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Description of key information

ORAL

Prinsen (2012) (% composition of substance in test material: 99.3%), K1

Since five out of six animals survived the 2000 mg/kg dose-level, the oral LD50 of octyltin tris (2-ethylexylmercaptoacetate) MOTE is considered to be between 2000 and 5000 mg/kg/day.

Bathe (1980) (% composition of substance in test material: 70%), K2

The acute oral LD50 in rats of both sexes observed over a period of 14 days is 2177 with 95 % CL of (1480-3227) mg/kg.

Pelikan (1970) k4 (% composition of substance in test material: not reported), K4

LD50 (mice) = 1500 mg/kg bw (95% CL 1100 - 2000 mg/kg bw).

Mesch (1992) k4 (% composition of substance in test material: not reported), K4

LD50 = 3400 mg/kg bw.

DERMAL

Prinsen (2010) (% composition of substance in test material: 97.9%), K1

Since all animals survived the 2000 mg/kg dose level, the dermal LD50 of Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE) is considered to be higher than 2000 mg/kg body weight.

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:
6 December 2011-24 Juanuary 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Acclimatization: at least 5 days
Caging: a maximum of 6 animals/sex per macrolon cage with sterilized wood shavings (Lignocel) as bedding material, environmental enrichment (Enviro-Dri) and wood black
Identification: ear tattoo
: 12 hours lighU12 hours dark cycle
room temperature : 20-24 °C.
Relative humidity during testing : 45-65%. The upper limit was incidentally up to 83% (not exceeding ca 1-2 hours) because of meteorological circumstances and/or wet cleaning of the room.


Ventilation: ca 10 air changes/hour
Diet/water : standard laboratory diet ad libitum. Each batch of this diet is analysed by the supplier (SDS Special Diets services, Whitham, England) for the nutrients and contaminants and the results are kept available in the archives. Tap water (N.V. Vitens) ad libitum. Results of routine physical, chemical and microbiological examin­ ation of drinking water as conducted by the supplier are kept available in the archives. The results of diet and water analyses were considered acceptable for this study.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
-
-
- Justification for choice of vehicle:B ecause the test substance is a liquid and considered non corrosive , the 2000 mg/kg body weight anaimls was recorded.
- Lot/batch no. (if required):ESOC21.341
- Purity: 97.7%

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg for dose-levels of 50 and 300 mg/kg and 1.8 ml/kg body weight for the 2000 mg/kg dose-level.

Doses:
2000 mg/kg, 300 mg/kg, 50 mg/kg.
No. of animals per sex per dose:
6 females at 2000 mg/kg
3 females at 300 mg/kg
3 females at 50 mg/kg.
Control animals:
no
Details on study design:
Duration of observation period following administration: 14 days
- Frequency of observations : observation were made 1 hour and within 4 hour after dosing. adn subsequently at least once daily throughout an observation period of 14 days.
- Weighing: the body weight of each animal was recorded just prior to dosing and of surviving animals on day 3, 7 and 14 of the study.
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 5 000 mg/kg bw
Mortality:
At 2000 mg/kg/day, one animal was sacrificed prematuraly, this animals shows protrusion of eyes, ataxia, paralysis and an abominal lump on day 1 of the study.
At 50 and 300 mg/kg, No mortality or clinical signs were observed during the 14-day study period.

Clinical signs:
At 2000 mg/kg/day (first and second group) clinical signs generally observed consisted of hunching in 4/6 animals within the first two days after dosing. Occasionnaly, ataxia, blephorasm, piloerection and an abdominal lump were observed in one or two animals within the first day after dosing.
At 50 and 300 mg/kg, no clinical sings were observed during the 14- day study period.
Body weight:
All surviving animals at all dose-levels gained weight at all dose-levels.
Gross pathology:
At 2000 mg/kg dose -level: first and second group: examination at necropsy did not reveal treateent-related gross alterations, other than the animal killed in extremis which schowed a stomach filled with sawdust.
At 300 mg/kg dose-level, examination at necropsy of the animals did not reveal treatment related gross alterations.
At 50 mg/kg dose-level, examination at necropsy of the animals did not reveal treatment-related gross alterations.
Other findings:
none
Interpretation of results:
other: not classified according to EU criteria
Conclusions:
Since five out of six animals survived the 2000 mg/kg dose-level, the oral LD50 of octyltin tris (2-ethylexylmercaptoacetate) MOTE is considered to be between 2000 and 5000 mg/kg/day.
Executive summary:

A sample of Octyltintris(2-ethylhexylmercaptoacetate) MOTE was examined for acute oral toxicity in an experiment with female rats (limit testing), according to EC Directive96/54/EEC, method 8.1 trisand OECD Guideline no.423. Dose levels of 2000, 300 and 50mg per kg bodyweight were examined and animals were observed for a maximum of 14 days after dosing.

No mortality or clinical signs were observed after treatment with a 50 and 300 mg/kg/ bwt. dose-levels.

The 2000 mg/kg bwt dose-level caused mortality in one out of the 6 animals dosed. Clinical signs observed consisted of Hunching, ataxia, blepharospasm, protrusion of eyes, piloerection and an abdominal lump.

Macroscopic examination of the surviving animals at the end of the observation period did not reveal any treatment related gross changes.

