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Administrative data

Description of key information

In the key in vivo skin irritation study with DTPMP (5-7Na), conducted according to OECD Test Guideline 404 and in compliance with GLP, DTPMP (5-7Na) was concluded to be not irritating to the skin of rabbits (SafePharm Laboratories, 1982d, reliability score 1).


 


In the key eye irritation study with DTPMP (5-7Na), conducted according to OECD Test Guideline 405 and in compliance with GLP, DTPMP (5-7Na) was concluded to be not irritating to the eyes of rabbits (SafePharm Laboratories, 1982e, reliability score 1).

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:
27.07.1982 to 30.07.1982
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
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Source: Hylyne Rabbits, Marston, Northwich, Cheshire, UK
Age: 12-16 weeks old
Weight at start of study: 2.83- 3.00 kg
Diet: Rabbit Diet, J. Waring (Feeds) Limited, ad libitum
Water: Tap water, ad libitum
Housing: Animals were individually housed in suspended metal cages
Environment
Temperature: 22±3°C
Air exchanges: Approximately 15 per hour
Photoperiod: 12 hours light: 12 hours dark
Humidity: 76-80%
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Remarks:
aqueous solution, administered undiluted.
Controls:
not required
Amount / concentration applied:
0.5 ml test substance (equivalent to 292 mg active salt) was applied to a 2.5 cm by 2.5 cm area. 
Duration of treatment / exposure:
4 hour(s)
Observation period:
72 hours
Number of animals:
Three
Details on study design:
Skin responses were evaluated 1, 24, 48 and 72 hours after removal of the patch and residual test substance.  Note: Fur removed only 4-16 hours prior to start of test (OECD guideline would require fur removal 24 hours prior to start of test).
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
8
Remarks on result:
other: No signs of irritation observed in any animal.
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:
0
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:
No skin reactions were present in any of the animals at 1hr, 24hr, 48hr and 72hr following removal of the patch.
Other effects:
None
Interpretation of results:
GHS criteria not met
Conclusions:
In the in vivo skin irritation study with DTPMP (5-7Na), conducted according to OECD Test Guideline 404 and in compliance with GLP, DTPMP (5-7Na) was concluded to be not irritating to the skin of rabbits.
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:
24.08.1982 to 27.08.1982
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
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Age at study initiation: Approximately 12-16 weeks old
Weight at study initiation: 2.15-2.34 kg, 
Source: Hylyne Rabbits Ltd., Marston, Northwich, Cheshire, UK.
Diet: Rabbit diet J. Waring (feeds) Ltd, ad libitum
Water: Tap Water, ad libitum
Housing: Individually housed in suspended metal cages
Acclimatisation period: Minimum of 5 days
Environment
Temperature: 19.5 ±2.5°C
Air exchanges: Approximately 15 air changes an hour
Photoperiod: 12 hours light: 12 hours dark
Humidity: 68-70%
Vehicle:
unchanged (no vehicle)
Remarks:
aqueous solution, administered undiluted.
Controls:
not required
Amount / concentration applied:
Amount applied: 0.1 ml
Duration of treatment / exposure:
0.1 ml test substance (equivalent to 58 mg active salt) was instilled into the conjunctival sac of the right eye of each animal.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
Three
Details on study design:
Comment: other: No indication that eye was rinsed.
Responses were evaluated 1, 24, 48 and 72 hours after dosing.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48 and 72
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
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
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
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
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
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
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
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
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
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
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
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
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test substance produced no evidence of an ocular irritation in any rabbit. A dulling of the normal lustre of the cornea was observed in all three rabbits at the one hour reading, accompanied in one rabbit by iritis. A diffuse crimson-red colouration of the conjunctivae accompanied by slight or distinct swelling with partial eversion of the eyelids was observed in two rabbits at this reading. Mild conjunctival inflammation and swelling was observed in the remaining animal. The reactions had reversed in all three animals by the 24 hour reading.
Other effects:
None reported.

CORNEA
No scored effects, but dulling of the cornea was observed in
all 3 animals, 1 hour after dosing.  Total score 0.

IRIS
Score 1 in 1 animal, 1 hour after dosing.  Total score 1.

CONJUCTIVAL REDNESS
Score 2 in 2 animals and score 1 in the third, 1 hour after
dosing.  Total score 5.

CONJUNCTIVAL CHEMOSIS
Score 2 in 1 animal and score 1 in 2 animals, 1 hour after
dosing.  Total score 4.  

From 24 hours after dosing, no abnormal symptoms observed
any animal.  

Group total score = 10.

Interpretation of results:
GHS criteria not met
Conclusions:
In the eye irritation study with DTPMP (5-7Na), conducted according to OECD Test Guideline 405 and in compliance with GLP, DTPMP (5-7Na) was concluded to be not irritating to the eyes of rabbits.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation


In the key in vivo skin irritation study with DTPMP (5-7Na), conducted according to OECD Test Guideline 404 and in compliance with GLP, DTPMP (5-7Na) was concluded to be not irritating to the skin of rabbits (SafePharm Laboratories, 1982d, reliability score 1). In the study, 0.5 ml of undiluted DTPMP (5-7Na) (aqueous solution containing 33 % w/w active acid) were applied onto the skin of 3 rabbits for 4 hours under occlusive dressing. Skin responses were evaluated at 1, 24, 48 and 72 hours after removal of the patch and residual test substance. No skin reactions were present in any of the animals at 1, 24, 48 and 72 hours following removal of the test substance patch.


