Registration Dossier

Administrative data

Description of key information

The results for skin irritation are mixed and range from no/mild irritation to corrosion.

In a skin irritation study (Safepharm Laboratories, 1982) a 50% w/w aqueous solution (0.5 ml, equivalent to 350 mg active acid) of DTPMP-H was applied under occlusive dressing for 4 hours. The test solution contained 12.8% HCl. Very slight oedema and erythema were observed and the overall scores indicated the acid is a mild skin irritant. This was a GLP compliant study, conducted according to OECD guidelines, with minor deviations unlikely to affect the outcome.

This observation is supported by two further tests in which DTPMP-H was applied onto the skin for 24 hours. The studies were conducted prior to introduction of GLP regulations and have less detailed reporting.

In the first study (Younger Laboratories, 1971) a formulation containing 58% active acid (dose equivalent to 412 mg active acid, containing approximately 15% HCl) was also slightly irritating to rabbit skin.

In a subsequent study (Younger Laboratories, 1973) a 50% solution, (dose equivalent to 426 mg active acid, containing approximately 15% HCl) was tested on intact and abraded skin. Mild erythema was seen at 24 h only and the formulation may be considered to be a mild irritant (although the study authors concluded it was non-irritant).

In another study (Monsanto, 1982) DTPMP-H (Dequest 2060s no further details on the formulation) was concluded to be irritating, but not corrosive to rabbit skin.

In a skin irritation/corrosion study (Huntingdon, 1983) with DTPMP-H, a 0.5 ml aliquot of the test substance was applied to abraded and intact skin of two rabbits. A square of gauze was used to keep the test material in contact with the skin. The treatment sites were occluded with 'elastoplast' elastic adhesive dressing backed with 'sleek' plaster for 24 hours. At the end of the treatment period the dressing and gauze pads were removed and the treatment sites wiped to remove any residual test substance. Well-defined to severe reactions, accompanied by necrotic lesions, were observed in both animals for abraded and intact skin. Due to the severity of the reactions only two animals were exposed to the test substance. The study was well documented, met generally accepted scientific principles, acceptable for assessment, but it was not compliant with GLP. The study results suggest classification Cat 1 for corrosivity would be applicable for DTPMP-H. However, the 16% (w/w) HCl content in the test material and the 24-hour application time, which is longer than the 4-hour exposure duration according to OECD Test Guideline 404, it is considered that the irritancy potential of DTPMP-H is overpredicted.

Four eye irritation studies that produced conflicting results have been reported.

In the key eye irritation study (Huntingdon, 1983) which was similar to OECD Test Guideline 405 and pre-GLP, DTPMP-H (Dequest 2060s - no further details on the formulation) caused severe damage to the eye of a single rabbit, which had to be euthanised as a result of the severity of the reaction. Additional animals were not tested due to the severity of the reaction in the tested rabbit.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
27.07.1982 to 03.08.1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hylyne Rabbits Ltd, Marston, Northwich, Cheshire
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.83 - 3.00 kg
- Housing: Individually in suspended metal cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ±4
- Humidity (%): 75-80
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: Within the dates 27.07.1982 to 03.08.1982.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Remarks:
Applied 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: Not specified.
- Type of wrap if used: Occlusive patch was held in place with two lengths of sleek adhesive strapping.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: four hours

SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: up to 72 hours
Score:
0.5
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
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
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
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
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
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
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Very slight erythema was observed in two rabbits at the one hour reading; in one animal this was accompanied by very slight oedema. The reaction had ameliorated in one animal by the 24 hour reading but very slight erythema only persisted in the second rabbit until day 7. One animal did not have any reaction at all.
Other effects:
None

ERYTHEMA AND ESCHAR FORMATION
1 hour      1,0,1 (very slight erythema)
24 hours   0,0,1(very slight erythema)
48 hours   0,0,1(very slight erythema)
72 hours   0,0,1(very slight erythema)

OEDEMA FORMATION
1 hour       0,0,1 (very slight oedema)
24, 48, 72 hours   0,0,0

There was no evidence of corrosion in any animal throughout
the test. 

