Registration Dossier

Administrative data

Description of key information

Skin irritation: Data waiving; RA to CAS 16415-12-6 (OECD TG 404, GLP): not irritating
Eye irritation (OECD 437, GLP): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because an acute toxicity study by the dermal route does not indicate skin irritation up to the relevant limit dose level (2 000 mg/kg body weight)
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Reason / purpose for cross-reference:
data waiving: supporting information
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean over 24, 48, and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean over 24, 48, and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean over 24, 48, and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
In a skin irritation study conducted in accordance with OECD 404 and GLP (reliability score 1), the source substance hexadecyltrimethoxysilane was minimally transiently irritating to the skin of one of three rabbits. There were no systemic effects reported. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in skin irritation potential.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 - 19 Aug 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Version / remarks:
(2013)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Schwabach, Germany
Species:
cattle
Strain:
other: not provided
Details on test animals or tissues and environmental conditions:
TEST METHOD
The bovine corneal opacity and permeability (BCOP) test is an in vitro test method used for identifying i) chemicals inducing serious eye damage and ii) chemicals not requiring classification for eye irritation or serious eye damage. The potential of a test substance to cause ocular corrosivity or severe irritancy is measured by its ability to induce opacity and increased permeability in an isolated bovine cornea. The opacity and permeability assessments of the cornea are combined to derive an in vitro
irritancy score (IVIS), which is used to classify the irritancy level of the test substance.

IDENTIFICATION OF THE SOURCE OF THE EYES, STORAGE AND TRANSPORT CONDITIONS
- Source: A. Moksel AG, Buchloe, Germany
- Transport medium and temperature conditions: HBSS containing Pen/Strep on ice

PREPARATION OF THE EYES (BEFORE EXPOSURE)
- Eyes free of defects (scratches, neovascularisation): yes
- Dissection of the eyes and treatment: Isolated corneas were mounted in cornea holders
- Type of cornea holder used: not specified, Duratec GmbH, Germany
- Description of the cornea holder: The cornea holders consist of an anterior and a posterior compartment, which interface with the epithelial and endothelial sides of the cornea
- Test medium and temperature conditions used in the cornea holder: RPMI 1640 (without phenol red) supplemented with 1% [v/v] fetal bovine serum and 2 mM [v/v] L-glutamine; prior to use: pre-warmed to 32 ± 1 °C
- Equilibration time: 1 h at 32 ± 1°C

DETERMINATION OF THE INITIAL OPACITY
- Method: Corneal opacity was determined by the amount of light transmission through the cornea via an opacitometer
- Specification of the device: opacitometer (BASF-OP3.0, Duratec GmbH, Germany)

Vehicle:
unchanged (no vehicle)
Controls:
other: number of eyes for the negative control: 3; number of eyes for the positive control: 3
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied in the test: 750 μL
- Concentration (if solution): liquids: 100%

VEHICLE
- Substance: physiol. saline
- Concentration (if solution): 0.9% NaCl solution
- Amount(s) applied in the test: 750 μL

POSITIVE SUBSTANCE
- Substance: ethanol
- Concentration (if solution): 100%
- Amount(s) applied in the test: 750 μL
Duration of treatment / exposure:
10 min
Observation period (in vivo):
Not applicable
Number of animals or in vitro replicates:
number of eyes for the test item: 3
Details on study design:
TEST CONDITIONS
- Open-Chamber method: Before the corneas were mounted in corneal holders (Duratec GmbH) with the endothelial side against the O-ring of the posterior chamber, they had been visually examined for defects and any defective cornea had been discarded. The anterior chamber was then positioned on top of the cornea and tightened with screws. The chambers of the corneal holder were then filled with RPMI (without phenol red) containing 1% FBS and 2 mM L-glutamine (complete RPMI). The posterior chamber was always filled first. The controls or test substance were applied directly to the epithelial surface of the cornea.

POST-EXPOSURE TREATMENT
- Removal of the test substance: After 10 minutes incubation at 32 ± 1°C either the test substance or the control substance was removed and the epithelium washed at least three times.
- Medium for washing the corneas: MEM containing phenol red
- Medium for final rinsing: complete RPMI (without phenol red)

DETERMINATION OF THE FINAL OPACITY
- Method: Corneal opacity was determined by the amount of light transmission through the cornea via an opacitometer
- Time of determination: Directly after refilling fresh RPMI without phenol red in the anterior chamber the final opacity was measured
- Specification of the device: BASF-OP3.0, Duratec GmbH, Germany

