Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The analogue OS2200 which shares the same functional group with OS9600, also has comparable values for the relevant molecular properties for acute dermal toxicity. The study has been conducted according to OECD guidance under GLPs.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report): OS2200
- Molecular formula (if other than submission substance): C20H39N3O3Si
- Molecular weight (if other than submission substance): 397.62746
- Smiles notation (if other than submission substance): CC(C)CC(\C)=N\O[Si](O\N=C(/C)CC(C)C)(C=C)O\N=C(/C)CC(C)C
- InChl (if other than submission substance): Mixture of all possible stereoisomers
- Structural formula attached as image file (if other than submission substance): see Fig.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Ltd., Bicester, Oxon, England
- Weight at study initiation: 214 to 238 g
- Housing: Individually in metal cages with wire mesh floors
- Diet (e.g. ad libitum): Ad libitum (SDS LAD 1)
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30 - 70% RH
- Air changes (per hr): 10 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 - 1900 hours) in each 24-hour period

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorso-lumbar region (one day prior to treatment, hair was clipped), 10% of the total body surface. The test substance was applied by spreading it evenly over the prepared skin.
- % coverage, type of wrap: The treated area (approximately 50 mm x 50 mm) was then promptly covered with gauze which was held in place with a non-irritative dressing encircled firmly around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm (30- 40°C) water and blotted dry with absorbent paper
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.1 mL/kg bw (2000 mg/kg bw)
Duration of exposure:
24 hours
Doses:
1
No. of animals per sex per dose:
5 rats per sex and dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and clinical signs: twice daily; body weight: Days 1, 8 and 15.
- Necropsy of survivors performed: Yes. All animals were killed on Day 15 by carbon dioxide asphyxiation and were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all examined tissues was recorded.
- Other examinations performed: clinical signs, body weight, macroscopic examination, other: Local dermal irritation at the treatment site was assessed daily and scored (Draize scoring method)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 392 mg/kg bw
Based on:
test mat.
Remarks on result:
other: (read-across from an analogue for which LD50 > 2000 mg/kg bw)
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic reaction to treatment.
Body weight:
In comparison with historical data from the Department of Industrial Toxicology of HRC, slightly low bodyweight gains were recorded for two males and two females on Day 8. All other rats achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No macroscopic abnormalities were observed for animals killed on Day 15.
Other findings:
Sites of application showed no irritation or other dermal changes.

Any other information on results incl. tables

The data matrix is included in the reporting format attached in Section 13.

The results from the read-across approach are expressed (calculated) on the basis of the molecular weight of OS9600 and OS2200 since the basic structures of the target and source substances are the same.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the read-across approach from the analogue substance OS2200, the acute lethal dermal dose of OS9600 to rats was determined to be greater than 1392 mg/kg bw.
Executive summary:

An acute dermal toxicity study was performed on the analogue substance OS2200 according to EU Method B.3. A group of ten rats (five males and five females) was given a single dermal application of the test substance, as supplied, at a dose level of 2000 mg/kg bw. All animals were killed and examined macroscopically on Day 15, the end of the observation period. There were no deaths and no signs of systemic reaction to treatment. Sites of application showed no irritation or other dermal changes. In comparison with historical data from the Department of Industrial Toxicology of HRC, slightly low bodyweight gains were recorded for one male and three females on Day 8. All other rats achieved satisfactory bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic examination on Day 15. The LD50 of the analogue OS220 was therefore > 2000 mg/kg bw. Based on these results, the read-across approach was applied and the acute lethal dermal dose of OS9600 to rats was determined to be > 1392 mg/kg bw.