Registration Dossier

Administrative data

Description of key information

Skin Irritation: Two in vivo studies are available for skin irritation. The study conducted by Younger (1961) is considered to be the key study as the methods used are comparable to modern-day guidelines and the results reported are sufficient for classification and labelling.  The study by Bullock (1972) is submitted as a supporting study, primarily because the results are not adequately reported for classification and labelling purposes.
Eye irritation: Two in vivo studies are available for eye irritation and are provided as a weight of evidence to negate the need for further in vivo studies on the grounds that further testing in animals is not scientifically justified and in vitro testing is not considered to be suitable for classification unless the substance is corrosive (Guidance to Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures). Trisodium trimetaphosphate is not considered to be corrosive and therefore further testing has not been conducted.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Remarks:
Study was performed prior to the update of the REACH Regulation and prior to the validation of in vitro test methods.
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
not applicable
Principles of method if other than guideline:
The finely ground powder and a 20.0% aqueous solution were applied to the clipped, intact skin of albino rabbits and removed after twenty-four hours with soap and warm water. The application was covered with plastic strips. Observations were made over a period of several days for irritation.
GLP compliance:
no
Remarks:
study predates GLP
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
The animals were albinos.
There is no further data on animals or conditions.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: the test material was applied as an aqueous solution and neat.
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
The test material was applied neat, the amount was not stipulated.
The test material was also applied as a 20.0% aqueous solution.

VEHICLE
- water
Duration of treatment / exposure:
24 hours
Observation period:
several days
Number of animals:
Six animals were used in Total.
Three animals were applicated with the neat form of the test material and three animals were applicated with the 20.0% aqueous solution.
Details on study design:
TEST SITE
- Area of exposure: no data
- % coverage: no data
- Type of wrap if used: plastic strips covered the test site.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test material was removed with warm water and soap.
- Time after start of exposure: 24 hours

SCORING SYSTEM: The data, scored according to the method of Draize, Woodard and Calvery (J. of Pharm. and Exp. Therapeutics, Volume 82, December, 1944).
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: This result is for the application of the substance in powder form
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: this result is for the application of the substance in powder form
Irritant / corrosive response data:
Applied in powder form: No redness or swelling was noted during or after a 24 h exposure.

Applied as 20.0% aqueous solution: No change in colour was noted after 1, and 4 hours. By 24 h there was barely perceptible erythema with no edema for an average score of 1.0 out of a possible 8. The erythema disappeared in all subjects within 24 h following removal of the application.
Other effects:
no data

Table 1 - Skin irritation in rabbits - sample applied as a finely ground powder

Animal #

Numerical evaluation at the end of

1 h

4 h

24 h

48 h

72 h

1

0

0

0

0

0

2

0

0

0

0

0

3

0

0

0

0

0

Avg.

0.0

0.0

0.0

0.0

0.0

A score of 0 is sufficient to classify the test material as non-irritating in powder form.

Table 2 - Skin irritation in rabbits - sample applied as a 20.0% aqueous solution

Animal #

Numerical evaluation

1 h

4 h

24 h

48 h

72 h

1

0

0

1

0

0

2

0

0

1

0

0

3

0

0

1

0

0

Avg.

0.0

0.0

1.0

0.0

0.0

A score of 1(/8) is sufficient to classify the test material as a slight irritant in liquid form.

Interpretation of results:
GHS criteria not met
Conclusions:
According to the author's system of classification the test material, in liquid form, was considered to be a slight skin irritant based on the results observed at 24 hours. In powder form the test material produced no perceptible effects and was therefore classed as non-irritating.

his study has been selected as the key study in accordance with Regulation (EC) No. 1907/2006 (REACH) because the results are sufficient in order to derive a reliable conclusion on classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). The conclusion on classification and labelling is supported by the data provided in the supporting study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Remarks:
Study was performed prior to the update of the REACH Regulation and prior to the validation of in vitro test methods.
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
No details on methodology included within study report.
GLP compliance:
no
Remarks:
Study pre-dates GLP
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied : 10 mg
Duration of treatment / exposure:
No data
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6 per treatment
Details on study design:
No data
Irritation parameter:
cornea opacity score
Basis:
other: all animals tested
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable, no effects noted
Remarks on result:
other: opacity
Irritation parameter:
iris score
Basis:
other: all animals tested
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable; no effects noted
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
other: all animals tested
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable; no effects noted
Irritation parameter:
chemosis score
Basis:
other: all animals tested
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable, no effects noted
Irritant / corrosive response data:
No effects were observed.
Other effects:
No data

Table 1 : In vivo eye irritation results in rabbits for sodium trimetaphosphate (2 animals)

Animal

Time point (hrs)

