Bis(dodecylthio)dimethylstannane

Endpoint summary

Description of key information

Read-across to structurally similar substance DMTE (Dimethyltin bis (2-ethylhexyl thioglycolate) CAS 57583-35-4)

Acute oral LD50 1150 mg/kg bw in rats (OECD 401)

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:

Not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Restriction: Composition/purity of the test material not reported.

Reason / purpose for cross-reference:

other: read-across target

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: naïve young adult male and female rats
- Weight at study initiation: 204 - 321 g
- Fasting period before study: Overnight prior to dosing
- Housing: animals were housed in groups of five in wire mesh suspension cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least five days


ENVIRONMENTAL CONDITIONS
- Temperature: 64 - 79°F
- Humidity (%): 30 - 70%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle


IN-LIFE DATES: From: July 30, 1996 To: August 22 1996

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.50 g/kg


DOSAGE PREPARATION (if unusual): The test material was administered undiluted using bulk density to determine the dose volume.

Doses:

625, 880, 1250, and 2500 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed frequently for gross signs of systemic toxicity and mortality on the day of test material administration, and at least twice daily thereafter for a total of 14 days. Body weights were measured for each animal on the day of dosing, on Day 7 of the observation period, and at the time of necropsy either at the end of the fourteen day observation period or following the death of any animal.
- Necropsy of survivors performed: yes

Statistics:

The LD50 and 95 % confidence intervals were calculated by the method of Litchfield and Wilcoxon (1949).

Preliminary study:

not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 150 mg/kg bw

Based on:

test mat.

95% CL:

>= 850 - <= 1 550

Mortality:

Animals in the 880 and 1250 mg/kg bw groups died within 48 hours of dosing and all animals in the 2500 mg/kg bw group died within 24 hours of dosing.

Males:
2.50 g/kg- all animals dead at day 1
1.25 g/kg- one animal dead
0.88 g/kg- no animals died
0.625 g/kg- no animals died

Females:
2.50 g/kg- all animals dead at day 1
1.25 g/kg- 4 animals died on day1
0.88 g/kg- two animals died on day 1 and a total of 4 died by day 2.
0.625 g/kg- no animals died

Based on the cumulative mortality observed during the 14 day observation period following a single oral dose of undiluted test material the acute oral LD50 value was calculated to be 1.15 g/kg with 95% Confidence Intervals of 0.85 g/kg and 1.55 g/kg.

Clinical signs:

other: Clinical signs noted during the observation period included varying degrees of depression, comatose, piloerection, eye squinting, hunched posture, laboured breathing, ataxia, faecal stains, urine stains, and an unkempt fur coat.

Gross pathology:

The gross necropsy findings in the animals that died during the observation period included spleen mottled, lungs haemorrhagic, lungs reddened, liver pale and mottled, liver exhibits area of pale blanching, spleen darkened, kidneys pale and/or congested, left kidney enlarged, stomach distended with gas, intestines reddened, intestines contain paste-like material, urinary bladder contains red or yellowish-red fluid and external staining. The only necropsy findings noted in animals which survived the 14 day observation period was tip of spleen darkened in one animal

Interpretation of results:

other: EU Category 4 (H302: Harmful if swallowed).

Conclusions:

Based on the cumulative mortality observed during the 14-day observation period following a single oral gavage dose of undiluted test substance the acute oral LD50 value was calculated to be 1150 mg/kg.

Executive summary:

The acute oral toxicity of undiluted test material was evaluated in accordance with the standardised guideline OECD 401, under GLP conditions.

During the study, the test material was administered undiluted to groups of five male and five female Sprague-Dawley rats at a dose level of 625, 880, 1250, and 2500 mg/kg. Following a single oral administration, the animals were observed for 14 days.

Clinical signs noted during the observation period included varying degrees of depression, comatose, piloerection, eye squinting, hunched posture, laboured breathing, ataxia, faecal stains, urine stains, and an unkempt fur coat. With exception of one animal, all surviving animals exhibited body weight gain at day 14. Gross necropsy findings for animals that died during the observation period included spleen - mottled, lungs - hemorrhagic, lungs - reddened, liver - pale and mottled, liver - exhibits area of pale blanching, spleen - darkened, kidneys - pale and/or congested, left kidney enlarged, stomach - distended with gas, intestines- reddened, intestines - contain paste-like material, urinary bladder - contains red or yellowish-red fluid and external staining. The only necropsy findings noted in animals which survived the 14 day observation period was tip of spleen darkened in one animal.

Based on the mortality observed, the acute oral LD50 value was calculated to be 1150 mg/kg with the 95% Confidence Limits of 850 and 1550 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 150 mg/kg bw

Quality of whole database:

Two studies are available to address this endpoint; both were conducted in accordance with standardised guidelines. The quality of the database is therefore considered to be good.

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

Read-across to structurally similar substance DMTE (Dimethyltin bis (2-ethylhexyl thioglycolate) CAS 57583 -35 -4)

- Harrod (1996), key study

The acute oral toxicity of undiluted test material was evaluated in accordance with the standardised guideline OECD 401, under GLP conditions. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study, the test material was administered undiluted to groups of five male and five female Sprague-Dawley rats at a dose level of 625, 880, 1250, and 2500 mg/kg. Following a single oral administration, the animals were observed for 14 days.

Clinical signs noted during the observation period included varying degrees of depression, comatose, piloerection, eye squinting, hunched posture, laboured breathing, ataxia, faecal stains, urine stains, and an unkempt fur coat. With exception of one animal, all surviving animals exhibited body weight gain at day 14. Gross necropsy findings for animals that died during the observation period included spleen - mottled, lungs - hemorrhagic, lungs - reddened, liver - pale and mottled, liver - exhibits area of pale blanching, spleen - darkened, kidneys - pale and/or congested, left kidney enlarged, stomach - distended with gas, intestines- reddened, intestines - contain paste-like material, urinary bladder - contains red or yellowish-red fluid and external staining. The only necropsy findings noted in animals which survived the 14 day observation period was tip of spleen darkened in one animal.

Based on the mortality observed, the acute oral LD50 value was calculated to be 1150 mg/kg with the 95% Confidence Limits of 850 and 1550 mg/kg.

 

- Hughes (1984), supporting study

The acute oral toxicity of the test material was evaluated in compliance to the conditions specified in the Regulation for Enforecement of the Federal Hazardous Substances Act (16 CFR 1500).

The test material was administered undiluted at dosages of 464, 1000, 2150, 4640 and 10000 mg/kg to five groups of five male Sprague-Dawley derived, albino rats. Animlas were observed for gross signs of toxicity and death for 14 days. At the end of the observation period, survivors were weighed, killed and subjected to a gross necropsy.

Deaths occurred between days one and three of the observation period.

Clinical signs of toxicity observed included diarrhoea, hunched posture, hyperactivity, depression, piloerection, ataxia, and emaciation. Gross necropsy results for animals that died during observation included  moderate autolysis, mottled livers, thin-walled stomachs containing a  green-yellow material, irritated intestines, pale and congested kidneys, darkened and mottled lungs, and staining around the mouth. Gross necropsies of surviving animals at the end of the study revealed no relevant findings.

Cumulative mortality (total number of deaths/total number dosed), by dose level: 464 mg/kg: 0/5 1000 mg/kg: 0/5 2150 mg/kg: 4/5 (days 1, 3) 4640 mg/kg: 5/5 (day 1) 10,000 mg/kg: 5/5 (day 1).

Under the conditions of the study, the acute oral LD50 value was found to be 1710 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 requires classification with respect to acute toxicity via the oral route as Category 4 (H302: Harmful if swallowed).