Potassium phosphinate

Endpoint summary

Description of key information

There were no data for sensibilisation with Potassium phosphinate however a murine Local Lymph Node Assay (LLNA)(OECD 429 , EU B 42 method, GLP) is available with Sodium hypophosphite . The test item was found to be non-sensitising

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

Study period:

2009-05-28 till 2009-06-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study in accordance with GLP standard procedure.

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 (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

other: CBA/J

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 9 weeks
- Weight at study initiation (± SD): 21.4 ± 1.0 g
- Housing: individually in disposable crystal polystyrene cages (22.0 cm x 8.5 cm x 8.0 cm)
- Diet: free access to SSNIFF R/M-H pelleted maintenance diet (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water: free access to tap water (filtered using a 0.22 micron filter)
- Acclimation period: at least 5 days before beginning of the study
- Other:
nulliparous and non-pregnant

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): ± 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00)

IN-LIFE DATES: Death on 2009-06-08.

Vehicle:

propylene glycol

Concentration:

0 (control), 2.5, 5, 10, 25 or 50%

No. of animals per dose:

4

Details on study design:

RANGE FINDING TEST TO ASSESS IRRITANT POTENTIAL THROUGH EAR THICKNESS MEASUREMENT:
- Compound solubility: Due to the unsatisfactory solubility of the test item in the first recommended vehicles (acetone/olive oil (4/1,v/v), dimethylformamide and methyl ethyl ketone), propylene glycol was chosen from the other proposed vehicles. A homogeneous suspension was obtained at the maximum concentration of 50%. Hence concentrations for the preliminary test were 5, 10, 25 and 50%
- Irritation: The irritant potential was assessed through ear thickness measurement. The test item was non-irritant in the preliminary test, whatever the concentration. The highest concentration retained for the main test was therefore the maximal practicable concentration, according to the criteria specified in the International Guidelines.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of the test method: murine Local Lymph Node assay (LLNA)
- Criteria used to consider a positive response:
The test item was considered as a skin sensitizer when the StimuIation indices (SI) for a dose group is >= 3. Other relevant criteria such as cellularity and ear thickness were also taken into account for the interpretation of results.

TREATMENT PREPARATION
Each dosage form preparation was prepared each day separately from each other and homogenized by magnetic stirring.

ADMINISTRATION:
On days 1, 2 and 3, 25 µL of the control or dosage form preparations (i.e. test substance or reference substance) was applied to the dorsal surface of both ears. To avoid licking and to ensure an optimized application of the test materials, the animals were placed under light isoflurane anesthezia during the administration. No massage was performed but the pipette's tip was used to spread the preparation over the application sites. No rinsing was performed between each application.

Positive control substance(s):

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

Statistics:

No data

Positive control results:

In the positive control group given hexyl cinnamic aldehyde (concentration 25%) a moderate increase in cellularity and a stimulation index exceeding the threshold value of 3 (SI = 15.30) were noted. The study was therefore considered valid.

Parameter:

SI

Remarks on result:

other: See table 1 in section remarks on results including tables and figures

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: See table 1 in section remarks on results including tables and figures

- Clinical examinations

- Systemic clinical signs and mortality: Neither mortality nor clinical signs were observed.

- Body weight: no change in body weight compared to the control group.

- Local irritation: Neither cutaneous reactions nor notable increase in ear thickness were observed in the animals of the treated groups.

 

- Proliferation assay

The quantity of cells obtained in each group was satisfactory and the cellularity correlated with incorporation of³H-TdR.

The cell viability was higher than 70% in each group. 

No notable lymphoproliferation was noted at any of the tested concentrations of the test substance.

- Table 1: Detailed overview of the study results

Treatment	Conc (%)	Cell viability	Cellularity index	# of nodes per group	dpm per group	dpm per node	Stimulation Index	Increase in ear thickness (% between day 1 and 6)	Irritation level (based on increase in ear thickness)
Vehicle		90.91		8	891.00	111.38		0
Test substance	2.5	90.14	1.60	8	1594.54	199.32	1.79	5.15	non-irritant
Test substance	5	82.14	1.15	8	898.61	112.33	1.01	3.03	non-irritant
Test substance	10	96.97	0.80	8	1099.35	137.42	1.23	2.04	non-irritant
Test substance	25	95.65	1.10	8	1185.10	148.14	1.33	4.04	non-irritant
Test substance	50	76.19	1.20	8	1268.55	158.57	1.42	2.94	non-irritant
Positive control	25	94.92	8.40	8	13631.16	1703.90	15.30

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Under the experimental conditions of this study, the test item sodium hypophosphite did not induce delayed contact hypersensitivity in the murine Local Lymph Node Assay.

Executive summary:

The potential of sodium hypophosphite to induce delayed contact hypersensitivity was assessed in mice according to the OECD guideline 429 and to the EU Method B.42. The study was conducted in compliance with the principles of Good Laboratory Practice regulations on the monohydrated form of the test item as the anhydrous form is highly hygroscopic and difficult to handle without specific precautions.

Five groups of 4 animals were exposed to the test substance on 3 consecutive days (concentrations 2.5%, 5%, 10%, 25% and 50%) in parallel with a negative control group receiving the vehicle propylene glycol and a positive control group receiving the moderate sensitiser alpha-hexylcinnamaldehyde. After 2 days of resting, the animals were sacrificed in order to perform the proliferation assay. Changes in body weight, ear thickness were noted and the animals were checked on a regular base for clinical signs, mortality and local irritation.

A significant lymphoproliferation was noted in the positive control given alpha-hexylcinnamaldehyde. The study was therefore considered valid. No noteworthy lymphoproliferation was noted with the test substance at any tested concentration. The Stimulation Index was below 3 (range: 1.01 to 1.79) and no dose response reaction was observed.

No systemic clinical signs and mortality, neither changes in body weight, nor local irritation was observed for all tested concentrations. As a result, sodium hypophosphite was considered as not sensitising.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

One study is recorded for this endpoint and was chosen as a key study. The delayed contact hypersensitivity of sodium hypophosphite was assessed using the murine Local Lymph Node Assay . This study was conducted in compliance with the principles of Good Laboratory Practices and performed according to the OECD guideline 429 and the EU Method B.42.

Results showed no cutaneous reactions and no increase in ear thickness. No lymphoproliferation was noted. Over the range of sodium hypophosphite tested concentrations (2.5% to the maximal practicable concentration of 50%), the Stimulation Index (SI) varied from 1.01 to 1.79.

Under these test conditions, sodium hypophosphite was considered as not sensitising.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Migrated from Short description of key information:
There is no reported case of respiratory sensitisation in humans.

Justification for classification or non-classification

Skin sensitisation:

According to the criteria laid down in EU regulation (EC) n°1272/2008 (CLP) and EU Directive 67/548/EEC, Potassium phosphinate has not to be classified for skin sensitisation.