Diisooctyl 2,2'-[(dioctylstannylene)bis(thio)]diacetate

Endpoint summary

Description of key information

ORAL TOXICITY

Auletta (1984)

Under the conditions of this study the acute oral LD50 of the test material is 1800 mg/kg with 95 % confidence interval of 1040 to 2560 mg/kg.

INHALATION TOXICITY

Under the conditions of the study following a 7 hour treatment to a mixture of 80% registered substance (DOTI) and 20% MOTI (CAS 26401-86-5), no mortality occurred. In some animals, a temporary conjunctivitis was observed during the post-treatment period.

DERMAL TOXICITY

Read-across to structurally similar substance (DOTE) (CAS No 15571 -58 -1)

Under the conditions of this study, the acute dermal toxicity LD50 (rat) of the test material was >2000 mg/kg bw(both sexes).

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:

03 April 1984 to 04 May 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: FIFRA (Federal Insecticide, Fungicide, and Rodenticide Act): Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals

Version / remarks:

Office of Pesticide Programs, U.S. Environmental Protection Agency, Office of Pesticides and Toxic Substances, October, 1982; Section 81-1, Acute Oral Toxicity Study

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: TSCA (Toxic Substances Control Act): Health Effects Test Guidelines; Office of Toxic Substances; Office of Pesticides and Toxic Substances; United States Environmental Protection Agency

Version / remarks:

August 1982, Acute Exposure, Oral Toxicity.

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Density: 1.087 g/mL

Species:

rat

Strain:

Sprague-Dawley

Remarks:

CDR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 to 12 weeks
- Weight at study initiation: males: 236 to 275 g, females: 219 to 244 g
- Fasting period before study: Animals were fasted overnight (for approximately 18 hours) prior to treatment.
- Housing: Group-housed (six/cage) during equilibration. Individually housed during study, in suspended, stainless steel cages with wire mesh bottoms
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature: 67 to 76 °F
- Humidity: 30 to 70 %
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

600, 800, 1200, 1700 and 2500 mg/kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 21 days
- Frequency of observations and weighing: viability checks were performed twice daily. Observations of pharmacologic and toxicological signs were performed approximately 1, 2, and 4 hours after dosing and daily thereafter for twenty-one days. Body weights were measured pre-fast and on days 7, 14 and 21.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 800 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 040 - <= 2 560

Mortality:

At 600 mg/kg 1 animal died, at 800 mg/kg 3 animals died, at 1200 mg/kg 2 animals died, at 1700 mg/kg 6 animals dies and at 2500 mg/kg 5 animals died. Table 1 shows mortalities during the study.

Clinical signs:

other: Several abnormalities were seen on the day of dosing and for several days thereafter. Signs seen in most or all groups included ataxia, hypo activity, red or clear oral, nasal or ocular discharge, wet rales, urinary and/or faecal staining, soft stool, unt

Gross pathology:

Post-mortem examinations of animals found dead revealed a variety of changes, primarily in the lungs (discolouration), adrenals (reddened), gastrointestinal tract (stomach and intestinal walls - discoloured, containing red or black fluid) and testes (found in body cavity). These changes appeared to represent post-mortem autolysis, ante mortem stress and/or an irritant or corrosive effect of the test material on the gastrointestinal mucosa. One female in the 800 mg/kg group had red fluid in the urinary bladder. Changes seen in animals killed after 21 days were generally similar to those seen in control animals killed by carbon dioxide inhalation, or were considered to represent normal physiological variation.

Table 1: Mortalities during the study

Dose level (mg/kg)	Mortality
	Male	Female	Total	Time of death
600	1/5	0/5	1/10	Day 4
800	0/5	3/5	3/10	Days 2 to 5
1200	0/5	2/5	2/10	Days 2 to 3
1700	2/5	4/5	6/10	Days 2 to 4
2500	1/5	4/5	5/10	Days 2 to 7

Interpretation of results:

other: Acute oral (Category 4) in accordance with EU criteria

Conclusions:

Under the conditions of this study the acute oral LD50 of the test material is 1800 mg/kg with 95 % confidence interval of 1040 to 2560 mg/kg.

Executive summary:

The acute oral toxicity of the test material was investigated in accordance with FIFRA and TSCA guidelines using male and female Sprague-Dawley derived rats.

Five animals per sex were dosed at the following concentrations: 600, 800, 1200, 1700 and 2500 mg/kg and then observed for 21 days. All animals were subjected to gross post-mortem examinations when they died during the study or when the study finished.

At 600 mg/kg 1 animal died, at 800 mg/kg 3 animals died, at 1200 mg/kg 2 animals died, at 1700 mg/kg 6 animals died and at 2500 mg/kg 5 animals died.

