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Description of key information

Skin sensitisation (in vivo): Not sensitising (equivalent or similar to OECD 406/GLP)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

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Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17th July 1991 - 2nd December 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed in 1991.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- lot/batch No.of test material:9059

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: The test material, a colourless liquid, was stored in the dark under ambient conditions.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Darley Oaks, Newchurch, Burton-on-Trent, Staffordshire, UK.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: young adult (less than one year old)
- Weight at study initiation: 332-484 g
- Housing: Aluminium cage had a grid floor beneath which was a peat moss filled tray.
- Diet: FDl Guinea Pig Diet, supplied by Special Diets Services, I Stepfield, Witham, Essex, CMB 3AD, supplemented with hay ad libitum
- Water: tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19-21°C
- Humidity (%):58%
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle
Route:
intradermal
Vehicle:
paraffin oil
Concentration / amount:
25%
Day(s)/duration:
6 days
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
100%
Day(s)/duration:
2 days
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
100%
Day(s)/duration:
1
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 females (test item and control)
Details on study design:
RANGE FINDING TESTS:
Dose Ranging Test for Induction
A preliminary dose ranging test was carried out to assess suitable concentrations for injection and topical application on 4 previously untreated guinea pigs. Injections were in the shaved scapular region and topical application was on the shaved flanks. Two guinea pigs were subjected to intradermal injections and a further 2 guinea pigs were exposed to topical application for 48 h of the test material at 4 different concentrations.

Injections - 100%, 50%, 25% and 10% v/v in paraffin oil
Topical application 100%, 50%, 25% and 10% v/v in paraffin oil

The injection sites were assessed for irritation 24, 48 and 72 h after injection, and the topical application sites were assessed for irritation 24 and 48 h after patch removal. Assessments were made using Scale A.

Scale A
No visible change = 0
Slight reaction = 1
Moderate reaction = 2
Severe reaction and/or necrosis = 3

Details of reaction scores are given in Table 1.

Moderate to severe irritation was noted at sites injected with DEP at concentrations of 100% and 50% v/v in paraffin oil. Slight irritation was noted at 25% and a concentration of 10% produced no irritant responses. A concentration of 25% v/v in paraffin oil was selected for the injection phase of induction in the test group. No irritation was noted at sites treated topically with the test material. A concentration of 100% was selected for the topical application phase of induction in the test group.

Dose Ranging Test for Challenge
Before challenging the test animals, a maximum non-irritant concentration of the test material was determined in a preliminary experiment on 4 dose ranging guinea pigs. The animals were pretreated at the induction phase with Freund's Complete Adjuvant only. The test material was applied to the shaved flanks of the guinea pigs for 24 h at concentrations of 100% and 50% v/v in paraffin oil using the same method as topical induction. Reactions were assessed 24 h later using Scale B.

Scale B
No visible change = 0
Slight or discrete erythema = 1
Moderate and confluent erythema = 2
Intense erythema and/or oedema = 3

Details of reaction scores are given in Table 3.

No irritation was noted at sites treated topically with DEP at concentrations of 100% and 50% v/v in paraffin oil. A concentration of 100% was selected for challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
Main Test - Injection Phase
In the main test, hair was shaved from an area 4 cm x 6 cm across the scapular region of 44 guinea pigs. These animals were allocated as follows:

Test group: 20 guinea pigs
Control group: 20 guinea pigs
Challenge dose ranging group: 4 guinea pigs

The test group guinea pigs were each given 6 intradermal injections, 3 in a line each side of and parallel to the mid-line in the shaved region as follows:
-0.10 ml Freund's Complete Adjuvant (anteriorminjection)
-0.10 ml test material (middle injection)
-0.10 ml of a 50:50 emulsion of test material in Freund's Complete Adjuvant (posterior injection)

The test material was injected at a concentration of 25% v/v in paraffin oil.
The 20 control group guinea pigs were similarly treated, but with the vehicle, paraffin oil, replacing the test materia1. One hour and 24 h after injection, the treated sites of both test and control groups were assessed for irritation
using Scale A.

The 4 guinea pigs intended for dose ranging for challenge were each given a 0.1 ml intradermal injection of Freund's Complete Adjuvant on either side of the mid-line of the shaved scapular region.

Main Test- Topical Application Phase
Six days after the injection phase, the injection site of each of the test and control group animals was shaved again and then wetted with 10% aqueous SLS to provoke a mild inflammatory response to enhance the possibility of sensitisation. After 24 h, a 2 cm x 4 cm patch of Whatman chromatography paper, charged with the test material at a concentration of 100%, was applied to the pretreated area of each of the test group animals. The patch was covered by an overlapping piece of impermeable plastic adhesive tape (Blenderm). The whole area was then firmly bound with Sleek occlusive tape, and the dressing was left in place for 48 h before removal. The control group guinea pigs were similarly treated, but with the vehicle, paraffin oil, replacing the test material. One hour and 24 h after patch removal, the treated sites of both test and control groups were assessed for irritation using Scale A to be described. The 4 guinea pigs intended for dose ranging for challenge were untreated at this stage.


