Silanediol, 1-methyl-1-(1-methylethoxy)-, 1,1-diacetate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 Nov 2001 - 14 Jan 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

442-070-9

EC Name:

-

Cas Number:

329039-38-5

Molecular formula:

Hill formula: C8 H16 O5 Si CAS formula: C8 H16 O5 Si

IUPAC Name:

(acetyloxy)(methyl)(propan-2-yloxy)silyl acetate

Details on test material:

- Name of test material (as cited in study report): Methyldiacetoxyisopropoxy Silane Derivatives
- Physical state: Clear, colorless liquid
- Analytical purity: 85.8 %
- Impurities (identity and concentrations): 12.9 % Acetoxydiisopropoxymethtylsilane, 1.3 % hydrolisis product (siloxane)
- Purity test date: 04.10.2001
- Lot/batch No.: AA001 (04/10/01)
- Stability under test conditions: Hydrolyzes to form poly(silicone), isopropanol, and acetic acid
- Storage condition of test material: Use ground strap and store under nitrogen in original container below 30 °C (85 °F) in hood.

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Elm Hill Breeding Labs, Inc., Chelmsford, MA
- Age at study initiation: 21 days
- Weight at study initiation: 371.2 - 426.1 g
- Housing: Group housed (suspended stainless-steel cages), bedding in hardwood chips (non-contact), Prochip, Harlan Teklad, Madison, WI (non-contact)
- Diet: TEK 8602 Guinea Pig Diet, Harlan Teklad, Madison, WI, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: Minimum 5 days, under the same conditions as for the actual test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12, full spectrum fluorescent lights

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

cotton seed oil

Induction 2

Concentration / amount:

Concentration of test material and vehicle used at intradermal induction:
Intradermal injection (0.1 mL/site)

a) 1:1 (v/v) mixture of Freund's Complete Adjuvant (FCA) and
cottonseed oil (CSO).
b) Test item at 1% in cottonseed oil (CSO).
c) Test item at 1% in a 1:1 (v/v) mixture of Freund's Complete Adjuvant (FCA).

Epidermal applications:
Undiluted test item (100%) was used for epidermal induction.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

cotton seed oil

Challenge 2

Concentration / amount:

Concentration of test material and vehicle used at intradermal induction:
Intradermal injection (0.1 mL/site)

a) 1:1 (v/v) mixture of Freund's Complete Adjuvant (FCA) and
cottonseed oil (CSO).
b) Test item at 1% in cottonseed oil (CSO).
c) Test item at 1% in a 1:1 (v/v) mixture of Freund's Complete Adjuvant (FCA).

Epidermal applications:
Undiluted test item (100%) was used for epidermal induction.

No. of animals per dose:

Number of animals in test group: 10 males and 10 females
Number of animals in negative control group: 5 males and 5 females
Number of animals in positive control group: 2 males and 3 females
Number of animals in primary irritation group: 2 males and 2 females

Details on study design:

RANGE FINDING TESTS: Intradermal injection (0.1 mL per site) at concentrations of 1, 10, 50 and 100% (diluted in cottonseed oil) were tested. Corrosivity was observed at 50 and 100%. Irritation was noticed at 10% and 1%. Therefore, the concentration selected for the main study was 1%.
Topical pretest with 0.1 mL of the test substance at 25, 50, 75 and 100% (diluted in cottonseed oil) for 24 hours was performed. No irritation up to the highest concentration was observed. Therefore, both the topical induction and the topical challenge were dosed at 100%.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three pairs of intradermal injections on day 0 and a single topical exposure on test Day 7
- Test groups: Injection pair 1: 0.1 mL FCA 1:1 with vehicle; Injection pair 2: 0.1 mL test substance in an appropriate vehicle at the selected concentration; Injection pair 3: 0.1 mL test substance 1:1 with FCA [intradermal]; undiluted test substance [epidermal]
- Control group: Injection pair 1: 0.1 mL FCA 1:1 with vehicle; Injection pair 2: 0.1 mL undiluted vehicle; Injection pair 3: 0.1 mL of 50% formulation of vehicle, 1:1 with FCA [intradermal]; vehicle [epidermal]
- Site: dorsal skin
- Frequency of applications: 2, three pairs of intradermal injection on Day 0 , second epidermal on the test Day 7
- Concentrations: 1% intradermal (0.1 mL/site), 100% epidermal (0.1 mL)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: 24 hours under occlusive dressing
- Test groups: undiluted test item
- Control group: undiluted test item
- Site: 2 x 2 cm area of the left flank for test item, right flank for vehicle
- Concentrations: 100%
- Evaluation (hr after challenge): 24 h and 48 h after removal of the bandage

Challenge controls:

0.1% DNCB in 95% ethanol

Positive control substance(s):

yes

Remarks:

Dinitrochlorobenzene (DNCB)

Results and discussion

Positive control results:

The positive control animals exhibited skin reactions of 2 or 3 at each observation point (100% sinsitized).

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0 %

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0 %. No with. + reactions: 0.0. Total no. in groups: 5.0.

Results 3

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0 %

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0 %. No with. + reactions: 0.0. Total no. in groups: 5.0.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Executive summary:

The cutaneous allergenic potential of methyldiacetoxyisopropoxy silane was investigated by the GPMT. The study was performed in male and female albino guinea pigs in accordance with OECD Guideline No. 406. No abnormal symptoms and overt toxicity were observed in all animals at the 24- and 48-hour reading after treatment with the test item at 100% in cotton seed oil. Also no skin effect was observed in the control group. Based on the findings of this adjuvant sensitization test methyldiacetoxyisopropoxy silane is regarded to have no skin sensitising properties.