DETERMINATION OF THE CORNEAL PERMEABILITY:
- Method: Sodium fluorescein solution was added to the anterior chamber of the cornea holder while the posterior chamber was filled with RPMI fresh medium. The amount of sodium fluorescein that crosses into the posterior chamber was quantitatively measured via spectrophotometry at 490 nm recorded as optical density (OD490)
- Amount and concentration of the dye: 1 mL sodium fluorescein solution (4 mg/mL)
- Incubation time: 90 min at 32 ± 1°C
Irritation parameter:
cornea opacity score
Run / experiment:
10 min
Value:
0.16
Vehicle controls validity:
valid
Remarks:
0.95
Negative controls validity:
not examined
Positive controls validity:
valid
Remarks:
18.16
Remarks on result:
no indication of irritation
Irritation parameter:
in vitro irritation score
Run / experiment:
10 min
Value:
0.25
Vehicle controls validity:
valid
Remarks:
1.16
Negative controls validity:
not examined
Positive controls validity:
valid
Remarks:
40.34
Remarks on result:
no indication of irritation
Irritation parameter:
other: permeability
Run / experiment:
10 min
Value:
0.006
Vehicle controls validity:
valid
Remarks:
0.014
Negative controls validity:
not examined
Positive controls validity:
valid
Remarks:
1.479
Other effects / acceptance of results:
The eye irritancy potential of the test item was investigated in the bovine corneal opacity and permeability assay resulting in an in vitro irritation score (IVIS) of 0.25. Therefore, the test item was considered as not requiring classification for eye irritation or serious eye damage. The in vitro irritation score obtained with the positive control fell within the two standard deviations of the current historical mean and therefore this assay is considered to be valid. The negative control responses resulted in opacity and permeability values that are less than the established upper limits for background bovine corneas treated with the respective negative control.

Table 1: Corneal opacity

Parameter

OD490

(Initial opacity)

OD490

(final opacity)

OD490

(change of opacity value)

 

Corrected opacity value

Mean

 Negative control

1.14

2.53

1.39

 

-

 

0.95

1.06

2.03

0.96

1.21

1.69

0.48

 Positive control

2.14

22.78

20.64

19.69

 

18.16

2.26

19.69

17.43

16.49

2.03

21.28

19.25

18.30

 

Test item

0.35

1.80

1.45

0.50

 

0.16

1.28

2.37

1.09

0.15

0.92

1.69

0.77

-0.18

Table 2: Permeability data

Parameter

OD490

 

Corrected OD490

 

Mean

 

Negative control

0.018

 

-

 

0.014

0.010

0.014

 

Positive control

1.890

1.876

 

1.479

1.208

1.194

1.380

1.366

 

Test item

0.008

-0.006

 

0.006

0.034

0.020

0.018

0.004

Table 3: In Vitro Irritation Score

 

Mean IVIS

Negative control

1.16

Positive control

40.34

Test item

0.25

Table 4: Historical Mean In Vitro Irritation Score of the Negative and Positive Control

 

Mean IVIS

Standard Deviation

Negative control

0.73

0.57

Positive control

48.80

10.37

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
According to the bovine corneal opacity and permeability assay, the test item can be considered as not requiring classification for eye irritation or serious eye damage.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

 

Only limited data on skin irritation is available for triethoxyhexadecylsilane (CAS 16415-13-7). Therefore, the risk assessment was performedbased on the available data from the source substancehexadecyltrimethoxysilane (CAS 16415-12-6). In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and following the Read across assessment framework (RAAF, ECHA 2017) read across from analogue substances has been applied to support the human health hazard assessment of triethoxyhexadecylsilane (CAS 16415-13-7).

 

In the skin irritation study conducted in accordance with OECD 404 and GLP (LPT, 2002), hexadecyltrimethoxysilane was minimally transiently irritating to the skin of one of three rabbits. Erythema and edema scores over 24, 48, and 72 h were 0.33 and 0, respectively. The effects were fully reversible within 5 days. There were no systemic effects reported.

According to Regulation (EC) No 1907/2006, Annex VIII, Section 8.1.1, Column 2, testing of in vivo skin irritation does not need to be conducted if an acute toxicity study by the dermal route does not indicate skin irritation up to the limit dose level of 2000 mg/kg bw. An acute dermal toxicity study performed in rats according to OECD TG 402 with the registered substance triethoxyhexadecylsilane (CAS 16415-13-7) is available indicating no signs of systemic toxicity when exposed to the limit dose of 2000 mg/kg bw. Neither erythema nor edema was recorded during the 14-day observation period. The acute dermal LD50 value was considered to be >2000 mg/kg bw. Thus, an in vivo skin irritation study does not need to be conducted based on no observed skin reactions with the test substance.

Since the acute dermal toxicity study was performed in rats a skin irritating potential cannot be excluded. Therefore, reliable data on skin irritation are considered from the structural related substance hexadecyltrimethoxysilane (CAS 16415 -12 -6).

As a weight of evidence approach all available data (acute dermal study and skin irritation study with read across) indicate no skin irritating potential for triethoxyhexadecylsilane.

 

Eye irritation

 

The eye irritation properties of the registered substance triethoxyhexadecylsilane (CAS 16415-13-7) have been investigated in an in vitro study performed according to OECD TG 437 and in compliance with GLP using the bovine corneal opacity and permeability test (BCOP, BSL, 2016). For the assessment of the eye irritation properties 750 µL of the test material was applied to the corneal surface of bovine eyes for 10 min. Positive (100% ethanol) and negative (0.9% NaCl) controls were included in the study and gave the expected results. Ten minutes after application mean values of cornea opacity (0.16), permeability (0.006) and In Vitro Irritancy Score (0.25) were calculated from three repetitions. Hence, triethoxyhexadecylsilane induced an IVIS <3 and thus the test material is considered to be not-irritating to the eye.

 

 

Justification for classification or non-classification

The available data on skin and eye irritation/corrosion of the registered substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.