Registration Dossier

Administrative data

Description of key information

Oral: LD50 880 mg/kg (rat)

Inhalation: LC50 240 mg/L (1 hour exposure; rat)

Dermal: LD50 1000 mg/kg in female rabbits; LD50 2150 mg/kg in male rabbits

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OTS 798.1175 (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 and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley, Inc., Indianapolis, IN
- Age at study initiation: naive young
- Weight at study initiation: 211-319 g for both sexes
- Fasting period before study: overnight prior to dosing
- Housing: housed in groups of 5
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days prior to being used in the test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26 degrees C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hours light/ 12 hours dark

IN-LIFE DATES: From: July 30, 1996 To: August 22, 1996
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
0.50, 0.80, 1.25 and 3.15 g/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (or other?) 14 days
- Frequency of observations and weighing: observed frequently for signs of systemic toxicity and mortality on the day of test initiation and at least twice daily thereafter; Body weights were measured at test initiation, Day 7 and post-mortem.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
LD50 values and 95 % confidence limits were calculated using the Litchfield and Wilcoxon method (1949)
Preliminary study:
No data
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
880 mg/kg bw
95% CL:
> 670 - < 1 150
Remarks on result:
other: reported as g/kg bw; results were converted to mg/kg bw
Mortality:
0.50 g/kg bw: Males: no mortality; Females: 1 dead at 24 h
0.80 g/kg bw: Males: no mortality; Females: 2 dead at 24 h, 2 dead at 48 h
1.25 g/kg bw: Males: 3 dead at 24 h; Females: 4 dead at 24 h, 1 dead at 48 h
3.15 g/kg bw: Males: 5 dead at 24 h; Females: 5 dead at 24 h
Clinical signs:
Clinical observations included depression, comatose, piloerection, eye squinting, hunched posture, labored breathing, ataxia, fecal stains, urine stains, and masticatory movement
Body weight:
Body weight generally increased for all animals in the 0.50 and males in the 0.80 g/kg dose groups. Most males in the 1.25 did not gain weight. At the 3.15 g/kg dose, 3 of 5 males gained weight. A slight decrease was noted in the body weights of females in the dose groups >=0.8 g/kg.
Gross pathology:
Gross necropsy results (for animals that died during the test):
Lungs: pale, reddened, or mottled
Liver: pale or mottled with darkened edges, or white/blanched areas
Spleen: pale, darkened, or mottled
Pancreas: darkened
Kidneys: enlarged, pale, and/or congested
Stomach: distended
Intestines: reddened, distended, and contained a viscous yellow/orange fluid
Bladder: contained a red fluid, external staining noted

No gross pathological changes were noted in the surviving animals.
Other findings:
Signs of systemic toxicity increased with increasing dose levels.
Interpretation of results:
other: Classified as Category 4 in accordance with EU criteria
Conclusions:
LD50 880 mg/kg bw
Executive summary:

The acute oral toxicity of undiluted Methyltin tris (2­ethylhexylthioglycolate) was evaluated in compliance with the conditions specified in the regulation for the enforcement of the Federal Insecticide, Fungicide, and Rodenticide Act (40 CFR), the Toxic Substances Control Act (40 CFR) and OECD Guideline 401.

