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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994-11-08 to 1995-05-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified reliable without restriction. The study appears to follow OECD 406 guidelines and adhered to GLP recommendations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1. During the third induction phase of this study, the test animals were inadvertently exposed to the test material 1-dodecene, trimer, hydrogenated (C1527-04-4) intended for Hilltop Biolabs Project No. 94-8435-21 instead of 1-dodecene, dimer (C1527-04-2). Due to this deviation in the test material administered, this study was compromised and was rerun at no cost to the Sponsor.
As a result of this deviation, there was a separate set of naive controls for both HTB Project No. 94-8434-21 and 94-8435-21, whereas the Protocol states that these two studies will have naive control animals in common.
2. The Protocol states under the Housing and Animal Care section that "Animals will be individually housed in wire mesh suspension cages." However, upon returning the test animals to their cages following the first induction phase of the repeat study, a female (T-14 TN127) was inadvertently placed in the same cage as a male (T-1O TN127).
In addition, the Protocol states under the Test Animals section that "Females will be nulliparous and non-pregnant." This deviation no longer ensures that this is true. Therefore, the female test animal was euthanized per the Sponsor's request. The study was completed using ten male and nine female animals in the test group
Deviations:
yes
Remarks:
see version/remarks
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
Equivalent study

Test material

Constituent 1
Reference substance name:
1-dodecene dimer, hydrogenated
IUPAC Name:
1-dodecene dimer, hydrogenated
Details on test material:
- Substance type: 1-dodecene dimer, hydrogenated
- Physical state: liquid, clear colourless
- Lot/batch No.: C1527-04-2
- Storage condition of test material: Room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc., Indianapolis, Indiana
- Age at study initiation: 6-11 weeks young adult
- Weight at study initiation: Primary irritation study: 426 to 501 grams; Induction and challenge study: 300 to 397 grams
- Housing: individually housed in wire mesh suspension cages
- Diet (e.g. ad libitum): Teklad Guinea Pig Diet ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: Not reported

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Specturm Mineral Oil Light U.S.P. (only for Primary Irritation Test)
Concentration / amount:
Primary Irritation Test: undiluted, 50%, 25%, 10%, 5%, 2.5%, 1%, 0.5% w/v in Spectrum Mineral Oil Light, U.S.P.
Induction and Challenge: undiluted (0.3 mL)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Specturm Mineral Oil Light U.S.P. (only for Primary Irritation Test)
Concentration / amount:
Primary Irritation Test: undiluted, 50%, 25%, 10%, 5%, 2.5%, 1%, 0.5% w/v in Spectrum Mineral Oil Light, U.S.P.
Induction and Challenge: undiluted (0.3 mL)
No. of animals per dose:
Primary Irritation: 2/sex (2 groups)
Induction and challenge: Test: 20 (10/sex); Naive controls: 10 (5/sex)
Details on study design:
RANGE FINDING TESTS: The irritation potential of the test material at levels of undiluted, 50%, 25%, 10%, 5%, 2.5%, 1%, and 0.5% were evaluated, such that each animal in a given pilot group was exposed to the same levels. Dilutions of the test material were prepared w/v in Spectrum Mineral Oil Light, U.S.P. The position of the different concentrations of the test material on the animals were varied to adjust for possible site-to-site variation in response.

The day prior to test material exposure, the hair was removed from each of the animal's backs using a small animal clipper. Closed patches were applied to the animals in the following manner: A 0.3 ml amount of each test preparation was applied into a 25 mm Hill Top Chamber®. The animal was placed into the restrainer and the chamber(s) were applied to the clipped surface as quickly as possible. The chamber(s) were occluded with rubber dental dam pulled taut and fastened to the bottom of the restrainer with clips. The restrainer was adjusted to minimize movement of the animal during exposure. Approximately six hours later, the dental dam and chamber(s) were removed, the animal was taken from the restrainer, and was placed in its cage.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: single group, undiluted test material
- Control group: naive controls
- Site: Left shoulder
- Frequency of applications: once a week for a total of three exposures
- Duration: 6 hours
- Concentrations: undiluted test material 0.3 mL

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after last induction
- Exposure period: same as induction
- Test groups: single group, undiluted test material
- Control group: naive controls
- Site: left shoulder, at perviously unused site
- Concentrations: undiluted 0.3 mL
- Evaluation (hr after challenge): Day following challenge
Positive control substance(s):
yes
Remarks:
a - Hexylcinnamaldehyde

Results and discussion

Positive control results:
Positive control data presented in Table below.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
undiluted
No. with + reactions:
18
Total no. in group:
20
Clinical observations:
slight to patchy erythema observed in 15 animals; slight but confluent or moderate patchy erythema observed in 3 animals.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: undiluted. No with. + reactions: 18.0. Total no. in groups: 20.0. Clinical observations: slight to patchy erythema observed in 15 animals; slight but confluent or moderate patchy erythema observed in 3 animals. .
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Undiluted
No. with + reactions:
19
Total no. in group:
20
Clinical observations:
Slight patchy erythema observed in 12 animals; slight but confluent to moderate patchy erythema observed in 7 animals
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: Undiluted. No with. + reactions: 19.0. Total no. in groups: 20.0. Clinical observations: Slight patchy erythema observed in 12 animals; slight but confluent to moderate patchy erythema observed in 7 animals.
Reading:
1st reading
Hours after challenge:
24
Group:
other: naive control
Dose level:
undiluted
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
Slight patchy erythema observed in 8 animals; slight but confluent to moderate patchy erythema observed in 1 animal
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: other: naive control. Dose level: undiluted. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: Slight patchy erythema observed in 8 animals; slight but confluent to moderate patchy erythema observed in 1 animal.
Reading:
1st reading
Hours after challenge:
48
Group:
other: naive control
Dose level:
Undiluted
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Slight patchy erythema observed in 7 animals; slight but confluent, moderate patchy erythema observed in 3 animals
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: other: naive control. Dose level: Undiluted. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Slight patchy erythema observed in 7 animals; slight but confluent, moderate patchy erythema observed in 3 animals.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
5% w/v
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
slight, patchy and slight but confluent or moderate patchy erythema
Remarks on result:
other: in induced animals
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
5%w/v
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
slight, patchy and slight but confluent or moderate patchy erythema
Remarks on result:
other: in induced animals
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Remarks on result:
not measured/tested

