Registration Dossier

Administrative data

Description of key information

A study performed according to OECD 423, tested Phosphorous acid, tri-C12-14-alkyl esters with 6 female SD albino rats. The test item was administered pure by gavage at 2000 mg/kg bw and no mortality was observed, no effects on behaviour and body weights and no effects was seen at macroscopically examinations of necropsy.

Phosphorous acid, tri-C12-14-alkyl esters oral LD50 cutt off was > 5000 mg/kg bw

This value was supported by the LD 50 determined > 5000 mg/kg bw in a 401 study with the triisodecyl phosphite used for read across.

Two other studies were performed with inhalation and dermal routes:

- on rats (nose only) with aerosol (mass median diameter calculated to be 0.48 µm) form during 1 hour, LC50 inhalation  > 12600 mg/m3 (maximum dose tested)

- a test was performed with rabbits, without vehicle and during 1 hour application. LD50 dermal  > 5000mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study following the guideline without any deviation but not performed under GLP
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
not specified
Test type:
acute toxic class method
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: élevage JANVIER, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 188 to 206 g
- Fasting period before study: the day before the treatment
- Housing: 3 animals per polycarbonate cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): 15 volume per hour
- Photoperiod: 12 hrs dark/ 12 hrs light
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: dose applied: 2000 mg/kg bw, corresponding to 2,32 mL/ kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females for the first administration and then 3 other females for confirmation
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observation for clinical signs and weighing at days 0, 2, 7 and 14
- Necropsy of survivors performed: yes
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured during the study
Clinical signs:
no clinical signs detected
Body weight:
weight evolution remained normal during the test and observation period
Gross pathology:
only white thickening of the stomach mucosa was found in 3 female / 6
Other findings:
no other findings
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the test, a oral LD50 cutt off > 5000 mg/kg bw was considered for Phosphorous acid, tri-C12-14-alkyl esters.
Executive summary:

Phosphorous acid, tri-C12-14-alkyl esters was tested in a acute toxicity class method, according to OECD 423 test guideline and without any deviation. The study was considered as reliable but was not performed under GLP conditions and a reliability 2 was then associated.

Six female Sprague Dawley rats were given 2000 mg/kg bw test substance by gavage and no clinical sign nor behaviour comportment were found. No mortality occured even after 14 day observation period.

Phosphorous acid, tri-C12-14-alkyl esters was then considered as not harmful if swallowed and could be not classified for this endpoint, according to the GHS classification criteria.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
quoted Klimlisch 1 in the frame of US HPV dossier in 2001, then quoted 2 for read across approach
Justification for type of information:
see Read-across justification attached.
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Species:
rat
Strain:
Sherman
Sex:
male/female
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
1 h
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 12.6 mg/L air
Based on:
test mat.
Exp. duration:
1 h
Remarks on result:
other: maximum attainable concentration
Mortality:
No animals died during the experiment.
Clinical signs:
other:
Gross pathology:
gross pathological examination revealed no remarkable findings
Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the LC 50 was determined > 12.6 mg/L air.
No death occured during the study and no clinical signs were observed.
Executive summary:

The study method was comparable to OECD 403 guideline. This study was quoted as reliability 1, reliable without restriction by the Phosphite Producers HPV Consortium and Phosphite Manufacturers Consortium in the US HPV dossier submitted in 2001 and EPA accepted their assessment.

Sherman Wistar rats were given Triisodecyl phosphite at the maximum attainable concentration of 12 mg/L by inhalation exposure, during 1 hour, whole body.

No death occured during the study and no clinical signs were observed. The LC 50 was determined > 12.6 mg/L air.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
quoted Klimlisch 1 in the frame of US HPV dossier in 2001, then quoted 2 for read across approach
Justification for type of information:
see Read-across justification attached.
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure) (migrated information)
Species:
rat
Strain:
New Zealand White
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died during the experiment.
Clinical signs:
There were no signs of toxicity, except for substantial skin irritation lasting over several days.
Gross pathology:
Gross pathological examination revealed no remarkable findings.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 was determined > 5000 mg/kg bw in the conditions of this limit test.
Executive summary:

The study method was comparable to OECD 402 guideline (except the use of 3 animals/ sex rather than 5 recommended by the guideline).

This study was quoted as reliability 1, reliable without restriction by the Phosphite Producers HPV Consortium and Phosphite Manufacturers Consortium in the US HPV dossier submitted in 2001 and EPA accepted their assessment.

Triisodecyl phosphite at the concentration of 5000 mg/kg bw was applied to the back of Albino rabbits, during 24 hours and observed for a 21- day period for signs of toxicity or mortality.

No death occured during the study and there were no signs of toxicity, except for substantial skin irritation lasting over several days. Gross pathological examination revealed no remarkable findings.

The LD 50 was determined > 5000 mg/kg bw in the conditions of this limit test.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification

Using data on Phosphorous acid, tri-C12-14-alkyl esters or read across with the analogue triisodecyl phosphite, and because the tested aerosol diameter was < 1µm (then the worst case is consider), Phosphorous acid, tri-C12-14-alkyl esters is considered to be not harmful neither by oral, inhalation nor by dermal route.