Signs seen in most or all groups included ataxia, hypo activity, red or clear oral, nasal or ocular discharge, wet rales, urinary and/or faecal staining, soft stool, unthrifty coat, hypopnea, hypothermia, food consumption decrease, emaciation and partially closed eyes. By Day 7 the incidence of abnormalities had subsided in animals dosed at the 600, 800, 1200 and 1700 mg/kg levels, although one animal in the 800 mg/kg dose group exhibited an unthrifty coat, emaciation, hypo activity and decreased food consumption for most of the post-dose period. Some survivors at the 2500 mg/kg level exhibited unthrifty coats, alopecia, abdominal griping, emaciation, hypo activity and food consumption decrease for much of the post-dose period. Most animals were free of significant abnormalities by study termination (Day 21), however. Animals that died exhibited substantial ante mortem weight losses, and several surviving animals exhibited weight losses at Day 7. However, all survivors gained weight between Days 7 and 21.

Post-mortem examinations of animals found dead revealed a variety of changes, primarily in the lungs (discolouration), adrenals (reddened), gastrointestinal tract (stomach and intestinal walls - discoloured, containing red or black fluid) and testes (found in body cavity).

Under the conditions of this study the acute oral LD50 of the test material is 1800 mg/kg with 95 % confidence interval of 1040 to 2560 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 800 mg/kg bw

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:

09 August 1977 to 22 August 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

fixed concentration procedure

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In house
- Weight at study initiation: 150 to 168 g (M) and 133 to 147 g (F)
- Fasting period before study: 16 hours before treatment
- Housing: Macrolon Type II cages, 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 to 23°C
- Humidity: 49 to 65 %
- Photoperiod: 12 hrs dark / 12 hrs light

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

- The dynamically operated inhalation system consists of the generator unit for generating the inhaled air saturated with test material vapour and the exposure unit for the absorption and exposure of the test animals.
- The compressed air of the household network was passed through two parallel special gas washed bottles after passing through a fine dust filter, pressure stabiliser, volume regulator and volume meter. These washed bottles were each equipped with G1 glass frits.
- The filling quantity of the special gas washed bottles over the frit was kept constant by means of a level control. The washed bottles as well as a glass tube coil for temperature pre-stabilisation of the air were in a temperature-controlled water bath in which had a temperature of 20 ± 0.2°C was maintained.
- After leaving the gas washed bottles, the steam was now saturated with test material steam. Air passed into two tube-shaped inhalation chambers.
- These inhalation chambers consisted of a glass tube (diameter 150 mm, length 1000 mm) with detachable end pieces and an insertable grid frame, which subdivided the upper part of the glass tube into 10 segments (1 animal per segment). The grid frame was resting on a half-blade made of stainless steel for excrement recording. The air / steam mixture emanating from the chambers was passed into the flue.
- The temperature and relative humidity in the chambers were monitored.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

7 h

Concentrations:

- Air was saturated with the test material

No. of animals per sex per dose:

10 animals per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- A relative humidity of 13% and a temperature of 20 to 21°C were measured in the chambers.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Remarks on result:

other: When the air was saturated with the test material for a 7 hour treatment period, no mortality occurred.

Mortality:

No deaths occurred during the exposure or observation period.

Clinical signs:

other: In the 14-day observation period some animals showed conjunctivitis

Body weight:

- Group 1: Male mean body weight increased from 164 to 278 g during the study and female mean bodyweight increased from 139 to 199 g.
- Group 2: Male mean body weight increased from 158 to 275 g during the study and female mean bodyweight increased from 140 to 200 g.

Gross pathology:

All male and female animals were suspected of slight thymus enlargement, which however can neither be quantified nor interpreted as a test material defect, since no control group was carried in the experiment.

Interpretation of results:

study cannot be used for classification

Conclusions:

Under the conditions of this study following a 7 hour treatment, no mortality occurred. In some animals, a temporary conjunctivitis was observed during the post-treatment period.

Executive summary:

The acute inhalation toxicity of the test material was investigated in a study using male and female Wistar rats.

Animals whole bodies were continually exposed to the test material at steam saturated in air for a period of 7 hours in an inhalation chamber. They were observed during this treatment time and for 14 days afterwards.

No mortalities occurred during the treatment or observation periods. Some of the animals showed conjunctivitis during 14-day observation period. Body weights increased during the observation period.

Following the 14 days observation period the animals were sacrificed and necropsy performed. All animals were suspected of slight thymus enlargement, which however can neither be quantified nor interpreted as a test material defect, since no control group was carried in the experiment.