The test material was administered undiluted to groups of five male and five female Sprague Dawley rats at a dose level of 3.15 g/kg, 1.25 g/kg, 0.80 g/kg, and 0.50 g/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 0.88 g/kg with the 95% Confidence Limits of 0.67 g/kg and 1.15 g/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 masticatory movement. All surviving animals exhibited body weight gain at day 14. Gross necropsy findings for animals that died during the observation period included lungs pale, reddened, or mottled, liver mottled, liver pale and mottled with lower edge of lobes of liver darkened, areas of liver exhibit white blanching, areas of liver pale, spleen pale, darkened, or mottled, pancreas darkened, kidneys pale and/or congested, kidneys enlarged, stomach distended with gas, intestines reddened, intestines distended with gas, intestines contain a viscous yellow to orange fluid, urinary bladder contains a pale red fluid, and external staining. No gross pathological changes were noted in animals that survived the observation period.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
880 mg/kg bw
Quality of whole database:
One study is available to address this endpoint; it was conducted in accordance with standardised guidelines under GLP conditions. The quality of the database is therefore considered to be good.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of 10 rats (males and females) were exposed to an aerosol of the test substance at concentrations of 200, 250, 300, and 350 mg/l/hour, for one hour. The test substance was administered via an atomizer configured to provide droplet sizes of 3-10 microns. After the 1-hour exposure period, animals were observed for 3 weeks, prior to sacrifice and necropsy.
GLP compliance:
no
Test type:
other: See principles of method section
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
This information was not provided in the report.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
not specified
Details on inhalation exposure:
Specific information was not provided
Analytical verification of test atmosphere concentrations:
not specified
Remarks:
No data provided in the report
Duration of exposure:
1 h
Concentrations:
200, 250, 300, 350 mg/L/hr
No. of animals per sex per dose:
10 animals consisting of both males and females, with the number of each not available
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days (or other?) 3 weeks
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: at least clinical signs, food consumption.
Statistics:
The acute inhalation LC50 and 95 % (19/20) confidence limits were calculated by the method of Litchfield and Wilcoxon (1949).
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
240 mg/L air
95% CL:
> 212 - < 271
Exp. duration:
1 h
Mortality:
Observed mortality (number of deaths/total number tested), by dose level tested:
200 mg/L/hr: 2/10 animals
250 mg/L/hr: 6/10 animals
300 mg/L/hr: 9/10 animals
350 mg/L/hr: 10/10 animals
Clinical signs:
other: Behavior of the surviving test animals, including food and water consumption and demeanor, remained normal. The lone surviving animal in the 300 mg/l/hr dose group, died on observation day 16.
Body weight:
No data
Gross pathology:
Gross findings included blood in lungs, dark spleen, pale kidneys, fluid in the chest cavity, and heart failure.
Other findings:
Food and water intake, excretions, and demeanor in the colony were all within normal limits.
The slope was 1.22 (1.04-1.43)
Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
LC50 240 mg/L/hr
Executive summary:

Groups of 10 rats, both male and female, inhaled the test material within a closed chamber of known volume. The test material was sprayed into the chamber by means of an atomiser. Animals were observed for 3 weeks.

Gross autopsy findings included: blood in the lungs, dark spleen, pale kidneys, fluid in the chest cavity and heart failure.

The inhalation LC50 was 240 mg/L/h.

Endpoint conclusion
Dose descriptor:
LC50
Value:
240 000 mg/m³
Quality of whole database:
One study is available to address this endpoint; the study is well documented, meets generally accepted scientific principles and is acceptable for assessment. The quality of the database is therefore considered to be good.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: 16 CFR 1500 "Method of testing toxic substances - Acute dermal toxicity (single exposure)"
Deviations:
yes
Remarks:
Study used less than the recommended number of test animals at each dose level; three male and two female rabbits weighed more than 3000 grams
Principles of method if other than guideline:
New Zealand White rabbits, initial body weights 2611 to 3836 g, were used to evaluate the acute dermal toxicity of the test substance. Test animals were caged individually under a 12-hour light/12-hour dark cycle and were acclimated for at least 32 days prior to testing. Food and water were provided ad libitum. Both sexes were initially tested at dose levels of 1000 and 2150 mg/kg; males were then treated with 4640 and 10 000 mg/kg and females were treated with 215 and 464 mg/kg, based on mortality data from the initial doses. Prior to dosing, the trunk of each animal was shaved and the skin of half the animals in each dose group was abraded. The test material was applied undiluted via occlusive patch around the trunk of each animal and wrapped in a layer of gauze and tape. Animals were restrained and observed for signs of systemic toxicity over the 24-hour exposure period. After 24 hours, the patches were removed, the exposed skin was cleaned, and test animals were observed daily for signs of irritation, systemic toxicity and mortality for 14 days. Animals were weighed and necropsied at death; surviving animals were euthanised, weighed and necropsied at the end of the observation period. Mortality data were evaluated by the method of Weil (1952, Biometrics, 8:249-263).
GLP compliance:
not specified
Test type:
other: Method of testing toxic substances- acute dermal toxicity
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Clerco Research Farm
- Weight at study initiation: 2611 to 3836 grams
- Fasting period before study: no data
- Housing: housed individually in wire mesh suspension cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 32 days prior to dosing

