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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:
August 16, 2016 to September 22, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
An OECD, GLP compliant Buehler study was commissioned for R&D purposes. Therefore, in the interest of animal welfare it was considered scientifically unjustified to re-run rhis study according to the LLNA assay

Test material

Constituent 1
Chemical structure
Reference substance name:
O,O-dibutyl hydrogen thiophosphate, compound with 1-octylamine (1:1)
EC Number:
300-947-2
EC Name:
O,O-dibutyl hydrogen thiophosphate, compound with 1-octylamine (1:1)
Cas Number:
93964-99-9
Molecular formula:
C8H19N.C8H19O3PS
IUPAC Name:
octan-1-amine dibutyl sulfanylphosphonate
impurity 1
Chemical structure
Reference substance name:
Octylamine
EC Number:
203-916-0
EC Name:
Octylamine
Cas Number:
111-86-4
Molecular formula:
C8H19N
IUPAC Name:
octan-1-amine
Test material form:
liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
Prior to use, all animals were acclimated for at least five days. Animals were individually housed in wire mesh suspension cages. The animals were maintained according to the recommendations contained in the National Academy Press 2011: ‘Guide for the Care and Use of Laboratory Animals’ The animals were supplied Purina Guinea Pig Chow and tap water ad libitum during both acclimation and test periods.
ENVIRONMENTAL CONDITIONS:
Light/dark cycle: 12 hours light and 12 hour dark cycle
Temperature – 64 – 79 F
Relative Humidity – 30-70%

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
other:
Remarks:
Mineral Oil
Concentration / amount:
25%
Day(s)/duration:
Once weekly for three weeks
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
Route:
epicutaneous, occlusive
Vehicle:
other:
Remarks:
Mineral Oil
Concentration / amount:
10%
Day(s)/duration:
Once
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20
Details on study design:
The test substance was evaluated for skin sensitization potential by applying 0.4 ml at a 25% concentration in mineral oil directly into Hilltop chambers and applying them to the clipped left shoulder of twenty albino guinea pigs in the following manner. The animals were held gently, and the chambers were applied as quickly as possible to the clipped left shoulder. The chambers were secured with Micropore tape and further secured with Kendall adhesive tape. Approximately six hours later, the tape and chambers were removed. Two additional induction doses were conducted following the same procedure, at weekly intervals.
Two weeks after the final application the animals received a topical primary challenge dose (6 hours contact) of the test substance at 10% concentration in mineral oil on a naïve site located on the right shoulder. Animals were scored for irritation at 24 and 48 hours after initiation of the primary challenge application.
Challenge controls:
Ten guinea pigs served as a naïve control group, and remained untreated through the induction phase. Six naïve control animals received only the primary challenge dose, at a 10% concentration. The four remaining guinea pigs were designated for a re-challenge, if necessary.
Positive control substance(s):
yes

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
19
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
19
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
15
Total no. in group:
20
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
Based on the results of this stuy, the test substance meets the CLP criteria for a skin sensitizer, category 1B.
Executive summary:

The test substance was evaluated for skin sensitization potential by applying 0.4 ml at a 25% concentration in mineral oil directly into Hilltop chambers and applying them to the clipped left shoulder of twenty albino guinea pigs in the following manner. The animals were held gently, and the chambers were applied as quickly as possible to the clipped left shoulder. The chambers were secured with Micropore tape and further secured with Kendall adhesive tape. Approximately six hours later, the tape and chambers were removed. Two additional induction doses were conducted following the same procedure, at weekly intervals.

Two weeks after the final application the animals received a topical primary challenge dose (6 hours contact) of the test substance at 10% concentration in mineral oil on a naïve site located on the right shoulder. Animals were scored for irritation at 24 and 48 hours after initiation of the primary challenge application.

Ten guinea pigs served as a naïve control group, and remained untreated through the induction phase. Six naïve control animals received only the primary challenge dose, at a 10% concentration. The four remaining guinea pigs were designated for a re-challenge, if necessary.

Following 0primary challenge of the test substance at 10% concentration, the incidence of grade 1 response or greater in the test group (19 of 20) was compared to that of the naïve control group (0 of 6). The incidence and severity of these responses were greater than those produced by the naïve control group indicating that a sensitization response had been induced. Based upon the results of the initial challenge dose it was decided that a re-challenge was necessary.

A subsequent re-challenge of the test substance at 5% concentration also resulted in responses greater than those produced in the naïve control group. Based upon the results of the challenge and re-challenge doses in terms of both incidence and severity of the responses, the test material would be considered a sensitizer.

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