Under the conditions of this study following a 7 hour treatment, no mortality occurred. In some animals, a temporary conjunctivitis was observed during the post-treatment period.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

other: read-across target

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif:RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:no data
- Age at study initiation:no data
- Weight at study initiation: 221-261 g
- Fasting period before study: no data
- Housing: individually
- Diet (e.g. ad libitum): not precised, ad libitum
- Water (e.g. ad libitum): not precised, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/day

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Remarks:

none

Details on dermal exposure:

The dose volume applied was 2 mL/kg bw.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

10 (5 males, 5 females)

Control animals:

no

Details on study design:

Prior to exposure, an area on the back of each test animal (~ >=10% of body surface) was shaved.
After 24 hours, the exposed skin was cleaned and the area of application was observed for 14 days.
Body weights were recorded on days 0 (prior to dosing), 7, and 14. Animals were observed once or twice daily for clinical signs of toxicity and mortality over the exposure period. Animals were sacrificed and necropsied at death or at the end of the exposure period, whichever came first.

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality

Mortality:

No mortality was observed over the course of this study. 
Due to the lack of observed mortality, the 14-day acute dermal LD50s of the test substance were reported as:
LD50 (males) = >2000 mg/kg bw
LD50 (females) = >2000 mg/kg bw
LD50 (both sexes) = >2000 mg/kg bw

Clinical signs:

other: On the day of application, all test animals (both sexes) exhibited slight piloerection. On days 1 and 2 post-application, all animals (both sexes) exhibited erythema at the application site. All clinical symptoms of toxicity disappeared by day 3 post-app

Gross pathology:

No test material-related gross organ changes were observed at necropsy.

Interpretation of results:

other: Not classified in accordance with EU Criteria

Conclusions:

Under the conditions of this study, the acute dermal toxicity LD50 (rat) of the test material was >2000 mg/kg bw (both sexes).

Executive summary:

The acute dermal toxicity of the test material to rats was investigated in accordance with the standardised guideline OECD 402, under GLP conditions.

The test was carried out with a mixture of DOT(2 -EHMA) and Octyltin tris(2-EHMA) (90:10 % w/w).

The test dose was 2000 mg/kg bw; the dose volume applied was 2  mL/kg bw.  After 24 hours, the exposed skin was cleaned and the area of  application was observed for 14 days.

Due to the lack of observed mortality, the 14-day acute dermal LD50s of  the test substance were reported as: LD50 (males) >2000 mg/kg bw LD50 (females) >2000 mg/kg bw LD50 (both sexes) >2000 mg/kg bw.

Under the conditions of this study, the acute dermal toxicity LD50 (rat) of the test material was >2000 mg/kg bw(both sexes).

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted on read-across material

Justification for type of information:

Read-across to structurally similar substance Dioctyltin bis (2-ethylhexylmercaptoacetate) (DOTE) (CAS No. 15571-58-1), see attached justification.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

ORAL TOXICITY STUDIES

Gunzel (1969)

The acute oral toxicity of the test material was investigated in a study similar to OECD 401, using male and female Sprague-Dawley rats.

The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

Five animals per sex per dose were treated at 0.5, 1.0, 1.4, 2.0, 2.8 and 4.0 g/kg test material and then observed for 13 days. After 13 days surviving animals were killed and autopsy was performed. Autopsy was also performed on animals that dies during the observation period.

Mortality was observed between 1 and 11 days after application of the test material. At 0.50 g/kg 2/10 animals died, at 1.0 g/kg 5/10 animals died, at 1.40 g/kg 4/10 animals died, at 2.00 g/kg 9/10 and at 2.80 g/kg and 4.00 g/kg all animals died during the observation period.

General apathy, cachexia, bloody noses and isolated comas were observed during the study. Emaciations, gastric ulcer,hereditary pneumonia and enteritis were seen on autopsy in the animals that died during the study.

Under the conditions of this study the acute oral toxicity LD50 was 1100 mg/kg.

Oral (Bathe, 1980)

The acute oral toxicity of the test material was investigated in a study similar to OECD 401, using male and female Tif: RAIF rats. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

Five animals per sex per dose were treated at 1000, 2000, 5000 and 7000 mg/kg test material formulated in poly ethylene glycol 400. Animals were fasted overnight before treatment. The animals were observed for 14 days following treatment.

At 1000 mg/kg there were no deaths, at 2000 mg/kg no males died but 3/5 females died, at 5000 mg/kg 3/5 males died and 5/5 females died and at 7000 mg/kg 3/5 males died and 4/5 females died.

