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Administrative data

Description of key information

In the single carcinogenicity study for 3-aminopropyl(triethoxy)silane, which is well documented and meets generally accepted scientific principles, there was no evidence of skin tumours following dermal exposure up to 209 mg/kg bw/day, the highest dose tested. Further testing is not considered necessary because:

•       The substance does not have a wide-dispersive use and exposure is expected to be low (see Section 9 for further details);

•       The substance is not classified for mutagenicity; and

•       There is no evidence from the repeated dose studies that the substance is able to induce hyperplasia or pre-neoplastic lesions.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented study, meeting generally accepted scientific principles but without evidence of GLP status. Study acceptable for assessment.
Qualifier:
no guideline followed
Principles of method if other than guideline:
No guideline is specified. In this study applications of the test material are made to the shaved skin of mice (40/sex/dose), three times weekly for 24 months. Microscopic examinations were restricted to the skin. The current OECD guideline for carcinogenicity studies (451) which describes treatment via the oral route notes that adaptations may be made for dermal treatment. These guidelines recommend: the use of at least 50 animals/sex/dose; microscopic examination of a wide range of tissues; more extensive examination and reporting.
GLP compliance:
not specified
Species:
mouse
Strain:
other: C3H/Bd
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Oak Ridge National Laboratory, Tennessee 37831, USA
- Age at study initiation: 9-12 weeks
- Weight at study initiation: no details
- Housing: 5/cage
- Diet: standard diet libitum
- Water: drinking water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no details
- Humidity (%): no details
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: no details
Route of administration:
dermal
Vehicle:
other: cyclohexane
Details on exposure:
TEST SITE
- Area of exposure: not stated.

TEST MATERIAL
- Amount(s) applied: 50 ul applied 3 times/week;
- Concentration (if solution): solution containing 30, 20 or 15% w/vol TS in cyclohexane. Doses said to be 43.8, 29.2 or 14.6 mg/wk.
These would be equivalent to 1460, 973 and 487 mg/kg bw/wk for a 30 g mouse or 209, 139 or 70 mg/kg bw/day (for a 30 g mouse).

VEHICLE
- Justification for use and choice of vehicle: none given
- Amount(s) applied (volume or weight with unit): see above
- Lot/batch no. (if required): no details
- Purity: no details

USE OF RESTRAINERS FOR PREVENTING INGESTION: no data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
24 months
Frequency of treatment:
3 times/week
Post exposure period:
none
Remarks:
Doses / Concentrations:
0, 14.6, 29.2, 43.8 mg/wk
Basis:
other: equivalent to 70, 139 or 209 mg/kg bw/day for a 30 g mouse
No. of animals per sex per dose:
test animals; positive controls (benzo(a)pyrene in cyclohexane: 40/sex/dose
vehicle controls (cyclohexane): 100/sex/dose
untreated room controls: 30/sex
Control animals:
yes, concurrent no treatment
yes, concurrent vehicle
other: positive control: benzo(a)pyrene in cyclohexane
Details on study design:
- Dose selection rationale: based on prior 2-week study
- Post-exposure recovery period in satellite groups: none
Positive control:
benzo(a)pyrene: up to 15 µg/week (0.01% in cyclohexane)
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

DERMAL IRRITATION (if dermal study): No data for 24-month study

BODY WEIGHT: Yes
- Time schedule for examinations: 6, 12, 18 and 24 months

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Restricted to skin
Other examinations:
None
Clinical signs:
not examined
Dermal irritation (if dermal study):
not examined
Mortality:
not examined
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
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:
not examined
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
The liver, spleen, kidney, ovary and lung were examined in the animals. The incidence of grossly observed neoplasms were in the similar range as the vehicle control, however, whether any of the incidences were statistically significant is unknown. See table 1 for further information.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
Examination was limited to the skin (see table 2). The incidence of papilloma was increased in the highest dose group, however, not statistically significant.
Other effects:
not specified
Details on results:
Concurrent vehicle controls – no historical control data included.
Dose descriptor:
NOAEL
Effect level:
43.8 other: mg/week (might be considered equivalent to 209 mg/kg bw/day for a 30 g mouse)
Sex:
male/female
Basis for effect level:
other: No increase in skin tumours. Very limited study.
Remarks on result:
other: Effect type: carcinogenicity

Table 1: Incidence of grossly observed neoplasms

Tumour incidence %

sex

Dose level (mg/wk)

Vehicle control (cyclohexane 117 mg/wk)**

14.6*

29.2*

43.8*

Liver

male

52***

58

58

48

female

18

18

12

12

Spleen

male

0

0

0

0

female

0

0

0

0

Kidney

male

1

0

2

0

female

3

4

0

0

Ovary/testis

male

0

0

0

2

female

44

50

50

45

Lung

male

13

18

15

15

female

10

12

12

8

* 40 animals/sex/dose

**100 animals/sex/dose

***the copy seen by this reviewer is indistinct - this value could be 52 or 92

Table 2: Histologically confirmed skin tumours (sexes combined)

Tumour type

Dose level (mg/wk)

Vehicle control (cyclohexane 117 mg/wk)**

Positive control B(a)P in cyclohexane (0.015/0.0075/0.00375 mg/wk)*

14.6*

29.2*

43.8*

Papilloma

1

11/14/28

0

0

2

Squamous carcinoma

0

60/43/19

0

0

0

Fibroma

0

0/1/1

0

0

0

Other

0

0/1/2

0

0

0

* 40 animals/sex/dose

**100 animals/sex/dose

Conclusions:
A 24-month dermal study designed to investigate the carcinogenicity of the test substance in mouse skin failed to demonstrate any carcinogenic potential. This study would not meet the criteria for a modern, comprehensive carcinogenicity study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
209 mg/kg bw/day
Study duration:
chronic
Species:
mouse

Justification for classification or non-classification

Based on the available data 3-aminopropyl(triethoxy)silane does not require classification for carcinogenicity according to Regulation (EC) No 1272/2008.

Additional information

A 24-month dermal study designed to investigate the carcinogenicity of 3-aminopropyl(triethoxy)silane in mice skin did not demonstrate any carcinogenic potential.

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