3-aminopropyltriethoxysilane

Carcinogenicity

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.