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Diss Factsheets

Administrative data

Description of key information

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:
14.11.2001 - 14.12.2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: study conducted according to Magnusson-Kligman-Method therefore comparable to OECD-Guideline Study.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method of Manusson and Kligman
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Test conducted before adoption of LLNA Guideline
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: specified as suitably licensed dealer
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 326 - 432 g
- Housing: stainless steel cages
- Diet: Lab Diet Certified Guinea Pig Diet #5026 ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 60 - 85 °F
- Humidity (%): 30 - 70%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
intradermal Screening: 0.1 mL (Test article + TiterMax/distilled water emulsion, 5 + 95), 0.1 mL (Test article + corn oil, 1:1 and 1:9)
Topical Screening: 0.4 mL (Test article +corn oil, 100%, 50%, 25%, 10%)
1st Induction: 0.1 mL (Test article + corn oil, 1:1) or 0.1 mL (Testarticle + TiterMax/distilled water emulsion, 5 + 95)
2nd Induction: 0.5 mL (Test article)
Challenge: 0.4 mL (Test Article + corn oil 1:1)
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
intradermal Screening: 0.1 mL (Test article + TiterMax/distilled water emulsion, 5 + 95), 0.1 mL (Test article + corn oil, 1:1 and 1:9)
Topical Screening: 0.4 mL (Test article +corn oil, 100%, 50%, 25%, 10%)
1st Induction: 0.1 mL (Test article + corn oil, 1:1) or 0.1 mL (Testarticle + TiterMax/distilled water emulsion, 5 + 95)
2nd Induction: 0.5 mL (Test article)
Challenge: 0.4 mL (Test Article + corn oil 1:1)
No. of animals per dose:
5
Details on study design:
Screening:
Prior to the induction phase of the test, screens were run both subcutaneously and topically on
both the test and the positive control article. Initially it was determined if five (5) percent of the
test article and one (1) percent of the positive control article2, (in a 50/50 emulsion of TiterMax⑧
(TM)3 and distilled waterよinected into the test system, causes local necrosis or ulceration or
any systemic toxicity.
One-tenth of one (0.1) milliliter of each of the article/TM/water suspensions were injected,
subcutaneously, into the shaved area between the shoulder blades of one (1) guinea pig for each
article, to determine the effect. If necrosis or ulceration was noted at 24 and/or 48 hours,
screening would have continued until a non-corrosive percentage of the mixture was determined.
The article/TM/water suspensions were prepared as per instructions supplied by CytRx⑧．
The test and positive control articles alone were similarly screened subcutaneously to determine
non-corrosive percentages of each (50% and 10% in com oil for the test article and 5%a nd 1% in
com oil for the positive control町ticle).
The highest non-irritating concentration (HNIC) for a topical application of each of the articles
was also determined. The test article diluted in com oil and the positive control article was
mixed in petroleum jelly4. Four (2M:2F) animals for each article and each set of four (4)
concentrations, were prepared by close-clipping the dorsal area of their trunks with an Oster⑧
small animal clipper equipped with a #40 (surgical) head. During all shaving procedures, care
was taken to avoid abrading the shaved skin. On the same day, four (4) sites on each animal
were treated with the appropriate article at decreasing concentrations, suspended or dissolved in
the appropriate, non-irritating vehicle. Four-tenths (0.4) of a milliliter of each article was applied
to each site via a 25 mm Hilltop Chamber (with the cotton patch). The animals were wrapped
after dosing, with a piece of three (3) inch Elastoplast⑧ elastic tape (Beiersdorf Inc., Norwalk,
CT), that had been split at one (1) end and lined on the adhesive side, opposite the split, with a
three (3) inch wide s仕ipof Pure Latex Dental Dam (HCM -Hygenic Corporation, Malaysia).
The wraps remained in place for 24 hours. After 24 hours, the wraps were removed. Any excess
test article was wiped away with ethanol5 at 45 hours after application. The test sites were scored
(see Table 1) three (3) hours after the ethanol wipe and again 24 hours later.
Because irritation was observed with the test article and the positive con仕ol article, the
concentrations below those which provided the least irritation were used for the challenge phase
of the study for each article

The induction phase of the test was divided into two (2) stages:
A) Intradermal Iniection
A four by six (4 x 6 ) cm section of the shoulder area of each animal in the test
groups was shaved, as detailed previously.
Three (3) pairs of subcutaneous in ections were made in two (2) rows; one (1) row
on each side of the midline. The injection sites w町ejust within the boundaries of
the two by four (2 x 4) cm patch, which was applied one (1) week later.
1st pair: 0.1 ml TM/water emulsion (1: 1), without the test or positive control
article.
2nd pair: 0.1 ml test or positive control article without TM, at the screen
determined percentage.
3rd pair: 0.1 ml of the test or positive control article emulsified in the TM/water
emulsion (1: 1), at the screen determined percentage.

B) Tpoical Application
Seven (7) days after the injections were made, the test article, at 100%, and the
positive control article, at 25% in petroleum jelly, were applied to the injection sites
of the appropriate animals. One-half of one milliliter (0.5 ml) of the respective
article was spread onto a two by four (2 x 4) cm patch of filter paper. The filter
paper was placed on the test site and covered with a piece of 1 114”Blenderm⑧ tape
(3M Medical -Surgical Division, St. Paul, MN). Dermicel⑧ and Elastikon⑧ tapes
(Johnson & Johnson Medical Inc., Arlington, TX) were then wound around the test
site of the animal. The wraps and patches were removed at 48hours.

