2-ethylhexyl 10-ethyl-4,4-dimethyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Preferred study for this SIDS endpoint. Composition/purity of the test substance not reported.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexyl 10-ethyl-4,4-dimethyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

EC Number:

260-829-0

EC Name:

2-ethylhexyl 10-ethyl-4,4-dimethyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

Cas Number:

57583-35-4

Molecular formula:

C22H44O4S2Sn

IUPAC Name:

2-ethylhexyl 2-{[({2-[(2-ethylhexyl)oxy]-2-oxoethyl}sulfanyl)dimethylstannyl]sulfanyl}acetate

Constituent 2

Reference substance name:

8-Oxa-3,5-dithia-4-stannatetradecanoic acid, 10-ethyl-4,4-dimethyl-7-oxo-,2-ethylhexyl ester

IUPAC Name:

8-Oxa-3,5-dithia-4-stannatetradecanoic acid, 10-ethyl-4,4-dimethyl-7-oxo-,2-ethylhexyl ester

Details on test material:

- Name of test material (as cited in study report): Dimethyltin bis (2-ethylhexylthioglycolate)
- Physical state: liquid
- Lot/batch No.: 1706-152
- Stability under test conditions: stable
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc, Indianapolis, IN, USA
- Age at study initiation: Naïve young adult male and female rats
- Weight at study initiation: 204-321 grams
- Fasting period before study: Overnight prior to dosing
- Housing: All animals were acclimated to the laboratory for at least five days before being used. Animals were housed in groups of five in wire mesh suspension cages and were supplied Teklad 4% Mouse/Rat Diet and tap water ad libitum during both acclimation and test periods except for withholding food over night prior to dosing. The animal room was maintained on a 12-hour light12-hour dark cycle and at a temperature of 64-79◦F and a relative humidity of 30-70%. There were no contaminants in either the feed or the water that were expected to affect the outcome of this study.
- Diet: ad libitum, Tekland 4% Mouse/Rat diet
- 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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: none

Details on oral exposure:

VEHICLE: not applicable

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

No. of animals per sex per dose:

10

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).

Results and discussion

Preliminary study:

not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 150 mg/kg bw

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 Dimethyltin bis (2-ethylhexylthioglycolate) 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, labored breathing, ataxia, fecal stains, urine stains, and an unkempt fur coat.

Gross pathology:

The gross necropsy findings in the animals that died during the observation period included lungs, liver, and 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

Applicant's summary and conclusion

Interpretation of results:

other: Classified as Category 3 according to EU criteria.

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 substance was evaluated in the OECD test guideline 401. 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.

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. Clinical signs noted during the observation period included varying degrees of depression, comatose, piloerection, eye squinting, hunched posture, labored breathing, ataxia, fecal 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 lungs, liver, and 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. The test substance was classified according to 40 CFR 156 as Toxicity Category III based on the response observed following oral administration.