Registration Dossier

Administrative data

Description of key information

There are no skin sensitisation data for HMDTMP (4-7Na). Therefore, data have been read-across from the analogue substancesCHDTMP-Na (CAS 102506-09-2), EDTMP-xNa (CAS 22036-77-7) and DTPMP-H (CAS 15827-60-8). See attachment to Section 13 for justification of read-across.

 

In the in vivo skin sensitisation study, conducted according to OECD Test Guideline 406 and in compliance with GLP, the test material CHDTMP-Na was not sensitising to guinea pig skin (Safepharm Laboratories, 1992).

 

In the in vivo skin sensitisation study, conducted according to a protocol similar to OECD Test Guideline 406 without information about GLP compliance, the test material EDTMP-xNa was not sensitising to skin (Monsanto, 1985).

 

In the in vivo skin sensitisation study, conducted prior to OECD Test Guideline 406 and pre-dating GLP, DTPMP-H (56.5% active ingredient) was not sensitising to skin (Unilever, 1979).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 July 1982 - 4 September 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Ltd., Burton-on Trent, Stratfodshire, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 370-450g
- Housing: The animals were housed in groups of up to three in solid-floor polypropylene cages furnished with softwood shavings.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 46-72
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12

Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal induction: 1% (w/v) in distilled water
Topical induction: undiluted as supplied
Topical challenge: undiluted as supplied and 75% (v/v) in distilled water
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal induction: 1% (w/v) in distilled water
Topical induction: undiluted as supplied
Topical challenge: undiluted as supplied and 75% (v/v) in distilled water
No. of animals per dose:
20 test and 10 control animals were used for the main study
Details on study design:
RANGE FINDING TESTS:

Selection of concentrations for intradermal induction:
Two animals were intradermally injected with preparations of test material (1% or 5% w/v in distilled water). The highest concentration that did not cause local necrosis, ulceration or systemic toxixicty, was selected for the intradermal induction stage of the main study.

Selection of concentration for topical induction:
Two guinea pigs (intradermally injected with Freund's complete adjuvant twenty one days earlier) were treated with the undiluted test material and three preparations of the test material (75%, 50% and 25% v/v in distilled water). The highest concentration producing only mild to moderate dermal irritation after the 48 hour occlusive exposure, was selected for the topical induction stage of the maiin study.

Selection of concentration for topical challenge:
The undiluted test material and three preparations of the test material (75%, 50% and 25% v/v in distilled water) were applied occlusively to the flanks of two guinea pigs for a period of 24 hours. These guinea pigs did not form part of the main study but had been treated identically to the control animals of the main study, up to day 14. The highest non-irritant concentration of the test material and one lower concentration were selected for the topical challenge stage of the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
On day 0 a row of three injections (0.1ml) was made on each side of the midline. The injections were: (1) Freund's complete adjuvant plus distilled water in the ratio 1:1, (2) a 1% (w/v) dilution of test material in distilled water, (3) a 1% (w/v) dilution of test material in a 1:1 preparation of Freund's complete adjuvant plus distilled water. One week later (Day 7), the same area on the shoulder region used previously for intradermal injections was clipped again and treated with a topical application of the undiluted test material, which was applied on filter paper which was held in place occlusively for 48 hours. Erythemaeous reactions were quantified one and twenty-four hours following removal of the patches. In the case of the induction of the control animals, intradermal injections were administered using an identical procedure to that used for the test animals, except that test material was omitted and substituted with distilled water. The topical applications followed the same procedure as for the test animals except that nothing was applied to the filter paper.