Clinical signs including sedation, dyspnoea, exophthalmos, ruffled fur and diarrhoea were observed in different severity levels in all dose groups. All animals recovered within 14 to 19 days. No test material related gross organ changes were seen in the autopsy.

Under the conditions of the study the acute oral LD50 of the test material was 3512 mg/kg with 95 % confidence limits of 2196 to 5630).

Protocol no. 1670 (1970)

The acute oral toxicity of the test material to mice was investigated in a study using male mice. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

Ten animals per dose were treated with the test material (formulated as an emulsion in CMC) at 0.5, 0.72, 1.0, 1.4, 2.0, 2.8 g/kg and then observed for 25 days. All animals were subjected to autopsy either at the end of the study, if they survived, or following death during the observation period.

At 0.5 mg/kg 1 animal died on Day 5, at 0.72 g/kg 2 animals died on Day 5, at 1.0 g/kg 1 animal died on Day 5, at 1.4 g/kg 3 animals died on Day 7, 2 animals died on Day 8 and 1 animal died on Day 22. At 2.0 g/kg 2 animals died on Day 5, 2 animals died on Day 7, 2 animals died on Day 8, 1 died on Day 9, 1 on Day 11 and 1 on Day 16. At 2.8 /kg: 3 animals died on Day4, 4 animals died on Day 5, 1 died on Day 7 and 1 on Day 9. Increasing apathy and cachexia was observed in the increasing dose concentration groups.

At autopsy abnormalities in the liver, stomach, lungs and bladder were observed with increasing frequency in the higher dose levels. No abnormalities were seen in the animals that survived the observation period.

Under the conditions of the study the acute oral LD50 of the test material to male mice was 1300 mg/kg with 95 % confidence intervals of 1000 to 1600 mg/kg.

Protocol no. 1671 (1970)

The acute oral toxicity of the test material to mice was investigated in a study using female mice. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

Ten animals per dose were treated with the test material (formulated as an emulsion in CMC) at 0.5, 0.72, 1.0, 1.4, 2.0, 2.8 g/kg and then observed for 23 days. All animals were subjected to autopsy either at the end of the study, if they survived, or following death during the observation period.

At 0.5 and 0.72 g/kg no deaths occurred, at 1.0 g/kg 1 animal died on Day 5 and 1 animal died on Day 6, at 1.4 g/kg 2 animals died on Day 5, 4 animals died on Day 6 and 1 animal died on Day 8. At 2.0 g/kg 1 animal died on Day 4, 1 animal died on Day 5, 3 animals died on Day 6 and 2 died on Day 7 and at 2.8 g/kg: 2 animals died on Day 4, 4 animals died on Day 5, 2 died on Day 6 1 died on Day 7 and 1 on Day 8. Increasing apathy and cachexia was observed in the increasing dose concentration groups.

At autopsy abnormalities in the liver, stomach, lungs ovaries and bladder were observed with increasing frequency in the higher dose levels. No abnormalities were seen in the animals that survived the observation period.

Under the conditions of the study the acute oral LD50 of the test material to male mice was 1400 mg/kg with 95 % confidence intervals of 1200 to 1700 mg/kg.

Auletta (1984)

The acute oral toxicity of the test material was investigated in accordance with FIFRA and TSCA guidelines using male and female Sprague-Dawley derived rats. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

Five animals per sex were dosed at the following concentrations: 600, 800, 1200, 1700 and 2500 mg/kg and then observed for 21 days. All animals were subjected to gross post-mortem examinations when they died during the study or when the study finished.

At 600 mg/kg 1 animal died, at 800 mg/kg 3 animals died, at 1200 mg/kg 2 animals died, at 1700 mg/kg 6 animals died and at 2500 mg/kg 5 animals died.

Signs seen in most or all groups included ataxia, hypo activity, red or clear oral, nasal or ocular discharge, wet rales, urinary and/or faecal staining, soft stool, unthrifty coat, hypopnea, hypothermia, food consumption decrease, emaciation and partially closed eyes. By Day 7 the incidence of abnormalities had subsided in animals dosed at the 600, 800, 1200 and 1700 mg/kg levels, although one animal in the 800 mg/kg dose group exhibited an unthrifty coat, emaciation, hypo activity and decreased food consumption for most of the post-dose period. Some survivors at the 2500 mg/kg level exhibited unthrifty coats, alopecia, abdominal griping, emaciation, hypo activity and food consumption decrease for much of the post-dose period. Most animals were free of significant abnormalities by study termination (Day 21), however. Animals that died exhibited substantial ante mortem weight losses, and several surviving animals exhibited weight losses at Day 7. However, all survivors gained weight between Days 7 and 21.

