Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1989-12-12 to 1990-02-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the full study protocol, was provided, including test materials and methods.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
equivalent or similar to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Principles of method if other than guideline:
According to the McKee et al. article (1998; cross-reference to the same study), the Draize method was followed, and the study is compliant with more recent guidelines from the EU and the Organization for Economic Cooperation and Development (OECD).

Draize, J. 1959. The Appraisal of the Safety of Chemicals in Food, Drugs, and Cosmetics. Association of Food and Drug Officials of the United States, Austin, TX.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MRD-89-527
- Substance type: C5 aliphatic
- Physical state: liquid
- Analytical purity: not reported
- Lot/batch No.: I
- Storage condition of test material: room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Products, Denver, Pennsylvania
- Age at study initiation: Approximately 12 weeks
- Weight at study initiation: Approximately 2 to 3 kg
- Housing: Individually housed in suspended stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 22 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 21°C
- Humidity (%): 40 to 60%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

IN-LIFE DATES: From: 1989-12-12 To: 1989-12-19

Test system

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:
Dermal responses were evaluated 45 minutes, 24, 48, and 72 hours after patch removal and on day 7. Body weights were recorded on the day of dosing (day 0). Animals were sacrificed after day 7 observations via an intravenous administration of sodium pentobarbital solution and discarded without further examination.
Number of animals:
4 males and 2 females
Details on study design:
TEST SITE
The dorsal surface from the shoulder region to the lumbar region of each rabbit was shaved approximately 20 to 21 hours prior to administration. Elizabethan-type collars were placed around the rabbits' neck approximately one week prior to study initiation. Animals were then re-shaved as needed. At dosing, 0.5 mL of undiluted test material was placed under a gauze patch that was secured with tape. A semi-occlusive dressing was placed over the patch. After approximately 4 hours of exposure, the dressing, patch, and Elizabethan collars were removed and the site was washed.

REMOVAL OF TEST SUBSTANCE
Residual test material was removed from the test site by using reverse osmosis water and paper towels.

SCORING SYSTEM:
The Draize method of scoring was used to score edema and erythema and eschar formation. Edema and erythema and eschar formation were scored on a 5 point scale (0 to 4), with 0 being no effect and 4 being the most severe. Additional dermal observations were made and included: atonia, blanching, leathering skin, fissuring, desquamation, necrosis, exfoliation, and eschar.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 to 72 hours
Score:
0.67
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 to 72 hours
Score:
0.5
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 to 72 hours
Score:
0.06
Irritant / corrosive response data:
Based on the study results, the overall dermal irritation score was 0.67. Administration on n-pentane to rabbit skin resulted in limited and transient dermal irritation. Dermal responses were observed in 5 animals 45 minutes after application, 2 with well-defined erythema and 3 with very slight erythema. 24 hours after application, 1 animal exhibited well-defined erythema and 3 animals exhibited very slight erythema. At the 48- and 72-hour observation periods, one animal exhibited well-defined erythema. At study termination, animals were free of dermal irritation.



Other effects:
One animal exhibited the following clinical signs of toxicity: decreased food consumption, soft stool, small amount of stool, no stool, and emaciation.

Any other information on results incl. tables

 

Erythma and Edema Scores

45 minutes

24 hours

48 hours

72 hours

7 days

Erythma

Animal 1

0

0

0

0

0

Animal 2

1

1

0

0

0

Animal 3

2

2

2

2

0

Animal 4

2

1

0

0

0

Animal 5

1

1

0

0

0

Animal 6

1

0

0

0

0

Mean

1.17

0.83

0.33

0.33

0.00

 

Edema

Animal 1

0

0

0

0

0

Animal 2

0

0

0

0

0

Animal 3

2

1

0

0

0

Animal 4

0

0

0

0

0

Animal 5

0

0

0

0

0

Animal 6

0

0

0

0

0

Mean

0.33

0.17

0.00

0.00

0.00

Applicant's summary and conclusion

Interpretation of results:
other: Not classified under EU DSD or CLP; not irritating.
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
According to the study authors, n-pentane was found to be mild irritant with a primary irritation index of 0.67. This classification was based on the descriptive ratings for skin irritation developed by Draize; however, based on mean erythema and oedema scores (0.5 and 0.06, respectively) over 72 hours (i.e., 24 to 72 hours), n-pentane would be considered non-irritating based on EU DSD or CLP guidelines.
Executive summary:

In a primary dermal irritation study, 4 male and 2 female New Zealand White rabbits were dermally exposed to 0.5 mL of n-pentane for 4 hours to dorsal surface from the shoulder region to the lumbar region of each rabbit. Animals then were observed for 7 days. Irritation was scored by the Draize method of scoring.

According to the study authors, n-pentane was found to be mild irritant with a primary irritation index of 0.67. The mean erythema score was 0.5 when averaged over 72 hours (i.e., 24 to 72 hours); the mean oedema score was 0.06 when averaged over 72 hours. n-Pentane would be considered non-irritating based on these mean erythema and oedema values under EU DSD or CLP guidelines.

This study received a Klimisch score of 1 and is classified as reliable without restriction because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the full study protocol, was provided, including test materials and methods. The study follows OECD guidelines 404.