B. CHALLENGE EXPOSURE
On Day 21, a quantity of the undiluted test material was applied to the shorn right flank of each animal on a square of filter paper which was held in place. To ensure that the maximum non-irritant concentration was used at challenge, the test material at a concentration of 75% (v/v) in distilled water was also similarly applied to a separate skin site on the right shorn flank. The vehicle alone was similarly applied to the left shorn flank. The patches were occluded, and torso wrapped. After 24 hours the dressing was removed, and their position identified with marker-pen. Approximately 24 and 48 hours after challenge dressing removal, erythematous reactions were quantified using the four point scale shown overleaf.
Positive control substance(s):
yes
Remarks:
DNCB (89% sensitisation rate)
Positive control results:
DNCB produced an incidence on 16/18 sensitising reactions.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Undiluted and 75% v/v in distilled water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Undiluted and 75% v/v in distilled water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
adjuvant and distilled water in the ratio of 1:1
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
adjuvant and distilled water in the ratio of 1:1
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
DNCB
No. with + reactions:
16
Total no. in group:
18
Remarks on result:
positive indication of skin sensitisation
Remarks:
produced an incidence on 16/18 sensitising reactions.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
DNCB
No. with + reactions:
16
Total no. in group:
18
Remarks on result:
positive indication of skin sensitisation
Remarks:
produced an incidence on 16/18 sensitising reactions.
Interpretation of results:
GHS criteria not met
Conclusions:
The in vivo skin sensitisation study, conducted according to OECD Test Guideline 406 and in compliance with GLP, found the test material CHDTMP Na to be not sensitising to guinea pig skin.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
21.02.1979 to 27.06.1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
This study was conducted before OECD TG 406 was available. It was conducted according to the Magnusson and Kligman guinea pig maximisation test.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method, which pre-dates REACH Regulation (EC No 1907/2006) and CLP Regulation (EC No 1272/2008).
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
Induction (intradermal injection): 1%
Induction (epicutaneous patch): 10%
Challenge 1: 2.5%
Challenge 2: 2.5%
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
Induction (intradermal injection): 1%
Induction (epicutaneous patch): 10%
Challenge 1: 2.5%
Challenge 2: 2.5%
No. of animals per dose:
Ten per challenge phase
Details on study design:
PRELIMINARY IRRITATION TESTS
Intradermal injection: previously untreated guinea pigs of the same sex and weighing approximately 320g were each injected intradermally on the clipped flanks with 0.1 ml aliquots of a range of concentrations of test substance in a suitable solvent. 24 hours later the reactions were examined for size erythema and oedema. The concentration which produced a definite irritation reaction (10 x 10 mm, pale pink, with or without oedema) was selected as the intradermal injection induction concentration.
Topical application (for neck induction and flank challenge) : 8mm diameter filter paper (Whatman 3B01) patches, in 11 mm "Fintest" aluminium patch test cups, were saturated with a range of concentrations of test substance in a suitable solvent and the cups applied to the shaved flanks of previously untreated guinea pigs of the same sex and weighing approximately 450g. The patches were held in place by adhesive plaster (Poroplast) wound around the trunk. 24 hours later the patches are removed, the reaction sites were examined 24 and 48 hours subsequently. The concentration that gave definite irritation was selected for shoulder induction. The highest non-irritant concentration was selected for sensitisation challenge.

Induction:
- Intradermal injection:
1) 2 injections of 50% F.C.A. in the solvent system chosen for the test sample.
2) 2 injections of test material at the concentration and in the solvent system chosen in the preliminary irritation tests. These injections were given into the periphery of the "bleb" caused by injection 1.
3) 2 injections of the test material of the concentration chosen in the preliminary irritation tests in a 50/50 mixture of F.C.A. and the chosen solvent system.
- Epicutaneous induction: 7 days later sensitisation was boosted by placing over the shoulder injection site a 2 x 4cm filter paper patch saturated with test substance at the selected concentration. The patch was occluded with thin polythene, held in place by Poroplast, and was left in place for 48 hours.

Challenge: 14 days after application of the shoulder patch the guinea pigs were challenged on one flank by occluded patch. For each animal an 8mm diameter filter paper patch in a patch test cup is saturated with test solution at the selected concentration. The cup is applied to the shaved flank and is held in place by Poroplast wound around the trunk. 24 hours later the patch was removed, the reaction was examined 24 and 48 hours subsequently. One week later the challenge was repeated on the opposite flank.
Challenge controls:
- Treated controls (First challenge only): guinea pigs of the same sex and weighing about 320g were treated exactly as the test animals, except that test substance was omitted from the intradermal injection and covered patch induction procedures. The treatment was given to the control animals at the same time as to the test animals. The animals were challenged exactly as the test animals
- Untreated controls (All challenges) At each challenge 4 previously untreated animals of the same sex and weighing the same as the test animals were each challenged in the same way as the test animals.
Positive control substance(s):
not specified
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
2.5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenge 1
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2.5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenge 1
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
2.5% (treated controls)
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenge 1
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
2.5% (treated controls)
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenge 1
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0% (untreated controls)
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenge 1
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0% (untreated controls)
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenge 1
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
2.5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenge 2
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2.5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenge 2
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0% (untreated controls)
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenge 2
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0% (untreated controls)
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenge 2
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Not specified
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
other: Data on positive control was not specified
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Not specified
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
other: Data on positive control was not specified

All animals gained weight during the study.

Interpretation of results:
GHS criteria not met
Conclusions:
The in vivo skin sensitisation study, conducted prior to OECD Test Guideline 406 and GLP, DTPMP acid (56.5% active ingredient) was concluded to be not sensitising to the skin of guinea-pigs.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Procedure based on method described by E.V Buehler in "Delayed Contact Hypersensitivity in Guinea Pig", Arch. Dermatol 91: 171-175 (1965) and H.L. Ritz and E.V Buehler in "Planning, Conduct and Interpretation of Guinea Pig Sensitisation Patch Test", in Current Concepts in Cutaneous Toxicity (Victor A. Drill and Paul Lazar, eds.), pp. 25-40; Academic Press, 1980.
GLP compliance:
not specified
Type of study:
Buehler test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Buehler test method.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% test material. Positive control induction in 80% ethanol, rechallenge in acetone as vehicle (concentration not reported).
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% test material. Positive control induction in 80% ethanol, rechallenge in acetone as vehicle (concentration not reported).
No. of animals per dose:
The positive control group and the test material group consisted of 5 males and 5 females, and these animals were treated during the induction and challenge phases of this study. A third group was included which consisted of 3 males and 3 females, and these anmals were treated only during the challenge phase to assess whether the challenge concentration was irritating.
Details on study design:
During the induction phase, the material was administered in a volume of 0.3 ml beneath a Hilltop Chamber. The chamber was covered with impermeable plastic and secured with an elastic adhesive bandage. The patch was removed 6 hours later and the skin was wiped free of any excess material. The treatment was repeated once a week for three weeks, for a total of three exposures.
After a two week rest period, animals were treated during the first challenge phase. The test material was administered in a similar fashion as in the induction phase,
but at a site which had not been exposed to the test material.
Challenge controls:
Yes
Positive control substance(s):
yes
Remarks:
DNCB (0.5% w/v in 80% ethanol at induction; 0.3% w/v in acetone at challenge)
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
DNCB (0.3% w/v in acetone)
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
DNCB (0.3% w/v in acetone)
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
DNCB (0.3% w/v in acetone) - irritation control group, exposed at challenge only
No. with + reactions:
2
Total no. in group:
6
Clinical observations:
very slight barely perceptible erythema in 2 animals
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
DNCB (0.3% w/v in acetone) - irritation control group, exposed at challenge only
No. with + reactions:
1
Total no. in group:
6
Clinical observations:
very slight barely perceptible erythema in 1 animal
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100% test material
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100% test material
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% test material - irritation control group, exposed at challenge only
No. with + reactions:
0
Total no. in group:
6
Clinical observations:
No dermal reactions were observed in any of the animals.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100% test material - irritation control group, exposed at challenge only
No. with + reactions:
0
Total no. in group:
6
Clinical observations:
No dermal reactions were observed in any of the animals.
Remarks on result:
no indication of skin sensitisation

0.3 ml of the test material was applied at induction and challenge as a 100% solution.

EDTMP-xNa is known to have 35.7% active salt content at pH 6 -8, and a specific gravity of 1.3 -1.36 g/ cm3.

The pKa of the salt at pH 7.3 is estimated to be 6. The conversion factor to determine the salt to acid equivalent for mass for EDTMP-6Na salt is 0.768.

Therefore, based on the known active salt proportion of the substance it is calculated that the at application to animal skin amount of active salt is 400 mg, and active acid 300 mg.

Interpretation of results:
GHS criteria not met
Conclusions:
The in vivo skin sensitisation study, conducted according to a protocol similar to OECD Test Guideline 406 without information about GLP compliance, the test material EDTMP-xNa was concluded to be not sensitising to skin.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are no skin sensitisation data for HMDTMP (4-7Na). Therefore, data have been read-across from the analogue substancesCHDTMP-Na (CAS 102506-09-2), EDTMP-xNa (CAS 22036-77-7) and DTPMP-H (CAS 15827-60-8). See attachment to Section 13 for justification of read-across.

 

In the in vivo skin sensitisation study, conducted according to OECD Test Guideline 406 and in compliance with GLP, the test material CHDTMP-Na was not sensitising to guinea pig skin (Safepharm Laboratories, 1992).The test material was described as a liquid but no information was given on the active salt concentration.

 

On study day 0, 20 guinea pigs were induced by three intradermal injections (0.1ml) on each side of the midline. The injections were: (1) Freund’s complete adjuvant plus distilled water in the ratio 1:1, (2) a 1% (w/v) dilution of test material in distilled water, (3) a 1% (w/v) dilution of test material in a 1:1 preparation of Freund’s complete adjuvant plus distilled water. One week later on day 7, the animals were induced again by topical application of the undiluted test material onto the same area of the shoulder region used previously for intradermal injections. The test material was applied on filter paper and held in place with an occlusive covering for 48 hours. Skin reactions were quantified at 1 and 24 hours following removal of the patches. 10 control animals were induced intradermally using an identical procedure to that used for the test animals, except that test material was omitted and substituted with distilled water. The topical applications followed the same procedure as for the test animals except that nothing was applied to the filter paper.

 

At challenge on day 21, a quantity of the undiluted test material was applied onto the clipped of hair right flank of each animal on a square of filter paper which was held in place under occlusive dressing. To ensure that the maximum non-irritant concentration was used at challenge, the test material at a concentration of 75% (v/v) in distilled water was also similarly applied to a separate skin site on the right clipped flank. The vehicle alone was similarly applied to the left shorn flank. The patches were occluded, and torso wrapped. After 24 hours the dressing was removed, and their position identified with marker-pen. Approximately 24 and 48 hours after challenge dressing removal, skin reactions were quantified.

 

No skin sensitisation was reported in any of the test animals. Negative and positive controls were valid.

 

In the in vivo skin sensitisation study, conducted according to a protocol similar to OECD Test Guideline 406 without information about GLP compliance, the test material EDTMP-xNa was not sensitising to skin (Monsanto, 1985).The test material was described as a liquid but no information was given on the active salt concentration.

 

During the induction phase, the undiluted test material was applied onto the skin of 10 test guinea pigs in a volume of 0.3 ml beneath a Hilltop Chamber. The chamber was covered with impermeable plastic and secured with an elastic adhesive bandage. The patch was removed 6 hours later and the skin was wiped free of any excess material. The treatment was repeated once a week for three weeks, for a total of three exposures. The positive control group consisted of 10 guinea pigs, which were induced by topical application of 0.5% w/v DNCB in 80% ethanol.

 

After a two-week rest period, the test animals were treated during the first challenge phase. The undiluted test material was applied topically in a similar manner as in the induction phase, but at a site which had not been exposed to the test material. The positive control animals were treated similarly, but exposure was to 0.3% w/v DNCB in acetone. In addition, a third group of 6 guinea pigs was included as served as negative control and to assess whether the test material was a skin irritant. The animals were exposed topically to the test material during the challenge phase only.  

 

No skin sensitisation was reported in any of the test animals. Negative and positive controls were valid.

 

In the in vivo skin sensitisation study, conducted prior to adoption of the OECD Test Guideline 406 and pre-dating GLP, the test material DTPMP-H (56.5% active ingredient) was not sensitising to the skin of guinea-pigs (Unilever, 1979).The study protocol was described as a Magnusson and Kligman Guinea Pig Maximisation test.

 

On study day 0, 10 guinea pigs were induced by three intradermal injections (0.1 ml). The injections were: (1) 50% Freund’s complete adjuvant plus in physiological silane, (2) a 1% (w/v) dilution of test material in physiological silane, (3) a 1% (w/v) dilution of test material in a 50/50 mixture of Freund’s complete adjuvant plus physiological silane. One week later on day 7, the animals were induced for second time by topical application of 10% v/v test material onto the skin of the same region previously used for intradermal injections. The test material was kept in contact with the skin under occluded dressing for 48 hours. 4 treated control animals were exposed exactly as the test animals, except that test substance was omitted from the intradermal injection and covered patch induction procedures.

 

Challenge was performed 14 days after the last induction application, on study day 21. During challenge, 2.5% v/v test material was applied topically for 24-hours under occlusive dressing onto the skin of the test animals. Following dressing removal, the skin reactions were assessed at 24 and 48 hours. The treated control animals were challenged in the same manner as the test animals. In addition, 4 untreated control group of animals was used, which were not induced, but were exposed to the test material during challenge only.

 

No skin sensitisation was reported in any of the test animals. Negative controls were valid.

 

 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data, no classification is required for skin sensitisation for HMDTMP (4-7Na) according to Regulation (EC) No 1272/2008.