Chlorotrioctylstannane

Endpoint summary

Description of key information

Oral
LD50> 4000 mg/kg rat (male/female), Günzel & Richter (1968)
LD50 28 641.6 mg/kg rat (male), Klimmer (1970)






  
  

Inhalation
LC50 250 mg/m³, rat (male/female), Sachsse & Ullmann (1974)







Intraperitoneal
LD50 325 mg/kg, rat (male/female), Günzel & Richter (1969)

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:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study does not specify any particular guidelines but was conducted to sound scientific principles; possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results. The study report is in German.

Qualifier:

no guideline followed

Principles of method if other than guideline:

The methodology used was similar to that outlined in OECD Guideline 401 (Acute Oral Toxicity). A limit dose of the test material was administered to male and female rats.

GLP compliance:

no

Remarks:

Study conducted in 1968, prior to introduction of GLP

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 90 to 120 g
- Acclimation period: 6 days

Route of administration:

oral: unspecified

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5 g CMC in 100 mL distilled water

Details on oral exposure:

- Formualtion: Emulsion
- Substance concentration: 40 g in 100 mL

Doses:

1 dose at 4.0 g/kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 12 days
- Necropsy of survivors performed: Yes. The following regions of the body were examined using the appropriate aids (e.g. magnifying glass, stereomicroscope, instruments): coat and skin, eyes, nose, mouth, ear, anus, preputial, vulva, subcutaneous tissue, stomach, pelvic cavity and peritoneum, oesophagus, small intestine, colon, mesenteric lymph nodes, liver, pancreas, spleen, kidneys, bladder, seminal vesicle, prostrate, testicle, epididymis, ovary, uterus, vagina*, chest cavity and pleura, heart, lung, trachea, thymus, cerebrum*, middle ear and application site.
Parameters marked with * only examined in cases of suspected pathology due to the intoxication or other special pathological-anatomical findings.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 other: g/kg

Based on:

test mat.

Mortality:

All ten animals survived the testing period.

Clinical signs:

other: In five animals (4 males/1 female) slight swelling of the spleen was observed. Five animals (1 male/4 females) appeared to be unaffected.

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of the study, the LD50 was determined to be > 4.0 g/kg in male and female rats.

Executive summary:

The potential of the test material to cause acute oral toxicity in the rat was investigated in accordance with sound scientific principles. The test material was administered to 5 male and 5 female rats as a limit dose in an emulsion, using a vehicle of carboxymethylcellulose (0.5 g CMC in 100 mL distilled water). The rats were treated with 4 g/kg of the test material.

Animals were observed for mortality and abnormal clinical signs for a period of 12 days after administration. All animals were weighed prior to treatment. All ten animals survived the test and were sacrificed at the end of the 12 day observation period.

In five animals (4 males/1 female), slight swelling of the spleen was observed whilst five animals (1 male/4 females) appeared to be unaffected.

Under the conditions of the study, the LD50 was determined to be > 4.0 g/kg in male and female rats.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study does not specify any particular guidelines but was conducted to sound scientific principles. The study report is in German.

Qualifier:

no guideline followed

Principles of method if other than guideline:

The methodology used was similar to that outlined in OECD Guideline 401 (Acute Oral Toxicity). Fasted rats were dosed once with the test material by gavage.

GLP compliance:

no

Remarks:

Study conducted in 1970, prior to introduction of GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 110 to 140 g
- Fasted before study: Yes (no data on fasting period)
- Housing: The animals were kept in containers in pairs
- Diet: ad libitum
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 40.0 mL/kg

DOSAGE PREPARATION: The test material was administered undiluted

Doses:

4.8, 5.76, 6.91, 10.0, 12.0, 14.4, 17.3, 24.9, 29.9, 36.0 and 40.0 mL/kg

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Daily
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs were monitored and gross pathological findings recorded

Statistics:

The LD50 and confidence limits were calculated using Probit analysis.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

27.54 mL/kg bw

Based on:

test mat.

95% CL:

23.89 - 31.77

Mortality:

At the highest dose of 40.0 mL/kg, all five rats died within the 14 day observation period. At 36.0 mL/kg, four out of the five rats which received this dose died. Three rats dosed at 29.9 mL/kg died, as did two rats that received a dose at 24.9 mL/kg. No further mortalities occurred with animals that were dosed at 17.3 mL/kg or lower.

Clinical signs:

other: Animals dosed at 14.4 mL/kg and higher were observed to demonstrate the usual, uncharacteristic poisoning symptoms of organo-tin compounds. Immobility, weariness and lack of interest in food were also observed. Rats dosed at 24.9 mL/kg rat and above were

Gross pathology:

The sections offered no abnormal findings.

