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Diss Factsheets

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Chlorpyrifos
EC Number:
220-864-4
EC Name:
Chlorpyrifos
Cas Number:
2921-88-2
Molecular formula:
C9H11Cl3NO3PS
IUPAC Name:
O,O-diethyl O-3,5,6-trichloropyridin-2-yl phosphorothioate
Test material form:
solid
Specific details on test material used for the study:
Substance ID: TSN100759
Lot Number: 7299412
Purity: 97.6%

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
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
Challengeopen allclose all
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

Results and discussion

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.

In vivo (non-LLNA)

Resultsopen allclose all
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

Applicant's summary and conclusion

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.