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Description of key information

Relevant data for skin sensitization potential of the target substance is available. In a dermal sensitization study (OECD 406) with ortho-phthalaldehyde in corn oil, 20 young adult female guinea-pigs of the Dunkin-Hartley strain were tested using the method of Magnusson and Kligman. Combining the results of visual and histopathological examinations, all animals of the test substance group were regarded as sensitised. Based on these results, ortho-phthalaldehyde is a dermal sensitiser and is considered to be classified for 'Category 1A' for skin sensitisation based on CLP criteria. This classification is further supported by the results of an LLNA, in which also a Skin Sens 1A, H317 classification is warranted.

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
Study period:
2000-03-27 to 2000-06-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted: 17th July 1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Suitable non-LLNA data was already available from 2000. Therefore, the generation of new LLNA data is not necessary.
Specific details on test material used for the study:
- Name used in the test report: o-PHTALALDEHYDE
- Chemical name: 1,2-Benzenedicarboxaldehyde
- Trade name: OPA
- CAS no.: 643-79-8
- Batch no.: FKGP908
- Appearance: Slight yellow sloid with scaly appearance
- Conditions of storage: at room temperature, in the dark
- Date of expiry: December 2000
Species:
guinea pig
Strain:
other: HsdPoc:DH
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann, Gartenstrasse 27, D-33178 Borchen
- Females (if applicable) non-pregnant: Yes
- Age at study initiation: ca. 6 weeks al the first application
- Weight at study initiation: 343 g to 423 g at the first application
- Diet (e.g. ad libitum): ad libitum, Altromin Standard Diet No. 3022
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: approx. 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.4
- Humidity (%): 52.1
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
corn oil
Concentration / amount:
10% (v/v) DMSO
Day(s)/duration:
24 h
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
0.5 g
Day(s)/duration:
48 h
Adequacy of induction:
not specified
Route:
intradermal
Vehicle:
DMSO
Remarks:
10% (v/v) in corn oil
Concentration / amount:
0.1% (w/v) test substance
Day(s)/duration:
24 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
1% (w/w) test substance
Day(s)/duration:
48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
intradermal
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Freund’s complete adjuvant (FCA), 1+1 (v/v) blended with physiological saline
Day(s)/duration:
24 h
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
0.5 mL test substance (0.1% w/v)
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.5 g acetone
Day(s)/duration:
24 h
Adequacy of challenge:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
0.1% (w/v) test substance
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.5 mL acetone
Day(s)/duration:
24 h
Adequacy of challenge:
not specified
No. of animals per dose:
20 animals for the test substance group
10 animals for the control group.
Details on study design:
RANGE FINDING TESTS:
- 3 female guinea pigs were pretreated with FCA. 4 different concentrations of the test substance were administered intradermally and 7 days later 4 concentrations (10.0, 5.0, 1.0, 0.1% (v/v)) of the test substance were administered epicutaneously. As no suitable concentration for the epicutanous exposure was found in the first preliminary test, a second one was conducted with 3 other untreated (no FCA) female guinea pigs. The modes of application were the same as in the definitive study. The duration of the epicutaneous exposure was 24 hours. The test substance was dissolved in 10 % (v/v) DMSO in corn oil for the intradermal injections, incorporated in white petrolatum for the first epicutaneous administration and dissolved in acetone for the second epicutaneous administration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: Intradermal induction: 24 h, epicutaneous induction: 48 h
- Test groups: 1
- Control group: 1
- Site: approx. 2 x 4 cm in the interscapular region
- Frequency of applications: 1 x intradermal, 1 x epicutaneous
- Concentrations:
Intradermal: cranial: all groups: Freund’s complete adjuvant (FCA), 1+1 (v/v) blended with physiological saline; middle injection row: negative control: 10 % (v/v) DMSO in corn oil; test substance group: test substance, 0.1 %(w/v) in 10 % (v/v) DMSO in corn oil; caudal: negative control group: FCA, 1+1 (v/v) blended with 10 % (v/v) DMSO in corn oil; test substance group: final concentration of the test substance: 0.1 %(w/v) in: 10 % (v/v) DMSO in corn oil, 1 + 1 (v/v) blended with FCA.
Epicutaneous: 1% test substance in white petrolatum

