Registration Dossier

Administrative data

Description of key information

In the key skin irritation study conducted to OECD 404 and to GLP (Safepharm Labs, 1995), tetrasodium HEDP was not irritating to the skin of rabbits. In other studies there was some evidence that some irritation might occur under occlusive conditions (24 hour exposure). On balance it was concluded that tetrasodium HEDP is not significantly irritating to the skin.  

In the key eye irritation study conducted to OECD 405 and to GLP (Safepharm Labs, 1995) tetrasodium HEDP was not irritating to the eyes of rabbits. There were minimal conjunctival effects at the one hour time interval, but these were not sufficient to trigger classification. However, in two other studies, tetrasodium HEDP has been found to be a mild to moderate irritant (disodium salt, CAS 7414-83-7). Since these results have been obtained on formulations, and higher doses of the pure salt could have been tested, the results obtained may underestimate the irritancy of the pure salt.

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:
04.01.1995 and 07.01.1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd.
- Age at study initiation: 12-16 weeks old
- Weight at study initiation: 2.39-2.67 kg
- Housing: Individually in suspended metal cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Five days minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-19 oC
- Humidity (%): 49%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 04.01.1995 and 07.01.1995
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: aqueous solution, administered undiluted.
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
4 hour(s)
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: Back
- % coverage: No data
- Type of wrap if used: patch held in place with a strip of surgical tape, then wrapped in elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was gently swabbed with cotton wool soaked in distilled water.
- Time after start of exposure:

SCORING SYSTEM: Draize.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
0
Max. score:
8
Irritant / corrosive response data:
There were no signs of skin irritation (only minimal erythema after one hour) in any of the animals.
Other effects:
None

ERYTHEMA AND ESCHAR FORMATION
1 hour   1,1,1
24, 48, 72 hours   0,0,0

OEDEMA FORMATION
No scored responses in any animal

Group total = 0, PDII = 0

Interpretation of results:
GHS criteria not met
Conclusions:
In a skin irritation study conducted to OECD 404 and to GLP (reliability score 1), tetrasodium HEDP was not irritating to the skin of rabbits at a concentration of 30%.
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:
11.05.1995 to 15.05.1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd.
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.90 to 3.12 kg
- Housing: Individually in suspended metal cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-19
- Humidity (%): 48-55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 11.05.1995 to 15.05.1995
Vehicle:
other: aqueous solution, administered undiluted.
Controls:
not required
Amount / concentration applied:
Amount applied: 0.1 ml
Duration of treatment / exposure:
NA
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
After consideration of the ocular responses produced in the first animal, two additional animals were tested. These animals received one drop of local anaesthetic to minimise pain.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: standard ophthalmoscope
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Score:
6.7
Reversibility:
fully reversible
Irritant / corrosive response data:
See below
Other effects:
None

CORNEA
No scored effects.  Total score 0.

IRIS
No scored effects.  Total score 0.


CONJUCTIVAL REDNESS
1 hour       1,1,2
24 hours    1,0,1
48, 72 hours   0,0,0
Total score 6.  

CONJUNCTIVAL CHEMOSIS
1 hour   1,1,1
24, 48, 72 hours   0,0,0
Total score 3.

CONJUNCTIVAL DISCHARGE
1 hour   1,1,1
24, 48, 72 hours   0,0,0
Total score 3.

Maximum group mean score = 6.7.

Interpretation of results:
GHS criteria not met
Conclusions:
In an eye irritation study conducted to OECD 405 and to GLP (reliability score 1) sodium salt of HEDP was not irritating to the eyes of rabbits. There wer minimal conjunctival effects at the one hour time interval, but these were not sufficient to trigger classification.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The most reliable studies were selected as the key studies. The available supporting data for eye irritation are not in agreement with the key study, and therefore the classification proposal for eye irritation is based on pH.


Justification for classification or non-classification

The proposal is not to classify tetrasodium HEDP for skin irritation under Regulation (EC) No 1272/2008.

It is proposed that tetrasodium HEDP is classified asEye Irritant Category 2’ ('H319: Causes serious eye irritation') under Regulation (EC) No 1272/2008.