N-butyl-N-[(triethoxysilyl)methyl]butan-1-amine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

N-butyl-N-[(triethoxysilyl)methyl]butan-1-amine

EC Number:

810-490-5

Cas Number:

35501-23-6

Molecular formula:

C15H35NO3Si

IUPAC Name:

N-butyl-N-[(triethoxysilyl)methyl]butan-1-amine

Constituent 2

Reference substance name:

N,N-Dibutylaminomethyl-triethoxysilan

IUPAC Name:

N,N-Dibutylaminomethyl-triethoxysilan

Test material form:

other: liquid

Details on test material:

Name: N,N-Dibutylaminomethyl-triethoxysilan
CAS No: 35501-23-6
Lot No: 310113
Physical State: liquid
Colour: colourless to yellowish
Storage Conditions: at room temperature, protected from light,
protected from water/ humidity
Purity: 97.7% (GC)
Stability: rapid hydrolysis in water
Date of analysis: 31 January 2013
Expiry Date: 21 January 2015

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Species/strain: healthy New Zealand White Rabbits, Crl: KBL (NZW)
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Sex: female
- Body weight at the beginning of the study: > 2 kg
- Age at the beginning of the study: animals no. 1 and no. 2: 31 weeks old animals no. 3: 19 weeks old
- Number of animals: 3

The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to Art. 9.2, No. 7 of the German Act on Animal Welfare the animals were bred for experimental purposes.

ENVIRONMENTAL CONDITIONS
- Semi barrier in an air-conditioned room
- Temperature: 18 ± 3 °C (recommendations of TVT, GV-SOLAS)
- Relative humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: at least 10 x / hour
- Free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits (lot no. 0724), rich in crude fibre
- Free access to tap water (drinking water, municipal residue control, microbiological controls at regular intervals)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Housed in ABS-plastic or Noryl rabbit cages, floor 4200 cm2
- Adequate acclimatisation period (at least 5 days) under laboratory conditions

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

A dose of 0.1 mL of the test item was applied to the test site.

Duration of treatment / exposure:

The test item was applied at a single dose in the conjunctival sac of one eye of each test animal after pulling the lower lid away from the eyeball. The lids were then gently held together for about 1 second in order to prevent loss of the material. The untreated contralateral eye served as control. The treated eye was not rinsed after the application.

Observation period (in vivo):

The animals were observed for 72 hours after dosing.

Number of animals or in vitro replicates:

3

Details on study design:

Preparation of the Animals:
Approximately 24 hours before the test and immediately prior to the application both eyes of each animal were examined. A health inspection was performed to ensure the good state of health of the animals. Approximately 24 hours before the application the eyes were also examined with the aid of a fluorescein solution (Fluoreszein SE Thilo, Alcon Pharma GmbH, lot no. H 401, expiry date: 04/2016). The eyes were rinsed with physiological saline 0.9% NaCl (B. Braun Melsungen, lot no. 1307034, expiry date: 06/2016) after the examination. None of the animals showed eye irritation, ocular defects, or pre-existing corneal injury.

Initial Test (In Vivo Eye Irritation/Corrosion Test Using One Animal):
The in vivo test was performed initially using one animal.

Application:
One hour before the application of the test item, 0.01 mg/kg of buprenorphine (Reckitt Benckiser, lot no. 5416, expiry date: 09/2016) was administered subcutaneously in order to achieve a therapeutic level of systemic analgesia. Approximately 5 minutes prior to the application of the test item, 2-3 drops of an ocular anaesthetic (proparacaine hydrochloride ophtalmic 0.5% solution, Ursapharm Arzneimittel, lot no. 282598, expiry date: 04/2016) were administered in both the treated and the control eye of each animal. The test item was applied at a single dose in the conjunctival sac of one eye of each test animal after pulling the lower lid away from the eyeball. The lids were then gently held together for about 1 second in order to prevent loss of the material. The untreated contralateral eye served as control. The treated eye was not rinsed after the application.

Confirmatory Test:
The results of the initial test did not indicate the test item to be corrosive or a severe irritant to the eye using the procedure described. In order to confirm the response, two additional animals were treated in the same manner.