 


In a supporting in vivo skin irritation study with DTPMP (5-7Na), conducted prior to the adoption of OECD Test Guidelines and pre-dating GLP, 0.5 ml undiluted DTPMP (5-7Na) (aqueous solution containing 43% w/w active salt including minor components, 57% water; active acid content not specified) were applied to the intact and abraded skin of six New Zealand white rabbits (duration not given). Following exposure, skin reactions were assessed (scoring system not given) at 24 and 72 hours. Grade 1 erythema was observed in 1/6 rabbits with intact skin at 24 hours after the end of exposure, which was fully reversible by 72 hours. Grade 1 erythema was observed in 4/6 rabbits with abraded skin at 24 hours after the end of exposure, which was still visible in only one animal by 72 hours. There was no oedema in any of the animals. DTPMP (5-7Na) was therefore concluded to be only mildly irritating to the skin of rabbits but not sufficient for classification (Monsanto, 1979, reliability score 2).


In a supporting in vivo skin irritation study with DTPMP (5-7Na), conducted prior to the adoption of OECD Test Guidelines and pre-dating GLP, 0.5 ml aqueous solution of DTPMP (5-7Na) (aqueous solution containing 33% w/w active salt; active acid content was not specified) was applied onto the skin of six New Zealand white rabbits. The back of each animal was clipped free of hair (Hazleton Laboratories, 1979, reliability score 2). One side of the clipped area was left intact, and the other side was abraded. The test substance was applied under a gauze patch to each of the abraded and intact sites, and an occlusive dressing was wrapped around the trunk of the animals. After 24 hours the dressings were removed and any skin reactions scored according to the Draize system. The evaluation was repeated 48 hours later (72 hours after the start of exposure). Very slight erythema was noted in 4/6 abraded and 3/6 intact sites at the 24-hour observation point. Three abraded sites also showed very slight oedema at 24 hours. All treated skin sites appeared normal at 72 hours. The combined primary irritation index for abraded and intact skin was 0.4. Therefore the test substance was concluded to be mildly irritating to rabbit skin but not sufficient for classification.


Eye irritation


In the key in vivo eye irritation study with DTPMP (5-7Na), conducted according to OECD Test Guideline 405 and in compliance with GLP, DTPMP (5-7Na) was concluded to be not irritating to the eyes of rabbits (SafePharm Laboratories, 1982e, reliability score 1). In the study, 0.1 ml of undiluted DTPMP (5-7Na) (aqueous solution containing 33 % w/w active acid) were instilled into the eyes of 3 rabbits. Eye irritation responses were evaluated 1, 24, 48 and 72 hours after dosing. The test substance produced no evidence of an ocular irritation in any rabbit. A dulling of the normal lustre of the cornea was observed in all three rabbits at the 1-hour reading, accompanied in one rabbit by iritis. A diffuse crimson-red colouration of the conjunctivae accompanied by slight or distinct swelling with partial eversion of the eyelids was observed in two rabbits at this reading. Mild conjunctival inflammation and swelling was observed in the remaining animal. The reactions had reversed in all three animals by the 24-hour reading.


In a supporting in vivo eye irritation study with DTPMP (5-7Na), conducted prior to the adoption of OECD Test Guidelines and pre-dating GLP, 0.1 ml of undiluted DTPMP (5-7Na) (aqueous solution composed of 43% w/w active salt including minor components, 57% water; active acid content not specified) was instilled into the eyes of six New Zealand white rabbits. Signs of irritation were graded at 24, 48 and 72 hours after instillation. There was no irritation in 2/6 animals. 4/6 animals had grade 5 corneal effects at 24 hours, 3/6 at 48 hours and none by 72 hours. Conjunctival effects were recorded for 2/6 animals at 24 hours, no animals at 48 hours, and 1/6 animals at 72 hours. No effects on the iris were observed. The overall irritation score was 2.3/110, and therefore DTPMP (5-7Na) was concluded to be mildly irritating to rabbit eyes but not sufficient for classification (Monsanto, 1979, reliability score 2).


 


In a supporting in vivo eye irritation study (Hazleton Laboratories, 1979, reliability score 2) with DTPMP (5-7Na), conducted prior to the adoption of OECD Test Guidelines and pre-dating GLP, 0.1 ml DTPMP (5-7Na) (aqueous solution containing 33% w/w active salt; active acid content was not specified) were instilled into the conjunctival sac of the left eye of 6 rabbits. The lids were then held together for one second. The right eye of each animal served as a control. The eyes were examined for signs of irritation at 1, 2, 3, 4 and 7 days after treatment. The irritation was scored using the scale of Draize. All animals had grade 1 conjunctival redness and grade 1 chemosis after 24 hours, but this had reversed by the second day. No other signs of irritation were recorded. Therefore the test substance was concluded to be mildly irritating to rabbit eyes but not sufficient for classification.

Justification for classification or non-classification

Based on the available data, DTPMP (5-7Na) does not require classification for skin or eye irritation according to Regulation (EC) No 1272/2008.


The Registration substance is a solid typically manufactured as an aqueous solution containing around 50% w/w water. Therefore, the only data available are for aqueous solution of DTPMP (5-7Na).