Table 1: Dose Levels, Number of Test Animals and Percentage Mortality

Undiluted dose of test material (mL/kg)	Number of rats per dose	Number of mortalities	Percentage mortality (%)
40.0	5	5	100
36.0	5	4	80
29.9	5	3	60
24.9	5	2	40
17.3	5	0	0
14.4	5	0	0
12.0	5	0	0
10.0	5	0	0
6.91	5	0	0
5.76	5	0	0
4.80	5	0	0

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of the study, the LD50 was determined to be 27.54 mL/kg (28 641.6 mg/kg) with 95 % CL of 23.89 to 31.77 mL/kg in male rats.

Executive summary:

The potential of the test material to cause acute oral toxicity in the rat was investigated in a study that was performed using methodology similar to that outlined in the standardised guideline OECD 401.

This study was performed with Wistar male rats. The animals (5/dose level) received a single dose of the undiluted test material via gavage. The dose levels were as follows: 4.8, 5.76, 6.91, 10.0, 12.0, 14.4, 17.3, 24.9, 29.9, 36.0 and 40.0 mL/kg. The animals were observed for 14 days and sacrificed after this period.

Mortalities were observed at the dose of 24.9 mL/kg and above. Animals dosed at 14.4 mL/kg and higher were observed to demonstrate the usual, uncharacteristic poisoning symptoms of organo-tin compounds. Immobility, weariness and lack of interest in food were also observed.

Rats dosed at 24.9 mL/kg and above were reported after 2 to 6 day to show signs of respiratory and circulatory paralysis and mortality. The animals that survived recovered after 4 to 6 days. With regards to gross pathology, the sections offered no abnormal findings.

Under the conditions of the study, the LD50 was determined to be 27.54 mL/kg (28 641.6 mg/kg) with 95 % CL of 23.89 to 31.77 mL/kg in male rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 000 mg/kg bw

Quality of whole database:

Two key studies are available and both were awarded a reliability score of 2 in accordance with the principles for assessing data quality set forth by Klimisch et al. (1997). The studies were conducted prior to GLP and do not specify any particular guidelines; however, both studies were conducted to sound scientific principles. The quality of the database is therefore considered to be adequate.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported

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:

Male and female rats were exposed to the test material as an aerosol mist for 4 hours.

GLP compliance:

no

Remarks:

Study conducted in 1974, prior to inception of GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: 54 Tif. RAI (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bred in-house at the testing facility
- Age at study initiation: 7 to 8 weeks old
- Weight at study initiation: 175 to 185 g (male and female)
- Housing: The male and female rats were segregated (9 animals to a cage) during observation period

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 1 °C
- Humidity: Approximately 50 % (relative)

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The exposure system used in the test was that described by Sachsse et al., 1974 (Sachsse K, Ullmann L, Voss G & Hess R: Measurement of inhalation toxicity of aerosols in small laboratory animals. Proceedings of the European Society for the study of Drug Toxicity Volume XV, 239, 1974). The animals were not exposed until the aerosol was evenly dispersed throughout the chamber (15 minutes).
- Method of holding animals in test chamber: The test animals were kept in separate PVC tubes positioned radially around the exposure chamber.
- Source and rate of air: The test material was sprayed into the exposure chamber by means of a pressure nozzle. The liquid was injected by a motor-driven syringe at a rate of 0.9, 3 and 12 mL/hr into a stream of compressed air (2 atm.) flowing through a spray nozzle at a rate of 10 L/min. The aerosol mist thus produced was discharged into the exposure chamber.
- Method of particle size determination: Gravimetrically

TEST ATMOSPHERE
- Brief description of analytical method used: The particle-size distribution in the aerosol was determined gravimetrically on Selectron-Filters, pore size 0.2 µm every hour with the aid of a Cascade Impactor (C.T. Casella and Co., Ltd).
- Samples taken from breathing zone: Yes. The aerosol in the immediate vicinity of the animals was sampled on membrane filters, pore size 0.2 µm (Satorius) hourly after the beginning of the test.

VEHICLE
- Concentration of test material in vehicle: 92, 224 and 718 mg/m³

TEST ATMOSPHERE
- At 92 mg/m³ the mean particle size distribution was 44, 19, 21 and 16 % of the particles >7, 3 to 7, 1 to 3 and <1 µm, respectively.
- At 224 mg/m³ the mean particle size distribution was 59, 16, 20 and 5 % of the particles >7, 3 to 7, 1 to 3 and <1 µm, respectively.
- At 718 mg/m³ the mean particle size distribution was 55, 14, 24 and 7 % of the particles >7, 3 to 7, 1 to 3 and <1 µm, respectively.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

92, 224 and 718 mg/m²

No. of animals per sex per dose:

9 animals per sex per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Clinical signs were recorded throughout the 7 day observation period.
- Necropsy of survivors performed: Yes

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 250 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

All of the 18 rats (9 male and 9 female) that were exposed to the lowest concentration of test material, 92 mg/m³, survived.
Three male and three female rats died between 24 and 48 hours after being exposed to the median test material concentration of 224 mg/m³. A further male rat died prior to the end of the 7 day observation period.
At the highest concentration of test material, 718 mg/m³, all 9 male and all 9 female rats had died within 24 hours of exposure.

