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Description of key information

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:
3 Feb to 12 March 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline study, to GLP, with slight deviations which are not expected to affect the outcome
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
temperature slightly outside of recommended range
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
yes
Remarks:
temperature slightly outside of recommended range
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An in vivo skin sensitisation study by the LLNA method does not need to be conducted because adequate data from a guinea pig maximisation test are available.
Species:
guinea pig
Strain:
other: Crl:(HA)BR
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage Michigan
- Age at study initiation: 5 to 8 weeks
- Weight at study initiation: 372 to 574 g
- Housing: Individually housed in suspended stainless steel cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 26 [OECD guideline recommends 20 +/- 3, but unlikely to affect the outcome]
- Humidity (%): 30-70
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 3 Feb 1999 To: 12 March 1999
Route:
intradermal and epicutaneous
Vehicle:
other: Freund's Complete Adjuvant (FCA) and sterile water for intradermal injections, no vehicle for topical applications
Concentration / amount:
1% w/v for intradermal injections
Undiluted (100%) for topical induction and challenge applications
Route:
epicutaneous, occlusive
Vehicle:
other: Freund's Complete Adjuvant (FCA) and sterile water for intradermal injections, no vehicle for topical applications
Concentration / amount:
1% w/v for intradermal injections
Undiluted (100%) for topical induction and challenge applications
No. of animals per dose:
20 males
Details on study design:
RANGE FINDING TESTS:
1st screening group: Four males treated intradermally, at a shaved site, with 0.1ml of DEIPA at 0.5, 1, 5 and 10% w/v in sterile water, each animal receiving all four concentrations. Injection sites evaluated for erythema and edema reactions at approx. 24-hours and 48-hours after injection.

2nd screening group: Four males received two 0.1ml intradermal injections of a 1:1 dilution of FCA and sterile water on the shoulder area. Twelve days after, all animals received a topical application of DEIPA at 1, 10, 25 and 50% w/v in sterile water covered with an occlusive patch. The patch was removed after 24 hours and the test site washed. Each animal received all four concentrations. Application sites were observed for dermal reactions at 24 and 48 hours after patch removal.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (Intradermal injections and topical application)
- Exposure period: Duplicate intradermal injections, 48-hour topical application
- Test groups: DEIPA in sterile water and FCA (1:1) injected, undiluted DEIPA for topical application
- Control group: FCA and sterile water
- Site: Midline over the shoulder region
- Frequency of applications: Intradermal injections administered on day 1, topical application on day 8.
- Duration: 0 to 8 days
- Concentrations: 1% w/v mixture in sterile water and FCA for the intradermal injection phase and undiluted for the topical application

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 24 hours
- Test groups: Undiluted DEIPA
- Control group: Undiluted DEIPA
- Site: Right and left side
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48
Challenge controls:
10 males in control group, undiluted DEIPA used for challenge topical application
Positive control substance(s):
yes
Remarks:
hexylcinnamaldehyde
Positive control results:
All 10 animals in the test group within this study exhibited mild to severe dermal reactions following challenge applications of undiluted HCA or a 50% mixture of HCA in mineral oil. None of the animals in the test group exhibited a dermal reaction to the vehicle at challenge. From these results, HCA is considered to be an extreme dermal sensitizer in guinea pigs by the maximization test. The positive control study was conducted within 6 months of the DEIPA sensitisation study.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 ml undiluted DEIPA
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None reported
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1 ml undiluted DEIPA. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None reported.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1 ml undiluted DEIPA
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None reported
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1 ml undiluted DEIPA. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None reported.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
undiluted DEIPA
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None reported
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
undiluted DEIPA
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None reported
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
50% alpha-hexylcinnamaldehyde
No. with + reactions:
10
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
50% alpha-hexylcinnamaldehyde
No. with + reactions:
5
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
undiluted alpha-hexylcinnamaldehyde
No. with + reactions:
10
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
undiluted alpha-hexylcinnamaldehyde
No. with + reactions:
7
Total no. in group:
10
Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a GLP study, conducted according to OECD guideline 406, DEIPA was determined to be non-sensitising in the guinea pig maximisation test.
Executive summary:

