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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it is in compliance with the OCED principles of GLPs.
Cross-reference
Reason / purpose:
reference to same study

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:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MRD-91-962
- Physical state: liquid
- Analytical purity: not reported
- Lot/batch No.: III
- Stability under test conditions: stable at room temperature
- Storage condition of test material: room temperature
- Other: clear, colorless liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc., Denver, Pennsylvania
- Age at study initiation: Approximately 6 weeks
- Weight at study initiation: 324 to 409 grams
- Housing: Individual (during test period) in suspended stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.33 to 21.67°C
- Humidity (%): 40 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours dark and 12 hours light

IN-LIFE DATES: From: 1991-07-21 To: 1991-09-04

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Freund's Complete Adjuvant (FCA)
Concentration / amount:
Induction Phase: 5% n-pentane in ethanol (Site 2); 5% n-pentane in FCA/Water (Site 3)
Challenge Phase: 1% n-pentane in ethanol
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Freund's Complete Adjuvant (FCA)
Concentration / amount:
Induction Phase: 5% n-pentane in ethanol (Site 2); 5% n-pentane in FCA/Water (Site 3)
Challenge Phase: 1% n-pentane in ethanol
No. of animals per dose:
20
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 6
- Test groups: FCA/Water; n-pentane in ethanol; n-pentane in FCA/Water
- Control group: FCA/Water; Ethanol; 5% Reverse Osmosis Water in FCA/Water
- Site: Mid-dorsal region, near the scapula
- Duration: 0 to 7 days
- Concentrations: same throughout

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Exposure period: 24 hours
- Test groups: n-pentane
- Control group: Ethanol
- Site: L Flank - n-pentane; R Flank - Carrier (ethanol)
- Concentrations: 1.0% n-pentane in ethanol
- Evaluation (hr after challenge): 24, 48
Challenge controls:
0.4 mL of carrier - ethanol (100% ) was administered topically to guinea pigs in the treatment and irritation control groups
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene (DNCB)

Study design: in vivo (LLNA)

Statistics:
Means and standard deviations of body weight data were calculated.

Results and discussion

Positive control results:
not reported

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% ethanol (0.4 mL)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No clinical signs observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100% ethanol (0.4 mL). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No clinical signs observed.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1% in ethanol
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No treatment-related clinical signs observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1% in ethanol. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No treatment-related clinical signs observed.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1% DNCB in acetone
No. with + reactions:
15
Total no. in group:
15
Clinical observations:
slight to severe erythema and edema were observed at 24 and 48 hours post challenge
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1% DNCB in acetone. No with. + reactions: 15.0. Total no. in groups: 15.0. Clinical observations: slight to severe erythema and edema were observed at 24 and 48 hours post challenge.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: not reported
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: not reported

Any other information on results incl. tables

Table 1. Incidence of Challenge in Guinea Pig - Ethanol

Dermal Observation

Dermal Score

No. of animals

0

1

2

3

4

Irritation Control Group

24 hr erythema

10

10

0

0

0

0

24 hr edema

10

10

0

0

0

0

48 hr erythema

10

10

0

0

0

0

48 hr edema

10

10

0

0

0

0

Treatment Group

24 hr erythema

20

20

0

0

0

0

24 hr edema

20

20

0

0

0

0

48 hr erythema

20

20

0

0

0

0

48 hr edema

20

20

0

0

0

0

Table 2. Incidence of Challenge in Guinea Pig – MRD-91-962

Dermal Observation

Dermal Score

No. of animals

0

1

2

3

4

Irritation Control Group

24 hr erythema

10

10

0

0

0

0

24 hr edema

10

10

0

0

0

0

48 hr erythema

10

10

0

0

0

0

48 hr edema

10

10

0

0

0

0

Treatment Group

24 hr erythema

20

20

0

0

0

0

24 hr edema

20

20

0

0

0

0

48 hr erythema

20

20

0

0

0

0

48 hr edema

20

20

0

0

0

0

Table 3. Incidence of Challenge in Guinea Pig – DNCB (Positive Control)

Dermal Observation

Dermal Score

No. of animals

0

1

2

3

4

Irritation Control Group - Acetone

24 hr erythema

15

15

0

0

0

0

24 hr edema

15

15

0

0

0

0

48 hr erythema

15

15

0

0

0

0

48 hr edema

15

15

0

0

0

0

Treatment Group – 0.1% DNCB in Acetone

24 hr erythema

15

0

0

9

6

0

24 hr edema

15

6

5

4

0

0

48 hr erythema

15

0

3

7

0

5

48 hr edema

15

5

3

7

0

0

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
n-Pentane showed no irritation or sensitization potential after intradermal and topical application in Guinea pigs (experimental days one and seven), followed by occluded dermal challenge on day 21. n-Pentane is not a dermal sensitiser.
Executive summary:

A dermal sensitisation study was conducted in guinea pigs (20 females/dose; 15 females for positive control) using n-pentane.

Induction Phase: An area near the scapula in the mid-dorsal region of all animals was clipped on the day prior to intradermal injection of tbe test material and/or carrier. 6 intradermal injections (0.1 mL each) were administered to 3 different sites as follows: Site 1: FCA/water to treated and control groups; Site 2: 5.0% n-pentane in carrier (ethanol) to the treated group, 100% ethanol to the control group; Site 3: 5.0% n-pentane in FCA/Water to the treated group, 5.0% carrier (reverse osmosis water) in FCA/Water to the control group. On day 7 following injection, 0.5 mL of a mild to moderately irritating dose of n-pentane was administered topically over the previously injected areas and covered with occlusive wrapping. Control animals received topical carrier applications instead.

Challenge Phase: 21 days post induction phase, 0.1 mL of n-pentane (1.0% in ethanol) was applied topically to the left flank of both treated and control irritation groups. 0.4 mL of the carrier (ethanol) was applied to the right flank. All applications were kept secure under occlusive wrapping for 24 hours and animals observed for dermal effects for 48 hours.

Sensitization was evaluated by comparing the reactions of treated animals with the reactions of control animals that received a single epidermal exposure to the test material. Control responses were used to distinguish true sensitization from local irritation produced by the same concentration of test material.

All animals survived to study termination and displayed a weight gain from their day 0 values. Abnormal clinical observations during scheduled intervals were limited to one treated group animal that was emaciated and had a small amount of stool. Another animal exhibited slight emaciation and poor food consumption. Clinical signs observed in these two animals were considered to be correlated to the stress of the wrapping procedure and not treatment-related. No signs of dermal irritation were observed at any dose in either patch group. DNCB elicited positive reactions from all tested animals 24 and 48 hours after removal of the patch challenge.

Based on the lack of signs dermal irritation observed in the study, n-pentane is not considered a dermal sensitiser. This study was given a Klimisch score of 1 and classified as reliable without restriction because it is in compliance with the OCED principles of GLPs.