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Diss Factsheets

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
26 Jan - 22 Mar 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (ECHA, 2012)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted in 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
The department of health of the government of the United Kingdom
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Reference substance name:
Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid
IUPAC Name:
Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid
Details on test material:
- Name of test material (as cited in study report): Only trade name available
- Physical state: colourless liquid
- Analytical purity: 100% (UVCB)
- Storage condition of test material: room temperature in the dark

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 301-441 g
- Housing: animals were housed individually or in pairs in solid-floor polypropylene cages furnished with woodflakes.
- Diet: Guinea Pig FD1 diet, Special Diets Services Limited, Wirtham, UK, ad libitum
- Water: mains tap water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 34-66
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
Induction: 25% (intradermal), undiluted (topical)
Challenge: undiluted and 75%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Induction: 25% (intradermal), undiluted (topical)
Challenge: undiluted and 75%
No. of animals per dose:
10 (controls), 20 (in test groups)
Details on study design:
RANGE FINDING TESTS:
Intradermal Induction:
Four concentrations (1%, 5%, 10% and 25% w/v in arachis oil BP) were investigated. A total of four guinea pigs were used. Each guinea pig received four 0.1 mL injections of only one concentration of the test material. The degree of erythema at the injection sites was assessed approximately 24, 48 and 72 h and up to 7 days after injection according to the Draize scale. The degree of oedema was not evaluated. Any evidence of systemic toxicity was also recorded. The highest concentration that caused only mild to moderate skin irritation, and which was well tolerated systemically, was selected for the intradermal induction stage of the main study.
Topical induction:
Two guinea pigs (intradermally injected with Freund´s Complete Adjuvant 17 days earlier) were treated with the undiluted test material and three preparations of the test material (75%, 50% and 25% v/v in arachis oil BP). Applications were made to the clipped flanks under occlusive dressing for 48 h. The degree of erythema and oedema was evaluated approximately 1, 24, and 48 h after dressing removal. The highest concentration producing only mild to moderate dermal irritation was selected for the topical induction stage of the main study.
Topical Challenge:
The undiluted test material and three preparations of the test material (75%, 50 % and 25% v/v in arachis oil BP) were applied to the clipped flanks of the two guinea pigs under occlusive dressings for 24 h. These guinea pigs did not form part of the main study but have treated identically to the control animals of the main study, up to Day 14. The degree of erythema and oedema was evaluated approximately 1, 24, and 48 h after dressing removal. The highest non-irritant concentration of the test material and one lower concentration were selected for the topical challenge stage of the main study.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/ water
Injection 2: test substance (25%) in arachis oil
Injection 3: test substance (25%) in a 1:1 mixture (v/v) FCA/ water
Epicutaneous: undiluted
- Control group:
Injection 1: a 1:1 mixture (v/v) FCA/ water
Injection 2: in arachis oil
Injection 3: arachis oil at 50% (w/v) in a 1:1 mixture (v/v) FCA/ water
Epicutaneous : nothing
- Site: flanks (intradermal) + shoulder region (topical)
- Frequency of applications: every 7 days
- Duration: 0-7
- Concentrations: 25% (intradermal), undiluted (topical)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: 24 h
- Test groups: test substance
- Control group: test substance
- Site: right flank (undiluted test substance), left flank (75%)
- Concentrations: undiluted and 75%
- Evaluation (hr after challenge): 24 and 48 h
Positive control substance(s):
no
Remarks:
positve control tested every six months

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25% (intradermal) + 100% (challenge, right flank))
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25% (intradermal) + 100% (challenge, right flank)). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25% (intradermal) + 75% (challenge, left flank)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25% (intradermal) + 75% (challenge, left flank). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25% (intradermal)+ 100% (challenge, right flank)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25% (intradermal)+ 100% (challenge, right flank). No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25% (intradermal) + 75% (challenge, left flank)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25% (intradermal) + 75% (challenge, left flank). No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25% (intradermal)+ 100% (challenge, right flank)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25% (intradermal)+ 100% (challenge, right flank). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25% (intradermal)+ 75% (challenge, left flank)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25% (intradermal)+ 75% (challenge, left flank). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25% (intradermal)+ 100% (challenge, right flank)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25% (intradermal)+ 100% (challenge, right flank). No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25% (intradermal) + 75% (challenge, left flank)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25% (intradermal) + 75% (challenge, left flank). No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

Range finding study

On the basis of the results of the range finding study the following concentrations were selected for the main study:

Intradermal Induction: 25% in arachis oil BP

Topical Induction: 100% (undiluted as supplied)

Topical Challenge: 100% (undiluted as supplied) and 75% v/v in arachis oil BP

Main study

Skin reactions observed after intradermal induction

Very slight or well-defined erythema was noted at the intradermal induction sites of all test group animals at the 24 h observation and in nineteen test group animals at the 48 hour observation.

Very slight erythema was noted at the intradermal induction sites of all control group animals at the 24 and 48 h observations.

Skin reaction observed after topical induction

Very slight or well-defined erythema and incidents of very slight oedema were noted at the induction sites of all test group animals at the 1 h observation with very slight erythema in ten test group animals at the 24 h observation. Bleeding from the intradermal induction sites of four test group animals was noted at the 1 h observation. Isolated incidents of small superficial scattered scabs or hardened dark brown/black-coloured scab were noted at the 24 h observation.

Bleeding from the intradermal induction sites was noted in one control group animal at the 1 h observation. No signs of erythema or oedema were noted at the treatment sites of control group animals at the 1 and 24 h observations.

Skin reaction observed after topical challenge

No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48 h observations.

Body weights

Body weight gains of guinea pigs in the test group, between Day 0 and Day 24, were comparable to those observed in the control group over the same period.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified