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Administrative data

Description of key information

ORAL
Weight of evidence:- Bathe (1972), Similar to OECD 401, LD50 > 6000 mg/kg bw (male and female rats)
Weight of evidence:- Gunzel & Richter (1968), Similar to OECD 401, LD50 > 4000 mg/kg bw (male and female rats)
Weight of evidence:- Klimmer (1971), Similar to OECD 401, LD50 2334 mg/kg bw (1993 - 2816 mg/kg bw) (male rats)
Weight of evidence:- Smith (1978), LD50 2334 - 2350 mg/kg bw (rats)
Weight of evidence:- Klimmer (1969), LD50 2500 mg/kg bw (male, rats)
INHALATION
An adaptation to standard information requirements was submitted to address this endpoint. As the inhalatory route was considered the least likely route of exposure, acute toxicity of the test material was addressed with information from more appropriate routes of exposure.
DERMAL
Key study:- Sanders (2012), OECD 402, EU Method B.3, LD50 > 2000 mg/kg bw (male and female rats)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Bathe (1972) was deemed to be reliable with restrictions (reliability score of 2) in line with the criteria for assessing data quality as described in Klimisch (1997). All other studies presented were assigned either a reliability score of 4 as they were presented in short abstracts or a reliability score of 3 if the full study was available but not sufficiently reported to fully assess the results and conclusions of the study.

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:
13 June 2012 - 27 June 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed to standardised guidelines OECD 402 and EU Method B.3 and in line with GLP. The study was reported to a high standard with a sufficient level of detail to assess the quality of the data presented.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
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
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: at lest 200 g (weight variation did not exceed ± 20 % of the mean weight for each sex).
- Housing: individually during 24 hour exposure period and in groups of five, by sex, for the remainder of the study in suspended solid-floor polypropylene cages.
- Diet: ad libitum
- Water: mains drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From 13 June 2012 to 27 June 2012
Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
TEST SITE
- Area of exposure: on the day before treatment the back and flanks of each animals were clipped free of hair
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: a piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- After the 24 hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material

TEST MATERIAL
- the appropriate amount of test material was moistened with arachis oil BP and applied as evenly as possible to the area of shorn skin

Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed to deaths and overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and once daily thereafter. The test site was observed daily for evidence of primary irritation and scored according to Draize (1977) (see table 1 in "Any other information on material and methods incl. tables). Individual bodyweights were recorded prior to application of the test material on day 0 and on days 7 and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
Animals showed expected gains in bodyweight over the study period, except for one male which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
There were no signs of dermal irritation.

Table 2: Individual Bodyweights and Weekly Bodyweight Changes

Animal no. and sex

Bodyweight (g) at day

Bodyweight change (g) during week

0

7

14

1

2

1M

309

314

328

5

14

2M

287

303

323

16

20

3M

282

305

332

23

27

4M

399

425

435

26

10

5M

367

358

380

-9

22

1F

202

204

214

2

10

2F

221

226

237

5

11

3F

217

220

232

3

12

4F

214

221

228

7

7

5F

201

202

217

1

15

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the LD50 of the test material in the Wistar strain of rat was determined to be greater than 2000 mg/kg bw.
Executive summary:

The acute dermal toxicity of the test material was investigated in accordance with standardised guidelines OECD 402 and EU Method B.3. During the study, a group of ten animals (five males and five females) was given a single, 24 -hour, semi-occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. Under the conditions of the study there were no deaths and no signs of systemic toxicity. Animals showed normal weight gains and there were no signs of dermal irritation. Furthermore, no abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Wistar strain of rat was therefore determined to be greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Study conducted to GLP and in accordance with standardised guidelines; the study has been assigned a reliability score of 1 according to the criteria of Klimisch (1997).

Additional information

ORAL

In Bathe (1972), the acute oral toxicity of the test substance was investigated. The study pre-dated GLP inception and was performed to a method similar to OECD 401, with the main difference being a 7 day observation period in place of a 14 day observation period. The study did lack some details in the reporting of both the methods and the results, however this was not found to affect the quality of the presented conclusions. The dose levels were extremely high, and although only a seven day observation period was used, all animals had recovered by the 6th day and all animals were examined for gross changes, of which there were none satisfactorily confirming that the test substance was not acutely toxic. As such, the study was assigned a reliability score of 2 in accordance with the criteria for assessing data quality as outllined in Klimisch (1997). Under the conditions of the test, the acute oral LD50 of the test substance in male and female rats was found to be greater than 6000 mg/kg bw.