Clinical signs:

other: After the 4-hour exposure the rats in concentrations where mortalities occurred (224 mg/m³ and 718 mg/m³) showed signs of dyspnoea, lateral position, cyanosis, apathy and ruffled fur. These symptoms became more accentuated as test material concentration i

Gross pathology:

Haemorrhages in the lungs and congested organs were observed in the animals that died during the study. In those that were sacrificed after the 7 day observation period, no test material related gross organ changes were seen.

Table 1: Mortality Results

Concentration (mg/m³)	Exposure time (hours)	No. of Animals		Died within
				0 - 4 hours		24 hours		48 hours		7 days
		M	F	M	F	M	F	M	F	M	F
92	4	9	9	0	0	0	0	0	0	0	0
224	4	9	9	0	0	0	0	3	3	4	3
718	4	9	9	0	0	9	9	9	9	9	9

Interpretation of results:

other: Category 2 in accordance with EU criteria

Conclusions:

Under the conditions of the study, the LC50 of the test material was found to be 250 mg/m³ (0.25 mg/L) in male and female rats.

Executive summary:

The acute inhalation toxicity of the test material was investigated in a study which was conducted in accordance with generally accepted scientific principles.

During the study, the test material was administered to three separate groups of albino rats, each group comprised of 9 males and 9 females. The rats were exposed to the test material for a period of 4 hours, via nose-only exposure, as an aerosol mist at concentrations of 92, 224 and 718 mg/m³. The individual concentrations of the test material were gravimetrically determined.

The exposure system used in the study was that described by Sachsse et al. (1974); the test material was sprayed into the exposure chamber by means of a pressure nozzle. The liquid was injected by a motor-driven syringe at a rate of 0.9, 3 and 12 mL/hr into a stream of compressed air (2 atm.) flowing through a spray nozzle at a rate of 10 L/min. The aerosol mist thus produced was discharged into the exposure chamber.

All of the 18 rats (9 male and 9 female) that were exposed to the lowest concentration of test material, 92 mg/m³, survived. Three male and three female rats died between 24 and 48 hours after being exposed to the median test material concentration of 224 mg/m³. A further male rat died prior to the end of the 7 day observation period. At the highest concentration of test material, 718 mg/m³, all 9 male and all 9 female rats had died within 24 hours of exposure.

The rats in concentrations where mortalities occurred (224 mg/m³ and 718 mg/m³) showed signs of dyspnoea, lateral position, cyanosis, apathy and ruffled fur. These symptoms became more accentuated as test material concentration increased. The surviving animals had recovered within 4 to 5 days. 

Haemorrhages in the lungs and congested organs were observed in the animals that died during the study. In those that were sacrificed after the 7 day observation period, no test material related gross organ changes were seen.

Under the conditions of the study, the LC50 of the test material was found to be 250 mg/m³ (0.25 mg/L) in male and female rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

250 mg/m³ air

Quality of whole database:

Study conducted in 1974, prior to introduction of GLP. Study does not specify any particular guidelines but was conducted to sound scientific principles; possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results. The study was assigned a reliability score of 2 in accordance with the principles for assessing data quality set forth by Klimisch et al. (1997). The quality of the database is therefore considered to be good.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute Oral Toxicity

There are two studies provided to address this endpoint; both were considered to be key as both were awarded the same reliability score of 2 in accordance with the principles for assessing data quality set forth by Klimisch et al. (1997). Both studies were performed in accordance with sound scientific principles prior to the inception of GLP. 

In the first key study (Günzel & Richter, 1968), the potential of the test material to cause acute oral toxicity in the rat was investigated in accordance with sound scientific principles.

The test material was administered to 5 male and 5 female rats as a limit dose in an emulsion, using a vehicle of carboxymethylcellulose (0.5 g CMC in 100 mL distilled water). The rats were treated with 4 g/kg of the test material.

Animals were observed for mortality and abnormal clinical signs for a period of 12 days after administration. All animals were weighed prior to treatment. All ten animals survived the test and were sacrificed at the end of the 12 day observation period.

In five animals (4 males/1 female), slight swelling of the spleen was observed whilst five animals (1 male/4 females) appeared to be unaffected.

Under the conditions of the study, the LD50 was determined to be > 4.0 g/kg in male and female rats.

In the second key study (Klimmer, 1970), the potential of the test material to cause acute oral toxicity in the rat was investigated in a study that was performed using methodology similar to that outlined in the standardised guideline OECD 401.

