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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 Nov - 01 Dec 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted Feb 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
May 2008
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
Aug 1998
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, No 8147
Version / remarks:
Nov 2000
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Remarks:
Food and Consumer Product Safety Authority (VWA), Utrecht, The Netherlands
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Silicic acid (H4SiO4), tetraethyl ester, reaction products with bis(acetyloxy)dioctylstannane
EC Number:
300-346-5
EC Name:
Silicic acid (H4SiO4), tetraethyl ester, reaction products with bis(acetyloxy)dioctylstannane
Cas Number:
93925-43-0
Molecular formula:
C4H8O2, C20H44O4SiSn, C24H52O6SiSn, C40H84O8SiSn2, C60H128O12Si2Sn3, C80H172O16Si3Sn4, C100H216O20Si4Sn5
IUPAC Name:
Silicic acid (H4SiO4), tetraethyl ester, reaction products with bis(acetyloxy)dioctylstannane
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle and test substance. In order to obtain homogeneity, the test substance formulation was heated in a water bath with a maximum temperature of 81.1 °C for a maximum of 1 hour and 37 minutes. The test substance formulation was allowed to cool down to a temperature of maximally 40 °C prior to dosing.

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) (outbred, SPF-Quality)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately 10 weeks
- Weight at study initiation: 290 ± 13 g (males); 197 ± 11 g (females);
- Housing: individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet: SM R/M-Z, pelleted (Ssniff Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0 (actual range: 19.6 – 21.9)
- Humidity (%): 40 - 70 (actual range: 40 - 56)
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: hydrogenated corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: approximately 25 cm² for males; approximately 18 cm² for females
- % coverage: 10
- Type of wrap if used: a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed with tap water
- Time after start of exposure: 24 h

TEST MATERIAL
- Concentration: 10 mL/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed twice daily for mortality and morbidity; individual body weights were determined on days 1 (pre-administration), 8, 15 and prior to sacrifice; clinical signs were determined at periodic intervals on the day of dosing (Day 1) and once daily thereafter until Day 15
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female was sacrificed for ethical reasons on Day 8 due to an excessive weight loss.
Clinical signs:
Lethargy was noted in 1/5 males on Day 2 and in 4/5 males on Day 1, and recurred in 2/5 males on Day 8. In females lethargy was observed in 3/5 females on Day 1, in 2/5 females on Days 7 or 8. Flat posture was observed in 1/5 males on Day 1. Hunched posture occured on Days 2-11 in 1/5 males, on Days 1-9 in 1/5 males, and on Days 2-6 in 3/5 males and recurred on Day 8 in 2/5, persisting until Day 10. Hunched posture was observed on Day 2 in 5/5 females, in 1/5 females persisting until Day 6 and recurred on Days 8-11, in 3/5 females until Day 8, 10 or 11, and in 1/5 females recurred on Day 5-11. Piloerection was observed on Day 1, on Days 1-3 or on Days 1-6 in 5/5 males and recurred in 3/5 on Day 8, persisting until Day 9 in 2/5. In females, piloerection was observed in 5/5 on Day 1, persisting until Day 6 in 2/5 and until Day 11 in 1/5, or persisting until Day 3 in 1/5 and recurred on Day 8-9. Chromodacryorrhoea was observed in 5/5 males and in 2/5 females on the day of the treatment, persisting until Day 2 in 4/5 males and 2/5 females and until Day 3 in 1/5 males. In 3/5 females chromodacryorrhoea occured on Day 2, and recurred in 2/5 females on Day 7 or 8. Shallow respiration was observed in 1/5 males and 1/5 females on Day 8. Lean appearance was noted in 2/5 males and in 1/5 females on Day 8. Restless behavior occured in 1/5 female on Day 7. Ptosis was noted in 3/5 males and 1/5 females on Day 1, in 2/5 males on Days 1-2, in 1/5 females on Day 7. Scales on the treated skin-area was noted in 1/5 males on Day 6 - 8.

For further details, see Table 1 under "Any other information on results incl. tables".
Body weight:
Excessive weight loss was observed in the female sacrificed for ethical reaons on Day 8. Slight body weight loss (2-10%)was noted between Days 1 and 8 in 5/5 males and 4/5 females. The body weight of the surviving animals had recovered by Day 15. For further details, see table 2 under "Any other information on results incl. tables".
Gross pathology:
The female that was sacrificed for ethical reasons on Day 8 showed a reduced size of the thymus at macroscopic post mortem examination. No abnormalities were observed at macroscopic post mortem examination in the 9 surviving animals.

