2,4,6-tri-n-propyl-2,4,6-trioxo-1,3,5,2,4,6-trioxatriphosphorinane

Endpoint summary

Description of key information

oral LD50 > 2000 mg/kg bw

dermal LD50 > 2000 mg/kg bw

Acute inhalation toxicity: Testing for acute toxicity via the inhalation route was not applicable as data on acute oral and acute dermal toxicity were available. According to REACH Regulation No. 1907/2006, Annex VIII, 8.5 data for a maximum of two routes of exposure need to be provided.

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:

1995-07-20 to 1995-08-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: PPA 4/94
- Expiration date of the lot/batch: June 1996
- Purity test date: 1995-03-06

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: darkness, room temperature, in a fume cupboard
- Stability under test conditions: stable
- Solubility and stability of the test substance in the vehicle: stable for 4 h

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the compound was administered as a 50 % solution in DMSO

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF breeding colony
- Age at study initiation: males approx. 7 weeks, females approx. 8 weeks
- Weight at study initiation: 167 +/- 2 g (males) and 163 +/- 3 g (females)
- Fasting period before study: 16 h
- Housing: makrolon cages in fully air conditioned rooms, on soft wood granulate in groups of 5
- Diet: ad libitum ssniff R/M-H (V1534)
- Water: tap water ad libitum, plastic bottles
- Acclimation period: not anecessary as breeded at identical conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3 °C
- Humidity (%): 50 +/- 20 %
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1995-07-20 To: 1995-08-03

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50 %

Doses:

one (limit) dose of 2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Symptoms were recorded twice daily, on weekends and holidays once. The animals were weighed weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, macroscopically visible changes

Statistics:

no statisitical analysis performed as all findings were reversible

Preliminary study:

not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: The following clinical signs were observed: reduced spontaneous activity, hunched posture, drawn in sides, pilo erection, high gait and unregular breathing. In the females additionally reduced palpebral fissure and uncoordinated gait observed. 2 days

Gross pathology:

Effects on organs:
The animals killed at the end of the observation period showed no macroscopically visible changes.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value of the test item was determined to be >2000 mg/kg bw.

Executive summary:

To assess the acute oral toxicity of the test substance, a single (limit) dose of 2000 mg/kg bw was administered as a 50 % solution in DMSO to 5 male and 5 female Wistar rats via gavage. The study was conducted according to OECD Guideline 401 (1987). During the 14 days observation period clinical signs of toxicity and body weight changes were recorded. No deaths occurred during the study. The following clinical signs were observed: reduced spontaneous activity, hunched posture, drawn in sides, piloerection, high gait and unregular breathing. In the females additionally reduced palpebral fissure and uncoordinated gait observed. All effects were reversible within two days. At necropsy, no macroscopical changes were found. Based on the available data, the LD50 value of the test item was determined to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline-conform study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-07-25 to 1995-08-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: PPA 4/94 from September 1994
- Expiration date of the lot/batch: June 1996
- Purity test date: 1995-03-06

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: darkness at room temperature in a fume cupboard
- Stability under test conditions: stable

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF breeding colony
- Age at study initiation: 8-9 weeks
- Weight at study initiation: females: 194+/- 8 g, males: 223+/-6 g
- Housing: macrolon cages in fully air conditioned rooms
- Diet: ssniff' R/M-H (V1534) ad libitum
- Water: tap water ad libitum
- Acclimation period: none, breeding at same conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal skin, shaved and intact skin, about 30 cm2
- Type of wrap if used: aliminum foil and elastic plaster bandage

REMOVAL OF TEST SUBSTANCE
- Washing: with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: symptoms were recorded twice daily, animals were weighed weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: none

Gross pathology:

no macroscopically visible changes

Other findings:

The treated skin area was partly brown-beige discoloured, red, dry, rough, sore, incrusted and scally.
Additionally open wound, pink coloured new skin and scales were observed.

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 value of the test item was determined to be > 2000 mg/kg bw.

Executive summary:

To assess the acute dermal toxicity of the test substance, a single (limit) dose of 2000 mg/kg bw was administered undiluted to the shaved and intact dorsal skin of 5 male and 5 female Wistar rats. The study was conducted according to OECD Guideline 402 (1987). After the 24 h exposure the occlusive wrap was removed and the test sites washed. During the 14 days observation period no clinical signs of toxicity and body weight changes were recorded. No deaths occurred during the study. The following local effects were recorded: The treated skin area was partly brown-beige discoloured, red, dry, rough, sore, incrusted and scally. Additionally open wound, pink coloured new skin and scales were observed. At necropsy, no macroscopical changes were found. Based on the available data, the LD50 value of the test item was determined to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline-conform study

Additional information

To assess the acute oral toxicity of the test substance, a single (limit) dose of 2000 mg/kg bw was administered as a 50 % solution in DMSO to 5 male and 5 female Wistar rats via gavage. The study was conducted according to OECD Guideline 401 (1987). During the 14 days observation period clinical signs of toxicity and body weight changes were recorded. No deaths occurred during the study. The following clinical signs were observed: reduced spontaneous activity, hunched posture, drawn in sides, piloerection, high gait and unregular breathing. In the females additionally reduced palpebral fissure and uncoordinated gait observed. All effects were reversible within two days. At necropsy, no macroscopical changes were found. Based on the available data, the LD50 value of the test item was determined to be > 2000 mg/kg bw.

To assess the acute dermal toxicity of the test substance, a single (limit) dose of 2000 mg/kg bw was administered undiluted to the shaved and intact dorsal skin of 5 male and 5 female Wistar rats. The study was conducted according to OECD Guideline 402 (1987). After the 24 h exposure the occlusive wrap was removed and the test sites washed. During the 14 days observation period no clinical signs of toxicity and body weight changes were recorded. No deaths occurred during the study. The following local effects were recorded: The treated skin area was partly brown-beige discoloured, red, dry, rough, sore, incrusted and scally. Additionally open wound, pink coloured new skin and scales were observed. At necropsy, no macroscopical changes were found. Based on the available data, the LD50 value of the test item was determined to be > 2000 mg/kg bw.

Justification for classification or non-classification

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for acute oral toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.