Registration Dossier

Administrative data

Description of key information

The key study for skin irritation which was conducted according to the appropriate OECD test guideline and in compliance with GLP reports the test substance to be a mild irritant (Safepharm 1982). However, according to the current EU regulation (EC 1272/2008) the substance is considered not irritating.

The key study for eye irritation finds the test material not irritating to the rabbit eye in a test carried out according to the appropriate OECD guideline and in compliance with GLP (Safepharm 1982). The HMDTMP test materials 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:
other: The study was conducted according to the appropriate OECD guideline and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals 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:
mean
Time point:
other: 24/48/72h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24/48/72h
Score:
0
Max. score:
4
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 content of the test material is 25%.

Interpretation of results:
GHS criteria not met
Conclusions:
A test report, conducted according to the appropriate OECD test guideline and in compliance with GLP reports the test substance to be a mild irritant. However, according to the current EU regulation (EC 1272/2008) the substance is considered not irritating.
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:
other: The study was conducted according to the appropriate OECD guideline and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
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
Duration of treatment / exposure:
single instillation
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:
mean
Time point:
other: 24/48/72h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24/48/72h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24/48/72h
Score:
0.1
Max. score:
3
Remarks on result:
other: (redness)
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24/48/72h
Score:
0
Max. score:
4
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 test material was found not irritating to the rabbit eye in a test carried out according to the appropriate OECD guideline, compliant with GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key studies were the only available data for skin and eye irritation. They were recent and reliable and therefore deemed suitable as key studies.

The test material 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.


Justification for classification or non-classification

Based on the available information, no classification is requied 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.