Tetrabutyltin

Endpoint summary

Description of key information

Mullaney (2004), the most recent study, is presented as the key study for acute oral toxicity as the reliability rating for this study is 1, according to the criteria of Klimisch et al. (1997).

The acute oral median lethal dose of the test material was estimated as being greater than 2500 mg/kg bodyweight.

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the rat following OECD Guideline 423.

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:

3 June 2004 to 28 June 2004

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 210 to 245 g
- Fasting period before study: overnight
- Housing: housed in groups of 3 in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: minimum of 5 days

Temperature: 19-25 ºC
Relative humidity: 30-70 %
Rate of air exchange: at least 15 changes per hour
Lighting: 12 hours of continuous light/darkness

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

- Justification for choice of vehicle: Test material did not dissolve/suspend in distilled water

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 females per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days with observations for deaths or overt signs of toxicity at 0.5, 1, 2 and 4 hours after dosing.
- Body weights were recorded prior to dosing and seven and fourteen days after treatment
- All animals were subject to gross pathological examination at the end of the study

Statistics:

Data evaluations included the relationship, if any, between the exposure of the animal to the test material and the incidence and severity of all abnormalities including behavioral and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects. Using the mortality data obtained, an estimate of the acute oral median lethal dose of the test material was made.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Mortality:

No deaths

Clinical signs:

other: There were no signs of systemic toxicity noted in animals treated at a dose level of 300 mg/kg. Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were hunched posture, lethargy, ataxia and pilo-erection. The animals appeare

Gross pathology:

No abonormalities detected at 300 mg/kg. Three of the five females had thickened non-gladular region of the stomach at the 2000 mg/kg dosage, no abnormalities were detected in the remaining animals .

Table 1: Summary of Clinical Observations

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During period After Dosing (Days)
		1/2	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	0	0	0	HO	HLAP	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-1 Female	0	0	0	0	H	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	0	0	0	HLA	HLAP	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Female	0	0	H	HLAP	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 Female	0	0	HA	HAP	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Female	0	0	HA	HAP	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	0 = No signs of systemic toxicity H = Hunched posture L = Lethargy A = Ataxia P = Pilo-erection

Only the results from the 2000 mg/kg group are shown as no effects were observed in the lower dosing group.

Table 2: Observations of Bodyweight:

At 300 mg/kg Dosage Level
	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
Female	Day 0	Day 7	Day 14	1	2
1 -0	210	227	246	17	19
1 -1	211	242	249	31	7
1 -3	220	259	271	39	12

At 2000 mg/kg Dosage Level
	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
Female	Day 0	Day 7	Day 14	1	2
2 -0	216	255	261	39	6
2-1	245	279	295	34	16
2-2	242	269	280	27	11
3-0	236	256	264	20	8
3-1	230	270	281	40	11
3-2	213	227	236	14	9

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

The acute oral median lethal dose of the test material was estimated as being greater than 2500 mg/kg bodyweight.

Executive summary:

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the rat following OECD Guideline 423. Groups of three females were dosed with 300 mg/kg bw and 2000 mg/kg bw (two groups).

No deaths were observed. Clinical observations were only seen in animals in the 2000 mg/kg bw group but animals appeared normal after one or two days. All animals gained bodyweight over the test peirod and the non-glandular region of the stomach appeared thickened at necroscopy of three animals treated with 2000 mg/kg.

The LD50 of the test material was estimated to be >2500 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 500 mg/kg bw

Quality of whole database:

Four studies are available to address this endpoint; the key study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997). The quality of the database id therefore considered to be high.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral route

In the key study, tetrabutylstannane [CAS # 1461-25-2] was examined for acute oral toxicity.

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the rat following OECD Guideline 423. Groups of three females were dosed with 300 mg/kg bw and 2000 mg/kg bw.

No deaths were observed. Clinical observations were only seen in animals in the 2000 mg/kg bw group but animals appeared normal after one or two days. All animals gained bodyweight over the test period and the non-glandular region of the stomach appeared thickened at necroscopy of three animals treated with 2000 mg/kg.

The LD50 of the test material was estimated to be >2500 mg/kg bw.

The following supporting studies are also available for information purposes only:

- In a Günzel (1969) study the LD50 was determined to be >4000 mg/kg.

- In the Calley (1967) paper tetrabutyltin exhibited a very low order of toxicity. The LD50 was determined to be 6000 ± 500 mg/kg.

- In the Schafer & Bowles (1985) paper the LDfr of tetrabutyltin for deer mice was equal to 913 mg/kg/day.

Dermal and Inhalation routes

No data has been provided for the dermal and inhalation routes as the oral route has been identified as more appropriate for exposure, in accordance with EC Regulation 1907/2006, Annex VIII, Column 2, point 8.5.

Also, no other routes need to be considered as the registration substance is a transported isolated intermediate and will therefore be used under strictly controlled conditions in line with article 18, 4.(b) of the REACH regulation EC/1907/2006 which states "procedural and control technologies shall be used that minimise emission and any resulting exposure", and therefore no exposure is expected. A CSR is not needed for this substance and DNEL values do not need to be calculated.

Justification for classification or non-classification

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