Post-mortem examinations of animals found dead revealed a variety of changes, primarily in the lungs (discolouration), adrenals (reddened), gastrointestinal tract (stomach and intestinal walls - discoloured, containing red or black fluid) and testes (found in body cavity).

Under the conditions of this study the acute oral LD50 of the test material is 1800 mg/kg with 95 % confidence interval of 1040 to 2560 mg/kg.

Gunzel (1976)

The acute oral toxicity of the test material was investigated in a study similar to OECD 401 guidelines using male and female Sprague-Dawley derived rats. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

Five animals per sex per dose were treated at 0.5, 1.2, 1.9, 2.6, 3.3 and 4.0 g/kg and observed for 22 days. Following this period animals were subjected to gross necropsy.

At 0.5 g/kg no animals died. At 1.2 g/kg 2 females died. At 1.9 g/kg 1 male and 2 females died. At 2.6 g/kg 1 male and 3 females died. At 3.3 g/kg 1 male and 3 females died. At 4.0 g/kg 4 males and 3 females died. At 1.9 g/kg 2 to 4 hours after application low to high-grade apathy was seen with increasing intensity. On the following days from the 1.2 g/kg dose upwards the following were observed: low to high grade apathy, coarse fur and low to high degree emaciation.

Hyperemia in the lungs and hemorrhagic-catarrhal gastroenteritis was seen at all dose levels at autopsy. At 3.3 g/kg additional partial gastritis and liver necrosis was seen.

Under the conditions of this study the acute oral LD50 of the test material is 3100 mg/kg with 95 % confidence interval of 2300 to 6400 mg/kg.

Hine and Banks

The acute oral toxicity of the test material was investigated in a study with rats. The study was awarded a reliability score of 4 in accordance with the criteria set forth by Klimisch et al. (1997).

Six groups of ten animals were dosed with the test material via intragastrical injection following an overnight fasting period at doses ranging from 0.4 to 7.5 g/kg. Animals were then observed for 30 days.

Under the conditions of the study the acute oral LD50 of the test material was 1000 mg/kg.

Read-across to structurally similar substance Dioctyltin bis (2-ethylhexylmercaptoacetate) (DOTE) (CAS No. 15571-58-1).

An acute oral toxicity to rat study (OECD 401) was carried out with a mixture of DOT (2 -EHMA) and MOT(2 -EHMA) (90:10%) . Two doses were tested (single dose of 1000 and 2000 mg/kg bw/d) with a 14 -days observation period. Animals in both dose groups exhibited clinical signs of toxicity and effects on mortality were observed. The LD50 was lower for female rats, the overall LD50 was 2000 mg/kg bw .

INHALATION TOXICITY

Gunzel (1978)

The acute inhalation toxicity of the test material was investigated in a study using male and female Wistar rats. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

Animals whole bodies were continually exposed to the test material (a mixture of 80% registered substance (DOTI) and 20% MOTI (CAS 26401-86-5))

at steam saturated in air for a period of 7 hours in an inhalation chamber. They were observed during this treatment time and for 14 days afterwards.

No mortalities occurred during the treatment or observation periods. Some of the animals showed conjunctivitis during 14-day observation period. Body weights increased during the observation period.

Following the 14 days observation period the animals were sacrificed and necropsy performed. All animals were suspected of slight thymus enlargement, which however can neither be quantified nor interpreted as a test material defect, since no control group was carried in the experiment.

Under the conditions of this study following a 7 hour treatment, no mortality occurred. In some animals, a temporary conjunctivitis was observed during the post-treatment period.

DERMAL TOXICITY

Read-across to structurally similar substance (DOTE) (CAS No 15571 -58 -1)

The acute dermal toxicity of the test material to rats was investigated in accordance with the standardised guideline OECD 402, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The test was carried out with a mixture of DOT(2 -EHMA) and Octyltin tris(2-EHMA) (90:10 % w/w).

The test dose was 2000 mg/kg bw; the dose volume applied was 2  mL/kg bw.  After 24 hours, the exposed skin was cleaned and the area of  application was observed for 14 days.

Due to the lack of observed mortality, the 14-day acute dermal LD50s of  the test substance were reported as: LD50 (males) >2000 mg/kg bw LD50 (females) >2000 mg/kg bw LD50 (both sexes) >2000 mg/kg bw.

Under the conditions of this study, the acute dermal toxicity LD50 (rat) of the test material was >2000 mg/kg bw(both sexes).

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 inhalation and dermal toxicity. However, the LD50 of the substance was determined in the key study to be 1800 mg/kg bw and as such the substance requires classification as Cat 4 with regards to its acute oral toxicity and is assigned H302: Harmful if swallowed.