Quaternary ammonium compounds, C12-14-alkyl[(ethylphenyl)methyl]dimethyl, chlorides

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given, followed methods comparable to guideline EPA OPPTS 870.2500

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

yes

Remarks:

1. In the study, abraded and non abraded skin sites were used; however, the guideline recommends unabraded skin. 2. Exposure period was 24 h; however, guideline recommends 4 h exposure period

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Type of coverage:

occlusive

Preparation of test site:

other: The test substance was applied to both abraded and intact skin

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Test material
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

24h

Observation period:

24 and 72h

Number of animals:

6

Details on study design:

Test site:
- Area of exposure: Back of animal
- Type of wrap if used: The patches consisted of two layers of light gauze cut in squares (2.5 cm on the side). The patches were secured to the test area by thin bands of adhesive tape and the trunk of each animal was wrapped in clear plastic trunk bands after application of the test substance.
- Type of test site: Two areas (intact and abraded) on the back of each animal placed approximately 10 cm apart

Scoring system:
- Skin reactions were scored for erythema and edema, according to Draize Woodland and Calvery scoring system.

Irritation parameter:

primary dermal irritation index (PDII)

Remarks:

Intact and abraded skin site

Basis:

mean

Time point:

24/48/72 h

Score:

6.29

Max. score:

8

Reversibility:

not fully reversible within: 72h

Remarks on result:

other: responses were not scored at 48 h

Irritation parameter:

erythema score

Remarks:

Intact skin site

Basis:

mean

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

not fully reversible within: 72h

Remarks on result:

other: responses were not scored at 48 h

Irritation parameter:

erythema score

Remarks:

Abraded skin site

Basis:

mean

Time point:

24/48/72 h

Score:

3.5

Max. score:

4

Reversibility:

not fully reversible within: 72h

Remarks on result:

other: responses were not scored at 48 h

Irritation parameter:

edema score

Remarks:

Intact skin site

Basis:

mean

Time point:

24/48/72 h

Score:

2.66

Max. score:

3

Reversibility:

not fully reversible within: 72h

Remarks on result:

other: responses were not scored at 48 h

Irritation parameter:

edema score

Remarks:

Abraded skin site

Basis:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 72h

Remarks on result:

other: responses were not scored at 48 h

Irritant / corrosive response data:

- Severe erythema and edema were observed in animals with abraded and intact skin.

Table 1. Individual animal data on the skin irritation response

Rabbit no.	Reaction	24 h		72 h
		Intact	Abraded	Intact	Abraded
1	Erythema	4	4	3	4
	Edema	2	3	3	3
2	Erythema	3	4	3	3
	Edema	2	3	3	3
3	Erythema	4	4	3	3
	Edema	3	3	3	3
4	Erythema	4	4	3	3
	Edema	2	3	3	3
5	Erythema	3	3	3	3
	Edema	3	3	3	3
6	Erythema	4	4	4	3
	Edema	2	3	3	3

 

Interpretation of results:

other: Category 1 (corrosive) based on CLP criteria

Conclusions:

Based on the results of the read across substance study, the test substance is considered to be corrosive to rabbit skin.

Executive summary:

A study was conducted to determine the skin irritation / corrosion potential of the read across substance, C12-16 ADBAC (active: >93%), according to US EPA OPPTS 870.2500. The experiment was performed in rabbits. The undiluted read across substance was applied on intact and abraded skin sites using occlusive patches for an exposure period of 24 h. The skin was then observed for erythema and edema formation and the scoring was done according to the Draize, Woodland and Calvery scoring system at 24 and 72 h from the onset of exposure. Severe erythema and edema were observed in all the test animals at both the abraded and intact sites. The mean Primary Irritation Index (PII) of the read across substance was calculated to be 6.29 and the mean values of erythema and edema were 3.33 (intact skin site), 3.5 (abraded skin site), 2.66 (intact skin site) and 3 (abraded skin site). Under study conditions, the read across substance was considered to be corrosive to rabbit skin (Wallace, 1975). Based on the results of the read across study, similar skin corrosion potential can be expected for the test substance, C12-14 ADEBAC.

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

August 09, 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

other: USA Federal Hazardous Substances Act (US-FHSA)

Deviations:

not specified

Remarks:

No guidelines were in force when the study was undertaken.

Qualifier:

according to guideline

Guideline:

other: Draize JH, Woodard G and Calvery HO, Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes, J. Pharm. & Ex. Ther. 82, 377, (1944)

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Sex: Male and female
Age/weight at study initiation: 1.8-2.4 kg

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

24 h

Observation period:

24 and 72 h after application

Number of animals:

3 animals per sex

Details on study design:

Preparation of test substance: Used as supplied
Area of exposure: Not specified – 0.5 mL applied under occlusive patches (1”x1” gauze covered by adhesive tape)
Dose route: Dermal application (occlusive) to abraded and unabraded areas
Observations: Sacrifice and Pathology
Scoring system: Draize et al. (1944) J. Pharm. Ex. Ther. 82: 377.
Examination Time points: 24 and 72 h

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Score:

ca. 8

Max. score:

8

Reversibility:

not specified

Remarks on result:

other: dermal irritant and corrosive

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24/72 h

Score:

ca. 4

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24/72 h

Score:

ca. 4

Max. score:

4

Reversibility:

not specified

Table 1: Skin Irritation table (intact)

3 Animals	Mean score*	Maximum value	Maximum duration of any effect	Maximum value at the end of the observation period
erythema/eschar	4	4	-	4
oedema	4	4	-	4
*Calculated on the basis of the scores at 24 and 72 h for all animals

Table 2: Skin Irritation table (abraded)

3 Animals	Mean score*	Maximum value	Maximum duration of any effect	Maximum value at the end of the observation period
erythema/eschar	4	4	-	4
oedema	4	4	-	4
*Calculated on the basis of the scores at 24 and 72 h for all animals

Interpretation of results:

other: Category 1 (corrosive) based on CLP criteria

Remarks:

(a corrosive classification can be expected for the neat test substance, based on the observed irritation response of 25% test substance)

Conclusions:

Under study conditions, the test substance was classified as skin corrosive.

Executive summary:

A study was conducted to determine the dermal irritation potential of the read across substance, C12-18 ADEBAC (active: 25%), according to the modified Draize test. 0.5 mL test substance (25%) was applied to abraded and non-abraded skin of 6 trabbits, under occlusive conditions for 24 h. The sites were individually examined and scored separately for erythema and edema at 24 and 72 h after removing wrapping and test substance. The mean scores for 24 and 72 h gradings were averaged to determine final irritation indices. Severe erythema and edema were observed in animals with abraded and non-abraded skin and the primary irritation index was calculated to be 8. Under study conditions, 25% test substance was concluded to be a primary dermal irritant and corrosive (Palankar, 1976). Based on the results of the read across study, neat test substance, C12 -14 ADEBAC, can be considered to be corrosive to skin.