B. CHALLENGE EXPOSURE
Main Test - Challenge Phase
Two weeks after the start of topical induction, both the test and control group guinea pigs were challenged with the test material, PEP, at a concentration of 100% and with the vehicle, paraffin oil. A 5 cm x 5 cm area of the left. flank was shaved and the test and control materials were applied to the prepared test site on 2 cm x 2 cm pieces of filter paper. The patches were held in place for 24 h using the same method as topical induction, after which time they were removed. The degree of response was determined by trained assessors 24 and 48 h after removal of the challenge patch when an allergic response would be at a peak. Any animal showing erythema at the site of challenge was considered to have shown a positive response.
Positive control substance(s):
yes
Remarks:
The sensitivity of this strain of guinea pig to a known sensitiser, 2,4-dinitro-chlorobenzene (DNCB) is checked at 6 monthly intervals.
Positive control results:
The most recent positive control test was completed on 26-07-91 when 65% of the test group animals reacted positively.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
other: 6 monthly interval test with DNCB
Hours after challenge:
0
Group:
positive control
Dose level:
0
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
0
Remarks on result:
other: 65% of the test group animals reacted positively.
Interpretation of results:
GHS criteria not met
Conclusions:
In an in vivo GPMT, the substance 1,2-Diethoxypropane is not sensitising.
Executive summary:

In a dermal sensitization study (8282) with 1,2-Diethoxypropane in paraffin oil, young adult female Dunkin-Hartley guinea pigs were tested in a maximisation test. For induction, 25% v/v 1,2-Diethoxypropane in paraffin oil (intradermal injections) and 100% v/v 1,2-Diethoxypropane in paraffin oil (topical application) was used. For challenge, 100% v/v 1,2-Diethoxypropane in paraffin oil was used for topical application. The evaluation of skin reactions after challenge was carried out at 24 and 48 hrs. The positive control was 2,4-dinitro-chlorobenzene (DNCB) conducted at 6 monthly intervals.

In the most recently conducted positive control test, 65% of the animals reacted positively. No clinical signs, other than skin reactions induced by treatment, were noted with 1,2-Diethoxypropane. Body weight gains were acceptable with the exception of one test group animal which showed a slightly lower weight gain than normal. Following challenge with 1,2-Diethoxypropane at a concentration of 100%, none of the 20 test group animals showed positive reactions to this application. None of the 20 control group animals, which had previously only been exposed to the vehicle, paraffin oil, showed a positive reaction to this application. There was no reaction in the test or control groups to challenge with the vehicle, paraffin oil.

Based on the results of this study, 1,2-Diethoxypropane is not sensitising.

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

There are no in vitro skin sensitisation studies avaiable. There is one in vivo GPMT available.

In a dermal sensitization study (equivalent or similar to OECD 406/GLP) with 1,2-Diethoxypropane in paraffin oil, young adult female Dunkin-Hartley guinea pigs were tested in a maximisation test. For induction, 25% v/v 1,2-Diethoxypropane in paraffin oil (intradermal injections) and 100% v/v 1,2-Diethoxypropane in paraffin oil (topical application) was used. For challenge, 100% v/v 1,2-Diethoxypropane in paraffin oil was used for topical application. The evaluation of skin reactions after challenge was carried out at 24 and 48 hrs. The positive control was 2,4-dinitro-chlorobenzene (DNCB) conducted at 6 monthly intervals. In the most recently conducted positive control test, 65% of the animals reacted positively. No clinical signs, other than skin reactions induced by treatment, were noted with 1,2-Diethoxypropane. Body weight gains were acceptable with the exception of one test group animal which showed a slightly lower weight gain than normal. Following challenge with 1,2-Diethoxypropane at a concentration of 100%, none of the 20 test group animals showed positive reactions to this application. None of the 20 control group animals, which had previously only been exposed to the vehicle, paraffin oil, showed a positive reaction to this application. There was no reaction in the test or control groups to challenge with the vehicle, paraffin oil. Based on the results of this study, 1,2-Diethoxypropane is not sensitising.

The results from this study are suitable to use in the human health assessment.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available information in the dossier, the substance 1,2 Diethoxypropane (CAS No. 10221-57-5) does not need to be classified for skin sensitisation when the criteria outlined in Annex I of 1272/2008/EC and Annex I of 286/2011/EC are applied.