Potassium carbamoylcarbamate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to GLP/OECD guideline without deficiency.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source:Nulliparous, non-pregnant female CBA/CaCrl strain mice obtained from Charles River (UK) Ltd, Margate.
- Age at study initiation: 8 to 10 weeks old.
- Weight at study initiation: 15 to 20 g
- Housing:Group housed during acclimatisation and individually housed from Day –1 in cages.
- Diet (e.g. ad libitum):SQC(E) Rat and Mouse Maintenance Diet No 1, from Special Diets Services Ltd, Witham, UK was freely available to the animals at all times.
- Water (e.g. ad libitum):Mains water was provided, ad libitum, via cage-mounted water bottles.
- Acclimation period: 8 to 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):20 to 24 degrees C
- Humidity (%):45 to 65%
- Air changes (per hr):15 to 20
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From 17 January 2012 To 31 January 2012

Vehicle:

dimethyl sulphoxide

Concentration:

0, 10%, 25%, 50% w/v

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS: A preliminary screening test was performed with one mouse. The mouse was treated by daily application of 25 µL of the test
article at the maximum suitable concentration (50% w/v in DMSO) to the dorsal surface of each ear for three consecutive days (Days 1, 2 and 3). The mouse was observed daily for five days from the initiation of treatment. Any signs of toxicity or irritation during this period were recorded.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures:3
- Exposure period: 24 hours
- Site:Outer aspect of both auditory pinnae.
- Frequency of applications:once daily
- Duration:Once daily on Days 1, 2 and 3.
- Concentrations: 0.25 mL/pinna

B. CHALLENGE EXPOSURE
- No. of exposures:1
- Day(s) of challenge:1
- Site: Tail vein injection.
- Concentrations:0.25 mL phosphate buffered saline incorporating 20 μCi of 3HTdR.
- Evaluation (hr after challenge):5 hours

Positive control substance(s):

other: α-hexylcinnamaldehyde formulated at a concentration of 25% in acetone / olive oil (4:1 v/v)

Positive control results:

The positive control article produced a Stimulation Index of 4.49.

Key result

Parameter:

SI

Variability:

599 +/- 196.1 DPM

Test group / Remarks:

Vehicle control

Remarks on result:

other: Control parameter

Key result

Parameter:

SI

Value:

0.55

Variability:

330 +/- 138.7 DPM

Test group / Remarks:

10% in DMSO

Key result

Parameter:

SI

Value:

1.22

Variability:

730 +/-565.8 DPM

Test group / Remarks:

25% in DMSO

Key result

Parameter:

SI

Value:

0.67

Variability:

401 +/- 126.5 DPM

Test group / Remarks:

50% in DMSO

Key result

Parameter:

SI

Value:

4.49

Variability:

2693 +/- 1860.1 DPM

Test group / Remarks:

Positive control

Individual DPMs and Stimulation Index (SI)

Concentration (%w/v) in DMSO	Group number	Animal number	DPM/ animal	Mean DPM/animal (Standard Deviation)	Stimulation Index (SI)^a
Vehicle	1	49	506	599 (± 196.1)	NA
		50	509
		51	941
		52	458
		53	583
10	2	54	146	330 (± 138.7)	0.55
		55	313
		56	421
		57	265
		58	504
25	3	59	711	730 (± 565.8)	1.22
		60	790
		61	186
		62	328
		63	1635
50	4	64	389	401 (± 126.5)	0.67
		65	285
		66	521
		67	540
		68	272
Positive control	5	69	1308	2693 (± 1860.1)	4.49
		70	1715
		71	1619
		72	3013
		73	5809

Key

DMSO    dimethyl sulphoxide

NA = Not applicable

^a= Stimulation Index of 3.0 or greater indicates a positive result

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

The Local Lymph Node Assay demonstrated that Potassium Allophonate does not have the potential to cause skin sensitisation.
The test article did not meet the criteria for classification as a sensitiser according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a skin sensitisation study conducted according to OECD Testing Guideline 429 with mice, potassium allophonate did not result in any skin sensitisation effects. Therefore, the current data indicate that potassium allophonate is not a skin sensitiser.

Migrated from Short description of key information:
Potassium allophonate was evaluated for skin sensitisation in a local lymph node assay (LLNA) in mice (OECD Testing Guideline 429). None of the test animals produced a skin sensitisation stimulation index over 3 in this study. Therefore, the current data indicate that potassium allophonate is not a skin sensitiser.

Justification for selection of skin sensitisation endpoint:
Study performed under Good Laboratory Practices (GLP)/Organisation for Economic Co-operation and Development (OECD) testing guidelines.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Migrated from Short description of key information:
Although no study data specifically evaluating potential respiratory sensitisation effects are available for potassium allophonate, based on the lack of human case reports indicating potassium allophonate is a respiratory sensitiser, as well as negative responses observed in both the skin sensitisation and skin irritation animal studies, potassium allophonate is not likely to be a respiratory sensitiser.

Justification for classification or non-classification

Potassium allophonate was found to be non-sensitising in a skin sensitisation study conducted in accordance with OECD Testing Guideline 429. Therefore, no classification is warranted for the skin sensitisation endpoint. No respiratory sensitisation study is available for potassium allophonate. Therefore, classification cannot be made due to lack of data.