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Toxicological information

Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study followed standard practices (see references below) and included quality assurance procedures involving auditing with the results reported to the clinical manager and management. Referenced Methods 1. Marzulli, F.N. and Maibach, H.I. 1973. Antimicrobials: Experimental Contact Sensitization in Man. J. of the Society of Cosmetic Chemists 24.399-421. 2. Marzulli. F.N. and Maibach, H.I. 1974. The Use of Graded Graded Concentrations in Studying Skin Sensitizers: Experimental Contact in Man. Food and Cosmetics Toxicology 12, 219-227. 3. American Academy of Dermatology: Patch Testing in Allergic Contact Dermatitis.

Data source

Reference
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Study type:
study with volunteers
Principles of method if other than guideline:
NA-SUL BSN (15.0% w/w in Squibb Mineral Oil) was occlusively applied to the skin of the infrascapular area of the back, between the shoulder
blades, using Finn Chambers (8 mm inner diameter aluminum chambers affixed to Scanpor Tape). The Induction Phase consisted of nine (9)
consecutive occlusive applications of the test material for a period of three weeks. The patches were removed approximately forty-eight (48) hours after each application. The subjects returned to the facility at forty-eight (48) hour intervals for evaluation of the treated sites, and to have
identical patches applied. Following the ninth evaluation, the subjects were released for a seventeen (17) day rest period prior to the Challenge
Phase.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: applied as 50% solution in light mineral oil
Details on test material:
NA-SUL BSN (lot #94776)
Composition is 50% barium dinonylnaphthalene sulfonate (BARIUM BIS( DI C8-C10, BRANCHED, C9 RICH, ALKYLNAPHTHALENE SULPHONATE) and 50% light mineral oil.

Method

Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
A human repeated insult patch test was conducted for Stonybrook Laboratories Inc. in order to assess the potential of the Sponsor's test material to induce allergic contact dermatitis. One hundred three subjects completed the study.
At challenge, one reaction of +1.0 was observed at the 48-hour and 96-hour challenge observation in response to the Sponsor's test material,
CRU #94776. A rechallenge was conducted in order to determine whether this reaction in subject 56 was due to allergic contact dermatitis.
Clinical history:
Subjects completed health history evaluations.
Controls:
At rechallenge, pharmaceutical mineral oil.
Route of administration:
dermal
Details on study design:
One hundred twenty-seven subjects were recruited to participate in this study. One hundred three subjects completed the study.
TEST MATERIAL PREPARATION
The test material was applied undiluted to the Finn chamber.
PATCHES AND TEST MATERIAL DOSING
Finn Chambers (Hermal Pharmaceutical Laboratories, Inc., Oak HiII, NY) consisting of 8 mm inner diameter aluminum chambers affixed to Scanpor Tape (Norgesplaster A/S, Norway) were used to apply each test material to the skin. The Finn chamber provided a tight occlusive seal to ensure
maximum penetration of the test material.
The Induction Phase consisted of nine (9) consecutive occlusive applications of the test material for a period of three weeks. The patches were removed approximately forty-eight (48) hours after each application. The subjects returned to the facility at forty-eight (48) hour intervals for
evaluation of the treated sites, and to have identical patches applied. Following the ninth evaluation, the subjects were released for a seventeen
(17) day rest period prior to the Challenge Phase.

Results and discussion

Results of examinations:
See table attached.

Any other information on results incl. tables

SUBJECTS' REACTIONS DURING THE CHALLENGE PHASE

 

Erythema grade

Number of reactions

at the 48-hour observation (N=103)

Number of reactions

at the 96-hour observation (N=103)

0

83

99

+0.5

19

3

+1.0

1

1

+2.0

0

0

+3.0

0

0

At challenge, one reaction of +1 was observed in response to test material CRU #94776 at the 48-hour and 96-hour observation. Subject #056 participated in a rechallenge test in order to detennine whether the reaction described above was due to allergic contact dermatitis. The subject was patched with test material CRU 94776 at concentrations of 5%, 10% and 15% and also with the vehicle, mineral oil. At rechallenge, there was one reaction greater than +0.5 at the 96-hour observation to test material CRU#94776B. This +1.0 reaction was judged to be an irritation response since the lower concentration of the same material, CRU #94776A showed no response.

Applicant's summary and conclusion

Conclusions:

A human repeated insult patch test was conducted for Stonybrook Laboratories Inc. in order to assess the
potential of the Sponsor's test material to induce allergic contact dermatitis. At challenge, one reaction of
+1 was observed in response to test material CRU #94776 at the 48-hour and 96-hour observation.
Subject #056 participated in a rechallenge test in order to detennine whether the reaction described above
was due to allergic contact dermatitis. The subject was patched with test material CRU 94776 at
concentrations of 5%, 10% and 15% and also with the vehicle, mineral oil.
At rechallenge, there was one reaction greater than +0.5 at the 96-hour observation to test material
CRU#94776B. This +1.0 reaction was judged to be an irritation response since the lower concentration
of the same material, CRU #94776A showed no response. Thus, test material #CRU 94776 is judged not
to have induced allergic contact dermatitis in any of the subjects completing the HRIPT.
Executive summary:

NA-SUL BSN (15.0% w/w in Squibb Mineral Oil) was occlusively applied to the skin of the infrascapular area of the back, between the shoulder blades, using Finn Chambers (8 mm inner diameter aluminum chambers affixed to Scanpor Tape). The Induction Phase consisted of nine (9) consecutive occlusive applications of the test material for a period of three weeks. The patches were removed approximately forty-eight (48) hours after each application. The subjects returned to the facility at forty-eight (48) hour intervals for evaluation of the treated sites, and to have identical patches applied. Following the ninth evaluation, the subjects were released for a seventeen (17) day rest period prior to the Challenge Phase. . The Challenge Phase was initiated during the sixth week of the study, with identical patches applied to previously unexposed sites. Patches were applied on Wednesday [February 15, 1995]. These patches were removed after forty-eight (48) hours. Skin reactions were graded in a manner identical to that described above. At challenge, one subject (#056) out of 103 experienced a reaction of +1 (suggestive of contact sensitization) at the 48- and 96-hour observations. A rechallenge test was conducted with subject #056 in order to determine whether the reaction was due to allergic contact dermatitis. In addition to NA-SUL BSN (15.0% w/w in mineral oin, the subject was challenged with NA-SDL BSN (10.0% w/w in mineral oil), NA-SUL BSN (5.0% w /w in mineral oin, and the vehicle (100% Squibb Mineral Oil). Upon rechallenge, there was one reaction greater than +0.5 at the 96-hour observation to the NA-SUL BSN (10.0% w/w in mineral oil) sample. This reaction was judged to be an irritation response since the 15.0% and 5.0% NA-SUL BSN concentrations failed to elicit a response. CONCLUSION: Under the conditions employed in this study, NA-SUL BSN (CRU #94776; 15.0% w/w in Squibb Mineral Oil) did not act as a skin sensitizer under occluded (severe exposure) conditions in any of the 103 human volunteers.