Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
2,4,6,8-tetramethyl-1,3,5,7-tetraoxacyclooctane
EC Number:
203-600-2
EC Name:
2,4,6,8-tetramethyl-1,3,5,7-tetraoxacyclooctane
Cas Number:
108-62-3
Molecular formula:
C8H16O4
IUPAC Name:
2,4,6,8-tetramethyl-1,3,5,7-tetraoxocane
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
- Identity: LZ1060 Metaldehyde
- Appearance: White powder
- Storage conditions: 4°C in the dark
- Expiry date: 20-October-2009

In vivo test system

Test animals

Species:
mouse
Strain:
CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd., Bicester, Oxon, England
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: good
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 18.8-21.9 g
- Housing: individually in polycarbonate cages with woodflake bedding
- Diet: Special Diet Services RMl (E) SQC
- Water (e.g. ad libitum): tap water
- Acclimation period: 5-6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12h lightning / 12 h darkness

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
The maximum practical concentration for pinna dosing was 25% w/v in acetone:olive oil (4:1 v/v). Based on this information the following concentrations were selected for the preliminary study: 5, 10 and25% w/v
The results of the preliminary study indicated that 25% w/v was a suitable high dose level for the main study. Based on this information the following concentrations were selected for the main study: 5, 10 and 25% w/v
No. of animals per dose:
Groups of four mice were treated at one of three concentrations (5, 10 and 25% w/v) of the test substance.
Details on study design:
The mice were treated by daily application of 25 ul of the appropriate concentration of the test substance to the dorsal surface of each ear for three consecutive days (Days 1-3). The test substance was applied to the dorsal surface of each ear using an automatic micropipette. The test substance was spread over the entire dorsal surface of the ear using the tip of the pipette. A further group of four mice received the vehicle alone in the same manner
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
None

Results and discussion

Positive control results:
This positive control study was conducted between 16 and 30 November 2006 using sixteen mice of the CBA/Ca strain supplied by Harlan UK Ltd., Bicester, Oxon, England. Groups of four mice were used in this study. Three dosage levels and a vehicle control were used with dosages of HCA selected based on previous experience with HCA at this laboratory as follows: 10, 25 and 50% v/v in AOO ( 4: 1 v/v acetone:olive oil).
In this study the stimulation indexes (test/control ratio) obtained for 10, 25 or 50% v/v HCA were 7.9, 13.5 and 19.8 respectively. This indicates that HCA showed the potential to induce skin sensitization (delayed contact hypersensitivity) and confirms the sensitivity of the technique to detect skin sensitization.

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
0.4
Variability:
no data
Test group / Remarks:
5% w/w test group conc.
Key result
Parameter:
SI
Value:
0.9
Variability:
no data
Test group / Remarks:
10% w/w test group conc.
Key result
Parameter:
SI
Value:
1
Variability:
no data
Test group / Remarks:
25% w/w test group conc.
Cellular proliferation data / Observations:
The test/control ratios obtained for 5, 10 and 25% w/v LZ1060 were 0.4, 0.9 and 1.0 respectively. As a test/control ratio of 3 or more was not recorded for any of the concentrations tested, LZ1060 is not considered to have the potential to cause skin sensitization (delayed contact hypersensitivity

Any other information on results incl. tables

Mortality and clinical signs:

There were no deaths and no signs of ill health or toxicity observed during this study. No signs of irritation were seen over the dosed area during the study. Greasy fur (cranial region) was noted for all control and test animals post-dose from Days 1 or 2. This sign had resolved completely in all animals by Day 6. Particles on ears were observed in all animals in the treated groups post dose from Day 1. This sign had resolved by Day 4.

Body weights:

A loss in body weight was recorded for one female in Group 2 and there was no bodyweight gain for one female in Group 4 during the study. All remaining animals gained weight during the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item is not regarded as a potential skin sensitizer.
Executive summary:

The study was performed to assess the skin sensitization potential of the test item using the murine local lymph node assay (LLNA). The study was performed in compliance with OECD Guideline No. 429. In order to find a suitable level for a main study, a preliminary study was conducted. One female was dosed at either 5, 10 or 25 w/v in acetone:olive oil (4:1 v/v). Results indicated that 25% w/v was a

suitable high dose level for the main study. In the main study, groups of four mice were dosed at three dosage levels and a vehicle control. Dosages were selected as follows: 5, 10 and 25% w/v in acetone:olive oil (4:1 v/v). In each phase of the study, the mice were treated by daily application of 25 ul of each of one of these three concentrations, or vehicle control, to the dorsal surface of both ears for three consecutive days.

In this assay the test/control ratios obtained for 5, 10 and 25% w/v were 0.4, 0.9 and 1.0 respectively, which indicates that LZ1060 Metaldehyde did not show the potential to induce skin sensitization

(delayed contact hypersensitivity). Responses to the positive control substance hexyl cinnamic aldehyde (HCA), in contemporaneous studies demonstrate the reliability and sensitivity of this assay to detect skin sensitization potential in this laboratory. The test item is not regarded as a potential skin sensitizer.