuracy of the information.

Principles of method if other than guideline:

The value is taken from a secondary source citing Schering, which is unpublished. Test guidelines or methods are not mentioned in the literature.

GLP compliance:

not specified

Test type:

other: Not reported

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 4 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test material was reported to be > 4000 mg/kg, which is above the limit of classification.

Executive summary:

The oral toxicity of the test material is reported from an unpublished secondary source. The LD₅₀ in rats is recorded as > 4000 mg/kg. No information is available regarding the method used, so it is not possible to assess the accuracy of the data. The reported LD₅₀ is above the limit of classification and so the substance is "not classified" according to Regulation 1272/2008.

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

other: Handbook data

Adequacy of study:

supporting study

Study period:

Not reported

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The data are taken from an abstract of a handbook with no reported methodology; it is not possible to assess the accuracy of the information.

Principles of method if other than guideline:

The value is taken from a secondary source citing Barth et al (1964). Test guidelines or methods are not mentioned in the literature.

GLP compliance:

not specified

Test type:

other: not reported

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

6 000 - 6 450 mg/kg bw

Based on:

test mat.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material was reported to have an LD50 of between 6000-6450 mg/kg which is above the limits of classification.

Executive summary:

The acute oral toxicity of the test material in rats was recorded as LD₅₀ 6000-6450 mg/kg. The data have been reported as a secondary source and information regarding the methodology is not available. It is not possible to assess the accuracy of the data. The reported LD₅₀ is above the limit of classification and so the substance is "not classified" according to Regulation 1272/2008.

Reference 6

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not reported

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The data is taken from an abstract of an internet source with no reported methodology; it is not possible to assess the accuracy of the information.

Principles of method if other than guideline:

Test guidelines or methods are not mentioned in the literature.

GLP compliance:

not specified

Test type:

other: not reported

Species:

rat

Strain:

not specified

Sex:

male

Route of administration:

oral: unspecified

Vehicle:

not specified

Sex:

male

Dose descriptor:

LD50

Effect level:

6 450 mg/kg bw

Based on:

test mat.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material was reported to have an LD50 of 6450 mg/kg which is above the limits of classification.

Executive summary:

The test material is recorded to have an LD₅₀ of 6450 mg/kg, a cited in the literature. There is no information available regarding the method used or what is actually the original source, so it is not possible to assess the accuracy of the data. The recorded LD₅₀ is above the limit of classification and so the substance is "not classified" according to Regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 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:

key study

Study period:

2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

tudy 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:

yes

Remarks:

additional blood sampling for determination of absorption

Principles of method if other than guideline:

Blood samples for toxicokinetics (0.5 mL nominal) were taken from all animals on Day 1 at 3 and 24 hours after dosing.

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 h

Doses:

2000 mg / kg bw

No. of animals per sex per dose:

5 male and female

Control animals:

not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Clinical signs following treatment

Dose level: 2000 mg/kg

Clinical sign	Animal number and sex
	29M	30M	31M	32M	33M
No observations	ü	ü	ü	ü	ü

 

Clinical sign	Animal number and sex
	34F	35F	36F	37F	38F
No observations	ü	ü	ü	ü	ü

 

Dermal reactions

Dose level: 2000 mg/kg

Day	Dermal reaction	Animal number and sex
		29M	30M	31M	32M	33M
2 to 15	Erythema Oedema Other	0 0 -	0 0 -	0 0 -	0 0 -	0 0 -

 

Day	Dermal reaction	Animal number and sex
		34F	35F	36F	37F	38F
2 to 15	Erythema Oedema Other	0 0 -	0 0 -	0 0 -	0 0 -	0 0 -

Individual body weights and weekly increments

Dose level (mg/kg)	Animal number and sex	Body weight (g) at:					Increment (g)
		Day -1	Day 1	Day 4	Day 8	Day 15	Day 1 to 8	Day 8 to 15
2000	29M	257	266	273	279	308	13	29
	30M	260	269	269	279	294	10	15
	31M	279	286	284	289	307	3	18
	32M	268	271	272	281	294	10	13
	33M	269	281	283	293	306	12	13
2000	34F	181	188	195	189	203	1	14
	35F	201	207	203	213	216	6	3
	36F	180	183	179	190	202	7	12
	37F	178	186	178	191	200	5	9
	38F	195	202	202	210	222	8	12

Necropsy findings

Dose level:2000 mg/kg

Animal number and sex	Time and manner of death (Day)	Necropsy comments
29M	15T	No macroscopic changes
30M	15T	No macroscopic changes
31M	15T	No macroscopic changes
32M	15T	No macroscopic changes
33M	15T	No macroscopic changes
34F	15T	No macroscopic changes
35F	15T	No macroscopic changes
36F	15T	Liver: raised area, right median lobe - 9 mm diameter           raised area protruding into thoracic cavity - moderate #
37F	15T	No macroscopic changes
38F	15T	No macroscopic changes

 

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute median lethal dermal dose of TIB KAT 216 to rats was found to exceed 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 001 ng/kg bw

Justification for classification or non-classification

The available information is conclusive but not sufficient for classification.