Any other information on results incl. tables

Table 1 Clinical signs

Test Days   1 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Hours after dosing   0 2 4                            

Males

Animal 1                                    
Lethargy (3) - 1 1 - - - - - - - - - - - - - -
Hunched posture (1) - 1 1 - - - - - - - - - - - - - -
Flat posture (1) - - - 1 1 1 1 1 - 1 1 1 - - - - -
Piloerection (1) - - 1 1 - - - - - - - - - - - - -
Chromodacryorrhoea (snout) (3) - - - 2 1 - - - - - - - - - - - -
ptosis (3) - 1 1 - - - - - - - - - - - - - -
Animal 2                                    
Lethargy (3) - 1 1 - - - - - - - - - - - - - -
Hunched posture (1) - - - 1 1 1 1 1 - - - - - - - - -
Piloerection (1) - - 1 1 1 - - - - - - - - - - - -
Chromodacryorrhoea (snout) (3) - 1 1 1 - - - - - - - - - - - - -
ptosis (3) - - 1 - - - - - - - - - - - - - -
Animal 3                                    
Lethargy (3) - - - 2 - - - - - - - - - - - - -
Hunched posture (1) - 1 1 1 1 1 1 1 1 1 1 - - - - - -
Piloerection (1) - 1 1 1 1 1 1 1 - 1 - - - - - - -
Chromodacryorrhoea (snout) (3) - 1 1 1 - - - - - - - - - - - - -
ptosis (3) - - 1 1 - - - - - - - - - - - - -
Animal 4                                    
Lethargy (3) - 1 1 - - - - - - 1 - - - - - - -
Hunched posture (3) - - - 1 1 1 1 1 - 1 1 1 - - - - -
Piloerection (1) - - 1 1 1 - - - - 1 1 - - - - - -
Scales (3) - - - - - - - 1 1 1 - - - - - - -
Chromodacryorrhoea (snout) (3) - 1 1 1 - - - - - 1 - - - - - - -
ptosis (3) - 1 1 - - - - - - - - - - - - - -
Animal 5                                    
Lethargy (3) - 1 1 2 - - - - - 1 - - - - - - -
Hunched posture (1) - - - 1 1 1 1 1 1 1 1 1 1 - - - -
Shallow respiration (3) - - - - - - - - - 1 - - - - - - -
Piloerection (3) - 1 1 1 1 - - - - 1 1 - - - - - -
Chromodacryorrhoea (snout) (3) - 1 1 1 - - - - - - - - - - - - -
lean (1) - - - - - - - - - 1 - - - - - - -
ptosis (3) - 1 1 1 - - - - - - - - - - - - -

Females

Animal 6                                    
Lethargy (3) - 1 1 - - - - - - 1 - - - - - - -
Hunched posture (1) - - - 1 1 1 1 1 - 1 1 1 1 - - - -
Piloerection (3) - 1 1 1 1 - - - - 1 1 - - - - - -
Chromodacryorrhoea (snout) (3) - 1 2 2 - - - - - - - - - - - - -
ptosis (3) - 1 1 - - - - - - - - - - - - - -
Animal 7                                    
Restless (3) - - - - - - - - 1 -              
Lethargy (3) - - 1 - - - - - - 1              
Hunched posture (1) - - - 1 1 1 1 1 1 1              
Shallow respiration (3) - - - 2 - - - - - 1              
Piloerection (1) - 1 1 1 1 1 1 1 1 1              
Chromodacryorrhoea (snout) (3) - - - 2 - - - - 1 1              
lean (1) - - - - - - - - - 1              
ptosis (3) - - - - - - - - - 1              
Animal 8                                    
Lethargy (3) - - 1 - - - - - - - - - - - - - -
Hunched posture (1) - - - 1 1 1 1 1 1 1 1 1 - - - - -
Piloerection (1) - - 1 1 1 1 1 1 - - - - - - - - -
Chromodacryorrhoea (snout) (3) - 1 1 2 - - - - - - - - - - - - -
Animal 9                                    
Hunched posture (1) - - - 1 1 1 1 1 1 1 1 1 1 - - - -
Piloerection (1) - - 1 1 1 1 1 1 - - - - - - - - -
Chromodacryorrhoea (snout) (3) - - - 2 - - - - - - - - - - - - -
Animal 10                                    
Lethargy (3) - - - - - - - - - 1 - - - - - - -
Hunched posture (1) - - - 1 - - 1 1 1 1 1 1 1 - - - -
Piloerection (1) - 1 1 1 1 1 1 1 1 1 1 1 1 - - - -
Chromodacryorrhoea (snout) (3) - - - 2 - - - - - 1 - - - - - - -
lean (1) - - - - - - - - - 1 - - - - - - -

Number in brackets = Max score

Table 2 Body weights (gram)

Days 1 8 15
Males
Animal 1 284 274 313
Animal 2 309 306 347
Animal 3 288 271 309
Animal 4 274 265 298
Animal 5 296 268 311
Mean ± SD 290 ± 13 277 ± 17 316 ± 18
Females
Animal 1 199 187 206
Animal 2 189 142 -
Animal 3 188 197 208
Animal 4 194 191 205
Animal 5 214 196 226
Mean ± SD 197 ± 11 183 ± 23 211 ± 10

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: not classified