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Diss Factsheets

Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 18, 1991-May 14, 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: Federal Hazardous Substances Act, CFR 16, Section 1500.41
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-(3,7-dimethylocta-2,6-dienyl)cyclopentan-1-one
EC Number:
268-706-3
EC Name:
2-(3,7-dimethylocta-2,6-dienyl)cyclopentan-1-one
Cas Number:
68133-79-9
Molecular formula:
C15H24O
IUPAC Name:
2-(3,7-dimethylocta-2,6-dienyl)cyclopentan-1-one

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Buckshire Corp. Perkasie, Pennsylvania 18944, USA
- Housing: Elevated stainless steel with wire mesh flooring, 1 rabbit per cage
- Diet (e.g. ad libitum): Wane 15% Rabbit Ration ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-21 degrees C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

IN-LIFE DATES: From: April 29, 1991 To: May 14, 1991

Test system

Type of coverage:
occlusive
Preparation of test site:
other: one site was left intact, the other was abraded
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:
24 hrs
Observation period:
14 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: back
- Type of wrap if used: occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, deionized water

OBSERVATION TIME POINTS
(indicate if minutes, hours or days)
30-60 minutes after end of exposure, 24 and 72 hrs, day 7 and 14

SCORING SYSTEM:
- Method of calculation: Draize

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24/72 hrs
Score:
4.12
Max. score:
8
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24/72 hrs
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24/72 hrs
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24/72 hrs
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 24/72 hrs
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 24/72 hrs
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 24/72 hrs
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24/72 hrs
Score:
1.5
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24/72 hrs
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24/72 hrs
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 24/72 hrs
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 24/72 hrs
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: 24/72 hrs
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Observations were reported at 24 and 72 hrs post exposure.
Irritant / corrosive response data:
All animals showed erythema and edema formation (highest score of 3) at the 24 and 72 hr observations on both intact and abraded skin. All animals also showed edema formation (highest score of 2) at the 24 and 72 hr observations on both intact and abraded skin. All but one animals showed denuded skin and/or exfoliation at the 14 day observation on both intact and abraded skin. No edema was seen on any animal at the day 14 observation.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
None of the 6 rabbits exhibited eschar formation on day 14 of the observation period. None of the reaction that typify skin corrosive, as noted in the ECHA Guidance, including ulcers, bleeding, bloody scabs, skin discoloration/blanching, alopecia, or hyperkeratosis were reported in any of the animals, and the effects of apritone on the skin were clearly reversible in this study. The test substance is therefore classified as a skin irritant.
Executive summary:

Bioresearch (1991) performed a test for skin corrosion/irritation following the procedures specified in USA Federal Hazardous Substances Act (16CFR 1500.41). Accordingly, Bioresearch (1991) applied apritone to the clipped skin on both sides of the bodies New Zealand White rabbits (n=6). The surface of the skin on one side of each rabbit was abraded through the stratum corneum without disturbing the dermis or causing bleeding, and the skin on the other side was left intact before applying the test article (0.5 ml apritone, neat, to each side). A gauze patch (1 in.2; 6.45 cm2) was then applied to each site of exposed skin, and an occlusive bandage was wrapped around the trunk of each animal and secured with elastic tape. The tape, bandage and gauze were removed after a 24-hour exposure period, and the sites were wiped with deionized water. The sites were scored, using the Draize method approximately 24 hours and again 72 hours after apritone was applied to the skin (i.e., 30 to 60 minutes and again 48 hours after patch removal). 

Bioresearch (1991) presented the primary skin irritation scores of each rabbit. Two of the 6 rabbits scored 3 (moderate to severe erythema ) for erythema/eschar formation at the 24-hour (intact and abraded skin) and 72-hour (abraded skin only) observation points. All other scores were 2 (well defined erythema). None of the rabbits scored 4 (severe erythema to eschar formation preventing grading of erythema) for erythema/eschar formation at either observation point.

One rabbit scored 1 (very slight, barely perceptible) for edema of both intact and abraded skin and another rabbit scored 1 only on the intact skin at the 72-hour observation point. All of the other scores were 2 (slight edema, edges of are well defined by definite raising) at both the 24-hour and 72-hour observation points.

Bioresearch calculated the average erythema/eschar formation scores and edema scores across the 6 rabbits for both intact skin and abraded skin, and then calculated a primary skin irritation index (PII) based on these averages, in accordance with 16CFR 1500.41. Thus, Bioresearch (1991) reported an overall PII of 4.12 for apritone from the results of this study. The PII is 4.08 if only the averages for abraded skin are excluded from the calculation.

The highest average individual scores for were 3 for erythema/eschar formation (in two of the six rabbits) and 2 for edema (in intact skin of 5 of the six rabbits at the 24-hour observation point; in intact skin of 4 of the six rabbits at the 72-hour observation point).

Bioresearch examined and scored the exposed skin again 7-days and 14 days after apritone had been applied, because signs of irritation persisted at the 72-hour observation period. One rabbit scored 1 (very slight, barely perceptible) for edema, and that score was only for the 7-day observation point and was the same for the intact and abraded skin of that single rabbit. One rabbit exhibited remnants of eschar formation on observation day 7, although no score was given for erythema/echar formation in this animal, most probably because the eschar observed was not accompanied by evidence of erythema. All of the other scores were 0 for both erythema/eschar formation and edema at both the 7-day and 14-day observation points.

However, Bioresearch (1991)These authors also noted the following:

  • Observation Day 7
    • Exfoliation of intact and abraded skin in 4 of 6 animals
    • Exfoliation and denudation only on abraded skin in 1 of 6 animals
    • Eschar formation in intact and abraded skin in 1 of 6 animals
  • Observation Day 14
    • Exfoliation of intact and abraded skin in 2 animals
    • Exfoliation of intact skin and denudation of abraded skin in 1 animal
    • Exfoliation and denudation of both intact and abraded skin in 1 animal
    • Denudation of both intact and abraded skin in 1 animal

 

None of the 6 rabbits exhibited eschar formation on day 14 of the observation period.

None of the reaction that typify skin corrosive, as noted in the ECHA Guidance (2017b), including ulcers, bleeding, bloody scabs, skin discoloration/blanching, alopecia, or hyperkeratosis were reported in any of the animals, and the effects of apritone on the skin were clearly reversible in this study.


[1]ECHA (2017b), see Section 3.2.1 Definitions for classification for skin corrosion/irritation, page 271; see also OECD TG 404, Paragraph #23 page 4; see also the U.S. OSHA Hazard Communication Standard (HCS 2012, e.g.,https://www.schc.org/assets/docs/ghs_info_sheets/Skin%20Corrosion%20%20Irritation%20(Final%202018-03).pdf) and the Definitions Chapter 6 of the UN International Labour Organisation (ILO) draft Integrated Proposal (https://www.ilo.org/legacy/english/protection/safework/ghs/ghsfinal/ghsc06.pdf).