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21 (after intradermal induction exposure)
- Exposure period: 24 hours
- Test groups: 1
- Control group: 1
- Site: 2 x 2 cm on the left flanks
- Concentrations: 0.1% test substance in acetone
- Evaluation (hr after challenge): 3 hours, 24 hours
Challenge controls:
Test patches of the same size, soaked with acetone were applied to the right flanks of all animals. Mode of fixation was the same as for the epicutaneous induction exposure.
Positive control substance(s):
yes
Positive control results:
Very slight to severe erythema and/or oedema in 8/10 animals 24 and/or 48 hours after the challenge exposure. 8/10 animals had a "positive skin reaction".
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
acetone
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:
negative control
Dose level:
acetone
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
18
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
19
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
other: 1st and/or 2nd reading
Hours after challenge:
24
Group:
positive control
Dose level:
10% in acetone
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
very slight to severe erythema and/or edema
Remarks on result:
positive indication of skin sensitisation

Table 1: Results of the Challenge exposure

Group

Number of animals at challenge exposure

Number of animals with positive reactions

Net rate of animals with positive skin reactions (%)

Negative control

10

0

-

Test substance

20

20

100

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
In conclusion, in an in vivo skin sensitisation test conducted in accordance to OECD 406 the test material is considered to be a skin sensitiser under UN GHS 'Category 1A'.
Executive summary:

In an dermal sensitisation study conducted according to OECD 406 with ortho-phthalaldehyde in corn oil, 20 young adult female HsdPoc:DH guinea pigs were tested using the Guinea Pig Maximisation Test of Magnusson and Kligman. Twenty female guinea pigs were used as a test substance group and another 10 females were used as a negative control group. There were two induction exposures (intradermally and epicutaneously) and one epicutaneous challenge exposure. 19/20 animals of the test substance group had a positive skin reaction at the visual examination 48 hours after challenge exposure. No animal of the control group had a positive skin reaction and the vehicle treated sites of all animals were normal. Histopathologically, 18/20 animals of the test substance group were found to have a positive skin reaction at the test substance treated sites (compared to the vehicle treated site of the same animal) and no positive skin reaction was noted in any control animal. Combining the results of visual and histopathological examinations, all animals of the test substance group were regarded as sensitised. Based on these results, ortho-phthalaldehyde is a dermal sensitiser and is considered to be classified for 'Category 1A' for skin sensitisation based on CLP criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Relevant data for skin sensitisation potential of the target substance is available. In an dermal sensitisation study conducted according to OECD 406 with ortho-phthalaldehyde in corn oil, 20 young adult female HsdPoc:DH guinea pigs were tested using the Guinea Pig Maximisation Test of Magnusson and Kligman. Twenty female guinea pigs were used as a test substance group and another 10 females were used as a negative control group. There were two induction exposures (intradermally and epicutaneously) and one epicutaneous challenge exposure. 19/20 animals of the test substance group had a positive skin reaction at the visual examination 48 hours after challenge exposure. No animal of the control group had a positive skin reaction and the vehicle treated sites of all animals were normal. Histopathologically, 18/20 animals of the test substance group were found to have a positive skin reaction at the test substance treated sites (compared to the vehicle treated site of the same animal) and no positive skin reaction was noted in any control animal. Combining the results of visual and histopathological examinations, all animals of the test substance group were regarded as sensitised. Based on these results, ortho-phthalaldehyde is a dermal sensitiser and is considered to be classified for 'Category 1A' for skin sensitisation based on CLP criteria. This result is supported by a LLNA from Anderson, 2009. In this study, conducted similar to OECD 429 with ortho-phthalaldehyde (>99% purity) dissolved in dimethylformamide, young adult Balb/c female mice (5 per dose group) were tested. No mortality occurred during the study and no clinical toxicity was observed. The EC3 value was calculated to be a test item concentration of 0.089%. The stimulation index was >3 at concentrations of 0.1% and 0.75% compared to the negative control. In this study, the test item is a dermal sensitiser under "Category 1A" according to UN GHS.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In a dermal sensitisation study according to OECD 406, female guinea pigs were tested positive for ortho-phthalaldehyde. Based on the results, classification of ortho-phthalaldehyde as Skin Sens 1A, H317 is warranted.

 

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