Hexadecyltrimethoxysilane

Endpoint summary

Description of key information

Skin irritation in rabbits (OECD TG 404, GLP): not irritating
Eye irritation in rabbits (OECD TG 405, GLP): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 Apr 2002 to 12 Aug 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(adopted 1992)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: LPT Laboratory of Pharmacology and Toxicology KG, Löhndorf/Wankendorf, Germany
- Age at study initiation: 2-2.5 months
- Weight at study initiation: 2.3-2.5 kg
- Housing: Individually in cages
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3
- Humidity (%): 55 ±15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 15.04.2002 To: 30.04.2002

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

physiological saline

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72h, 4 and 5 days

Number of animals:

Three males

Details on study design:

TEST SITE
- Area of exposure: dorsal area of trunk
- % coverage: No data, but area was 6 cm².
- Type of wrap if used: Gauze patch held in place with non-irritating tape (semi-occlusive)

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 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:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Other effects:

No systemic effects reported.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Erythema and eschar	Edema
	Max. score: 4	Max. score: 4
1 h	0/0/1	0/0/0
24 h	0/0/1	0/0/0
48 h	0/0/1	0/0/0
72 h	0/0/1	0/0/0
4 days	-/-/1	-/-/0
5 days	-/-/0	-/-/0
Average 24h, 48h, 72h	0/0/1	0/0/0
Reversibility*	c	n/a
Time for reversion	Day 5	-

* Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

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), hexadecyl(trimethoxy)silane was minimally transiently irritating to the skin of one of three rabbits. There were no systemic effects reported.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12.04.2002 to 30.07.2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(adopted 1997)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Laboratory of Pharmacology and Toxicology, Löhndorf, GERMANY
- Age at study initiation: 2.5-3.5 months
- Weight at study initiation: 2.4 kg
- Housing: 1/cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 55±15
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2002-04-15 To: 2002-05-03

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye is the control in each case

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 ml

Duration of treatment / exposure:

Single administration, not irrigated. Observed up to 72 h.

Observation period (in vivo):

1, 24, 48, 72 h.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: after Draize, according to OECD 405

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

Conjunctival redness (grade 1) at 1 h and 24 h; conjunctival chemosis (grade 1) at 1 h. No corneal or iridial effects, or any other observations. The overall irritation score (24, 48, and 72 h) was 0.3 (max. score 13).

Other effects:

None.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctival redness	Conjunctival chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	0/0/0	0/0/0	1/1/1	1/1/1
24 h	0/0/0	0/0/0	1/1/1	0/0/0
48 h	0/0/0	0/0/0	0/0/0	0/0/0
72 h	0/0/0	0/0/0	0/0/0	0/0/0
Average 24h, 48h, 72h	0/0/0	0/0/0	0.3/0.3/0.3	0/0/0
Maximum average score (max 13)	0	0	0.3	0
Reversibility*	-	-	c	c
Average time (unit) for reversion	-	-	48 h	24 h

* Reversibility: c. = completely reversible; n. c. = not completely reversible; n. = not reversible

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

In an eye irritation study conducted according to OECD 405 and GLP (reliability score 1), hexadecyltrimethoxysilane was not irritating to the eyes of rabbits. There were no other effects reported.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

In the key skin irritation study conducted in accordance with OECD TG 404 and GLP (LPT, 2002b), the semi-occlusive application of hexadecyl(trimethoxy)silane for 4 h caused in one of the three rabbits very slight erythema (grade 1) from 60 min up to 4 days after patch removal. The effect was fully reversible within 5 days. The mean erythema and edema scores over 24/48/72 h out of all three animals were 0.33 and 0, respectively. There were no systemic effects reported. In conclusion, the test substance is not irritating to the skin.

Eye irritation:

In the key eye irritation study conducted according to OECD TG 405 and GLP (LPT, 2002c), hexadecyl(trimethoxy)silane was not irritating to the eyes of rabbits, after instillation of 0.1 ml of the test substance into the rabbits eye. No effects on cornea and iris were observed in any animal throughout the whole study period. Redness (grade 1) was observed in all animals at 1 h and 24 h, and was fully reversible within 48 h. Chemosis (grade 1) was observed in all animals at 1 h, but was fully reversible within 24 h. The resulting mean scores over 24/48/72 h out of all three animals were 0, 0, 0.33, and 0 for cornea, iris, redness, and chemosis, respectively. There were no other effects reported.

These findings were supported by an eye irritation study conducted in rabbits according to OECD TG 405 and GLP (Asta Pharma, 1989c). No effects on cornea and iris were observed in the 3 animals throughout the whole study period. Redness (grade 2) was observed in 2/3 animals at 1 h, reversed to grade 1 in 3/3 animals after 24 h and was fully reversible within 6 days. Chemosis (grade 1/2) was observed in the animals, but was fully reversible within 6 days. The resulting mean scores over 24/48/72 h out of all three animals were 0, 0, 0.9, and 1.1 for cornea, iris, redness, and chemosis, respectively. Conjunctival discharge (grade 3) was observed in all animals 1 h after treatment, clearly decreased within 24 h (max. grade 1 in 2/3 animals), and was fully reversible within 48 h.

In conclusion, the test substance is not irritating to the eye under the applied conditions.

Justification for classification or non-classification

The available data on skin and eye irritation 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.