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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
Study period:
1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: OECD (1981, Guideline number not specified)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EPA Health’s Effects Test Guidelines (Federal Register Vol. 50, No. 188)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Currently no LLNA study is available for assessment. The Buehler test has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.

Test material

Constituent 1
Chemical structure
Reference substance name:
4-chlorophthalic anhydride
EC Number:
204-251-9
EC Name:
4-chlorophthalic anhydride
Cas Number:
118-45-6
Molecular formula:
C8-H3-Cl-O3
IUPAC Name:
5-chloro-1,3-dihydro-2-benzofuran-1,3-dione

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
Male Hartley guinea pigs were received from Buckshire Corporation, Perkasie, PA. They weighed 400.6 to 592.3 g on Test Day 1. They were housed two per cage upon arrival and were individually housed following selection for testing. Polycarbonate cages were used. The animals were acclimated for approximately 4 weeks prior to dosing. Water and feed were provided ad libitum. The temperature and humidity were generally maintained at 68 to 74°F and 57 to 92%, respectively. Room lights were on a 12-hour light/dark cycle.

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
Once weekly for 3 weeks (group 1)
Challengeopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
Two weeks after last induction (group 1)
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
Once at the time of challenge (group 2)
No. of animals per dose:
10/Test group (100% 4-CLPA topical)
5/Positive Control group
Details on study design:
10/Test group (100% 4-CLPA topical)
5/Positive Control group

Treatment Group 1: 10 animals were exposed once weekly for three weeks; challenge two weeks later to 4-CLPA at 100%.

Treatment Group 2: 10 animals were exposed once at the time of challenge to 4-CLPA at 100%.

Treatment Group 3: 5 animals were exposed once weekly for three weeks; challenge two weeks later to DNCB at 0.05%.

Treatment Group 4: 5 animals were exposed once at the time of challenge to DNCB at 0.05%.

Body weights were recorded on Test Day 1 and on the last day of the study for all groups. Observations for signs of irritation/sensitization were recorded approximately 24 and 48 hours following the challenge treatment according to the method of Ritz and Buehler (1980) as follows:

0 = No reactions
0.5 = Very faint erythema, usually non-confluent
1 = Faint erythema, usually confluent
2 = Moderate erythema
3 = Strong erythema, with or without edema

To facilitate scoring following the challenge dose only, skin sites were depilated with Neet depilatory approximately 2 hours prior to the 24-hour scoring.

Evaluation Criteria:
Incidence and severity indices were calculated for test and control animals following the challenge dose. The incidence index is an expression of the number of animals showing a response of greater than or equal to 1 at 24 or 48 hours, versus the total number of animals in the group. The severity index was determined for the 24- and 48-hour intervals by dividing the sum total of the grades in a given treatment group by the total number of animals in that group.
Positive control substance(s):
yes
Remarks:
Dinitrochlorobenzene (DNCB, 0.05% in 90% ethanol)

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Group 1
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Group 1
Reading:
1st reading
Hours after challenge:
24
Group:
other: Test Challenge
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Group 2
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Test Challenge
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Group 2
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.05% DNCB
No. with + reactions:
3
Total no. in group:
5
Clinical observations:
None
Remarks on result:
other: Group 3
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.05% DNCB
No. with + reactions:
2
Total no. in group:
5
Clinical observations:
None
Remarks on result:
other: Group 3
Reading:
1st reading
Hours after challenge:
24
Group:
other: Positive Challenge
Dose level:
0.05% DNCB
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Remarks on result:
other: Group 4
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Positive Challenge
Dose level:
0.05% DNCB
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Remarks on result:
other: Group 4

Any other information on results incl. tables

All animals gained weight over the course of the study.  No skin reactions occurred for either the induced or the challenge only test article-treated animals.  One animal had white skin discoloration at the 24-hour reading and desquamation at the 48-hour reading.  Very faint to moderate erythema was seen in the induced positive control animals at both the 24‑ and 48-hour readings.  One animal had slight edema at the 48-hour reading.  No reactions were observed in the non-induced positive control challenge animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was determined to be not skin sensitising.
Executive summary:

Skin sensitisation was determined in a study performed according to an OECD guideline (guideline number not specified) and was in compliance with GLP criteria. In this Buehler test, 40 male Hartley guinea pigs were exposed in four different scenarios, although all under semiocclusive conditions. Group 1 was exposed once weekly for 3 weeks and challenge occurred 2 weeks after the last challenge, all with 100% test substance. Group 2 was exposed only once at the time of challenge with 100% test substance. The exposure scenario for group 3 and 4 were similar to group 1 and 2, respectively, but in these groups experiments were conducted with positive control substance Dinitrochlorobenzene (DNCB, 0.05% in 90% ethanol). Skin reactions were evaluated 24 and 48 hours after patch removal. All animals gained weight over the course of the study.  No skin reactions occurred for either the induced or the challenge only test article-treated animals.  One animal had white skin discoloration at the 24-hour reading and desquamation at the 48-hour reading.  Very faint to moderate erythema was seen in the induced positive control animals at both the 24‑ and 48-hour readings. One animal had slight edema at the 48-hour reading. No reactions were observed in the non-induced positive control challenge animals. Based on these results the test substance is considered not to be skin sensitsing.