Group total = 6, PDII = 6/12 = 0.5

Interpretation of results:
GHS criteria not met
Conclusions:
In a skin irritation study conducted to GLP and OECD 404 (reliability score 1) Briquest 543-50A (DTPMP acid) was mildly irritating to the skin of two rabbits and not irritating to the skin of one rabbit. The mild irritation was not sufficient to trigger classification.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
12.01.1983 to 14.01.1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
other: Consumer Product Safety Commission of the USA in the Code of Federal Regulations, Title 16, Section 1500.41.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
other: Abraded and intact
Vehicle:
unchanged (no vehicle)
Controls:
not required
Duration of treatment / exposure:
Approximately 24 hours.
Observation period:
72 hours
Number of animals:
Two
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 hours
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Same scores for intact and abraded skin.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Necrosis. Same scores for intact and abraded skin.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Necrosis. Same score for intact and abraded skin at 24 and 72 hours.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 and 72 hours
Score:
3
Max. score:
4
Reversibility:
other: Not investigated
Remarks on result:
other: Same score for intact and abraded at 24 and 72 hours.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24 hours
Score:
3
Max. score:
4
Reversibility:
other: Not investigated
Remarks on result:
other: Same score for intact and abraded.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 72 hours
Score:
2
Max. score:
4
Reversibility:
other: Not investigated
Remarks on result:
other: Same score for intact and abraded.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.

Well-defined to severe reactions, accompanied by necrotic lesions, were observed in both animals. Due to the severity of the reactions only two animals were exposed to the test substance.

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
In a skin irritation study (reliability score 2), which was comparable to an OECD 404 study, Dequest 2060s was corrosive to the skin of two rabbits. Due to the severity of the reaction, additional animals were not tested.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Principles of method if other than guideline:
No data
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not required
Duration of treatment / exposure:
No data
Observation period:
72 hours
Number of animals:
Three
Remarks on result:
other: the test substance was concluded to be irritating but not corrosive to rabbit skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.

The summary is as follows (no further details included):

"The report creates a slight problem in that two sites per animal were exposed instead of "the test site" referred to in EEC Annex V B4,1.6.3. Analyses of the results can be performed in alternative ways.

1) Each test site analysed separately, whence the test could be regarded as having been carried out on 6 animals.

The scores "per animal" averaged over 1, 24, 48 and 72 hours are:

erythema 1.75, 1.75, 2.0, 1.0, 2.0, 2.0........1.75

oedema 1 , 1 , 1 , 1 , 1 ,1.......1.0

2) The two test sites are averaged for each animal, whence the test is regarded as, having been carried out on 3 animals.

The scores per animal averaged over 1, 24, 48 and 72 hours are:

Erythema: Animal 1, 1.75; Animal 2, 1.5; Animal 3, 2.

Oedema: Animal 1, 1; Animal 2, 1; Animal 3, 1.

Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Conclusions:
The authors of a letter regarding the skin irritation/corrosion of Dequest 2060s (reliability score 4) summarised the findings of a skin irritation study for which the full study report is not currently available, and concluded that Dequest 2060s is irritating, but not corrosive to the skin of rabbits.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Limited detail on test substance, methods and animals/conditions. 24-hour exposure duration under occlusive dressing.
Principles of method if other than guideline:
Method: other: Insufficient detail to fully assess comparability with OECD guideline.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data


IN-LIFE DATES: No data
Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml (although the recommended dose of 0.5 ml was achieved for the formulation, this means that the limit dose for the active acid was not attained. The level of irritation of the anhydrous active acid may therefore be underestimated by this study.However, the presence of HCl in the formulation would be predicted to exacerbate the effect seen).
Duration of treatment / exposure:
24 hour(s)
Observation period:
Seven days (1, 24, 48, 72, 120 and 168 hours)
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: No data
- % coverage: No data but 1X1 inch square patch used
- Type of wrap if used: Occlusive plastic wrap.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No Data
- Time after start of exposure: No data


SCORING SYSTEM: Draize
Irritation parameter:
other: Average maximum score
Basis:
mean
Time point:
other: 24 hours
Score:
1
Max. score:
8
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritant / corrosive response data:
After one hour there were no skin changes, but by 24 hours there was grade 1 erythema (no oedema) in all three animals. This erythema had disappeared by 48 hours.
Other effects:
None

Scored responses were as follows.  
1 hour        0,0,0
24 hours    1,1,1 (barely perceptible erythema; no oedema)
48-168 hours    0,0,0

The average maximum score was 1.0 out of a possible 8.

Interpretation of results:
GHS criteria not met
Conclusions:
In a skin irritation study (reliability score 2) conducted prior to the adoption of OECD test guidelines and GLP, diethylenetriamine penta(methylene phosphonic acid) was mildly irritating to rabbit skin.
Executive summary:

In a skin irritation study (reliability score 2) conducted prior to the adoption of OECD test guidelines and GLP, 0.5 ml undiluted 58% w/w solution of diethylenetriamine penta(methylene phosphonic acid) was applied to the clipped, intact skin of three New Zealand white rabbits for 24 hours. A 1x1 inch square patch was used and covered with an occlusive dressing. Skin reactions were scored at 1, 24, 48, 72, 120 and 168 hours using the Draize scoring system. After one hour there were no skin changes, but by 24 hours there was grade 1 erythema (no oedema) in all three animals. This erythema had disappeared by 48 hours. Therefore the test substance was mildly irritating to the skin of rabbits.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: 4a Only an summary report was available for review.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Conducted prior to the adoption of OECD test guidelines.
Deviations:
yes
Remarks:
Limited detail on test substance, methods and animals/conditions. 24-hour exposure duration under occlusive dressing.
Principles of method if other than guideline:
Method: other: Insufficient detail to fully assess comparability with OECD guideline.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data


IN-LIFE DATES: No data
Type of coverage:
not specified
Preparation of test site:
other: abraded and intact
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml (although the recommended dose of 0.5 ml was achieved for the formulation, this means that the limit dose for the active acid was not attained. The level of irritation of the anhydrous active acid may therefore be underestimated by this study.However, the presence of HCl in the formulation would be predicted to exacerbate the effect seen).
Duration of treatment / exposure:
24 hour(s)
Observation period:
Seven days (4, 24, 48, 72 and 168 hours)
Number of animals:
Six
Details on study design:
TEST SITE
- Area of exposure: No data
- % coverage: No data
- Type of wrap if used: No data


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data
- Time after start of exposure: No data


SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hour
Score:
0.5
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual animal readings were not available.
Irritant / corrosive response data:
Very mild (grade 1) erythema at 24 hours in all six animals for intact and abraded skin. This mild reaction had reversed by 48 hours.
Other effects:
None reported.

Skin reactions were as follows.
Erythema 
Intact:  
4 hours 0,0,0,0,0,0
24 hours 1,1,1,1,1,1
48, 72, 168 hours 0,0,0,0,0,0

Abraded:
4 hours 0,0,0,0,0,1
24 hours 1,1,1,1,1,1
48, 72, 168 hours 0,0,0,0,0,0

Oedema formation
In intact and abraded skin throughout the test  0,0,0,0,0,0.

Interpretation of results:
GHS criteria not met
Conclusions:
In a skin irritation study (reliability score 4), only available as a summary table, and conducted prior to the adoption of the OECD test guidelines, DTPMP-H (Dequest 2060) was only very slightly irritating to rabbit skin.
Executive summary:

