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Diss Factsheets

Administrative data

Description of key information

Study Type

 Species

Findings

 Guideline

Reliability 

Buehler test

Guinea Pigs

Not a sensitizer 

OECD 406, EPA 81-6 

1

Buehler test

Guinea Pigs

Not a sensitizer 

EPA 81-6

1

Buehler test

Guinea Pigs

Not a sensitizer 

OECD 406

2

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: MAFF Dermal Sensitization Study, 1985
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
1234
Specific details on test material used for the study:
Substance ID: TSN100759
Lot Number: 7299412
Purity: 97.6%
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. Portage, Michigan
- Age at study initiation: 5 weeks
- Weight at study initiation: 368.8-435.4 g
- Housing: Five per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.4 mL neat
Day(s)/duration:
6 hour exposure, treated once weekly for three consecutive weeks
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
A single 0.4 ml aliquot of neat DER 331 epoxy resin or 0.5% solution of DNCB (dinitro chlorobenzene) in DPGME solvent were used as positive controls.
Day(s)/duration:
6 hour exposure, treated once weekly for three consecutive weeks
Route:
epicutaneous, occlusive
Vehicle:
other: DPGME
Concentration / amount:
0.4 mL of 1% test substance solution
Day(s)/duration:
6 hours exposure
Adequacy of challenge:
highest non-irritant concentration
Route:
epicutaneous, occlusive
Vehicle:
other: DPGME
Concentration / amount:
Fifteen naive animals were dosed; five received a single 0.4 ml aliquot of 1% solution of the test material in DPGME solvent, five received 0.4 ml of neat DER 331, and five received 0.4 ml of 0.5% DNCB.
Day(s)/duration:
6 hours
No. of animals per dose:
Induction and challenge: 10
Positive control: 10
Naive animals: 15
Details on study design:
RANGE FINDING TESTS: A preliminary skin irritation screen was conducted in order to determine a slightly irritating dose, if obtainable, as well as to establish the highest non-irritating concentration of the test material. Guinea pigs were clipped free of hair, on the left and right side (and may have been clipped on their back), the day prior to dosing. The crystalline test substance was gently heated to achieve a liquid state. Single application of 0.4 mL of neat liquefied test material, or as a 0.5, 1, 3.75, 5, 10, 20, 40, or 80% solution of liquefied test substance in dipropylene glycol monomethyl ether (DPGME), was topically applied to the skin of guinea pigs for six hours in Hill Top Chambers. The following day the application sites were depilated prior to scoring. Skin irritation readings were recorded approximately 24 and 48 hours after test material removal. Multiple animals were used in verifying that 1% solution of the test substance in DPGME was the highest non-irritating dose level.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: Three weeks
- Test groups: One
- Control group: Positive control group and naive group
- Site: Left side
- Frequency of applications: Once per week
- Duration: 6 hour exposure
- Concentrations: Neat

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Exposure period: 6 hours
- Test groups: One
- Control group: Positive control group and naive group
- Site: Left side
- Concentrations: 1%
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
Neat DER 331 or 0.5% DNCB, the positive control materials, was applied to the right side of the guinea pigs.
Fifteen naive animals were dosed; five received a single 0.4 ml aliquot of 1% solution of the test material in DPGME solvent, five received 0.4 ml of neat DER 331, and five received 0.4 ml of 0.5% DNCB.
Positive control substance(s):
yes
Remarks:
dinitro chlorobenzene or DER 331 epoxy resin
Positive control results:
Challenge application with 0.4 ml of DER 331 epoxy resin caused slight to moderate erythema, considered to reflect a hypersensitivity response, at the test site on eight of ten animals at the 48-hour read. None of the DER 331 naive animals showed any evidence of irritation, at the 48-hour read. Challenge application with 0.4 ml of 0.5% DNCB caused slight to moderate erythema, considered to reflect a hypersensitivity response, at the test site on ten of ten animals, at the 48-hour read. None of the 0.5% DNCB naive animals showed any evidence of irritation, at the 48-hour read.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
DER 331 (Neat)
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
DER 331 (Neat)
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.5% DNCB
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.5% DNCB
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
other: Test substance naive group
Dose level:
1%
No. with + reactions:
1
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Test substance naive group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
other: Positive control naive group
Dose level:
DER 331 (Neat)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Positive control naive group
Dose level:
DER 331 (Neat)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
other: Positive control naive group
Dose level:
0.5% DNCB
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Positive control naive group
Dose level:
0.5% DNCB
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Group:
negative control
Remarks on result:
other: Negative control was not included
Interpretation of results:
GHS criteria not met
Conclusions:
No delayed contact hypersensitivity in guinea pig
Executive summary:

