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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:
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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate)
EC Number:
229-722-6
EC Name:
Pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate)
Cas Number:
6683-19-8
Molecular formula:
C73H108O12
IUPAC Name:
3-{[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoyl]oxy}-2,2-bis({[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoyl]oxy}methyl)propyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoate
Details on test material:
- Substance type: Organic
- Physical state: Solid

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
propylene glycol
Concentration / amount:
0.1%
Challenge
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

Results and discussion

Positive control results:
Positive controls were not reported.

In vivo (non-LLNA)

Resultsopen allclose all
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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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