In a GLP study, conducted according to OECD guideline 406, the dermal sensitising potential of DEIPA was assessed in a guinea pig maximisation test. Following the initial screening phase, 20 animals were assigned to the test group and 10 to the control group. On day 1, animals in the test group received duplicate 0.1 ml intradermal injections either side of the midline over the shoulder region, of a 1:1 dilution of Freund’s Complete Adjuvant (FCA) in sterile water, 1% w/v suspension of test material in sterile water and 1% w/v suspension of test material in sterile water in FCA. Concurrently, the control group received duplicate 0.1 ml injections of a 1:1 dilution of FCA in sterile water, sterile water alone and a 1:1 dilution of sterile water in FCA. On day 7, the animals in both groups were pre-treated with 10% w/w sodium lauryl sulphate in petrolatum applied topically at the injection sites. One day later, undiluted test material or vehicle (sterile water) was applied topically over the injection sites to animals in the test and control group respectively, and covered with an occlusive dressing for 48 hours before removal of the material with a damp cloth.

All animals received a challenge dose 2 weeks after the topical application. The undiluted test material and vehicle were applied to the right and left side of the animal and covered with an occlusive dressing for 24 hours before removal with a damp cloth. The challenge sites were examined for dermal reaction at 24 and 48 hours following patch removal.

None of the animals in either the test or control group exhibited a dermal reaction to the challenge application of the test or control substances. There were no significant changes in body weights or treatment-related clinical signs of toxicity reported.

In this study, DEIPA can be considered as non-sensitising to the skin of guinea pigs.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a GLP study (reliability 1), conducted according to OECD guideline 406, the dermal sensitising potential of DEIPA was assessed in a guinea pig maximisation test. Following the initial screening phase, 20 animals were assigned to the test group and 10 to the control group. On day 1, animals in the test group received duplicate 0.1 ml intradermal injections either side of the midline over the shoulder region, of a 1:1 dilution of Freund’s Complete Adjuvant (FCA) in sterile water, 1% w/v suspension of test material in sterile water and 1% w/v suspension of test material in sterile water in FCA. Concurrently, the control group received duplicate 0.1 ml injections of a 1:1 dilution of FCA in sterile water, sterile water alone and a 1:1 dilution of sterile water in FCA. On day 7, the animals in both groups were pre-treated with 10% w/w sodium lauryl sulphate in petrolatum applied topically at the injection sites. One day later, undiluted test material or vehicle (sterile water) was applied topically over the injection sites to animals in the test and control group respectively, and covered with an occlusive dressing for 48 hours before removal of the material with a damp cloth. All animals received a challenge dose 2 weeks after the topical application. The undiluted test material and vehicle were applied to the right and left side of the animal and covered with an occlusive dressing for 24 hours before removal with a damp cloth. The challenge sites were examined for dermal reaction at 24 and 48 hours following patch removal. None of the animals in either the test or control group exhibited a dermal reaction to the challenge application of the test or control substances. There were no significant changes in body weights or treatment-related clinical signs of toxicity reported. In this reliable study, DEIPA can be considered as non-sensitising to the skin of guinea pigs (Glaza, 1999).

According to an expert review summarising this study, “In a guinea pig maximisation test there was no evidence of reactions indicative of skin sensitisation" (NICNAS, 2009).

References

NICNAS (2009). Australian National Industrial Chemicals Notification and Assessment Scheme. Full Public Report. DEIPA. File No: STD/1344. December 2009.http://www.nicnas.gov.au/publications/CAR/new/Std/StdFULLR/std1000FR/std1344FR.pdf 


Migrated from Short description of key information:
In a GLP study (reliability 1), conducted according to OECD guideline 406, DEIPA was determined to be non-sensitising in the guinea pig maximisation test (Glaza, 1999).

Justification for selection of skin sensitisation endpoint:
GLP, OECD guideline study (reliability 1).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No human or laboratory animal respiratory sensitisation data were available. However, DEIPA is not expected to be a respiratory sensitiser based on its lack of skin sensitising potential. In addition, chemicals (like DEIPA) with relatively low vapour pressures are less likely to vaporise and become airborne (ECHA, 2012b), thus limiting the possibility for respiratory exposure during normal conditions of use.


Migrated from Short description of key information:
No human or laboratory animal respiratory sensitisation data were available. However, DEIPA is not expected to be a respiratory sensitiser due to its lack of skin sensitising potential and the limited possibility of respiratory exposure under normal conditions of use (based on its physico-chemical properties).

Justification for selection of respiratory sensitisation endpoint:
No study available and testing for respiratory sensitisation is not required

Justification for classification or non-classification

Based on the available data, DEIPA would not be classified as a skin or respiratory sensitiser under EU CLP regulations.

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