Cornea

Iris

Conjunctivae

Score

Opacity

Area

Score

Iris

Score

Erythema

Oedema

Redness

Male

0

0

0

0

0

0

0

0

0

0

24

0

0

0

0

0

0

0

0

0

48

0

0

0

0

0

0

0

0

0

72

0

0

0

0

0

0

0

0

0

Female

0

0

0

0

0

0

0

0

0

0

24

0

0

0

0

0

0

0

0

0

48

0

0

0

0

0

0

0

0

0

72

0

0

0

0

0

0

0

0

0

Table 2 : In vivo eye irritation results (total scores) in rabbits for sodium trimetaphosphate

 

Dose/Response Data

Eye Structure

Number Responding/Mean Score for 6 Rabbits

24 Hours

48 Hours

72 Hours

Cornea

0/0

0/0

0/0

Iris

0/0

0/0

0/0

Conjunctivae

0/0

0/0

0/0

Interpretation of results:
GHS criteria not met
Conclusions:
The paper concludes that the irritant rating of sodium trimetaphosphate in rabbits is a non-irritant.
This study is considered to support a conclusion of no classification under Regulation (EC) No. 1272/2008 (EU CLP), as part of a weight of evidence approach, as the the data clearly shows that at all time points and for relevant parameters no effects were observed.
Endpoint:
eye irritation, other
Remarks:
In vivo. Study was performed prior to the update of the REACH Regulation and prior to the validation of in vitro test methods.
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
no data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Twenty milligrams of finely ground sample were placed in the conjunctival sac of the right eye of each of three albino rabbits and observations were made over a period of several days for inflammation. The eyes were rinsed with warm isotonic saline solution after twenty-four hours.
GLP compliance:
no
Remarks:
study predates GLP
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
The animals were albinos.
There is no further data on the animals or the conditions in which they were kept.
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 20.0 mg

Duration of treatment / exposure:
24 hours
Observation period (in vivo):
several days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were rinsed with warm isotonic saline solution
- Time after start of exposure: 24 h


SCORING SYSTEM: The data, are scored according to the method of Draize, et al.


TOOL USED TO ASSESS SCORE: no data
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 hour
Score:
22
Max. score:
110
Reversibility:
not fully reversible within: 168 hours
Irritant / corrosive response data:
After one hour there was copious lacrimation, slight edema and redness, and mild dullness of the corneal area. Congestion reduced slightly in 24 hours and within 72 hours iris clarity was nearly normal. The eye of one animal was free of inflammation in five days. The mild conjuctivitis still present on the remaining animals disappeared in seven days.
Other effects:
Moderate discomfort was shown immediately following application.

Table 1 - Eye irritation in rabbits after application of sodium trimetaphosphate.

Animal #

Numerical evaluation at the end of

 1 h

 4 h

 24 h

 48 h

 72 h

 120 h

 168 h

1

21

19

15

10

6

 0

 0

2

24 

 24

 19

 14

 8

 4

 0

3

21 

 21

 15

 10

 8

 2

 0

Avg.

22.0 

 21.3

 16.3

 11.3

 7.3

 2.0

 0.0

The compound was classed as a mild eye irritant under the Draize system (Not sufficient for classification under Regulation (EC) No. 1272/2008 (EU CLP).

Interpretation of results:
study cannot be used for classification
Conclusions:
The compound was classed as a mild eye irritant with a maximum irritation score of 22 out of 110 after 1 hour according to the classification scheme used in the study, However this does not indicate the substance would be classifed under Regulation (EC) No. 1272/2008 (EU CLP). The study supports the conclusion that trisodium trimetaphosphate has low overall potential for eye irritation in vivo. In addition, the study itself is not suitable to support a classification as the individual eye scores are not reported.
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 selection of skin irritation / corrosion endpoint:
This study has been selected as the key study in accordance with Regulation (EC) No. 1907/2006 (REACH) because the results are sufficient in order to derive a reliable conclusion on classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). No effects are noted.

Justification for selection of eye irritation endpoint:
No study is selected as a weight of evidence approach in accordance with Annex XI, section 1.2. of Regulation (EC) No. 1907/2006 (REACH) has been used to address the endpoint 'eye irritation' and no effects were noted.

Justification for classification or non-classification

Skin irritation: The data available to assess the skin irritation potential of trisodium trimetaphosphate concludes that the substance is not classified in accordance with Regulation (EC) No. 1272/2008 (EU CLP). It is not considered scientifically justified on ethical grounds to repeat in vivo studies for this endpoint as the data provided is sufficient.

Eye irritation: The data available to assess the eye irritation potential of trisodium trimetaphosphate concludes that the substance is not classified in accordance with Regulation (EC) No. 1272/2008 (EU CLP). It is not considered scientifically justified on ethical grounds to repeat in vivo studies for this endpoint as the data provided is sufficient.

Respiratory irritation: There are no data available (workplace observations or studies) to suggest that trisodium trimetaphosphate is a respiratory irritant.