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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
This study was designed to determine the effects in rats resulting from repeated percutaneous exposure to A-1120 for 9 doses over an 11 day period.
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
N-(3-(trimethoxysilyl)propyl)ethylenediamine
EC Number:
217-164-6
EC Name:
N-(3-(trimethoxysilyl)propyl)ethylenediamine
Cas Number:
1760-24-3
Molecular formula:
C8H22N2O3Si
IUPAC Name:
N-[3-(trimethoxysilyl)propyl]ethane-1,2-diamine
Details on test material:
- Name of test material (as cited in study report): N-beta-(aminoethyl)-gamma-aminopropyltrimethoxysilane (A-1120)
- Substance type: Alkoxysilane
- Physical state: Colourless liquid


- Analytical purity: 77.3 %


- Impurities (identity and concentrations): No data
- Purity test date: No data
- Lot/batch No.: 0634JA120390
- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
11 days
Frequency of treatment:
9 applications
Doses / concentrationsopen allclose all
Dose / conc.:
257.5 mg/kg bw/day (nominal)
Dose / conc.:
772.5 mg/kg bw/day (nominal)
Dose / conc.:
1 545 mg/kg bw/day (nominal)
No. of animals per sex per dose:
20/sex/control and high dose
10/sex/ mid and low dose
Control animals:
other: filtered water

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 1 545 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No signs of systemic toxicity.

Target system / organ toxicity

Critical effects observed:
no

Any other information on results incl. tables

No clinical signs of toxicity except local effects on skin. Barely perceptible erythema was observed occasionally in males of the 772.5 and 1545 mg/kg bw/day groups and in females of the 1545 mg/kg bw/day group during the first week of treatment. Exfoliation and/or excoriation, were observed during the treatment period in males and females of the 772.5 and 1545 mg/kg bw/day groups. One female of the 257.5 mg/kg bw/day group also showed excoriation during the treatment period. During the 19 -day recovery period, exfoliation and/or excoriation were observed in males and females of the 1545 mg/kg bw/day group. No skin reactions were observed after day 17.

Decreases in food consumption were observed in males of the 772.5 and 1545 mg/kg bw/day during the treatment period. Some body weight decreases were observed but there was no clear dose-response. Slight increases in water consumption were observed in females of the 772.5 and 1545 mg/kg bw/day groups during the study. However, the increases were not considered to be toxicologically significant due to the lack of any associated changes in clinical pathology parameters and the small magnitude of the changes. There were no treatment-related effects on haematology, clinical chemistry, isoenzymes or urinalysis at the end of the treatment period. There was no effect on haematological parameters at the end of the recovery period.

There were slight increases in adrenal weights in the mid and high dose groups, but in light of the lack of pathological findings these were not considered to be toxicologically significant.

Various signs of skin irritation were observed. Exfoliation and excoriation were noted at the end of the treatment period of males in the mid and high dose groups, and females of all groups. Microscopic findings in these groups were hyperkeratosis, acanthosis, epidermitis and dermatitis. Ulceration and dermal fibrosis were observed occasionally in the same treated groups. Residual effects, as indicated by minimal hyperkeratosis and dermatitis were observed in males and females of the high dose group at the end of the 19 -day recovery period.

Applicant's summary and conclusion

Conclusions:
Treatment of rats to N-(3-(trimethoxysilyl)propyl)ethylenediamine for nine cutaneous applications during an 11-day period produced transient clinical, necropsy and microscopic observations indicative of mild to moderate skin irritation in males treated with 772.5 and 1545 mg/kg bw/day and females treated with 257.5 mg/kg bw/day and above. There was no clear indication of systemic toxicity. Therefore the NOAEL for systemic effects is at least 1545 mg/kg bw/day in rats.