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Toxicological information

Skin sensitisation

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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-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
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

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)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
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.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
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)

Study design: in vivo (LLNA)

Statistics:
no data

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)

Resultsopen allclose all
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.
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).
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.
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).

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.