Observation Period:
The animals were observed for 72 hours after dosing.

Clinical Observation:
The eyes were examined for signs of irritation throughout the observation period. The eye irritation was scored and recorded according to the grades in the table below. For the calculation only the 24, 48 and 72-hour readings were used. At the end of the observation period the treated eyes were examined with the aid of a fluorescein solution. The eyes were rinsed with physiological saline 0.9% NaCl after the examination.

Evaluation of Results:
Individual reactions for each animal were recorded according to the scoring system described in Table 2 at each time of observation. For the calculation only the 24, 48 and 72-hour readings were used. Nature, severity and duration of clinical observations were described. The body weight changes were summarised in a tabular form.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, and 72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, and 72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, and 72 h

Score:

0

Max. score:

3

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, and 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

After the application into the eyes of three female NZW rabbits the test item produced neither irritant nor corrosive ocular effects.

Neither mortalities nor significant clinical signs of toxicity were observed.

Upon fluorescein examinations at the end of the observation period of 72 hours no corneal lesions were found in any animal.

Conjunctival discharge was observed in all animals 1 hour post-application.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present study, a single ocular application of the test item N,N-Dibutylaminomethyl-triethoxysilan to rabbits at a dose of 0.1 mL produced no irritant effects. Neither mortalities nor significant clinical signs of toxicity were observed.

In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of Commission Directive 2001/59/EC, the test item N,N-Dibutylaminomethyl-triethoxysilan has no obligatory labelling requirement for eye irritation.

According to Annex I of Regulation (EC) 1272/2008, the test item N,N-Dibutylaminomethyl-triethoxysilan has no obligatory labelling requirement for eye irritation.

According to GHS (Globally Harmonized Classification System) the test item N,N-Dibutylaminomethyl-triethoxysilan has no obligatory labelling requirement for eye irritation.

Executive summary:

SUMMARY RESULTS

On the basis of the test results given below and in conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC the substance should be assigned the following risk phrase:

No phrase

On the basis of the test results given below and in conformity with the criteria given in Annex I of Regulation (EC) 1272/2008, the substance should be:

Not classified

On the basis of the test results given below and in conformity with the criteria given in GHS (Globally Harmonized System of Classification and Labelling of Chemicals), the substance should be:

Not classified

Species/strain: New Zealand White Rabbits Crl: KBL (NZW)

Number of animals: 3

Amount of substance: 0.1 mL per test site

First time of effects: all animals: 1 hour post-application discharge grade 1

Last time of effects: all animals: 1 hour post-application discharge grade 1

Reversibility of the observed effects: all animals: the changes were fully reversible within 24 hours post-application

Method: OECD 405, EC 440/2008, Method B.4, OPPTS 870.2400

The calculated mean scores (Table 1) did not exceed the limit values according to Directive 2001/59/EC, to Regulation (EC) 1272/2008 and to GHS.

Table 1: Average Irritation Scores – (24, 48, 72-hour reading)

Animals No.	Gender	Conjunctival Redness	Conjunctival Chemosis	Iris	Cornea Opacity
1	Female	0.00	0.00	0.00	0.00
2	Female	0.00	0.00	0.00	0.00
3	Female	0.00	0.00	0.00	0.00

Conclusion:

Under the conditions of the present study, a single ocular application of the test item N,N-Dibutylaminomethyl-triethoxysilan to rabbits at a dose of 0.1 mL produced no irritant effects. Neither mortalities nor significant clinical signs of toxicity were observed.

In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of Commission Directive 2001/59/EC, the test item N,N-Dibutylaminomethyl-triethoxysilan has no obligatory labelling requirement for eye irritation.

According to Annex I of Regulation (EC) 1272/2008, the test item N,N-Dibutylaminomethyl-triethoxysilan has no obligatory labelling requirement for eye irritation.

According to GHS (Globally Harmonized Classification System) the test item N,N-Dibutylaminomethyl-triethoxysilan has no obligatory labelling requirement for eye irritation.