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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:
November 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study in compliance with guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Ametryn
EC Number:
212-634-7
EC Name:
Ametryn
Cas Number:
834-12-8
Molecular formula:
C9H17N5S
IUPAC Name:
N2-ethyl-6-(methylsulfanyl)-N4-(propan-2-yl)-1,3,5-triazine-2,4-diamine
Details on test material:
Identity: Ametryn Technical
Chemical name: N2-Ethyl-N4-isopropyl-6-methylthio- 1,3,5-triazine-2,4-diamine
Intended use: Herbicide
Lot number: 1018
Expiry: Not advised
Purity: 96.8%
Appearance: White powder
Storage conditions: Room temperature in the dark
Date received: 15 May 1995

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
Fifteen healthy male albino guinea-pigs of the Dunkin/Hartley strain were obtained from D. Hall, Newchurch, Staffordshire, England.
The animals were in the weight range of 249 to 355 g on arrival and approximately four to five weeks of age. All the guinea-pigs were acclimatised to the experimental environment for six days prior to the start of the main study.
An additional six animals, from the same supplier, were used for the preliminary investigations.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Alembicol D (a product of coconut oil, supplied by Alembic products, Saitney, Chester, England)
Concentration / amount:
Based on the results of the preliminary investigations, the following concentrations of Ametryn Technical were selected:

Induction intradermal injection - 20% w/v in Alembicol D

This was the highest concentration that could be dosed intradermally and caused irritation but not adversely affect the animals.

Induction topical application - 50% w/v in Alembicol D

Topical challenge - 50 and 25 % w/v in Alembicol D

This was the maximum practical concentration and did not give rise to irritating effects.

Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Alembicol D (a product of coconut oil, supplied by Alembic products, Saitney, Chester, England)
Concentration / amount:
Based on the results of the preliminary investigations, the following concentrations of Ametryn Technical were selected:

Induction intradermal injection - 20% w/v in Alembicol D

This was the highest concentration that could be dosed intradermally and caused irritation but not adversely affect the animals.

Induction topical application - 50% w/v in Alembicol D

Topical challenge - 50 and 25 % w/v in Alembicol D

This was the maximum practical concentration and did not give rise to irritating effects.

No. of animals per dose:
Control animals: 5
Test animals: 10
Details on study design:
Fifteen healthy male albino guinea-pigs of the Dunkin/Hartley strain were obtained from D. Hall, Newchurch, Staffordshire, England.
The animals on the main study were allocated without conscious bias to two groups: control animals and test animals.
During the induction phase, the control animals were treated similarly to the test animals with the exception that the test substance was omitted from the intradermal injections and topical application.
The dermal reactions resulting from the challenge applications were assessed, using an arbitrary numerical scoring system, at 24 and 48 hours.
Challenge controls:
see above
Positive control substance(s):
yes

Results and discussion

Positive control results:
The sensitivity of the guinea-pig strain used is checked periodically at Huntingdon Life Sciences with known sensitisers (hexyl cinnamic aldehyde (HCA), mercaptobenzothiazole (MBT) and benzocaine). The results are considerated valid.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Anterior site, exposed to Ametryn Technical, 50% wlv in Alembicol D, Posterior site, exposed to Ametryn Technical, 25% w/v in Alembicol D
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
One animal died prior to challenge application
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Anterior site, exposed to Ametryn Technical, 50% wlv in Alembicol D, Posterior site, exposed to Ametryn Technical, 25% w/v in Alembicol D. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: One animal died prior to challenge application .
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Anterior site, exposed to Ametryn Technical, 50% wlv in Alembicol D, Posterior site, exposed to Ametryn Technical, 25% w/v in Alembicol D
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
One animal died prior to challenge application
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Anterior site, exposed to Ametryn Technical, 50% wlv in Alembicol D, Posterior site, exposed to Ametryn Technical, 25% w/v in Alembicol D. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: One animal died prior to challenge application .
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
#
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: #. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
#
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: #. No with. + reactions: 0.0. Total no. in groups: 5.0.

Any other information on results incl. tables

A test animal was considered to show positive evidence of delayed contact hypersensitivity if the observed dermal reaction at challenge was definitely more marked and/or persistent than the maximum reaction seen in animals of the control group.

In this study, Ametryn Technical did not produce evidence of skin sensitisation (delayed contact hypersensitivity) in any of the ten test animals.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information