In a skin irritation study (reliability score 4), only available as a summary table, and conducted prior to the adoption of the OECD test guidelines, 0.5 ml undiluted DTPMP-H (Dequest 2060) was applied to the intact and abraded skin of six New Zealand white rabbits. The exposure was stated to be 24 hours, but there was no information on the type of dressing used, or whether the application site was washed. Skin reactions were then graded according to the scoring system of Draize at 4, 24, 48, 72 and 168 hours. Very mild (grade 1) erythema was observed at 24 hours in all six animals for intact and abraded skin. This mild reaction had reversed by 48 hours. DTPMP-H was very slightly irritating to rabbit skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
17.01.1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
other: Consumer Product Safety Commission of the USA in the Code of Federal Regulations, Title 16, Section 1500.42.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Buxted rabbit, Buxted, Sussex, England
- Age at study initiation: ca. 14 weeks
- Weight at study initiation: 3.4 kg
- Housing: individually housed in a metal cage with perforated floor
- Diet: Grain Harvester 474 Special rabbit pellets, ad libitum
- Water: tap waterm ad libitum
- Acclimation period: "the rabbit selected for the study were suitably acclimatised to the laboratory environment"

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19
- Humidity (%): 30-70
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:
NA
Observation period (in vivo):
One hour after instillation
Number of animals or in vitro replicates:
One
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no mention of washing

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: One hour
Score:
4
Max. score:
4
Reversibility:
other: Not investigated, animal euthanised after one hour
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: One hour
Score:
1
Max. score:
2
Reversibility:
other: Not investigated
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: One hour
Reversibility:
not reversible
Remarks on result:
other: Necrosis
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: One hour
Score:
3
Max. score:
4
Reversibility:
other: Not investigated
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: not investigated as severe effects seen at 1 hour observation and the animal was euthanised for welfare reasons.
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: not investigated as severe effects seen at 1 hour observation and the animal was euthanised for welfare reasons.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: not investigated as severe effects seen at 1 hour observation and the animal was euthanised for welfare reasons.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: not investigated as severe effects seen at 1 hour observation and the animal was euthanised for welfare reasons.
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: not included as severe effects were seen at 1 hour observation in one animal, which was euthanised for welfare reasons.
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: not included as severe effects were seen at 1 hour observation in one animal, which was euthanised for welfare reasons.
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: not included as severe effects were seen at 1 hour observation in one animal, which was euthanised for welfare reasons.
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: not included as severe effects were seen at 1 hour observation in one animal, which was euthanised for welfare reasons.
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: not included as severe effects were seen at 1 hour observation in one animal, which was euthanised for welfare reasons.
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: not included as severe effects were seen at 1 hour observation in one animal, which was euthanised for welfare reasons.
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: not included as severe effects were seen at 1 hour observation in one animal, which was euthanised for welfare reasons.
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: not included as severe effects were seen at 1 hour observation in one animal, which was euthanised for welfare reasons.

There was almost instantaneous destruction of the corneal epithelium. This was accompanied by corneal opacification, which over portions of the cornea was severe. Distinct iritis was observed. Well-defined conjunctival swelling with the eye about half closed and necrosis of the nictitating membrane and palpebral and bulbar conjunctivae were observed. The animal was killed one hour after instillation due to the severity of the reactions observed.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In an eye irritation study (reliability score 2), which was comparable to OECD 405, Dequest 2060s (DTPMP acid) was immediately corrosive to the eye of a rabbit. Additional rabbits were not tested due to the severity of the reaction.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the key skin irritation study (Safepharm, 1982) a 50% aqueous solution (0.5 ml, equivalent to 350 mg active acid) was applied under occlusion for 4 hours. The test solution contained 12.8% HCl. Very slight oedema and erythema was observed and the overall scores indicated the acid is a mild skin irritant. This was a GLP compliant study, conducted according to OECD guidelines, with minor deviations unlikely to affect the outcome. Although the dose of the active acid was not the limit recommended for this test, the very weak response suggests it is only mildly irritating despite the presence of HCl in the formulation.

This observation is supported by two further tests, although they were conducted prior to introduction of GLP regulations and have less detailed reporting.

In the first study (Younger Laboratories, 1971) a formulation containing 58% active acid (dose equivalent to 412 mg active acid, containing a maximum of 56.8 mg HCl) was also slightly irritating to rabbit skin.

