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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:
February 7 - March 17, 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study followed EPA guidelines and was carried out in compliance with Product Safety Labs Standard Operating Procedures. There were no deviations that impacted the integrity or validity of the study. The test material is a close analog of DI C8-C10, BRANCHED, C9 RICH, ALKYLNAPHTHALENE SULFONIC ACID (DNNSA).
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
40 CFR Part 158, subdivision F: Pesticide Assessment Guidelines
Hazard Evaluation-Human and Domestic Animals
NTIS:PB86-10B95B: Section 81-6; pp. 59-62
GLP compliance:
no
Remarks:
This study was carried out in compliance with Product Safety Labs Standard Operating Procedures. There were no deviations that impacted the integrity or validity of the study.
Type of study:
Buehler test
Justification for non-LLNA method:
Adequate data are available from studies that were conducted before the LLNA test became available

Test material

Constituent 1
Chemical structure
Reference substance name:
Calcium bis(di C8-C10, branched, C9 rich, alkylnaphthalene sulphonate)
Molecular formula:
[C26H39SO3]2Ca to [C30H47SO3]2Ca
IUPAC Name:
Calcium bis(di C8-C10, branched, C9 rich, alkylnaphthalene sulphonate)
Test material form:
other: applied as 50% solution in light paraffenic and naphthenic petroleum distillates
Details on test material:
The test substance identified as NA-SUL 729, Lot #3158, was received on February 1, 1991, and was further identified with PSL Code Number
E10201-1. The test substance was a clear amber viscous liquid. The sample was used as received, undiluted.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:

Acclimation period - 7 days.
Allocation:
Test Group 10 Guinea Pigs
Positive Control Group 10 Guinea Pigs
Naive Control Group 5 Guinea Pigs
Replacement Naives 5 Guinea Pigs
Caging - Gang-caged in suspended stainless steel cages with mesh floors.
Room temperature - 64-72cF
Food - Purina Guinea Pig Pellets ad-libitum.
Water - tap water supplied by automatic water system.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% (undiluted) - 0.4 ml
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% (undiluted) - 0.4 ml
No. of animals per dose:
see table
Details on study design:
see table
Challenge controls:
see table
Positive control substance(s):
yes
Remarks:
0.08% Dinitrochlorobenzene (DNCB) in 80% ethyl alcohol

Results and discussion

Positive control results:
All animals had a faint to moderate erythematous response 24 and 48 hours post-challenge. Nine sites were calculated to be positive. Most
sites also exhibited edema. By 72 hours the incidence of positive reactions decreased to 4. The level of severity remained faint to moderate.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.4 ml
No. with + reactions:
5
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.4 ml. No with. + reactions: 5.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.4 ml
No. with + reactions:
5
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.4 ml. No with. + reactions: 5.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
72
Group:
test chemical
Dose level:
0.4 ml
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: test group. Dose level: 0.4 ml. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
0.4 ml
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 0.4 ml. No with. + reactions: 7.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0.4 ml
No. with + reactions:
5
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 0.4 ml. No with. + reactions: 5.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
72
Group:
test chemical
Dose level:
0.4 ml
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: test group. Dose level: 0.4 ml. No with. + reactions: 4.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
1
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 1.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
1
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 1.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
72
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.4 ml
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.4 ml. No with. + reactions: 9.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.4 ml
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.4 ml. No with. + reactions: 9.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
72
Group:
positive control
Dose level:
0.4 ml
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: positive control. Dose level: 0.4 ml. No with. + reactions: 4.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
positive control
Dose level:
0.4 ml
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.4 ml. No with. + reactions: 9.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
positive control
Dose level:
0.4 ml
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.4 ml. No with. + reactions: 9.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
72
Group:
positive control
Dose level:
0.4 ml
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: positive control. Dose level: 0.4 ml. No with. + reactions: 8.0. Total no. in groups: 10.0.

Applicant's summary and conclusion

Interpretation of results:
other: minimal sensitizer
Remarks:
Criteria used for interpretation of results: US EPA pesticides
Conclusions:
Based on these findings and an the evaluation of the test system, NA-SUL 729, Lot #3158 is considered to be a minimal contact sensitizer
when applied as received, undiluted, once a week for 3 weeks.
Executive summary:

A guinea pig sensitization test following the Buehler procedure (EPA Guideline 81-6) was conducted with NASUL 729.After establishing the highest non-irritating dose concentration to be100%,a 3week induction period was initiated during which10young adult male guinea pigs were treated with the test substanceand 10were treated with 0.08%Dinitrochlorobenzene (DNCB) in 80%ethyl alcohol (positive controls). During the induction period the animals were dosed once week until a total of three dose applications was achieved. Fourteen days after the third application a challenge dose was applied to anaive site on each guinea pigandapproximately 24, 48 and72hours later the animals were scored for a sensitization response (erythema and edema). A naive control group of five animals was maintained under the same environmental conditions and treated with the test substance at challenge only. Because of the positive response observed in the naive animals after challenge, the animals from all groups were allowed to rest for 7 days and were then re-challenged. A second group of naive animals was also dosed at this time.

 

All guinea pigs appeared active and healthy throughout the test period. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. All animals gained weight.

 

INDUCTION PHASE:

Test Animals:Very faint erythema and edema were observed at 1 test site 24 hours after the first inductions. Virtually all animals exhibited erythema which varied from very faint to moderate after the second and third inductions. Edema was also noted at almost all sites after the second and third induction.

Positive Control Animals(0.08%DNCB in80%Ethyl Alcohol):sixanimals exhibited erythema 24 hours after the first induction and all had faint to moderate-severe erythema with faint edema after the

second and third inductions.

 

CHALLENGE PHASE:

FIRST CHALLENGE:

Test Animals:Five test sites exhibited a positive response 24 and 48 hours after challenge. At one site moderate erythema with edema was noted. Most other sites exhibited only faint erythema. By 72 hours all signs of irritation disappeared.

Naive Control Animals:Onenaive site exhibited very faint erythema at 24 and 48 hours postchallenge. By 72 hours erythema had cleared from the site. No irritation was noted atanyother naive site.

Positive Control Animals(0.08% DNCB in80%Ethyl Alcohol):~lanimals had a faint to moderate erythematous response24and48hours post-challenge. Nine sites were calculated to be positive. Most

sites also exhibited edema. By72hours the incidence of positive reactions decreased to4. Thelevel of severityremainedfaint to moderate.

 

RE-CHALLENGE:

Test Animals:Seven test sites hadapositive response at 24 hours after re-challenge. The severity of erythema was very faint non-confluent to faint confluent. By 72 hours very faint erythema remained at most of these sites.

Naive Control Animals:No irritation was noted atanyof the naive control sites after rechallenge.

Positive Control Animals(0.08%DNCE in80%Ethyl Alcohol):Nine positive responses were observed at 24 and 48 hours after the second challenge. Erythema varied in severity from very faint to

strong. By 72 hours eight sites were positive.

 

Based on these findings, NA-SUL 729,#3158 is considered to be a minimal contact sensitizer

when applied as received, undiluted, once a weekfor3 weeks. The positive response to 0.08% DCNB in 80% Ethyl Alcohol validates the test system used in this study.