Registration Dossier

Administrative data

Description of key information

There are no skin or eye irritation data for HMDTMP (4-7Na). Therefore, data have been read-across from HMDTMP-xNa (CAS 56744-47-9). See attachment to Section 13 for justification of read-across within HMDTMP Category.

 

The key skin irritation study for HMDTMP-xNa (CAS 56744-47-9), conducted according to OECD Test Guideline 404 and in compliance with GLP, concluded that the test substance was not irritating to skin (Safepharm Laboratories, 1982).

 

The key eye irritation study for HMDTMP-xNa (CAS 56744-47-9), conducted according to OECD Test Guideline 405 and in compliance with GLP, concluded that test substance was not irritating to rabbit eyes (Safepharm Laboratories, 1982).

 

The HMDTMP sodium salt in both key studies was an aqueous solution with 25% acid content. Therefore, it is prudent to consider that these results may underestimate the irritancy potential of HMDTMP (4-7Na).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27.7.1982 - 30.7.1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.21-3.09kg
- Housing: individually housed in suspended metal cages
- Diet: standard laboratory diet, ad libitum
- Water: ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Air changes (per hr): ca. 15
- Humidity (%): not controlled but remained within a range of 76-80 %RH
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, 72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal/flank area
- Type of wrap if used: test material was held in contact with skin with an occlusive patch, and the trunk of the animal wrapped in an elasticated corset


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any resdual material was immediately removed by gentle swabbing with cotton wool soaked in lukewarm water. if the material was found to be insoluble in water, ether or acetone could be used.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize 1959
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Reported primary irritation index (Group total / 12) was 0.1. The test material produced minimal cutaneous irritation in 1/3 rabbits. There was no evidence of corrosion in any animal. Very slight erythema was observed in one rabbit at the one hour reading only. Two rabbits did not show any observable response to treatment throughout the 72 hours observation period.

The active acid in the test material is 25%.

Interpretation of results:
GHS criteria not met
Conclusions:
The in vivo skin irritation study, conducted according to OECD Test Guideline 404 and in compliance with GLP, found HMDTMP sodium salt (CAS 56744-47-9) to be not irritating to rabbit skin.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24.8.1982 - 27.8.1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hylyne Rabbits Ltd., Marston, Northwich, Cheshire
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.26-2.85kg
- Housing: individual housing in suspended cages
- Diet: standard laboratory diet, ad libitum
- Water: ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 +/- 2.5
- Humidity (%): humidity was not controlled but remained within a range of 68-70%RH
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1ml
- Concentration (if solution): undiluted
Observation period (in vivo):
Assessment of damage/irritation was made 1, 24, 48 and 72 hours following treatment.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM: Draize 1959

TOOL USED TO ASSESS SCORE: UV light, opthalmoscope, fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test material produced no evidence of positive ocular irritation in any rabbit. A dulling of the normal lustre of the cornea was observed in one rabbit at the one hour reading only. Mild conjunctival inflammation, with or without slight swelling was observed in all three rabbits at this reading. The reactions had ameliorated completely in two rabbits by the 48 hours reading. Mild conjunctival inflammation only was seen in the remaining rabbit until the 48 hour observation.
Interpretation of results:
GHS criteria not met
Conclusions:
The in vivo eye irritation study, conducted according to OECD Test Guideline 405 and in compliance with GLP, found HMDTMP sodium salt (CAS 56744-47-9) to be not irritating to the rabbit eye.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are no skin or eye irritation data for HMDTMP (4-7Na). Therefore, data have been read-across from HMDTMP-xNa (CAS 56744-47-9). See attachment to Section 13 for justification of read-across within HMDTMP Category.

 

The key skin irritation study for HMDTMP-xNa (CAS 56744-47-9), was conducted according to OECD Test Guideline 404 and in compliance with GLP (Safepharm Laboratories, 1982). Following 4-hour single topical application of 0.5 ml undiluted test substance, kept under occlusive dressing onto the skin of 3 rabbits, skin reactions were observed at 1, 24, 48 and 72 hours after test substance removal. The test material produced minimal cutaneous irritation in 1/3 rabbits. There was no evidence of corrosion in any animal. Very slight erythema was observed in one rabbit at the one hour reading only. Two rabbits did not show any observable response to treatment throughout the 72-hour observation period. The study concluded that the test substance was not irritating to rabbit skin.

 

The key eye irritation study for HMDTMP-xNa (CAS 56744-47-9), was conducted according to OECD Test Guideline 405 and in compliance with GLP (Safepharm Laboratories, 1982).

Following single ocular instillation of 0.1 ml undiluted test material into the eyes of 3 rabbits, eye irritation reactions were observed at 1, 24, 48 and 72 hours following exposure. The test material produced no evidence of positive ocular irritation in any rabbit. A dulling of the normal lustre of the cornea was observed in one rabbit at 1-hour reading only. Mild conjunctival inflammation, with or without slight swelling was observed in all three rabbits at this reading. The reactions had ameliorated completely in two rabbits by the 48-hour reading. Mild conjunctival inflammation only was seen in the remaining rabbit until the 48 hour observation. The study concluded the test substance was not irritating to rabbit eyes.

 

The test material used in the key skin and eye irritation studies was an aqueous solution with 25% active acid content. For skin irritation, the applied volume of 0.5 ml is equivalent to an estimate of 0.2 g active acid, 0.2 g active salt. For eye irritation, the applied volume of 0.1 ml is equivalent to an estimate of 0.03 g active acid, 0.04 g active salt.

 

Sodium and potassium salts of HMDTMP may be placed on the market in products where the number of sodium or potassium ions ranges from 1 to 8. The available study data are for a sodium salt where x=6. The pH of aqueous solutions of these salts is dependent on the value of “x”. The irritation/corrosion properties of the solutions are determined by the pH.

Justification for classification or non-classification

Based on the available information, no classification is required for skin or eye irritation of HMDTMP (4-7Na) according to Regulation (EC) No 1272/2008. Reliable studies for skin and eye irritation of the sodium salt demonstrate a low degree of irritation, well below the threshold for classification.