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Description of key information

The irritant/corrosive potential of the test substance TCPP was studied on the skin of the rabbit in accordance with the OECD Guideline No. 404 for testing of Chemicals (Martins, Bayer AG, 1991; IRI, 1989c).  The results of this experiment indicate that the test substance is not irritating to the skin.


 


The irritant/corrosive potential of the test substance TCPP was studied on the eye of the rabbit in accordance with the OECD Guideline No. 405 for testing of Chemicals (Martins, Bayer AG, 1991).  The results of this experiment indicate that the test substance is not irritating to the eye.


 


Hazards identified by EU Assessment in May 2008:
"There is an extensive database in animals, indicating that TCPP is non-irritant in the rabbit eye and skin. The lack of any substantial skin or eye irritation and the lack of irritation observed in the acute inhalation studies suggest that TCPP would be unlikely to produce significant respiratory tract irritation."
Additional information:
TCPP was tested on 8 volunteers. 50 µl on a cotton pad was fixed on the arm by a tape. During the 7 days observation time the treated skin of the 8 volunteers remained unmodified. The substance was not irritating (Kimmerle G., 1973).

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:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed to GLP. Endpoint study record transfered from EU Risk Assessment Report 2008.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
Tolgard TMCP
received 30 November 1988
colourless liquid
stored in the dark under ambient conditions
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Cheshire Rabbit Farms Ltd, Tarporley
- Age at study initiation: not given
- Weight at study initiation: not given
- Housing:individually in aluminium cages
- Diet (e.g. ad libitum): Rabbit Diet ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: minimum of 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-20C
- Humidity (%): 49%
- Air changes (per hr): not given
- Photoperiod (hrs dark / hrs light):12h light/ dark cycle


IN-LIFE DATES: From: 18 Jnauary 1989 To: 22 January 1989
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 ml of test material was applied to the intact, clipped skin of three rabbits under a 2.5 cm x 2.5 cm patch of gauze.
Duration of treatment / exposure:
At the end of the 4 hour exposure period the patches were removed, the test sites were wiped carefully with water-moistened tissues.
Observation period:
The skin reactions were assessed 1, 24, 48 and 72 hours after patch removal using the OECD recommended scoring system.
Number of animals:
3
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritant / corrosive response data:
Oedema formation was not recorded in any of the animals. Well-defined erythema was recorded at two treated sites, with very slight erythema at one site 1 hour after patch removal. By 24 hours, all treated sites showed very slight erythema and all sites were normal 48 hours after patch removal. TCPP produced mild transient skin irritation, which was fully reversible by 48 hrs.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
IUCLID4 Test substance: other TS

TS-Freetext:
Tris chloroisopropyl phosphate purity 97.85% including all
isomers as per 1.1 - 1.4.

- Name of test material (as cited in study report): Tris-chlorisopropylphosphat
- Molecular formula (if other than submission substance): C9H18Cl3O4P
- Molecular weight (if other than submission substance): 327.6
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state: colourless clear liquid
- Analytical purity: 97.85%
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.: 002871/1989 of 13.12.1989 production process sample
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions: guarenteed for test period
- Storage condition of test material: room temperature in dark
- Other: pH 3.7
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Interfauna UK Ltd, Huntingdon
- Age at study initiation: not given
- Weight at study initiation: 3.4-3.5 kg
- Housing:individually in stainless steel or plastic cages
- Diet (e.g. ad libitum): Standard diet Ssniff K 4 100-120 g/day
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period:at least 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-3C
- Humidity (%): apprx 50%
- Air changes (per hr): 10 per hour
- Photoperiod (hrs dark / hrs light):12 hours light/dark cycle


IN-LIFE DATES: From:8-January-1991 To:15 January 1991
Type of coverage:
semiocclusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
other: treated animals served also as control
Amount / concentration applied:
A volume of 0.5 ml of the test material was applied via a patch to the shaved skin (6cm2) of each of three rabbits. A further patch, moistened with water was also applied on the opposite shaved dorso-lateral area of the trunk.
Duration of treatment / exposure:
After an exposure period of 4 hours, patches and dressing were removed and the treated sites were carefully washed with water.
Observation period:
Dermal irritation was scored (following the OECD recommended scoring system) and recorded at termination of exposure as well as 1 hr, 24 hrs, 48 hrs, 72 hrs, 7 days and 14 days after exposure.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- % coverage:
- Type of wrap if used: Hansamed patch held in place with Fixonmull semiocclusive dressing Beiersdorf


REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with water
- Time after start of exposure: 4 hrs


SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
The test substance did not cause oedema formation in any of the animals (primary irritation score 0). Well-defined erythema (score 2) was evident at the test site of two rabbits 1 hour after termination of exposure but by 24 hrs only slight erythema was evident (score 1) and all evidence of erythema formation had disappeared by 48 hrs. In the other rabbit, slight erythema was observed at 1 hr but had disappeared by 24 hrs. The mean skin irritation index for each of the two most sensitive rabbits was 0.3. TCPP therefore does not have a local irritant potential in the rabbit skin.
Other effects:
no data

