Amidinourea phosphate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06. Dec 2019 - 03. Apr 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

22 July 2010

Deviations:

yes

Remarks:

The observed differences in the environmental parameters were considered not to adversely affect the results or integrity of the study.

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Amidinourea phosphate

EC Number:

241-659-6

EC Name:

Amidinourea phosphate

Cas Number:

17675-60-4

Molecular formula:

C2H6N4O.xH3O4P

IUPAC Name:

diaminomethylideneurea;phosphoric acid

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Batch No.: 18VL8610
Expiry Date: 06 October 2020
Storage Conditions: room temperature, protected from light

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

Age of animals at starting: 9 weeks old
Body weight range at starting: 19.1 – 20.8 grams
Acclimatization time: 13 days
Animal health: Only healthy animals were used for the study. Health status was certified by the veterinarian.
The minimum /maximum values of temperature and relative humidity were recorded twice every day during the acclimatization and experimental phases.

Study design: in vivo (LLNA)

Vehicle:

dimethyl sulphoxide

Concentration:

25% (w/v)

No. of animals per dose:

4

Details on study design:

For the main assay, concentrations of 10% (w/v), 5% (w/v) and 2% (w/v) in DMSO were considered to be acceptable based on preliminary study results.
All mice were observed daily (until day 6) for any clinical signs of systemic toxicity or local irritation at the application site. Both ears of each mouse were observed for erythema and scored. Ear thickness was also measured using a thickness gauge on Day 1 (pre-dose), Day 3 (approximately 48 hours after the first dose) and Day 6. Additional quantification of the ear thickness was performed by ear punch weight determination after the euthanasia of the experimental animals.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

Results were interpreted according to OECD Guideline 429

Results and discussion

Positive control results:

Valid: positive control substance produces a significant lymphoproliferative response increases (SI>3)

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

2.8

Test group / Remarks:

10% (w/v) in DMS

Results 2

Key result

Parameter:

SI

Value:

1.2

Test group / Remarks:

5% (w/v) in DMS

Results 3

Key result

Parameter:

SI

Value:

1.3

Test group / Remarks:

2% (w/v) in DMS

Cellular proliferation data / Observations:

No mortality or systemic toxicity was observed during the main study. No test item residue was observed on the ears of the animals. There were no indications of any irritancy at the site of application.
No evidence of test item related effects were observed on the mean body weight changes in the main study

Any other information on results incl. tables

DPM. DPN and Stimulation Index Values for all Groups

Test Group Name	Animal Number	Measured DPM	Total DPM	No. of Nodes	DPN	Mean DPN	Stimulation Index Values
Background	-	36	-	-	-	-	-
(5 (w/v) % TCA)
Negative control (DMSO)	9372	482	446.0	2	223.0	391.0	1.0
	9378	558	522.0	2	261.0
	9373	1541	1505.0	2	752.5
	9381	691	655.0	2	327.5
GUP - Guanylurea Phosphate  10% (w/v) in DMSO	9377	1995	1959.0	2	979.5	1109.0	2.8
	9386	2807	2771.0	2	1385.5
	9383	1597	1561.0	2	780.5
	9376	2617	2581.0	2	1290.5
GUP - Guanylurea Phosphate  5% (w/v) in DMSO	9390	1117	1081.0	2	540.5	481.4	1.2
	9385	1133	1097.0	2	548.5
	9384	1022	986.0	2	493.0
	9389	723	687.0	2	343.5
GUP - Guanylurea Phosphate  2% (w/v) in DMSO	9374	965	929.0	2	464.5	510.0	1.3
	9388	1372	1336.0	2	668.0
	9379	1509	1473.0	2	736.5
	9387	378	342.0	2	171.0
Positive control (25% (w/v) HCA) in DMSO	9380	5377	5341.0	2	2670.5	3201.3	8.2
	9382	6174	6138.0	2	3069.0
	9391	9959	9923.0	2	4961.5
	9375	4244	4208.0	2	2104.0

Notes:

1. Total DPM = Measured DPM – Background DPM value of TCA

2. DPN = (Measured DPM – Background DPM value of TCA) / Number of nodes

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

GUP - Guanylurea Phosphate, tested in a suitable vehicle, was shown to have no sensitisation potential (non-sensitizer) in the Local Lymph Node Assay.