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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
Study period:
02 March 1981 to 03 April 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions, on a related material.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
(only 10 animals/group; absolute ethanol used as vehicle)
GLP compliance:
yes
Remarks:
Deviation from GLP regulations: No retain was obtained of the vehicle control, absolute ethaol (USP)
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Neodol 91 alcohol
- Molecular formula (if other than submission substance): unspecified
- Molecular weight (if other than submission substance): 143
- Smiles notation (if other than submission substance): OCCCCCCCCC*
- InChl (if other than submission substance): no data
- Structural formula attached as image file (if other than submission substance): see Fig. 1
- Substance type: technical product
- Physical state: liquid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: 84% linear monobranched at the 2 position
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: stable
- Storage condition of test material: no data
- Other: identification of substance confirmed by analysis (WRC-RIR-125 and 159)

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Camm Research Laboratories, Wayne, New Jersey, USA
- Age at study initiation: no data
- Weight at study initiation: 529 - 561 g (group means)
- Housing: Stainless steel cages, 5 animals per cage
- Diet (e.g. ad libitum): Purina Lab Guinea Pig Chow 5025, ad libitum
- Water (e.g. ad libitum): Tap water, Edstrom automatic watering system, ad libitum
- Acclimation period: at least 13 days; up to 20 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average 22.5 (range 21.7 - 23.9)
- Humidity (%): average 49.6 (range 30-60)
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: absolute ethanol
Concentration / amount:
Induction and challenge: 1.01%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: absolute ethanol
Concentration / amount:
Induction and challenge: 1.01%
No. of animals per dose:
10 (5 males, 5 females); applies to all groups
Details on study design:
RANGE FINDING TESTS:
1 animal/sex was treated epicutaneously (at two sites) with 1, 50 or 100% Neodol 91 (where applicale dissolved in absolute ethanol) under occlusion for 6 hours. Only the 1% solution did not elicit a reaction indicative of irritation.

MAIN STUDY - Non-adjuvant Buehler test
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 3 weeks
- Test groups: 1
- Control group: 2 (vehicle and positive controls)
- Site: back/trunk
- Frequency of applications: one day/week, on 3 consecutive weeks
- Duration: 6 hours
- Concentrations: 1.01 % (volume 0.5 ml)
- Reactions were scored approximately 24 and 48 hours after treatment (Draize grading system)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 28 (i.e. 2 weeks after final induction)
- Exposure period: 6 hours
- Test groups: 1
- Control group: 3 (vehicle, positive and irritation controls)
- Site: back/trunk (two patches, on sensitized and virgin application sites)
- Concentrations: 1.01% (volume 0.5 ml)
- Evaluation (hr after challenge): 24 and 48 (Draize grading system)

No rechallenge.

OTHER: Exposure sites were shaved (48 hours) and depilated (24 hours) prior to exposure.

Each treatment involved dispensing the appropriate dose on a 1"x1" gauze pad attached to a 2" wide strip of Blenderm (R) surgical tape (Minnesota mining and Manufacturing, Saint Paul, Minnesota), then applying the patch to the anterior central portion of the back/trunk and securing with Saran wrap (Dow Chemical co., Indianapolis, Indiana). Animals were placed in a stainless steel wire restrained for the six-hour application duration for the first and second applications (for the 3rd and challenge applications, they had outgrow n the restrainers and so these were not used; nevertheless the patches and wraps remained in situ). Excess test material was removed with a moisterned gauze pad.
Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
2,4-Dinitrochlorobenzene (0.1% solution in diethyl ether)

Study design: in vivo (LLNA)

Statistics:
none

Results and discussion

Positive control results:
The positive controls showed a significant response at challenge  with all test sites showing an increased degree of irritation. However, reactions were similar to those seen during induction and so were not unambiguously indicative of sensitization.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
"Barely perceptible" redness at original site (i.e. induction site) in 6/10 animals (indicative of mild irritation); no reactions at challenge site
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: "Barely perceptible" redness at original site (i.e. induction site) in 6/10 animals (indicative of mild irritation); no reactions at challenge site.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1% DNCB
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Reactions were similar to those seen during induction and so were not unambiguously indicative of sensitization.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1% DNCB. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Reactions were similar to those seen during induction and so were not unambiguously indicative of sensitization..
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1% DNCB
No. with + reactions:
9
Total no. in group:
9
Clinical observations:
One animal died (not treatment related). Reactions were similar to those seen during induction and so were not unambiguously indicative of sensitization.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.1% DNCB. No with. + reactions: 9.0. Total no. in groups: 9.0. Clinical observations: One animal died (not treatment related). Reactions were similar to those seen during induction and so were not unambiguously indicative of sensitization..

Any other information on results incl. tables

RESULTS OF TEST 

There was slight irritation in the  test group during the induction period. The average Draize score was 0.38 at week  1, 0.5 at week 2 and 0.28 at week 3. By week 5 the score was zero (no irritation seen).


Average irritation at challenge for the treated group was 0, positive  controls were 1.55, vehicle controls 0.08 and irritation controls 

 (challenge application only) 0.13.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
In a reliable study, conducted to a protocol similar to OECD guideline 406, Neodol 91 (1% in ethanol) was not sensitising to the skin of guinea pigs when tested using the Buehler non-adjuvant method. The study was performed in compliance with GLP.

Classification: not sensitizing
Executive summary:

[In view of the structural and chemical similarities, it is considered that the results of this study can be used for read-across to Undecanol, linear and branched.]