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

IN-LIFE DATES: From: February 21, 1983 To: March 15, 1983
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk
- % coverage: no data
- Type of wrap if used: sleeve of rubber dental damming which was wrapped around the trunk of each rabbit and secured with staples. An outer layer of gauze and tape and was also wrapped around the trunk of each animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle sponging with a moist towel
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Dosages were 215, 464, 1000 and 2150 mg/kg in females; 1000, 2150, 4640 and 10 000 mg/kg in males. Both sexes were initially treated with dosages of 1000 and 2150 mg/kg. Males were then treated with dosages 4640 and 10,000 mg/kg and females were treated with dosages of 215 and 464 mg/kg.
- Constant volume or concentration used: concentration

VEHICLE
-No vehicle used
Duration of exposure:
24 hours
Doses:
1000, 2150, 4640, and 10 000 mg/kg (males);
215, 464, 1000, and 2150 mg/kg (females)
No. of animals per sex per dose:
2
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animlas were observed for gross signs of systemic toxicity, dermal irritation, and death for 14 days. Animals were weighed at the end of the 14-day observation period.
- Necropsy of survivors performed: yes
Statistics:
no data
Preliminary study:
not applicable
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 000 mg/kg bw
95% CL:
460 - 2 020
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2 150 mg/kg bw
95% CL:
1 000 - 4 620
Mortality:
Cumulative mortality (total number of deaths/total number dosed), by sex and dose level:
215 mg/kg: 0/2 females
464 mg/kg: 0/2 females
1000 mg/kg: 1/2 females (day 3); 0/2 males
2150 mg/kg: 2/2 females (days 3, 6); 1/2 males (day 4)
4640 mg/kg: 2/2 males (days 4, 6)
10 000 mg/kg: 2/2 males (day 3)
Clinical signs:
Frequently observed clinical signs included death, uncoordinated movements, and shaking and hypersensitivity to external stimuli. All clinical sign disappeared in surviving animals by the end of the exposure period. The most frequently observed irritative effects were erythema, edema, atonia, desquamation, and blanching.
Body weight:
Males- Body Weight (g)
Animal no. Skin condition Day 0 Day 15 Body Weight Gain Day 0-15 (g)
1000 mg/kg
1 abraded 3836 3866 30
2 intact 3084 3699 615
Mean (SD) 3460 (532) 3782 (62) 322 (414)
2150 mg/kg
5 abraded 2698 2879 181
6 intact 2611 rabbit died prior to observation
Mean (SD) 2964 (446) 2879 181
4640 mg/kg
9 abraded 2818 rabbit died prior to observation
10 intact 3085 rabbit died prior to observation
Mean (SD) 2952 (189)
10 000 mg/kg
13 abraded 2985 rabbit died prior to observation
14 intact 2944 rabbit died prior to observation
Mean (SD) 2964 (29)
Gross pathology:
Gross necropsy results for animals that died during observation included irritated intestines, blanched stomach, reddened lungs, pale or congested kidneys, and oral, ocular, and/or nasal discharge. Necropsies of surviving animals at the end of the study revealed no relevant findings.
Other findings:
Upon removal of the binders from the animals, the binder and the exposed area were dry with no sample apparent on most of the animals. The 10 000 mg/kg males and one 2150 mg/kg female had moist sites with sample apparent after application.
Females- Body Weight (g)Animal no.     Skin condition       Day 0                   Day 15          Body Weight Gain Day 0-15 (g)215 mg/kg15                abraded           2904                     3209                         30516                intact            3201                     3568                         367Mean (SD)                           3052  (210)              3388  (254)                  336 (44)464 mg/kg11                abraded           2783                     2895                         11212                intact            2758                     3065                         307Mean (SD)                           2770  (18)               2980 (55)                    210 (138)1000 mg/kg3                 abraded           3280                     rabbit died prior to observation4                 intact            2649                     3051                         402Mean (SD)                           2964 (446)               3051                         4022150 mg/kg7                 abraded           2955           rabbit died prior to observation8                 intact            2629           rabbit died prior to observationMean (SD)                           2792 (231)
Interpretation of results:
other: Classified as Category 3 in accordance with EU criteria
Conclusions:
The acute dermal LD50 value was found to be 2.15 g/kg in male and 1.0 g/kg in female New Zealand White rabbits.
Executive summary:

