Registration Dossier

Administrative data

Description of key information

No studies are available for the registered substance Methylcyclopentane. Based on the read-across approach, information on the structural analogue n-Hexane is used.

One key study for skin irritation was identified (Shell, 1987a; Klimisch score=1).  Two key read-across eye irritation studies in hexane were identified (Committee on Acute Exposure Guideline Levels, 2013 and US DHHS, 1999).

Skin Irritation - irritating to the skin (OECD 404)

Eye Irritation - Not an ocular irritant (OECD 405)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it closely follows OECD guideline 404.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sittingbourne Research Centre Breeding Unit
- Age at study initiation: 4-9 months
- Weight at study initiation: 2926-4988 g
- Housing: singly in 67 x 43 x 45 cm stainless steel, wire-mesh cages, identified by metal ear tags
- Diet (e.g. ad libitum): Standard Rabbit Diet, S.Q.C., ad libitum
- Water (e.g. ad libitum): filtered water ad libitum
- Acclimation period: at least two weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-19 degree C
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

Type of coverage:
semiocclusive
Preparation of test site:
shaved
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:
4 hrs
Observation period:
7 days
Number of animals:
3 male/3 female
Details on study design:
TEST SITE
- Area of exposure: Hair was short between the shoulders and hindquarters. A 2x2 cm lint patch with 0.5 ml of test substance was applied.
- Type of wrap if used: The patch was covered with a single layer of gauze held in place with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were washed with water.
- Time after start of exposure: 4 hrs

SCORING SYSTEM: Animals were scored for erythema and edema on a scale of 0 (no effects) to 4 (severe effects).
Irritation parameter:
erythema score
Basis:
mean
Remarks:
group score erythema
Time point:
24/48/72 h
Score:
0.8
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
group score edema
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritant / corrosive response data:
SBP 60/95 LNH caused mild irritation lasting through 72 hrs.

Skin Irritation Results – SBP 60/95 LNH

Animal

Observation

Hours

Day

4

24

48

72

7

806-M

Erythema

1

1

1

1

0

Oedema

0

0

0

0

0

821-M

Erythema

1

1

1

1

0

Oedema

0

0

0

0

0

803-M

Erythema

1

1

1

0

0

Oedema

0

0

0

0

0

812-F

Erythema

1

1

1

1

0

Oedema

0

0

0

0

0

813-F

Erythema

1

1

1

0

0

Oedema

0

0

0

0

0

820-F

Erythema

1

1

1

0

0

Oedema

0

0

0

0

0

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The average erythema score (24,48, and 72 hours) was 0.8. The average oedema score (24,48, and 72 hours) was 0.0.
Executive summary:

This study examined the skin irritancy of the test substance SBP 60/95 LNH. Groups of six rabbits had 0.5 mL of test substance applied to their dorsal skin. The test area was covered semi-occlusively, and exposure lasted 4 hrs. The test area was then washed.

Animals were scored at 30 min., 24 hrs, 48 hrs, 72 hrs, and 7 days after removal of the test substance. The average erythema score (24,48, and 72 hours) was 0.8. The average oedema score (24,48, and 72 hours) was 0.0. 

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1987-04-27 to 1987-05-08
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because there was no GLP statement provided, and limited data on methods were reported, but the study seemed to be well-conducted.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sittingbourne Research Centre
- Age at study initiation: 3 - 6 months
- Housing: single, hanging stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 19 degrees Celsius
- Humidity (%): not reporte
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light

IN-LIFE DATES: not reported
Type of coverage:
semiocclusive
Preparation of test site:
shaved
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:
4 hours
Observation period:
30 minutes, 24, 48, 72 hours and 7 days after patch removal
Number of animals:
3 male and 3 female
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.8
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Minimal erythema was observed after patch removal. Half of the rabbits were still affected at 72 hours but all skin effects were cleared by day 7.
Executive summary:

In a primary dermal irritation study 3 male and 3 female young adult New Zealand White rabbits were dermally exposed to 0.5 ml of SBP 60/95 low n-hexane for 4 hours to the dorsal area. Animals then were observed for 7 days.

In this study SBP 60/95 low n-hexane was slightly irritating to the skin based on the mean erythema and edema scores.

