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Description of key information

Skin sensitization (OECD 406, RL1): guinea pig (m/f), not skin sensitizing

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21.05.-14.06.1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted before the LLNA-test became mandatory.
Species:
guinea pig
Strain:
other: PDH
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: SAVO-Ivanovas, Kisslegg
- Age at study initiation: about 6 - 8 weeks
- Housing: Healthy young guinea-pigs were allocated to individual cages. They were housed under conventional conditions in a 60 m2 room with artificial light (light phase: 6 a.m.-6 p.m.) and were allowed at least 7 days of acclimatization before the start of treatment. The cages used (MakrolonR cages type IV) had a floor area of 55 x 33 cm (1815 cm2) and a height of 20 cm, and were placed on mobile racks. The room temperature during the study period was 22 - 28 °c and the relative atmospheric humidity 33 - 60 %. Temperature and atmospheric humidity were registered by a thermo-hygrograph (Type 252, Wilhelm Lambrecht KG, Göttingen).

- Diet: Altromin Standard Diet TPF (R) 3012 (see item 7) and tap water (Südhessische Gas und Wasser AG, Darmstadt and Wasserwerk E. Merck, Darmstadt) from Makrolon drinking bottles were available to the guinea-pigs ad libitum. The diet is checked periodically by an independent and German Government approved testing laboratory ,- according to the regulations of the manufacturer. Analysis includes both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides and antibiotics. Drinking water employed in this type of study is regularly investigated microbiologically, physico-chemically, and chemically. The analytical results show that the limits set by German regulations for animal feed and by German regulations for human drinking water have not been exceeded.
Route:
intradermal
Vehicle:
paraffin oil
Concentration / amount:
0.05 g/100 mL
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
10 g/100 mL
Day(s)/duration:
Day 8/ 48 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
1 g/100 mL
Day(s)/duration:
Day 22/ 24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Two groups of 10 males and 10 females were used.
Positive control substance(s):
yes
Remarks:
The sensitivity of the test system has been demonstrated with DNCB = 2,4 dinitro-1-chlorobenzene (challenge concentration 0.01 %) in another study
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1%
No. with + reactions:
2
Total no. in group:
20
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none

Findings in the induction phase

After intradermal injection the usual irritation seen after treatment with Freund's complete adjuvant was observed. The injection sites were swollen and red. Later necrosis and scabs were observed. Similar findings were seen with liquid paraffin. After removal of the patches redness and scales were observed at the topical application sites.

Positive reactions (percent) after challenge

Group       Test                     Time points

material              24 h                     48 h              Total

1             Liquid paraffin     0/20 ( 0 %)       0/20 ( 0 % )       0/40 (0%)

2            test item              0/20 ( 0 %)       2/20 (10 % )       2/40 (5%)

Clinical findings and mortality

The clinical behavior of the guinea-pigs was normal during the study period. All animals survived the study period.

Body weight

The body weight development (Table 3) did not differ from that of the animals of the vehicle group. All animals survived the study period.

Interpretation of results:
GHS criteria not met
Conclusions:
The test material was not a skin sensitiser under the test conditions of this study.
Executive summary:

Objective

The purpose of this Guinea-pig maximization test was to assess the skin sensitizing potential of the test material when applied to the skin of the animal.

This study should provide a rational basis for risk assessment to the sensitizing potential of the test item in man.

 

Study Design

For this purpose Induction was performed in two stages. At first the test material was intradermally injected with and without Freund's complete adjuvant. Then, after one week, the test material was topically applied under occlusive patch conditions for 48 hours. The challenge was performed two weeks later by topical application. The patches were then applied for 24 hours.

 

Results

induction phase:

The injection sites were swollen and red. Later necrosis and scabs were observed. Similar findings were seen with liquid paraffin. After removal of the patches redness and scales were observed at the topical application sites

 

after challenge:

No irritation was observed in the test group. 24 h after challenge with the test item, a barely perceptible erythema was observed in two female animals and considered as not positive. At the 48 h reading the challenge sites in two female animals were covered with scales. These reactions were evaluated as a positive skin reaction.

 

The total positive reaction was 5%.

 

Conclusion

The test material was not a skin sensitiser under the test conditions of this study.

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

Objective

The purpose of this Guinea-pig maximization test was to assess the skin sensitizing potential of the test material when applied to the skin of the animal.

This study should provide a rational basis for risk assessment to the sensitizing potential of the test item in man.

 

Study Design

For this purpose Induction was performed in two stages. At first the test material was intradermally injected with and without Freund's complete adjuvant. Then, after one week, the test material was topically applied under occlusive patch conditions for 48 hours. The challenge was performed two weeks later by topical application. The patches were then applied for 24 hours.

 

Results

induction phase:

The injection sites were swollen and red. Later necrosis and scabs were observed. Similar findings were seen with liquid paraffin. After removal of the patches redness and scales were observed at the topical application sites

 

after challenge:

No irritation was observed in the test group. 24 h after challenge with the test item, a barely perceptible erythema was observed in two female animals and considered as not positive. At the 48 h reading the challenge sites in two female animals were covered with scales. These reactions were evaluated as a positive skin reaction.

 

The total positive reaction was 5%.

 

Conclusion

The test material was not a skin sensitiser under the test conditions of this study.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data on skin sensitization do not meet the criteria for classification according to Regulation (EC) 1272/2008.