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Administrative data

Description of key information

The substance was found to be not sensitizing in guinea pigs. The key study was a guinea pig optimization test in which none of the 20 animals showed skin reactions after the challenge reaction.

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:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The test performed is rather insensitive, since injection of propylene glycol results in necrosis, which gives a high background level of reaction volume. Positive control data not included in the report. Dose selection not justified.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
10 h light instead of 12 h. The adjuvant was used during the 2nd and 3rd week. Age of the animals unknown. missing initial individual body weights.
GLP compliance:
no
Type of study:
Maurer optimisation test
Justification for non-LLNA method:
A valid in vivo study is available, therefore no LLNA has been performed
Species:
guinea pig
Strain:
other: Pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bred on the premises
- Weight at study initiation: 400 - 450 g
- Housing: Individually in Macrolon cages type 3,
- Diet (e.g. ad libitum): Ad libitum, NAFAG, No. 830, Gossau SG
- Water (e.g. ad libitum): Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 14/10
Route:
intradermal
Vehicle:
propylene glycol
Concentration / amount:
0.1%
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
0.1%
No. of animals per dose:
20
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10 (intradermal injections, every second day except week-ends)
- Exposure period: 3 w
- Site: Right flank and back
- Frequency of applications: every second day (except weekends)
- Concentrations: 0.1 %

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 14 after the last induction (intradermal challenge) and 10 after the first challenge (epicutaneous challenge)
- Exposure period: 11 d and 24 h
- Site: Left flank
- Concentrations: 0.1 %
- Evaluation (hr after challenge): 24
Challenge controls:
Vehicle and 5 % in vaseline
Positive control substance(s):
no
Positive control results:
Positive controls were not reported.
Reading:
1st reading
Hours after challenge:
24
Group:
other: test group intradermal challenge
Dose level:
0.1 %
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
none
Reading:
1st reading
Hours after challenge:
24
Group:
other: negative control group intradermal challenge
Dose level:
Vehicle
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
none
Reading:
rechallenge
Hours after challenge:
24
Group:
other: test group epicutaneous challenge
Dose level:
subirritant dose
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Reading:
rechallenge
Hours after challenge:
24
Group:
other: negative control epicutaneous challenge
Dose level:
Vehicle
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none

Table 1. Reaction volumes (μL) after intradermal injection of propylene glycol (vehicle).

Animal No Induction After skin sensitization Positive reactor (+)
Application No
Mean (x‾) Standard deviation(s)
(x‾-s)
1 2 3 4
1 12 24 120 50 51 48 99 158 +
2 88 81 30 45 61 28 89 28 -
3 60 88 200 80 107 63 170 25 -
4 32 77 106 52 67 32 99 110 +
5 73 196 160 80 127 60 187 292 +
6 30 204 30 80 86 82 168 60 -
7 64 71 100 70 76 16 92 100 +
8 12 220 115 0 87 103 190 15 -
9 22 15 140 110 72 63 135 88 -
10 25 270 112 72 120 106 226 192 -
11 32 84 0 70 47 38 85 36 -
12 231 53 120 96 125 76 201 22 -
13 5 21 90 160 69 71 140 60 -
14 67 120 40 52 70 35 105 144 +
15 32 252 120 130 134 90 224 202 -
16 100 34 120 72 82 37 119 15 -
17 45 11 245 140 110 105 215 70 -
18 134 204 80 260 170 79 249 36 -
19 156 34 100 220 128 79 207 96 -
20 72 14 38 43 42 24 66 22 -
Group mean 65 104 103 94


88 5/20

 

Table 2. Reaction volumes (μL) after intradermal injection of test material (0.1 %).

Animal No Induction After skin sensitization Positive reactor (+)
Application No Mean (x‾) Standard deviation (s) (x‾-s)
1 2 3 4
1 79 92 54 120 86 27 113 187 +
2 154 132 70 104 115 36 151 63 -
3 66 70 99 86 80 15 95 64 -
4 121 158 58 88 106 43 149 90 -
5 90 70 99 83 85 12 97 265 +
6 73 70 36 22 50 25 75 240 +
7 254 204 108 14 145 106 251 235 -
8 117 132 97 48 98 37 135 44 -
9 88 110 150 108 114 26 140 139 -
10 43 157 88 102 97 47 144 176 +
11 96 143 49 121 102 40 142 109 -
12 216 437 43 22 179 192 371 101 -
13 108 130 64 62 91 34 125 250 +
14 154 72 72 88 96 39 131 35 -
15 200 132 63 134 132 56 188 77 -
16 130 181 104 150 141 32 173 108 -
17 145 136 44 88 103 47 150 150 -
18 121 104 63 62 87 30 117 72 -
19 145 132 42 56 94 52 146 99 -
20 160 151 84 144 135 34 169 22 -
Group mean 128 141 74 85


126 5/20
Interpretation of results:
GHS criteria not met
Conclusions:
The test article was found to be devoid of skin-sensitizing (contact allergenic) potential in albino guinea-pigs
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Experimental data regarding skin sensitization is available from three reports, all of them pre-dating GLP requirements. The key study was chosen because it is the only one which is adequate in design and reporting. Limitations are that positive control data not included in the report and that the dose selection was not justified. The test is an optimization test in guinea pigs performed with a suspension of 0.1% in propylene glycol. As the test item is of overall solubility, the chosen dose was probably the highest that could be injected. In 1980, another study in guinea pig with a similar design was performed, however due to the low number of animals, it is of limited value for hazard assessment. A report on a human patch test with 50 volunteers is available. No incidence of skin reactions was reported. Overall, the substance is concluded to be non-sensitizing. Absence of findings in animal studies is consistent with the very high molecular weight of 1178 Da of the test substance. Such substances are too large to penetrate the skin.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008.