Tetrakis(hydroxymethyl)phosphonium chloride, oligomeric reaction products with urea

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 1992/10/19 and 1992/11/29

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study is performed according to OECD 406 and in compliance with GLP . However, the purity is not identified.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes (incl. QA statement)

Remarks:

1992-06-11

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

An in vivo study has already been performed for this endpoint.

Test material

Test material information

Constituent 1

Test material form:

other: liquid stored at room temperature

Details on test material:

- Purity: no data
- Physical state: pale straw coloured liquid
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall Limited, Burton-on-trent, Staffordshire, U.K.
- Age at study initiation: 8 - 12 weeks old
- Weight at study initiation: 308 - 426 g
- Housing: in groups of up to three in solid-floor polypropylene cages furnished with softwood shavings
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21 °C
- Humidity (%): 46 - 59 %
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: no data

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

- Intradermal Induction: 0.1% (w/v) in distilled water, 0.1% (w/v) in a mixture of Freunds Complete Adjuvant (FCA) + water (1:1)
- Topical Induction: 75% (v/v) test material in distilled water
- Topical Challenge: 50% test material and 25% test material (v/v) in distilled water:
equivalent to 41% Active ingredient (AI (v/v), 27% AI (v/v) and 14% AI (v/v) respectively.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

Concentration / amount:

- Intradermal Induction: 0.1% (w/v) in distilled water, 0.1% (w/v) in a mixture of Freunds Complete Adjuvant (FCA) + water (1:1)
- Topical Induction: 75% (v/v) test material in distilled water
- Topical Challenge: 50% test material and 25% test material (v/v) in distilled water:
equivalent to 41% Active ingredient (AI (v/v), 27% AI (v/v) and 14% AI (v/v) respectively.

No. of animals per dose:

4 (intradermal pre-test), 2 (epidermal pre-test), 2 (challenge pre-test)
20 (test material)
10 (control)

Details on study design:

RANGE FINDING TESTS:
Based on the results of the pre-test, the test item concentration of 0.1% (w/v) was selected for intradermal induction in the main study. For the induction by epidermal application, the concentration of 75% test material was chosen. For the topical challenge, the test material concentrations of 25 % and 50% were chosen.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: D0 and D7
- Test groups: test substance in FCA + water and in water alone
- Control froups: FCA + water and water alone
- Site: dorsal skin of the scapular region
- Frequency of applications: 2 applications
- Duration: 48 hours (epidermal application)
- Concentrations: 0.1% (w/v) (intradermal), 75% (v/v) (epidermal)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: 24 hrs
- Test groups: test substance only
- Control group: vehicle alone
- Site: right flank (test item) and left flank (vehicle)
- Concentrations: 25% and 50%
- Evaluation (hr after challenge): 24 and 48 hours after challenge

Challenge controls:

Negative control animals were treated by vehicle topical application (water)

Positive control substance(s):

yes

Remarks:

2,4-dinitrochlorobenzene (DNCB)

Results and discussion

Positive control results:

2,4-Dinitrochlorobenzene (DNCB), produced a 89% (16/18) sensitization rate. This is considered a satisfactory response rate for DNCB under the conditions of the test.

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 2

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25%

No. with + reactions:

10

Total no. in group:

19

Clinical observations:

Scattered mild redness (score 1)

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 10.0. Total no. in groups: 19.0. Clinical observations: Scattered mild redness (score 1).

Results 3

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 4

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25%

No. with + reactions:

3

Total no. in group:

19

Clinical observations:

Scattered mild redness (score 1)

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 3.0. Total no. in groups: 19.0. Clinical observations: Scattered mild redness (score 1).

Results 5

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

1.0% DNCB

No. with + reactions:

16

Total no. in group:

18

Results 6

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

1.0% DNCB

No. with + reactions:

16

Total no. in group:

18

Any other information on results incl. tables

Table 7.4.1/1: Reaction at challenge at 24 h and 48 h in negative control group and test group

Animal number	Reaction at challenge
	24 h	48 h
Control group
21	0	0
22	0	0
23	0	0
24	0	0
25	0	0
26	0	0
27	0	0
28	0	0
29	0	0
30	0	0
Test group (25% test material)
1	1	0
2	1	0
3	0	0
4	0	0
5	1	1
6	0	0
7	1	1
8	1	0
9	-	-
10	1	0
11	0	0
12	1	1
13	0	0
14	0	0
15	1	0
16	1	0
17	0	0
18	1	0
19	0	0
20	0	0

-: No data, animal killed for humane reasons on day 18 (presence of a wound on the neck)

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information

Conclusions:

Under the test conditions, the test material produced a 53% (10/19) sensitization rate. Tetrakis (hydroxymethyl) phosphonium chloride, oligomeric reaction products with urea is classified in Category 1, H317 (may cause an allergic skin reaction) according to the CLP regulation (1272/2008) and as a skin sensitizer (Xi-R43) according to the Directive 67/548/EEC.

Executive summary:

In a dermal sensitization study (SPL, 1992),with Tetrakis (hydroxymethyl) phosphonium chloride, oligomeric reaction products with urea (THPC-urea) in water, young adult Dunkin-Hartely guinea pigs (20 treated females + 10 controls) were tested using the method of guinea pigs maximisation test (OECD 406, method B6 in Commission Directive 84/449/EEC) and in compliance with GLP. In this study, THPC-NH4 oligomer induced evidence of skin sensitisation in 53% of the animals at challenge readings (score 1 at 24h and 48 h) following topical application at 14% Active Ingredient (AI) (v/v). At a concentration of 50% for topical application, animals exhibited skin irritation.

Under the conditions of the test, THPC-urea should be classified in Category 1A, H317 (may cause an allergic skin reaction) according to the CLP regulation (1272/2008) including ATP2 and as a skin sensitizer (Xi-R43) according to the Directive 67/548/EEC.