In Gunzel and Richter (1968), the acute oral LD50 of the test substance was investigated in a pre-GLP study also similar to OECD 401 in design. The method used a limit test of 4000 mg/kg bw with a 9 day observation period. The reporting of the study was extremely brief and information on points such as the vehicle used was not included. Therefore in accordance with the criteria for assessing data quality as described by Klimisch (1997), the study was assigned a reliability score of 4 as it was not possible to assess the accuracy of the information using the presented information. Under the conditions of the test, the acute oral LD50 of the test substance in male and female rats was found to be greater than 4000 mg/kg bw.

In the Klimmer (1971) study, the acute oral toxicity of the test substance in two vehicles was examined. The test substance was dosed first as a 10 % solution in oil, then as a 20 % solution in Tween 80 as the first test produced no mortalities. The study pre-dated GLP inception, and the method was as far as could be determined, comparable with OECD 401. Limitations were present in the reporting of the study, and would have benefitted from a detailed justification on the choice of vehicles. The study was therefore assigned a reliability score of 3 in accordance with the criteria for assessing data quality defined in Klimisch (1997). The acute oral LD50 as a 20 % solution in Tween 80 was determined to be 2334 mg/kg bw (1993 -2816 mg/kg bw) in male rats under the conditions of the test.

The following MSDS were submitted as supporting information:

WITCO (2000): Acute oral LD50 >4000 mg/kg bw (rats)

ACROS (2010): Acute oral LD50 2500 mg/kg bw (rats)

ALFA AESAR (2010): Acute oral LD50 2500 mg/kg bw (rats)

ARKEMA (2007): Acute oral LD50: 1900 mg/kg bw to greater than 8000 mg/kg bw (rats).

GELEST (2003): Acute oral LD50: 2334 mg/kg (rats).

TCI (2010): Acute oral LD50: 2500 mg/kg (rats)

Smith (1978), a review paper, consisting of the assessment of literature papers on the toxicity of organotins was also available as supporting information, the data in this review was also presented as short abstracts. The paper reports the acute oral LD50 in rats as 2334-2350 mg/kg bw.

Klimmer (1969), a toxicological overview of organotin compounds is presented in a similar manner. Unlike most of the values reported in this study, the acute oral LD50 for the registered substance is reported to be the author's own values. It is not clear whether the information presented on the registered substance is the only source for this information or whether a fuller account of the study performed to derive the data is available. The acute oral LD50 of the substance in fasted male rats was reported to be 2500 mg/kg in an oil + tylose suspension.

All information presented in the IUCLID Data Set (2006), were summaries of other sources. The first (a study report from 1959) reported the LD50 in rats as 2220 mg/kg, the second (a study reported from 1992) reported and LD50 of >4000 mg/kg in male and female mice and the third entry (a personal communication dated 1962) reported an LD50 of 5250 mg/kg in the rat.

As the information from these sources were presented as short abstracts, a reliability score of 4 was considered to be fitting, in line with the criteria for assigning data quality in line with the principles described by Klimisch (1997).

DERMAL

The key study, Sanders (2012) investigated the acute dermal toxicity of the test material was investigated in accordance with standardised guidelines OECD 402 and EU Method B.3 and performed in line with GLP. As such, the study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outllined in Klimisch (1997). During the study, a group of ten animals (five males and five females) was given a single, 24 -hour, semi-occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. Under the conditions of the study there were no deaths and no signs of systemic toxicity. Animals showed normal weight gains and there were no signs of dermal irritation. Furthermore, no abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Wistar strain of rat was therefore determined to be greater than 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
No study selected since this endpoint has been addressed on a weight of evidence bases with the following studies.

Bathe (1972) was deemed to be of the highest quality as the study was performed in line with good scientific principles and reported in a good level of detail. However an observation period of 6 days after administration was used which is considerably shorter than that used in the standardised guidelines. Several studies Smith (1978) and Klimmer (1969) both reported LD50 values after 14 and 21 days observation respectively. All the presented information is consistent with the findings of Bathe (1972) and indicates that the substance is not acutely toxic via the oral route. It was therefore considered appropriate to assess the data as a weight of evidence.

Justification for selection of acute toxicity – dermal endpoint
Only one study is available

Justification for classification or non-classification

The substance was demonstrated to have a high LD50 (> 2000 mg/kg bw) in rats, in accordance with the Regulation (EC) No 1272/2008 and Directive 67/548/EEC. The substance does not meet the criteria for classification for acute toxicity via the oral or dermal routes.

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