[3-(2,3-epoxypropoxy)propyl]triethoxysilane

Carcinogenicity

Description of key information

The dermal oncogenic potential of [3-(2,3-epoxypropoxy)propyl]triethoxysilane was assessed by applying 25 μl aliquots of 10% test substance in acetone to the shaved skin of 40 male C3H/HeJ mice (DePass et al., 1989). Applications were made three times per week until the death of the animals. A negative control group received acetone alone. No treatment-related skin tumours were observed, nor was there evidence of an increased incidence of internal tumours. No skin tumours were observed in the acetone control group, but two mice had subcutaneous sarcomas outside the treated area. The mean survival times were 492 and 502 days for the treated and control animals, respectively. The mortality rate was not significantly different the two groups.

Key value for chemical safety assessment

Carcinogenicity: via dermal route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Life-time

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The study did not meet current guideline requirements for carcinogenicity. It does, however, add weight of evidence for carcinogenicity.

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study was conducted to investigate the dermal oncogenicity potential of four silanes.

GLP compliance:

not specified

Species:

mouse

Strain:

C3H

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Jackson Laboratories, USA
- Age at study initiation: No data
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: Five per stainless steel cage with wire-mesh floor.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data - just stated to be 'controlled lighting'.


IN-LIFE DATES: No data

Route of administration:

dermal

Vehicle:

acetone

Details on exposure:

TEST SITE
- Area of exposure: No data
- % coverage: No data
- Type of wrap if used: No data
- Time intervals for shavings or clipplings: Weekly


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25µl
- Concentration (if solution): 10% by volume in acetone
- Constant volume or concentration used: yes


VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Purity: 'high purity'


USE OF RESTRAINERS FOR PREVENTING INGESTION: No data

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

Life-time of animals

Frequency of treatment:

Three times per week

Post exposure period:

None

Remarks:

Doses / Concentrations:
2mg
Basis:
other: Approximate dose

No. of animals per sex per dose:

40

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: The concentration chosen for this lifetime study was the highest one that resulted in neither unacceptable grossly visible local irritation, such as ulceration or flaking and peeling of the skin, nor reduced body weight gain.
- Rationale for animal assignment (if not random): Random

Positive control:

None

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily (no further information)


DETAILED CLINICAL OBSERVATIONS: No data


DERMAL IRRITATION (if dermal study): No data


BODY WEIGHT: No data


HAEMATOLOGY: No data


CLINICAL CHEMISTRY: No data


URINALYSIS: No data

Sacrifice and pathology:

Complete necropsies were performed on all mice. The dorsal skin from all animals plus tissues with suspect tumours were examined histologically after sectioning and staining with hematoxylin and eosin (no further information given).

Statistics:

Mortality rates and skin tumour incidence were compared by the product-limit method. The Mantel-Cox and Breslow statistics were used to test the equality of the survival and time-to-tumour curves.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

no effects observed

Details on results:

A poorly differentiated fibrosarcoma was found on the right front leg of one mouse. This tumour was not considered to be biologically significant because sarcomas of various types have been diagnosed in the acetone control mice (5/724) at this test laboratory. One fibrosarcoma was found on an acetone control mouse of this study. Another test substance treated mouse had a subcutaneous nodule in the inguinal area which was diagnosed as an area of caseous necrosis, without evidence of neoplasm. Many additional lesions were found on the skin of treated animals. These included hyperkeratosis, melanosis, epidermal hyperplasia, epidermal necrosis and dermatitis. These skin lesions were concluded to be treatment-related.

Dose descriptor:

NOAEL

Effect level:

>= 25 other: mg

Sex:

male

Basis for effect level:

other: No neoplastic effects.

Dose descriptor:

NOAEL

Sex:

male

Basis for effect level:

other: Non-neoplastic skin lesions at the single dose tested.

Remarks on result:

not determinable

Remarks:

no NOAEL identified.

Conclusions:

The results indicate that γ-glycidoxypropyltriethoxysilane was not carcinogenic when applied to the skin of male C3H/HeJ mice under the conditions of this study.

Executive summary:

The dermal oncogenic potential of γ-glycidoxypropyltriethoxysilane was assessed by applying 25µl aliquots of 10% test substance in acetone to the shaved skin of 40 male C3H/HeJ mice. Applications were made three times per week until the death of the animals. A negative control group received acetone alone. No treatment-related skin tumours were observed, nor was there evidence of an increased incidence of internal tumours. No skin tumours were observed in the acetone control group, but two mice had subcutaneous sarcomas outside the treated area. The mean survival times were 492 and 502 days for the treated and control animals, respectively. The mortality rate was not significantly different the two groups.

Justification for classification or non-classification

[3-(2,3 -Epoxypropoxy)propyl]triethoxysilane is not classified for carcinogenicity under Regulation (EC) No 1272/2008

Additional information

There is only one study available for the carcinogenic potential of [3-(2,3-epoxypropoxy)propyl]triethoxysilane. However, due to important methodological flaws (only one dose was tested in 40 animals, three times per week; the guideline for carcinogenicity recommends at least three doses in 100 animals per dose, seven times per week, no positive control) this study has been allocated a reliability score of 4.