Challenge
Two (2) weeks after the topical induction applications, the challenge applications were made.
Prior to dosing, a five by five (5 x 5) cm area of the flank of each guinea pig, in the test groups
for the test and positive control article, as well as the negative control groups for each article, was
shaved as detailed previously. The test or positive control articles, at the screen determined
highest non-irritating concentrations, were applied to the flanks of the appropriate animals
Four-tenths (0.4) of a milliliter of each article was applied to each site via a 25 mm Hilltop
Chamber (with the cotton patch). The animals were wrapped after dosing, with a piece of three
(3) inch Elastoplast⑧ elastic tape, that had been lined on the adhesive side with a three (3) inch
wide strip of Pure Latex Dental Dam. The wraps remained in place for 24 hours. Twenty-one
hours after unwrapping, any remaining article was removed with an ethanol wipe and the test site
was shaved if necessa巧r. Three hours later, the test site was scored according to the attached
Draize Scale (Table 1). Twenty-four and 48 hours later, the sites were again scored.
Two (2) indices were calculated企omthe erythema scores for each article, one (1) to evaluate the
incidence of erythema (reaction) and the other to evaluate the severity of erythema. The indices
for incidence and severity were calculated for the control groups and for the induction groups
企omthe erythema responses observed at the 48, 72 and 96 hour post-challenge examinations.
The incidence index was calculated by counting the number of animals showing an e巧北hema
response [one (1) or greater] for as pecified time period and di vi ding by the number of test sites
(animals) examined at the time period (# responses/# per group). The severity index was
calculated by adding the erythema scores [one (1) or greater] for a specified time period and
dividing by the number of scores added (sum of erythema scores/# scores added). The two (2)
indices were used to evaluate the sensitization potentials of the articles. The edema scores were
noted but were not used in the calculation of any indices.
Initial and terminal body weights were recorded for the non-screen animals. Sacrificing was
accomplished via carbon dioxide asphyxiation. All animals appeared healthy throughout the
study
Challenge controls:
10 % Squalane Solution, only Challenge application
and positive control substance
Positive control substance(s):
yes
Remarks:
1-Chloro-2,4-Dinitrobenzene
Positive control results:
see table below.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
questionable erythema in two animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: questionable erythema in two animals.
Reading:
1st reading
Hours after challenge:
72
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
questionable erythema in one animal
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: questionable erythema in one animal.
Reading:
1st reading
Hours after challenge:
96
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
questionable erythema in one animal
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 96.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: questionable erythema in one animal.
Reading:
1st reading
Hours after challenge:
48
Group:
other: contol Group of Test Group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
questionable erythema in two animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: contol Group of Test Group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: questionable erythema in two animals.
Reading:
1st reading
Hours after challenge:
72
Group:
other: contol Group of Test Group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
questionable erythema in one animal
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: other: contol Group of Test Group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: questionable erythema in one animal.
Reading:
1st reading
Hours after challenge:
96
Group:
other: contol Group of Test Group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
qustionable erythema in one animal
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 96.0. Group: other: contol Group of Test Group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: qustionable erythema in one animal.
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
5%
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 5%. No with. + reactions: 5.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
72
Group:
positive control
Dose level:
5%
No. with + reactions:
3
Total no. in group:
5
Clinical observations:
questionable erythema in one animal
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: positive control. Dose level: 5%. No with. + reactions: 3.0. Total no. in groups: 5.0. Clinical observations: questionable erythema in one animal.
Reading:
1st reading
Hours after challenge:
96
Group:
positive control
Dose level:
5%
No. with + reactions:
3
Total no. in group:
5
Clinical observations:
questionable erythema in one animal
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 96.0. Group: positive control. Dose level: 5%. No with. + reactions: 3.0. Total no. in groups: 5.0. Clinical observations: questionable erythema in one animal.
Reading:
1st reading
Hours after challenge:
48
Group:
other: contol Group of positive control
Dose level:
5%
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
questionable erythema in one animal
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: contol Group of positive control. Dose level: 5%. No with. + reactions: 1.0. Total no. in groups: 5.0. Clinical observations: questionable erythema in one animal.
Reading:
1st reading
Hours after challenge:
72
Group:
other: contol Group of positive control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
questionable erythema in three animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: other: contol Group of positive control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: questionable erythema in three animals.
Reading:
1st reading
Hours after challenge:
96
Group:
other: contol Group of positive control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
questionable erythema in two animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 96.0. Group: other: contol Group of positive control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: questionable erythema in two animals.
Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
This test article is not a sensitizer in guinea pigs under the conditions of this test
Executive summary:

Five (3M:2F) Hartley-strain albino, outbred, viral antibody free, guinea pigs (SPF Hartley guinea pig Aai: (HA) Outbred), 348・432grams, were utilized as the test group. An additional five (2M:3F) Hartley-strain guinea pigs, 326・414grams,

were utilized as the control group. For induction, each animal in the test group received three (3) pairs of intradermal injections, with and without the test article.

During the second week of the induction phase, topical applications of the test Article were made to the induction site of each animal in the test group. Two (2) weeks after the topical induction applications, the challenge applications were made. These 24 hour challenge applications were made to virgin sites on the flank of each animal in the test and control groups, at the screen determined, highest non-irritating concentration of 50% in com oil. Observations of erythema, edema and other effects were recorded 48, 72 and 96 hours after the challenge applications.

Index: Incidence   Severity
 Group  Test / Control Test / Control 
 Scoring Interval:    
 48 hours 0 / 0  0 / 0
 72 hours 0 / 0  0 / 0 
 96 hours  0 / 0 0 / 0 
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Migrated from Short description of key information:

For Skin Sensitisation, one in vivo Guideline study is available.

In this Study no adverse effects were observed.

Justification for selection of skin sensitisation endpoint:

Only one valid study available.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

As no effects were observed in the performed study and no other information are available concerning classification, the substance is not classified.