1,3,5,7-Tetraazatricyclo[3.3.1.13,7]decane, mononitrate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Author:

Jong et al.

Year:

2002

Bibliographic source:

Toxicology 176, 123-134

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

no

Remarks:

Non GLP, but good documentation and similar to guideline.

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Methenamine

EC Number:

202-905-8

EC Name:

Methenamine

Cas Number:

100-97-0

Molecular formula:

C6H12N4

IUPAC Name:

1,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane

In vivo test system

Test animals

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: RIVM
- Age at study initiation: 6-8 week
- Housing: Makrolon cages
- Diet (e.g. ad libitum): Chow pellets ((Hope Farms, Woerden, the Netherlands) and water ad libitum


ENVIRONMENTAL CONDITIONS
Conventional conditions in light, humidity and temperature

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

2.5, 5, 10, 20 %

No. of animals per dose:

no specified (probably 4 per dose, as requiered in OECD guideline)

Details on study design:

According to de Jong et al., 2002 (Toxicology 176, 123-134).
In order to enhance possible low responses of weak sensitizers animals were pretreated with sodium dodecyl sulfate 1% (SDS) on the dorsum of the ears one hour before administration.
Test 1 (Short protocol): Animals were treated on days 0-1-2 and lymph node cell proliferation was determined on day 5.
Test 2 (Repeated protocol): Animals were treated on days 0-1-2. 7-14-28-35-42-49, and 56-57-58 and lymph node cell proliferation was determined on day 61.

Positive control substance(s):

not specified

Statistics:

EC3 was estimated by the benchmark approach.

Results and discussion

Positive control results:

No positive control

In vivo (LLNA)

Results

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Not given

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information

Conclusions:

Results of the LLNA affirm the classification of methenamine as a skin sensitizer.

Executive summary:

In a Local Lymph Node Assay (LLNA) similar to OECD Guideline 429, an EC3 (test concentration, which causes a Stimulation Index (SI) of the auricular lymph nodes of 3.0) of 30.6% was determined for methenamine, while an EC3 as low as 0.96% was determined for formaldehyde in the same study. The test was performed treating young adult (6-8 weeks of age) female BALB/c mice with methenamine dissolved in a acetone-olive oil mixture (4:1). Test concentrations were 2.5, 5, 10 and 20%. In order to enhance possible low responses of weak sensitizers animals were pretreated with sodium dodecyl sulfate 1% (SDS) on the dorsum of the ears one hour before administration. In second test with repeated exposures the fist test was coonfirmed revealing a Stimulation Index of 5.78. Results of the LLNA affirm the classification of methenamine as a skin sensitizer