Test for irritant effect on the skin (expos.: 4hrs)

 Animal No.:  Body weight  Draize grade after                                 Irritat.Index    
     1h     24h     48h     72h     7d     14d        
     e  e  o  e  o  e  o  e  e  o  e
 M20  3,4 kg (female)  2  0  1  0  0  0  0  0  0  0  -  -  0,3*  0,0
 M25  3,4 kg (female)  1  0  0  0  0  0  0  0  0  0  -  -  0,0  0,0
 M8  3,5 kg (female)  2  0  1  0  0  0  0  0  0  -  -  0,3*  0,0

e = erythema and eschar formation

o = oedema formation

- = not examined

* 0,3 = no irritation (irritation index 0,0 to 0,99)

Executive summary:

The irritant/corrosive potential of the test substance TCPP was studied on the skin of the rabbit in accordance with the OECD Guideline No. 404 for testing of Chemicals.

The results of this experiment indicate that the test substance is not irritating to the skin.

The substance does not have a significant local irritating potential to the 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:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
IUCLID4 Test substance: other TS

TS-Freetext:
Tris chloroisopropyl phosphate purity 97.85% including all
isomers as per 1.1 - 1.4.

- Name of test material (as cited in study report): Tris-chlorisopropylphosphat
- Molecular formula (if other than submission substance): C9H18Cl3O4P
- Molecular weight (if other than submission substance): 327.6
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state: colourless clear liquid
- Analytical purity: 97.85%
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.: 002871/1989 of 13.12.1989 production process sample
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions: guarenteed for test period
- Storage condition of test material: room temperature in dark
- Other: pH 3.7
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Interfauna UK Ltd, Huntingdon
- Age at study initiation: not given
- Weight at study initiation: 3.6-3.7 kg
- Housing:individually in stainless steel or plastic cages
- Diet (e.g. ad libitum): Standard diet Ssniff K 4 100-120 g/day
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period:at least 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-3C
- Humidity (%): apprx 50%
- Air changes (per hr): 10 per hour
- Photoperiod (hrs dark / hrs light):12 hours light/dark cycle


IN-LIFE DATES: From:8-January-1991 To:15 January 1991
Vehicle:
unchanged (no vehicle)
Controls:
other: treated animals served also as control (one eye TCPP, the other remained untreated and served as control)
Amount / concentration applied:
100 µl TCPP in one eye.
Duration of treatment / exposure:
24 h
Observation period (in vivo):
7 d
Number of animals or in vitro replicates:
3 females
Details on study design:
A volume of 0.1 ml of the test material was instilled into the conjunctival sac of one eye of each of three rabbits. The other eye remained untreated and served as control. The treated eyes were rinsed with saline 24 hours post-treatment.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
L14 Female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
L25 Female
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
M5 Female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
L14 Female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
L25 Female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
M5 Female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
14 Female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
L25 Female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
M5 Female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
L14 Female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
L25 Female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
M5 Female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
There were no signs of irritation in any of the treated eyes at any of the observation times of 24, 48 and 72 hours. One animal had evidence of aqueous humour discharge at 48 hours, but this did not persist.

Test for irritant effect on the eye (expos.24hrs):

 Animal No.+Body weight  Tissue  Signs  Draize grades                    
M5, female (3,7 kg)    1h  24h  48h  72h  7d  14d  21d   Irritation index
  cornea  o  0 0,0 
     a  0  0  0  
   fluorescein  0  -  -  
   a  0  -  -  -  
   iris    0  0  0  - 0,0 
conjunctivae  r  0 0,0 
     0  0  - 0,0 
  aqueous humour    0  0  
  discharge    1  0 0  0  
L25, female(3,6 kg)   cornea  o  0  0  - 0,0 
   0  0  
  fluorescein   i  -  -  
     a  -  0  -  
  iris    0,0 
   conjunctivae  r 0,0 
     0  - 0,0 
   aqueous humour    0  0  0  -  -  
  discharge     0  0  
       1  0  
 L14, female(3,7 kg)  cornea  o  0 0,0 
     a 0  0  0  
  fluorescein   i  -  -  
     a  -  -  
  iris     0  0 0,0 
  conjunctivae   - 0,0 
     0 0,0 
  aqueous humour     -  
   discharge    1  0  0  0  0  -  -  

o = opacity

a = area

i = intensity

r = redness

s = swelling

- = not examined

Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not considered irritating to the eye.
Executive summary:

The irritant/corrosive potential of the test substance TCPP was studied on the eye of the rabbit in accordance with the OECD Guideline No. 405 for testing of Chemicals.

The results of this experiment indicate that the test substance is not irritating to the eye.

The substance does not have a significant local irritating potential to the eye.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Justification for classification or non-classification

EU Risk Assessment of 2008: "Based on the available studies, TCPP needs no classification for irritation according to EU guidelines."

Update March 2018: The conclusion of non-classification for irritation is confirmed and compliant with EU Regulation 1272/2008.