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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report similar or equivalent to OECD 406. GLP.

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The LLNA assay was waived due to the availability of adequate data from an in vivo skin sensitization study. These in vivo data were acquired in 1991 prior to the entry into force of the amendments to Annex VII.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
MCP 968 is a straw colored homogenous liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
44 guinea pigs (22 males, 22 females) of outbred Hartley albino strain from Charles River Kingston (Kingston, NY) initially weighted 332.8-404.1 g and approximately one month old were used. The animals were housed individually in suspended stainless steel cages and provided with tap water ad lib. The temperature of the study room was maintained at 65-75F with a relative humidity of 40-60%. Light/dark cycle of 12/12.

Animals were acclimated to the laboratory for at least 13 days before study initiation.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Squibb mineral oli (SMO)
Concentration / amount:
0.4 ml, 100%, 75% or 50%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Squibb mineral oli (SMO)
Concentration / amount:
0.4 ml, 100%, 75% or 50%
No. of animals per dose:
Induction and Challenge: 20 guinea pigs
Challenge Control: 10 guinea pigs
Positive Control: 10 guinea pigs
Details on study design:
A pilot prescreening in study was performed to evaluate the irritation potential of the test material under occluded conditions. Four guinea pigs were treated with each of four concentrations (100, 75, 50, 25% w/w in SMO). MCP 968 (neat) and at concentrations of 50 and 25% w/w produced no dermal responses. The 75.0% concentration produced a slight dermal response. Therefore a neat concentarion was used as the induction ose.

The entire back of 20 guinea pigs was clipped with electric clippers. On the following day the patches were applied using a Hill Top Chamber with 25 mm Webril swatch saturated with 0.4 ml of MCP968 (100%). The induction guinea pigs were wrapped and the test article removed. The patches were reapplied to the same site once a week for weeks for a total of three sic-hour exposures; MCP 968 (neat) was used for each application.

The challenge patch application was performed following a 14-day rest period. The day before dosing, fresh application sites for primary challenge were prepared by clipping the hair from the entire backs of the Induction and Challenge control guinea pigs. On the flowing day (first day) challenge patches were applied to the sites using MCP 968 (100%) for approximately 6 hours. On the second day sites were depilated for 5-10 minutes and scored within approx. 2 hours (24-hour reading). The sites were scored again on the third day for 48-hour reading without additional depilation.

Challenge controls:
DNCB was administered in the same manner as MCP 968 but using a 0.05% (w/v) concentration in acetone.
also a naive control group
Positive control substance(s):
yes
Remarks:
DNCB

Results and discussion

Positive control results:
The 0.05% w/v concentration of DNCB in acetone has been determined to be the highest non-irritating concentration for challenge. No skin irritation was observed during the induction phase. During the challenge phase, the positive control animals were considered to have been sensitized, based on the test criterion of a minimum of "+2" response for positively-responding animals.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
neat
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
severity 0.1
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: neat. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: severity 0.1.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
untreated
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
severity 0.1
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: untreated. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: severity 0.1.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.05%
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
severity 3.6
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.05%. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: severity 3.6.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
neat
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: neat. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
untreated
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
severity 0.1
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: untreated. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: severity 0.1.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.05%
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
severity 2.0
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.05%. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: severity 2.0.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Based on the results at challenge, the test material did not induce a sensitisation response in guinea pigs in this study. This finding does not warrant the classification of the test article as a skin sensitiser under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

Hartley Albino guinea pigs were dermally exposed to the test material neat. For the challenge phase, the test material concentration was also neat. Response grades, severity and incidence at the time of the challenge exposure for the test article indicated no dermal responsiveness in the induction/challenge group above that observed in the naive challenge control group. Response grades, severity and incidence at the time of the challenge exposure for DNCB resulted in a significantly higher response in the induction/challenge group than that observed in the naive challenge control group. The animals were clinically observed five days per week and no treatment-related changes were noted.Based on the results at challenge, the test material did not induce a sensitisation response in guinea pigs in this study. This finding does not warrant the classification of the test article as a skin sensitiser under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.