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Toxicological information

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:
27 Aug 1985 - 20 Nov 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The study was conducted according to a test protocol that is comparable to the appropriate OECD guideline, with acceptable restrictions. The restrictions were the use of less animals than specified in the OECD test guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 1992
Deviations:
yes
Remarks:
Only 3 animals in the control group and 15 animals in the test group.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An appropriate guinea pig maximisation test is available which would not justify conducting an additional LLNA due to animal welfare.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tetra Oximino Silane

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazelton Labs, Denver, PA, USA
- Age at study initiation: 5-6 weeks
- Housing: up to 3 per cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22±4
- Humidity (%): 50±15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1985-08-27 To: 1985-09-26

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
Intradermal 5%; epicutaneous 25%
Challenge
Route:
epicutaneous, semiocclusive
Vehicle:
propylene glycol
Concentration / amount:
50%
No. of animals per dose:
test: 15
negative control: 3 at challenge
Details on study design:
RANGE FINDING TESTS: said to have been conducted if necessary, but no details given in the report reviewed. The study schedule does not include a pretest, so it was probably not done.

A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections; 0.1 ml):
Injection 1: 5% test article in propylene glycol
Injection 2: FCA alone
Injection 3: 5% test article in FCA
Epicutaneous: 0.3 ml: 25% TS in propylene glycol
- Control groups:
Intradermal (3 pairs of injections; 0.1 ml):
Injection 1: vehicle
Injection 2: FCA alone
Injection 3: vehicle in FCA
Epicutaneous: 0.3 ml propylene glycol
- Site: two rows of 3 sites, one row either side of dorsal mid-line
- Frequency of applications: intradermal treatment day 0; topical induction day 7
- Duration: induction period continues to day 21
- Concentrations: intradermal 5%, epicutaneous 25%


B. CHALLENGE EXPOSURE
- No. of exposures: 1 (at two sites: TS and vehicle)
- Day of challenge: day 22
- Exposure period: 24h
- Test groups: 0.2 ml: 50% TS in propylene glycol
- Control groups: 0.2 ml: 50% TS in propylene glycol
- Site: flanks
- Concentrations: 50%


Challenge controls:
Negative: 6 animals were used at the induction stages. Only 3 were challenged with 50% TS. 3 animals were retained for a possible rechallenge.
Positive: dinitrochlorobenzene; no details are given
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene

Results and discussion

Positive control results:
Dinitrochlorobenzene apparently yielded 100% response; no details are given.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
14
Total no. in group:
15
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
14
Total no. in group:
15
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
1
Total no. in group:
3
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
3

Any other information on results incl. tables

Table 1: Incidence of dermal response to challenge dosing.

GROUP

MATERIAL

INTERVAL

DERMAL SCORES

SENSITIZATION INCIDENCE

 

 

 

0

1

2

3

 

Test

TS 50%

24h

1/15

1/15

4/15

9/15

14/15

 

48h*

1/15

2/15

4/15

8/15

14/15

 

Vehicle (propylene glycol)

24h

0/15

0/15

0/15

0/15

0/15

 

48h

0/15

0/15

0/15

0/15

0/15

Vehicle control

TS 50%

24h**

2/3

1/3

0/3

0/3

1/3

 

48h

3/3

0/3

0/3

0/3

0/3

 

Vehicle (propylene glycol)

0/3

0/3

0/3

0/3

0/3

0/3

 

0/3

0/3

0/3

0/3

0/3

0/3

Positive control

Dinitrochlorobenzene (no details given)

 

 

 

 

 

100% no details given

Skin reactions were graded:

0 no reaction

1 scattered mild redness

2 moderate and diffuse redness

3 intense redness and swelling

* 5 animals had eschar and 2 had necrosis

**1 animal had eschar

Applicant's summary and conclusion

Interpretation of results:
other: Sensitising (according to CLP regulation)
Conclusions:
A guinea-pig maximisation test conducted with GLP but limited in some respects reported a response to challenge (using 50% test substance) in 14 of 15 animals at 24 and 48 h. Responses in 1 of 3 and 0 of 3 were reported at 24 and 48 hours, respectively, in the small negative control group. A response of 30% or more in an adjuvant test indicates sensitisation.
Executive summary:

A guinea-pig maximisation test conducted with GLP but limited in some respects reported a response to challenge (using 50% test substance) in 14 of 15 animals at 24 and 48 h. Responses in 1 of 3 and 0 of 3 were reported at 24 and 48 hours, respectively, in the small negative control group. A response of 30% or more in an adjuvant test indicates sensitisation.