Any other information on results incl. tables

Potential of α-Hexylcinnamaldehyde, tech., 85% as a 5% w/v Formulation in Acetone to Produce Delayed Contact Hypersensitivity in Guinea Pigs

 

Animal Sex (Male/Female)

Numerical Score

24-Hour

48-Hour

Test Material in Induced Animals

Male

±

±

Male

±

±

Male

±

±

Male

±

±

Male

1

±

Female

±

±

Female

1

±

Female

1

1

Female

1

±

Female

1

1

Mean

0.8

0.6

Test Material in Naïve Animals

Male

±

±

Male

±

±

Male

±

±

Female

±

±

Female

0

±

Mean

0.4

0.5

Historical Positive Control Data generated at Hill Top Biolabs on April 26, 1994, and April 27, 1994.

Skin Grades in Guinea Pigs 24 and 48 Hours Following a 6 Hour Patch Application of1 -dodecene, dimer (C1527-04-2) at Various Concentrations in Spectrum Mineral Oil Light, U.S.P.

 

Animal Sex (M/F)

Numerical Score

Undiluted

50% w/v

25% w/v

10% w/v

24-hr

48-hr

Sitea

24-hr

48-hr

Sitea

24-hr

48-hr

Sitea

24-hr

48-hr

Sitea

M

1

1

(1)

1

1

(2)

1

1

(3)

±

±

(4)

M

±

±

(2)

±

±

(3)

1

1

(4)

±

1

(1)

F

±

±

(3)

±

±

(4)

1

1

(1)

±

±

(2)

F

1

1

(4)

1

1

(1)

1

1

(2)

1

1

(3)

 

5% w/v

2.5% w/v

1% w/v

0.5% w/v

 

24-hr

48-hr

Sitea

24-hr

48-hr

Sitea

24-hr

48-hr

Sitea

24-hr

48-hr

Sitea

M

1

1

(1)

±

1

(2)

±

1

(3)

±

±

(4)

M

±

1

(2)

±

1

(3)

±

±

(4)

±

±

(1)

F

1

1

(3)

1

1

(4)

1

1

(1)

1

1

(2)

F

±

±

(4)

1

1

(1)

1

±

(2)

±

±

(3)

aPatch site locations 1-4 presented in parentheses were used in accordance with those specified in the Protocol.

Group

Material

Conc

Incidence of Responses

Mean Severity Score2

24 Hours

48 Hours

24 hour

48 hour

0

±

1

2

3

0

±

1

2

3

 Primary Challenge

Test

1 -dodecene, dimer

Undiluted

1

15

3

0

0

0

12

7

0

0

0.6

0.7

 

Naïve Control

1 -dodecene, dimer

Undiluted

1

8

1

0

0

0

7

3

0

0

0.5

0.7

Scoring Scale:

0= no reaction

+ = slight, patchy erythema

1 = slight but confluent, or moderate patchy erythema

2 = moderate erythema

3 = severe erythema with or without edema

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The mean severity scores for the test group and naïve controls were determined to be 0.6 and 0.5 and 0.7 and 0.7 at 24 hours and 48 hours post-challenge, respectively. Given that the reactions observed in the test and naïve control group were similar, it is concluded that the test material, 1-dodecene dimer, hydrogenated, is not a dermal sensitizer in this delayed contact hypersensitivity study conducted in the guinea pig.
Executive summary:

In a dermal sensitization study (Morris, T.D., 1995; Klimisch score = 1), 30 naïve young adult Hartley guinea pigs (male and female) were topically exposed to 1-dodecene dimer, hydrogenated using the Buehler method. A primary test was conducted initially where the irritation potential of the test material at levels of undiluted, 50%, 25%, 10%, 5%, 2.5%, 1%, and 0.5% w/v in Spectrum Mineral Oil Light, U.S.P was evaluated. The test exposures lasted 6 hours. During the induction phase, undiluted test material was placed on the clipped left shoulders of test animal once a week for 3 weeks for a total of 3 exposures. After the last induction exposure, the animals were left untreated for approximately two weeks (14 days) before primary challenge. At challenge, test animals, which had three previous exposures to the test material at appropriate intervals, were again exposed in the challenge phase approximately two weeks after the last induction exposure. In addition, ten naive animals, which had never been exposed to the test material, were concurrently treated with the same test material concentration. Appropriate historical positive control data was used for this study.

 

Slight patchy erythema was the main observation in the study while slight to confluent but moderate patchy erythema was observed in a few test and naïve control animals. The mean severity scores for the test group and naïve controls were determined to be 0.6 and 0.5 and 0.7 and 0.7 at 24 hours and 48 hours post-challenge, respectively.

 

Given that the reactions observed in the test and naïve control group were similar, it is concluded that the test material, 1-dodecene dimer, hydrogenated, is not a dermal sensitizer in this delayed contact hypersensitivity study conducted in the guinea pig.

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