In a subsequent study (Younger Laboratories, 1973) a 50% solution, (dose equivalent to 426 mg active acid, containing 10% HCl) was tested on intact and abraded skin. Mild erythema was seen at 24 h only and the formulation may be considered to be a mild irritant (although the study authors concluded it was non-irritant).

In another study (Monsanto, 1982) DTPMP-H (Dequest 2060s no further details on the formulation) was concluded to be irritating, but not corrosive to rabbit skin.

In a skin irritation/corrosion study (Huntingdon, 1983) with DTPMP-H, a 0.5 ml aliquot of the test substance was applied to abraded and intact skin of two rabbits. A square of gauze was used to keep the test material in contact with the skin. The treatment sites were occluded with 'elastoplast' elastic adhesive dressing backed with 'sleek' plaster for 24 hours. At the end of the treatment period the dressing and gauze pads were removed and the treatment sites wiped to remove any residual test substance. Well-defined to severe reactions, accompanied by necrotic lesions, were observed in both animals for abraded and intact skin. Due to the severity of the reactions only two animals were exposed to the test substance. The study was well documented, met generally accepted scientific principles, acceptable for assessment, but it was not compliant with GLP. The study results suggest classification Cat 1 for corrosivity would be applicable for DTPMP-H. However, the 16% (w/w) HCl content in the test material and the 24-hour application time, which is longer than the 4-hour exposure duration according to OECD Test Guideline 404, it is considered that the irritancy potential of DTPMP-H is overpredicted.

The key eye irritation study (Huntingdon, 1983) in which a single rabbit had 0.1 ml of DTPMP-H instilled into the lower conjunctival sac revealed almost instant destruction of the corneal epithelium, accompanied by corneal opacification (severe in places) and distinct iritis. Well-defined conjunctival swelling with the eye about half closed and necrosis of the nictitating membrane and palpebral and bulbar conjunctivae were observed. The animal was killed one hour after instillation due to the severity of the reactions observed. No additional animals were tested due to the severity of the reaction in the single animal.

In another study (Younger Laboratories, 1973a), which again used an aqueous formulation (0.1 ml, equivalent to 85.2 mg active acid, including HCl; containing 11.4-14.2 mg HCl) in a similar protocol, more severe effects were reported with severe initial pain, corneal cloudiness, reduced response to light, necrosis in the conjunctival sac and slight ulceration of the lower cornea. In the same study rabbits were also observed after application of the test sample for 1 minute followed by rinsing. Again there was an initial severe pain response with conjunctival necrosis, slight oedema, copious discharge and corneal cloudiness.

In a further eye irritation study (Younger Laboratories, 1973b) that was available as a limited summary only, and conducted prior to OECD Test Guideline and GLP, 0.1 ml of undiluted test material was instilled into one eye of each of six New Zealand white rabbits. Immediate, severe discomfort with thrashing about and squealing was observed. Ten minutes after instillation, necrosis of the conjunctival sac, slight oedema, copious discharge, and slight dullness over the cornea were observed. There was no apparent further change after one hour. After 24 hours there were very slight to well defined areas of corneal cloudiness, iris reaction was slow, necrosis in conjunctival sac, slight/moderate oedema and copious discharge containing whitish exudate were noted. There was a slight improvement between 48 and 168 hours. After 14 days slight ulceration in lower cornea was recorded.

In another eye irritation study (Younger Laboratories, 1971) rabbits were treated with 0.1 ml of a 58% solution (equivalent to 82 mg active acid, including HCl; 24 hour contact time) placed in the conjunctival sac. The formulation contained a maximum of 11.4 mg HCl. Treatment resulted in moderate erythema, moderate discharge and slight oedema, with full recovery after 7 days.


Justification for classification or non-classification

Based on the available information, skin irritation Category 2 "H315: Causes skin irritation" and eye damage Category 1 "H318: Causes serious eye damage" are required for DTPMP acid according to Regulation (EC) No 1272/2008.