This study received a Klimisch score of two and is classified as reliable with restrictions because there was no GLP statement provided, and limited data on methods were reported, but the study seemed to be well-conducted.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
other: data from collection of data
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
no guideline followed
Principles of method if other than guideline:
human volunteers exposed to n-hexane vapor were asked to rate ocular discomfort.
GLP compliance:
not specified
Specific details on test material used for the study:
n-hexane
Species:
human
Strain:
other: Caucasian
Details on test animals or tissues and environmental conditions:
male volunteers
Vehicle:
other: air (inhalation experiment)
Amount / concentration applied:
54 ppm for 2 h during physical light exercise in an inhalation chamber
Duration of treatment / exposure:
2 h
Observation period (in vivo):
2 h during exposure
Details on study design:
volunteers were asked for symptons of eye irritation
Irritation parameter:
other: rating ocular discomfort
Basis:
mean
Remarks on result:
probability of weak irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
2 h exposure in human volunteers
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
2 h exposure in human volunteers
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
2 h exposure in human volunteers
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
2 h exposure in human volunteers
Irritant / corrosive response data:
maximal very weak indications for eye irritation of n-hexane vapor found.
Interpretation of results:
study cannot be used for classification
Conclusions:
The study was about hexane vapor, which was mildly irritant to human eyes.
Executive summary:

The study was about hexane vapor, which was mildly irritant to human eyes.

Endpoint:
eye 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
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
no guideline followed
Principles of method if other than guideline:
Tests in inhalation chambers
GLP compliance:
not specified
Specific details on test material used for the study:
hexane (isomer composition and purity were not specified)
Species:
human
Vehicle:
other: air (tested in inhalation chambers)
Duration of treatment / exposure:
3-5 min
Number of animals or in vitro replicates:
10 volunteers
Irritation parameter:
other:
Basis:
mean
Time point:
other: after 3-5 min. in inhalation chamber
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
3-5 min exposure in human volunteers
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
3-5 min exposure in human volunteers
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
3-5 min exposure in human volunteers
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
3-5 min exposure in human volunteers
Interpretation of results:
study cannot be used for classification
Conclusions:
Hexane is not irritant to the eye, when humans are exposed up to 500 ppm in the air for a few minutes.

Direct contact with n-hexane vapor (3000 ppm for 24 wk with 5 d/wk for 8 hr/d) with the eyes of rabbits resulted in lacrimation and hyperemia of the conjunctivae.
Executive summary:

Hexane is not irritant to the eye, when humans are exposed up to 500 ppm in the air for a few minutes.

Direct contact with n-hexane vapor (3000 ppm for 24 wk with 5 d/wk for 8 hr/d) with the eyes of rabbits resulted in lacrimation and hyperemia of the conjunctivae.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No studies are available for the registered substance Methylcyclopentane. Based on the read-across approach, information on the structural analogue n-Hexane is used.

Skin Irritation

In a key skin irritation study (Shell, 1987a; Klimisch score = 1), the skin irritancy of the test substance a hexane solvent containing <5% n-hexane was examined. Groups of six rabbits had 0.5 mL of test substance applied to their dorsal skin. The test area was covered semi-occlusively, and exposure lasted 4 hours. The test area was then washed. Animals were evaluated for erythema and oedema at 30 min., 24 hrs, 48 hrs, 72 hrs, and 7 days after removal of the test substance. The average erythema score (24,48, and 72 hours) was 0.8. The average oedema score (24,48, and 72 hours) was 0.0. 

Eye Irritation

In a key read-across eye irritation study, Hexane was tested for irritation potential on an average of 10 volunteers of mixed sexes for 3-5 minutes in an inhalation chamber (Nelson et al.1943). Hexane was not observed to be irritating to the eye, when humans were exposed up to 500 ppm in the air for a few minutes (US DHHS, 1999).

In another Key read-across study, Hexane vapor (54 ppm) has been reported to be mildly irritating to human eyes (Committee on Acute Exposure Guideline Levels, 2013) after a 2 hour exposure.

Justification for classification or non-classification

There is no data available for Methylcyclopentane. Data is available from a structural analogue n-Hexane and used as read across.

Based on available read across data, Methylcyclopentane warrants classification for skin irritation as a Category 2 skin irritant (H315: causes skin irritation) under the

Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP).

Based on available read across data, Methylcyclopentane does not warrant classification for ocular irritation under the Regulation (EC) 1272/2008 on classification, labelling,

and packaging of substances and mixtures (CLP).