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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:
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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
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.

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(N,N-bis(2-hydroxyethyl)amino)propan-2-ol
EC Number:
229-764-5
EC Name:
1-(N,N-bis(2-hydroxyethyl)amino)propan-2-ol
Cas Number:
6712-98-7
Molecular formula:
C7H17NO3
IUPAC Name:
1-[bis(2-hydroxyethyl)amino]propan-2-ol
Test material form:
other: Viscous, clear colourless liquid
Details on test material:
- Name of test material (as cited in study report): Diethanolisopropanolamine (DEIPA)
- Substance type: Technical product
- Physical state: Liquid
- Analytical purity: 93%
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: Not specified
- Lot/batch No.: 980035B
- Expiration date of the lot/batch: Not specified
- Stability under test conditions: Not specified
- Storage condition of test material: Room temperature

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
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
Challengeopen allclose all
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

Results and discussion

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.

In vivo (non-LLNA)

Resultsopen allclose all
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

Applicant's summary and conclusion

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.

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