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Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
10 October 2007 to 30 Octobre 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Cross-reference
Reason / purpose for cross-reference:
other: read-across target
Reference
Endpoint:
short-term repeated dose toxicity: oral
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 Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE) (EC Number 248-227-6 and CAS No 27107-89-7) based on structural similarity and hydrolytical behaviour, see attached justification.
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
2 weeks range finding study performed to select the dose-levels of the OECD 421 study
GLP compliance:
yes (incl. QA statement)
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethylhexyl 10-ethyl-4-[[2-[(2-ethylhexyl)oxy]-2-oxoethyl]thio]-4-octyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate
EC Number:
248-227-6
EC Name:
2-ethylhexyl 10-ethyl-4-[[2-[(2-ethylhexyl)oxy]-2-oxoethyl]thio]-4-octyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate
Cas Number:
27107-89-7
Molecular formula:
C38H74O6S3Sn
IUPAC Name:
2-ethylhexyl 10-ethyl-4-({2-[(2-ethylhexyl)oxy]-2-oxoethyl}sulfanyl)-4-octyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecan-1-oate
Constituent 2
Reference substance name:
2-ethylhexyl 10-ethyl-4-[[2-[(2-ethylhexyl)oxy]-2-oxoethyl]thio]-4-octyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate = MOT(EHMA)
IUPAC Name:
2-ethylhexyl 10-ethyl-4-[[2-[(2-ethylhexyl)oxy]-2-oxoethyl]thio]-4-octyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate = MOT(EHMA)
Details on test material:
Test substance name : Octyltin tris (2-ethylhexylmercaptoactate)
Chemical name : Octyltin tris(2-ethylhexylmercaptoactate)
Other name : MOTE, AR1211
Colour / appearance : colorless liquid
CAS reg. Number : 27107-89-7
Batch number : ESOC21.1314
Purity : 97.9%
Storage conditions : 2-10 °C in the dark in closed container
- TNO dispense reference nr : 0700C7
Total quantity : approx. 100 gram
Receipt at TNO : 14 August 2007
Expiry date : 15 June 2008
- TNO dispense reference nr : 080010
Total quantity : approx. 300 gram
Receipt at TNO : 17 January 2008
Expiry date : 15 June 2008

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Wistar outbred rats, 9-10 weeks, were obtained from a colony maintained under SPF conditions from Charles River Wiga GmbH, Sulzfeld, Germany. For the first dose-range finding study 22 male and 22 female animals

Administration / exposure

Route of administration:
oral: feed
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
2 weeks
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
10 mg/kg diet
Dose / conc.:
30 mg/kg diet
Dose / conc.:
100 mg/kg diet
Dose / conc.:
500 mg/kg diet
No. of animals per sex per dose:
There was one control group and four test groups. Each of the test groups received a different dose level of the test material. Each group consisted of 4 males and 4 females. The dose levels were selected in consultancy with the sponsor. The various groups are characterised in the scheme below.

Group code Colour code Dietary level of test substance(mg/kg diet) Number of animals
Males Females
1 Control White 0 4 4
2 Low-dose Blue 10 4 4
3 Mid-dose Green 30 4 4
4 High-dose Red 100 4 4
5 Top-dose Yellow 500 4 4

Control animals:
yes, plain diet
Positive control:
not used

Examinations

Observations and examinations performed and frequency:
Body weights were recorded at least once pretest and twice weekly from the start of the treatment (for the last time on the day of scheduled necropsy).
Food consumption was measured twice weekly for each cage (2 rats per cage) from the start of the treatment. Water consumption was estimated by visual inspection of the drinking bottles.
Sacrifice and pathology:
Animals of the dose-range finding studies were sacrificed 2 weeks after the start of the administration of the test material.

Samples of the following tissues and organs of all animals were preserved in a neutral aqueous phosphate-buffered 4% solution of formaldehyde, except for the testes which were preserved in Bouin’s fixative:
- Kidneys
- Liver
- Spleen
- Testes
- Thymus
These organs were weighed (paired organs together) as soon as possible after dissection to avoid drying. The organs were discarded when the results of the subsequent main study indicated no need for microscopy on tissues from the dose-range finding studies.
Absolute and relative organ weights (ratio calculated to bodyweight) were recorded.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No mortalities and clinical signs were observed in the male and female animals.
Mortality:
no mortality observed
Description (incidence):
No mortalities and clinical signs were observed in the male and female animals.
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
Mean body weight of the male and female animals was comparable between the control and the treated groups. Apart from a statistically significant increase in body weight change of the male animals of the low-dose group during the entire study (day 0-14), no remarkable changes in growth were observed. This change was not considered to be related to treatment.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Mean food consumption (expressed as g/animal/day and g/kg bw/day) was comparable between the control and the treated groups.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
no effects observed
Description (incidence and severity):
No effects on water consumption occurred.
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Mean absolute and relative organ weight of the male and female animals were comparable between the control and the treated groups.
Gross pathological findings:
no effects observed
Description (incidence and severity):
Macroscopic examination at necropsy did not reveal treatment-related findings.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No relevant changes were observed at all dose-levels after 2 weeks exposure with the test susbtance on body weight, food consumption, organ weight and necropsy parameters. The NOAEL was therefore considered to be 500 mg/kg diet - this concentration is equivalent to 29.1 mg/kg bw/d in males and to 34.1 mg/kg bw/d in females.
Executive summary:

In order to select the dose-levels for the main OECD 421 study the test material was studied in first dose-range finding studies of 2 weeks at the following dose levels: 0, 10, 30, 100 and 500 mg/kg diet (ppm).

No relevant changes were observed at all dose-levels after 2 weeks exposure with the test susbtance on body weight, food consumption, organ weight and necropsy parameters.  The NOAEL was therefore considered to be 500 mg/kg diet - this concentration is equivalent to 29.1 mg/kg bw/d in males and to 34.1 mg/kg bw/d in females.

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