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Diss Factsheets

Administrative data

Description of key information

Buehler test (guinea pigs, concentration 25 % ): not sensitizing (GLP, EPA OTS 798.4100 (1989) Guideline; Toxikon 1992)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
EPA OTS 798.4100 (Skin Sensitisation)
Version / remarks:
1989
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The study has been conducted before the implementation of the LLNA method.
Specific details on test material used for the study:
- Name of test material (as cited in study report): Piperidine
- Physical state: Liquid, Colorless
- Lot/batch No.: 20221AA
- Storage condition of test material: Room Temperature
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elm HilI Breeding Labs, Chelmsford, MA, U.S.
- Age at study initiation: 21-43 days
- Weight at study initiation: 250 - 400 grams
- Housing: group housed in stainless steel cages
- Diet: diet of commercial guinea pig ration (Agway Prolab, Agway, Waverly, NY); ad libitum
- Water: tap water; ad libitum
- Acclimation period: 6 days (Preliminary Irritation Study) and 9 days (Sensitization Study)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10 to 13
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
water
Route:
epicutaneous, occlusive
Vehicle:
water
No. of animals per dose:
28
Details on study design:
RANGE FINDING TESTS:
The Preliminary Irritation Study
- Number of animals: 4 previously unexposed animals. This phase was run before the start of the challenge phase.
- Site: Before each application of the test or control substance the animals were clipped and shaved on the left shoulder, in an area of about 3 x 4 cm.
- Amount: 0.4 ml
- Method: Closed patches for the experimental group were prepared as folIows: Test substance was applied directly to the skin and covered with a gauze pad. The patch was applied to the prepared skin sites as soon as possible and kept in place with occlusive bandaging. At the end of the exposure the patch was removed and any residual test substance was washed off with water.
- Concentrations: 100 %, 50 %, 25 % and 10 %.
- Exposure period: 6 hours
- Scoring system: Draize Scoring
- Readings: 24 hour after the test substance application and up to 72 hours the highest nonirritant and minimal irritant concentrations were determined.
- The test substance was found to be moderately to strongly irritating at concentrations of 100 % (necrosis) and 50 % (Erythema Grade 2.0 to 3.0) and non-irritating at a concentration of 25 % in the Preliminary Irritation Study. Therefore, the 25% concentration was considered the minimally irritating concentration and the maximal nonirritating concentration and applied at both the induction and challenge phases.

MAIN STUDY
A. INDUCTION EXPOSURE
- Exposure period: 6 hours
- Test groups: 25 % test substance
- Control group: Negative Control: water; Positive Control: Dinitrochlorobenzene
- Site: Before each application of the test or control substance the animals were clipped and shaved on the left shoulder, in an area of about 3 x 4 cm.
- Method: closed patch technique (see above)
- No. of exposures and frequency of applications: The test substance was applied once per week for 3 consecutive weeks (week 01, 02, 03) on one side of the animal. The positive control substance was applied in the same manner.
- Duration: 3 weeks
- Concentrations: 25 % (0.4 ml)
- Reading: Induction scoring was performed 24 hours after the test substance application.

B. CHALLENGE EXPOSURE
- No. of exposure: one
- Day(s) of challenge: During week 05, the challenge test was performed on freshly clipped skin sites in the same way as the 6 hour closed patch test of the induction phase.
- Exposure period: The skin was exposed to the test substance for 24 hours.
- Site: The day preceding the challenge, a 4 x 3 cm virgin skin site was shaved on the backs of the experimental and control animals.
- Evaluation (hr after challenge): At 24 hours after application of the challenge dose, the area of the challenge was marked and the whole back shaved. Two hours after shaving, the test site was examined for erythema and edema. The reaction was graded as follows:
0.0 = No reaction
0.5 = Very faint erythema, usually confluent
1.0 = Faint erythema, usually confluent
2.0 = Moderate erythema
3.0 = Strong erythema with or without edema
Reading of the skin area was repeated 48 hours after the challenge and the skin reactions were graded.
- Rechallenge
It was not considered necessary to rechallenge the sensitized guinea pigs at 1 and 2 weeks after the primary challenge (weeks 06 and 07).

OTHER:
The results were summarized and expressed in the following terms:
Incidence - The number of animals showing a response of 1 or more, at 24 or 48 hours, divided by the number of test animals.
Severity - The sum of the test grades divided by the number of animals tested.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No signs of toxicity and irritation
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No signs of toxicity and irritation
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.05 %
No. with + reactions:
4
Total no. in group:
4
Clinical observations:
Mean erythema and edema score of 2.25
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.05 %
No. with + reactions:
4
Total no. in group:
4
Clinical observations:
Mean erythema and edema score of 2.75
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No signs of toxicity and irritation
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No signs of toxicity and irritation
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a dermal sensitization study with the test item (Purity unknown) in water in total 28 male and female Hartley guinea pigs were tested using the Buehler test according to the guideline EPA OTS 798.4100 (1989). In a preliminary irritation study the concentration of 25 % was identified as the maximal non-irritating concentration. Epicutaneous, occlusive induction and challenge was performed using the closed patch method. A solution of 25 % test substance was applied occlusively for a exposure period of 6 hours, once per week for three consecutive weeks. Challenge was performed in the same way with an exposure period of 24 hours. As a positive control 0.05 % Dinitrochlorobenzene was used.

24 and 48 hours after challenge no erythema and or oedema were observed. No signs of toxicity were detected. The positive control induced the appropriate response.  

The sensitisation study is acceptable (reliability 2), but does not fully satisfy the guideline requirements for a sensitisation study (OECD 406) in rabbits (no data on test substance purity is given).

In the study, the test item is not a dermal sensitizer after epicutaneous, occlusive induction and challenge using a non-irritating concentration of 25%.

 

There are contradictory publications on experience with the test item in humans (see IUCLID Chapter 7.10.4). In four clinical cases of allergic contact dermatitis due to wearing rubber gloves, two patch-tested patients were found to be hypersensitive to the test item, which was analytically confirmed to be a constituent of the material from which the rubber gloves were made (Kaniwa 1994). In workers handling the test item at work no cases of skin sensitisation were observed in the period from 1989 to 1998 (BG Chemie, Toxicological Evaluations, Piperidine, Nr.72, 2000). Similarly, 448 patients without occupational exposure showed no allergic reactions to the test item upon testing in the period from 1996 to 1998 (IVDK 1990).


Justification for selection of skin sensitisation endpoint:
Only one study available.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008


The available experimental test data for sensitisation are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. As a result the substance is not warranted to be classified for sensitisation, under Regulation (EC) No.1272/2008.