Ethoxyquin

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Peer-reviewed assessment report (attached in section 13)

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Version / remarks:

US EPA FIFRA § 81-5

Deviations:

yes

Remarks:

Purity of the test compound was not determined by the laboratory prior to conduct of the test.

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not applicable

GLP compliance:

yes

Remarks:

self-certified to US EPA regulations at 40 CFR Parts 160 and 792

Test material

Test material information

Constituent 1

Reference substance name:

Ethoxyquin

EC Number:

202-075-7

EC Name:

Ethoxyquin

Cas Number:

91-53-2

Molecular formula:

C14H19NO

IUPAC Name:

ethoxyquin

Details on test material:

Chemical name
IUPAC: 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline
CAS: 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc. Denver PA USA

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

4h

Observation period:

≥ 7d

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure:
- % coverage:
- Type of wrap if used: semi-occlusive dressings / bandages

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
Application sites were evaluated in accordance with the method of Draize at approximately 30 - 60 minutes and 24, 48 and 72 hours after patch removal and daily thereafter through Day 7 since erythema still persisted in few animals at 72 hours.

SCORING SYSTEM:
- Method of calculation: Draize / according to OECD 404

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.333

Max. score:

1

Reversibility:

fully reversible within: 4 days or earlier

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritant / corrosive response data:

The test material induced very slight erythema on five animals. Desquamation was noted on two sites. There were no edema or other dermal findings. With the exception of desquamation on two sites, all dermal irritation completely subsided by Day 4 or earlier.

Other effects:

There were no deaths during the study. There were no remarkable body weight changes during the study period.

Any other information on results incl. tables

Table Individual and mean skin irritation scores according to Draize

	Erythema						Edema
Animal No.	708	712	715	725	735	742	708	712	715	725	735	742
After 1h	1	1	0	0	1	1	0	0	0	0	0	0
After 24h	0	1	1	0	1	0	0	0	0	0	0	0
After 48h	0	0	0	0	1	0	0	0	0	0	0	0
After 72h	0	0	1 d	0	1 d	0	0	0	0	0	0	0
Mean score 24-72h	0.333						0.0
Additional criteria specified in Directive 93/21/EEC Point 3.2.6.1 fulfilled: No

d = Desquamation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

As information was provided via a peer-reviewed assessment report, it can be considered as sufficiently reliable to assess the skin irritation potential of ethoxyquin in rabbits. Based on the observations after 24, 48 and 72 hours, the overall mean scores for erythema, eschar formation and edema were 0.33, 0.0 and 0.0, respectively. One hour after patch removal, erythema (but no edema) was seen in four out of six rabbits. If this observation time point is included, primary irritation index would be 0.4. Perhaps because of this calculation, classification by the notifier was “slightly irritating”. However, in fact, no classification according to Dir 67/548/EEC is required.
According to Regulation 1272/2008, classification as Skin irritation category 2 is triggered if:
(1) Mean value of ≥ 2,3 - ≤ 4,0 for erythema/ eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or
(2) Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or
(3) In some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above.
Based on the available results, this is not the case, so classification as skin irritant is also not triggered according to Regulation 1272/2008.

Executive summary:

In a primary dermal irritation study (US EPA FIFRA § 81-5, equivalent to OECD 404), six New Zealand White rabbits were dermally exposed to 0.5 ml of neat ethoxyquin for 4 hours.  Animals then were observed for ≥ 7 days.  Irritation was scored by the method of Draize.

There were no deaths during the study. The test material induced very slight erythema on five animals. Desquamation was noted on two sites. There were no edema or other dermal findings. With the exception of desquamation on two sites, all dermal irritation completely subsided by Day 4 or earlier. There were no remarkable body weight changes during the study period.

In this study, ethoxyquin is not a dermal irritant, no classification is triggered.