Since five out of six animals survived the 2000 mg/kg dose-level, the oral LD50 of octyltin tris (2-ethylexylmercaptoacetate) MOTE is considered to be between 2000 and 5000 mg/kg/day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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
Study period:
2nd December - 16th December 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: ca. 8 weeks old at start of study
- Weight at study initiation: 215 - 251 g. Mean weight was 237 g.
- Fasting period before study: NDA
- Housing: a maximum of 5 animals/sex per macrolon cage with sterilised wood shavings (Woody Clean) as bedding material and environmental enrichment (shreds of paper); individual housing during dermal exposure.
- Diet (e.g. ad libitum): standard laboratory diet
- Water (e.g. ad libitum): ad libitum
- Acclimation period: mimimum of 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 45-65%. Upper limit may be higher for short periods of time, because of meteorological circumstances and/or wet cleaning of the room.
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark


IN-LIFE DATES: From: 2nd December 2009 To: 16th December 2009
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 20 cn^2
- % coverage: at least 10 % of body surface
- Type of wrap if used: gauze affixed with tape wrapped around the trunk of the rat


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water
- Time after start of exposure: ca. 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.79 mL/kg bw. equivalent to 2000 mg/kg bw
- Concentration (if solution): N/A
- Constant volume or concentration used: constant concentration of test substance per kg bw.
- For solids, paste formed: N/A


VEHICLE
- N/A
Duration of exposure:
Ca. 24 hours
Doses:
2000 mg/kg bw.
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of each animal was recorded just prior to dosing and of each surviving animal on days 3, 7 and 14 of the study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal reactions, macroscopial findings
Statistics:
No statistics reported.
Preliminary study:
NDA
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality observed during the 14-day study period.
Clinical signs:
No clinical signs were observed during the 14-day study period.
Body weight:
Apart from a slight dip in body weight of some of the animals on day 3 of the study, all animals gained weight during the 14-day study (see Table 1).
Gross pathology:
Examination at necropsy of the animals did not reveal distinct treatment related gross alterations.
Other findings:
In general, no signs of skin irritation were observed during the study. On days 1 and/or 3, three females showed minor skin effects, consisting of very slight or well-defined erythema and very slight or slight scaliness.

Table 1. Individual and mean bodyweights, dose amounts applied and mortality data.

Animal number Sex Dose (ml) applied Bodyweights (g) recorded on day: Mortality
0 3 7 14
12 Male 0.38 215 203 230 262 -
14   0.45 251 255 281 315 -
16   0.43 238 241 266 298 -
18   0.43 241 231 260 281 -
20   0.43 242 244 267 300 -
Mean bodyweight 237 235 261 291 0/5
11 Female 0.32 180 174 191 211 -
13   0.32 181 183 199 211 -
15   0.29 163 154 177 189 -
17   0.32 180 162 188 206 -
19   0.31 174 171 190 213 -
Mean bodyweight 176 169 189 206 0/5
Interpretation of results:
other: not classified according to EU criteria
Conclusions:
Since all animals survived the 2000 mg/kg dose level, the dermal LD50 of Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE) is considered to be higher than 2000 mg/kg body weight.
Executive summary:

Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE) was examined for acute dermal toxicity in an experiment with 8 week old male and female Wistar rats (limit testing), according EEC Directive 96/54/EEC, method B.3 and OECD Guideline no. 402. A dose level of 2000 mg per kg body weight was examined and the dermal contact period was 24 hours.

Since all animals survived the 2000 mg/kg dose level, the dermal LD50 of Octyltin tris(2-ethylhexylmercaptoacetate) is considered to be higher than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
> 2 000 mg/kg bw

Additional information

ORAL

Prinsen (2012) (% composition of substance in test material: 99.3%), K1

A sample of Octyltintris(2-ethylhexylmercaptoacetate) MOTE was examined for acute oral toxicity in an experiment with female rats (limit testing), according to EC Directive96/54/EEC, method 8.1 trisand OECD Guideline no.423. Dose levels of 2000, 300 and 50mg per kg bodyweight were examined and animals were observed for a maximum of 14 days after dosing.

No mortality or clinical signs were observed after treatment with a 50 and 300 mg/kg/ bwt. dose-levels.

The 2000 mg/kg bwt dose-level caused mortality in one out of the 6 animals dosed. Clinical signs observed consisted of Hunching, ataxia, blepharospasm, protrusion of eyes, piloerection and an abdominal lump.

Macroscopic examination of the surviving animals at the end of the observation period did not reveal any treatment related gross changes.

Since five out of six animals survived the 2000 mg/kg dose-level, the oral LD50 of octyltin tris (2-ethylexylmercaptoacetate) MOTE is considered to be between 2000 and 5000 mg/kg/day.

Bathe (1980) (% composition of substance in test material: 70%), K2

An acute oral toxicity study was performed on male and female 7 - 8 week old Tif: RAIf (SPF) rats. The doses applied were 400, 1000, 2000, 5000, and 7000 mg/kg bw using polyethylene glycol as a vehicle.

The acute oral LD50 in rats of both sexes observed over a period of 14 days is 2177 with 95 % CL of (1480-3227) mg/kg.

INHALATION

No data has been provided for the inhalation route as the oral and dermal routes have been identified as more appropriate for exposure, in accordance with EC Regulation 1907/2006, Annex VIII, Column 2, point 8.5.

DERMAL

Prinsen (2010) (% composition of substance in test material: 97.9%), K1

Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE) was examined for acute dermal toxicity in an experiment with 8 week old male and female Wistar rats (limit testing), according EEC Directive 96/54/EEC, method B.3 and OECD Guideline no. 402. A dose level of 2000 mg per kg body weight was examined and the dermal contact period was 24 hours.

Since all animals survived the 2000 mg/kg dose level, the dermal LD50 of Octyltin tris(2-ethylhexylmercaptoacetate) is considered to be higher than 2000 mg/kg body weight.

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.