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Diss Factsheets

Administrative data

Description of key information

Buehler test in guinea pigs (OECD TG 406, GLP): not sensitising

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:
09 Aug 2004 to 15 Sep 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(adopted 1992)
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
The current accepted and preferred method for skin sensitisation testing according to the REACH legislation (EC no 1907/2006) and CLP Regulation (EC No 1272/2008) is the murine local lymph node assay (LLNA). A validated test method, OECD TG 429 (OECD 2002) is available for the LLNA. The guideline acknowledges the limits of the LLNA, and states that there are instances where test substance classes or substances containing functional groups shown to act as potential confounders make the use of guinea pig tests more appropriate. It is concluded that the LLNA is not applicable where the properties of the test material cause interference in the accuracy of the LLNA (OECD 2002). The statement in the OECD TG 429 is given with reference to the findings of Basketter et al. (2009a), who demonstrated false positives in silicone based substances which had previously been demonstrated to be non-sensitisers in the guinea pig maximisation test (GPMT). The importance of available evidence from guinea pig results, consideration of chemical reactivity, epidermal bioavailability and clinical and experimental human data are emphasised as central to reaching appropriate regulatory decisions for substances which have been shown to fall outside the specificity of the LLNA (Basketter et al., 2009b). The non-applicability of the LLNA for silicone based substances has also been demonstrated by Petry et al. (2012). The sensitisation potential of polyfunctional silicone materials was tested in a comparative study investigating the GPMT and the LLNA assays, which found the five tested substances to be negative in the GPMT whereas they were concluded to be weak to moderate skin sensitisers in the LLNA (Petry et al., 2012).
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands, Netherlands, and Harlan Winkelmann GmbH, Germany.
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 250-300 g
- Housing: Stainless steel cages.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±15
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09.08.2004 To: 15.09.2004
Route:
epicutaneous, semiocclusive
Vehicle:
corn oil
Concentration / amount:
50%
Day(s)/duration:
Day 1, between Days 8-10 and 15-17
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
corn oil
Concentration / amount:
20%
Day(s)/duration:
Day 29
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Test: 20.
Control: 10.
Details on study design:
RANGE FINDING TESTS: Five animals were selected from those available and the flanks clipped free of hair. Each animal was dosed with 2 concentrations of the test substance, 1 on either flank. A gauze patch measuring at least 20x20 mm was soaked with 0.4 ml of the selected concentration of the test substance. This was then placed onto the selected treatment site. When both sites of the animal had been treated, they were secured in position by wrapping the trunk with a length of adhesive strapping. All animals were treated in this manner such that a total of 5 concentrations (100%, 50%, 20%, 10% and 5% in corn oil) of the test substance were each dosed in duplicate. The adhesive strapping and patches were removed after 6 hours contact with the skin. The treated sites were washed with water at approximate body temperature to remove any remaining test substance. Twenty four and 48 hours after removal of the dressings, the treated sites were examined for signs of reaction to treatment.
A moderate erythema (score of 2) was apparent at sites treated with the undiluted test substance. A slight erythema was observed at sites treated with the test substance at a concentration of 50%. Therefore, a concentration of 50% was selected for use during the induction phases of the main study. A concentration of 20% in corn oil was selected for use at challenge, being judged the highest non-irritant.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance in corn oil (0.4 ml)
- Control group: corn oil (0.4 ml)
- Site: left flank
- Frequency of applications: weekly (day 1, days 8 to 10 and 15 to 17 of the study)
- Duration: 3 weeks
- Concentrations: 50% in corn oil (test group)
- Examination of treated sites: 24 and 48 hours

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (challenge)
- Day of challenge: 29
- Exposure period: 6 h
- Test groups: test substance in corn oil and corn oil only
- Control group: test substance in corn oil and corn oil only
- Site: posterior right flank (test substance) and anterior right flank (corn oil)
- Concentrations: 20%
- Evaluation (hr after challenge): approximately 24 and 48 h after patch removal

Animals used in the main sensitisation assessment were weighed on Day 1 of the study and again on termination of the study following completion of the challenge procedures.

All animals were killed following the end of the experimental procedure. No necropsy examination was performed in these animals.
Challenge controls:
Corn oil
Positive control substance(s):
no
Positive control results:
N/A
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
20% TS in corn oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
corn oil only
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
20% TS in corn oil
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
corn oil only
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Group:
positive control
Remarks on result:
not measured/tested

A slight to moderate erythema (scores of 1 and 2) was observed in animals of the test group at the first induction, following 6 hours topical exposure to the test substance at 50% concentration. A slight erythema (score of 1) was noted in 2 of the 20 animals of the test group, following the second induction. No reaction was observed in any animal at the third induction.

No response was observed to the test substance at a concentration of 20% in corn oil in either test or control group animals 24 and 48 hours following 6 hours topical exposure. No reaction was observed to the vehicle alone.

Changes in body weight of animals during the period of the study were generally similar in animals from both test and control groups.

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
In a guinea pig skin sensitisation study (Buehler test) conducted to OECD 406 and to GLP (reliability score 1) hexadecyl(trimethoxy)silane did not induce any skin sensitisation in any of the animals tested at any time point. There were no clinical signs of systemic toxicity.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

For the assessment of the skin sensitizing potential of hexadecyl(trimethoxy)silane a guinea pig skin sensitisation study (Buehler test) was conducted according to OECD TG 406 and in compliance with GLP (Research Toxicology Centre SpA, 2004). The animals were induced thrice (every 7 days) with 0.4 ml of 50% test substance (20 animals of the test group) or with the vehicle corn oil (10 animals of the control group) for 6 hours, each, under semiocclusive conditions. The challenge was performed in the same way as the induction, but with 0.4 ml of 20% test substance, which has shown not to be irritant in a preliminary test. The skin reactions were scored 24 and 48 h after application. Hexadecyl(trimethoxy)silane did not induce any skin sensitisation in any of the animals tested at any time point. There were no clinical signs of systemic toxicity and no reactions were observed in the negative control animals. In conclusion, hexadecyl(trimethoxy)silane is not sensitising to the skin under the conditions applied.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No data available.


Justification for classification or non-classification

The available data on skin sensitisation of the registered substance do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification.