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Description of key information

The studies are a read across from CHDTMP-Na (CAS 102506-09-2), EDTMP-xNa (CAS 22036-77-7) and DTPMP-H (CAS 15827-60-8). The test material was found not sensitising to guinea pig skin as reported in the three reliable studies (Safepharm 1992; Monsanto, 1985, 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:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
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 nothign was applied to the filter paper.


B. CHALLENGE EXPOSURE
On Day 21, a quantity of the unduluted 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:
rechallenge
Hours after challenge:
24
Group:
test group
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:
rechallenge
Hours after challenge:
48
Group:
test group
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:
rechallenge
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:
rechallenge
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
Interpretation of results:
GHS criteria not met
Conclusions:
The result is read across from BCIXN-Na (CAS 102506-09-2). The test material was found not sensitising to guinea pig skin as reported in a reliable study conducted in compliance with GLP.
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:
according to
Guideline:
other: Buehler test
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 thrid 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 test material was applied for 6 hours 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 at a new site with no previous application of test material.
Challenge controls:
Yes
Positive control substance(s):
yes
Remarks:
DNCB
Key result
Reading:
rechallenge
Group:
positive control
Dose level:
acetone as vehicle
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
greater of the 24/48 hour score
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
rechallenge
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
24/48 hour reading
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Group:
other: challenge (irritation) control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
6
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.

Dequest 2046 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 test material was found not sensitising in a Buehler test, conducted according to an appropriate test protocol but not in compliance with GLP.
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
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
2.5%
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:
48
Group:
test group
Dose level:
2.5%
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:
2.5%
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
2.5%
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
2.5%
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 group
Dose level:
2.5%
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:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
no indication of skin sensitisation

All animals gained weight during the study.

Interpretation of results:
GHS criteria not met
Conclusions:
In a guinea pig maximisation study conducted before OECD TG 406 and GLP (reliability score 2) DTPMP was not sensitising to the skin of guinea-pigs.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No data was available for skin sensitisation for HMDTMP (4 -7Na). The studies were therefore read across from the structurally analogous substances CHDTMP-Na (CAS 102506-09-2), EDTMP-xNa (CAS 22036-77-7) and DTPMP-H (CAS 15827-60-8). See Section 1.4 of the CSR for more details on the validity of read-across.

 


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 sodium salts according to Regulation (EC) No 1272/2008.