The test substance was evaluated for dermal sensitization potential using the Buehler method. The study was conducted according to OECD guideline 406 and EPA guideline 81-6. Ten male Hartley albino guinea pigs received three dermal applications of 0.4 mL of test substance, during the three-week induction period and during the challenge application two weeks after the last induction application. Five naive animals also received 0.4 mL of test substance at the challenge phase. The condition of the test sites was assessed approximately 24 and 48 hours after the challenge application. Challenge application with 0.4 mL of test substance caused erythema at the test site in only one of the ten animals, and none of the naïve animals showed any evidence of irritation, at the 48-hour read. An additional ten male Hartley albino guinea pigs/test material received three dermal applications of 0.4 mL of neat DER 331 epoxy resin or 0.5% DNCB (dinitro chlorobenzene), respectively, which are run every six months as positive controls. Five naive animals also received a 0.4 mL aliquot of neat DER 331 epoxy resin or 0.5% DNCB, respectively, at the challenge phase. Challenge application with 0.4 mL of DER 331 epoxy resin caused slight to moderate erythema, considered to reflect a hypersensitivity response, at the test site on eight of ten animals at the 48-hour read. None of the DER 331 naive animals showed any evidence of irritation, at the 48-hour read. Challenge application with 0.4 mL of 0.5% DNCB caused slight to moderate erythema, considered to reflect a hypersensitivity response, at the test site on ten of ten animals, at the 48-hour read. The animals were in apparent good health and gained weight over the study period. Therefore, under the conditions of this study, the test substance did not cause delayed contact hypersensitivity in guinea pigs.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Specific details on test material used for the study:
Batch: 341-HRR-153
Purity: 99.3%
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Route:
intradermal
Vehicle:
arachis oil
Concentration / amount:
25% w/v in arachis oil B.P.
Day(s)/duration:
Day 0
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.1 - 0.2 mL undiluted test material
Day(s)/duration:
Day 21
No.:
#2
Route:
intradermal
Vehicle:
arachis oil
Concentration / amount:
75% v/v in arachis oil B.P .
Day(s)/duration:
Day 21
No. of animals per dose:
20 test animals and 10 control animals
Key result
Reading:
1st reading
Dose level:
75%
No. with + reactions:
0
Total no. in group:
19
Interpretation of results:
GHS criteria not met
Conclusions:
Test substance was not sensitizing to guinea pigs.
Executive summary:

A test was performed to assess the skin contact sensitization potential of the test material in the albino guinea pig. The method used followed that described in the USA Environmental Protection Agency (E.P.A. Guidelines. The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 91/325/EEC).

 

Twenty test and ten control animals were used for the main study. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

Intradermal Induction 25% w/v in arachis oil B.P.

Topical Induction undiluted as supplied

Topical challenge undiluted as supplied and 75% v/v in arachis oil B.P .

 

The test material produced a 0% (0/19) sensitisation rate and was classified as a non-sensitiser to guinea pig skin. The test material did not meet the criteria for classification as a sensitizer according to EC labelling. No risk phrase is required.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
no
Type of study:
Buehler test
Specific details on test material used for the study:
Dursban Technical
Lot Number: EK 830516110
Purity: Not reported
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
0.3 mL at 100% (w/v)
Day(s)/duration:
6 hour exposure; treatment was repeated 7 and 14 days after the initial exposure on the same site
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
100% (w/v)
Day(s)/duration:
6 hours exposure
Adequacy of challenge:
not specified
No. of animals per dose:
Test: 12 (6M + 6F)
Control: 12 (6M + 6F)
Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100% (w/v)
No. with + reactions:
0
Total no. in group:
12
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100% (w/v)
No. with + reactions:
1
Total no. in group:
12
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
other: test group vehicle alone
Dose level:
100% (w/v)
No. with + reactions:
0
Total no. in group:
12
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
other: test group vehicle alone
Dose level:
100% (w/v)
No. with + reactions:
0
Total no. in group:
12
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
No delayed contact hypersensitivity in guinea pig
Executive summary:

A study was performed to determine the skin sensitization potential of the test substance in the albino guinea pig based on the Buehler Test.

The study was designed to meet the requirements of OECD 406.

No incidence of skin reactions observed in both test and control animals.

These results indicated that the test substance does not cause delayed contact hypersensitivity in the albino guinea pig using the Buehler Test.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Justification for type of information:
Conduct of an In vivo study is a data requirement in other geographies (Asian countries such as India, China, Japan etc.) and therefore, an in vivo study was conducted which was adequate to evaluate the endpoint.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Three studies performed for evaluation of skin sensitization potential of chlorpyrifos followed Buehler method, all studies concluded that the test material is non skin sensitizer. 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

There was no evidence of dermal sensitisation in guinea pigs. The substance does not need to be classified for skin sensitisation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.