This study was performed with Wistar male rats. The animals (5/dose level) received a single dose of the undiluted test material via gavage. The dose levels were as follows: 4.8, 5.76, 6.91, 10.0, 12.0, 14.4, 17.3, 24.9, 29.9, 36.0 and 40.0 mL/kg. The animals were observed for 14 days and sacrificed after this period.

Mortalities were observed at the dose of 24.9 mL/kg and above. Animals dosed at 14.4 mL/kg and higher were observed to demonstrate the usual, uncharacteristic poisoning symptoms of organo-tin compounds. Immobility, weariness and lack of interest in food were also observed.

Rats dosed at 24.9 mL/kg and above were reported after 2 to 6 day to show signs of respiratory and circulatory paralysis and mortality. The animals that survived recovered after 4 to 6 days. With regards to gross pathology, the sections offered no abnormal findings.

Under the conditions of the study, the LD50 was determined to be 27.54 mL/kg (28 641.6 mg/kg) with 95 % CL of 23.89 to 31.77 mL/kg in male rats.

Acute Inhalation Toxicity

The acute inhalation toxicity of the test material was investigated in a study which was conducted in accordance with generally accepted scientific principles.

During the study, the test material was administered to three separate groups of albino rats, each group comprised of 9 males and 9 females. The rats were exposed to the test material for a period of 4 hours, via nose-only exposure, as an aerosol mist at concentrations of 92, 224 and 718 mg/m³. The individual concentrations of the test material were gravimetrically determined.

The exposure system used in the study was that described by Sachsse et al. (1974); the test material was sprayed into the exposure chamber by means of a pressure nozzle. The liquid was injected by a motor-driven syringe at a rate of 0.9, 3 and 12 mL/hr into a stream of compressed air (2 atm.) flowing through a spray nozzle at a rate of 10 L/min. The aerosol mist thus produced was discharged into the exposure chamber.

All of the 18 rats (9 male and 9 female) that were exposed to the lowest concentration of test material, 92 mg/m³, survived. Three male and three female rats died between 24 and 48 hours after being exposed to the median test material concentration of 224 mg/m³. A further male rat died prior to the end of the 7 day observation period. At the highest concentration of test material, 718 mg/m³, all 9 male and all 9 female rats had died within 24 hours of exposure.

The rats in concentrations where mortalities occurred (224 mg/m³ and 718 mg/m³) showed signs of dyspnoea, lateral position, cyanosis, apathy and ruffled fur. These symptoms became more accentuated as test material concentration increased. The surviving animals had recovered within 4 to 5 days. 

Haemorrhages in the lungs and congested organs were observed in the animals that died during the study. In those that were sacrificed after the 7 day observation period, no test material related gross organ changes were seen.

Under the conditions of the study, the LC50 of the test material was found to be 250 mg/m³ (0.25 mg/L) in male and female rats.

Acute Toxicity: Other Routes

The potential of the test material to cause acute toxicity via the intraperitoneal route in the rat was investigated in accordance with sound scientific principles. The study was assigned a reliability score of 2 in accordance with the principles for assessing data quality set forth by Klimisch et al. (1997).

The test material was administered as an emulsion using a vehicle of carboxymethylcellulose (0.5 g CMC in 100 mL distilled water) to male and female Sprague Dawley rats. The test material was administered at dose levels of 90, 180, 250, 360, 500 and 720 mg/kg to 5 animals per sex per dose.

Mortality and abnormal clinical signs were recorded initially after administration of the test material and once daily, for a period of 7 days thereafter. All animals were weighed prior to treatment. A necroscopy was performed for all the animals that died during the study and for the surviving rats on completion of the test.

No mortality and clinical signs were observed at the lower dose levels of 90 mg/kg and 180mg/kg.

In the 250 mg/kg dose group, 1 female animal died 3 days after test material administration. In the 360 mg/kg dose group, 3 female animals died 1 day after application; the remaining two females and two males died on day 2 after test material administration. In the 500 mg/kg dose group, 4 males and 5 females died 1 day after dosing, with the remaining male animal dying on day 2. In the 720 mg/kg dose group, all animals died 1 day after test material administration. The only clinical sign recorded for animals in these dose groups was apathy.

Observations recorded at necropsy for animals dying during the study and those sacrificed at the end of the observation period included hydrops ascites, test material remained in abdomen, haemorrhagic erosion in stomach, intestines were stuck together and hydrothorax. A further sign observed in the sacrificed animals was swollen liver.

Under the conditions of the study, the LC50 was determined to be 325 mg/kg with 95 % CL of 271 to 390 mg/kg in male and female rats.

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 via the oral route.

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 inhalation as Category 2 (H330: Fatal if inhaled).