The test material was applied undiluted to the skin of sixteen New Zealand White rabbits (two males and two females per dose level) at dosages of 0.215, 0.464, 1.0, 2.15 (females) or 1.0, 2.15, 4.64 and 10.0 g/kg (males) for 24 hours. Animals were observed for gross signs of systemic toxicity, dermal irritation, and death for 14 days. At the end of the 14­day observation period, survivors were weighed, killed, and given a gross necropsy.

Deaths occurred between days 3 and 6 of the observation period. Clinical changes associated with the test material included death, shaking behavior, uncoordinated movement, ataxia and hypersensitivity. The most frequently observed irritative effects included erythema, edema, atonia, desquamation and blanching. Gross necropsies performed on the animals that died revealed irritated gastrointestinal tracts, pale or congested kidneys and reddened lungs. Gross necropsies performed on survivors at the end of the study revealed no gross alterations. The acute dermal LD50 value was found to be 2.15 g/kg in male and 1.0 g/kg in female New Zealand White rabbits.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 000 mg/kg bw
Quality of whole database:
One study is available to address this endpoint; the study is well documented, meets generally accepted scientific principles and is acceptable for assessment. The quality of the database is therefore considered to be good.

Additional information

Oral

The acute oral LD50 of MMT(2-EHMA) was 880 mg/kg in rats.

The study was considered reliable. In this study, the LD50 was 880 (95 % CI 670 to 1150) mg/kg. Mortality rates for both sexes were 1/10, 4/10, 8/10, and 10/10 for dose levels of 500, 800, 1250, and 3150 mg/kg, respectively. At 0.50 and 0.80 g/kg no males died. One 0.50 g/kg female was dead at 24 hours. At 0.80 g/kg, 2 females were dead at 24 hours and 2 were dead at 48 hours. Three males and 4 females of the 1.25 g/kg group were dead at 24 hours and 1 female at 48 hours. Five males and 5 females of the 3.15 g/kg group were dead at 24 hours.

Clinical observations included depression, comatose, piloerection, eye squinting, hunched posture, laboured breathing, ataxia, faecal/urine stains, and masticatory movement. No gross pathological changes were reported in surviving animals.

 

Inhalation

The acute inhalation LC50 of MMT(2-EHMA) was 240 mg/L.

The study reported an acute inhalation LC50 of 240 (212 to 271) mg/L in a 1-hr aerosol exposure to male and female rats. The mortality rate was 2/10, 6/10, 9/10 and 10/10 animals at dose levels of 200, 250, 300 and 250 mg/L/hr, respectively. Gross findings included blood in lungs, dark spleen, pale kidneys, fluid in the chest cavity, and heart failure. The slope of the dose-response curve was 1.22 (1.04 to 1.43).

 

Dermal

The acute dermal LD50 of MMT(2-EHMA) in rabbits was 1000 (460 to 2020) mg/kg for females and 2150 (1000 to 4620) mg/kg for males. There were no deaths at 215 and 464 mg/kg, 0/2 males and 1/2 females died at 1000 mg/kg and 1/2 males and 2/2 females died at 2150 mg/kg. All animals died at 4640 and 10 000 mg/kg. A variety of clinical abnormalities were observed and disappeared in surviving animals by the end of the exposure period. Clinical signs included death, uncoordinated movements, shaking, and hypersensitivity to external stimuli.

Gross necropsy results for animals that died during the study included irritated intestines; blanched stomach; reddened lungs; pale or congested kidneys; and oral, ocular and/or nasal discharges.

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 and dermal routes as Acute toxicity Category 4 and 3, respectively (H302: Harmful if swallowed; H311: Toxic in contact with skin).