Phosphoryl trichloride

Endpoint summary

Description of key information

Older studies with phosphoryl trichloride regarding toxicity by the oral, dermal and inhalation routes are available.

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published, non-GLP study summary

Qualifier:

no guideline followed

Principles of method if other than guideline:

No further details are reported.

GLP compliance:

no

Remarks:

: study pre-dates GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Rats weighing 180-200 g were used to determine the lethal dose of phosphoryl trichloride, phosphorus trichloride and phosphorus pentachloride.

Route of administration:

oral: gavage

Vehicle:

vegetable oil

Details on oral exposure:

Phosphoryl trichloride was administered to the 6 animals as a suspension in vegetable oil.

Doses:

Not reported

No. of animals per sex per dose:

6 animals in total; number per dose per sex not stated

Control animals:

no

Details on study design:

Rats weighing 180-200 g were used to determine the lethal dose of phosphoryl trichloride on introduction into the stomach. The substance was administered at each dose to 6 animals in the form of suspensions in vegetable oil. Hodge and Stener (1943) were followed to classify the toxicity of the test substance.

Statistics:

None

Preliminary study:

None

Sex:

not specified

Dose descriptor:

LD50

Effect level:

380 mg/kg bw

95% CL:

304 - 475

Mortality:

Not recorded

Clinical signs:

other: Depression, loss of coordination in movements, apathy, adynamia and sometimes the appearance of an ichorous discharge from the eyes. The respiration was reduced to 50-80 per minute. Twenty to 40 minutes after administration at a dose corresponding to the

Gross pathology:

In the autopsies, the lungs were of a bright red color, the liver was dark brown and it was full of blood. The stomach was swollen and there were heavy blood infusions on the mucous membranes.

Other findings:

None

The acute oral LD50 of phosphoryl trichloride in the rat was found to be 380 (304-475) mg/kg bw under the conditions of this study.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of phosphoryl trichloride was found to be 380 (304-475) mg/kg bw.

Executive summary:

The acute oral LD50 of phosphoryl trichloride in the rat was found to be 380 (304-475) mg/kg bw under the conditions of this study.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

380 mg/kg bw

Quality of whole database:

Several older non-guidelie studies are available. The information given in these studies are sufficient for evaluation.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published study of good quality

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Study design comparable to OECD TG 403

GLP compliance:

no

Remarks:

: study pre-dates GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Exposure concentrations are not detailed

No. of animals per sex per dose:

20 (female)

Control animals:

no

Sex:

female

Dose descriptor:

LC50

Effect level:

0.303 mg/L air (analytical)

Exp. duration:

4 h

Total particulate concentration ranged from 0.06-0.1 mg/L, the median particle diameter was estimated to be 5.0 µm.

During exposure, animals were restless and showed signs of irritation (pawing and scratching of the nose and head). Porphyrin deposition around the eyes was observed. Gasping and convulsions preceded death. All deaths occurred within 48 hours of exposure. Necropsy of decedents revealed dark red lungs. Microscopic investigation showed epithelial desquamation in the trachea and bronchi, resulting in bronchial and bronchiolar obstruction, with oedematous and haemorrhagic changes apparent in the alveoli. No findings were observed in survivors.

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

The acute (4 hour) inhalation LC50 of phosphoryl trichloride was found to be 0.303 mg/L in female rats under the conditions of this study.

Executive summary:

Groups of 20 female rats were exposed (whole body) for 4 hours to atmospheres containing liquid aerosols of the test material at various concentrations. The mean particle size is reported to be 5.0 µm.

During exposure, animals were restless and showed signs of irritation (pawing and scratching of the nose and head). Porphyrin deposition around the eyes was observed. Gasping and convulsions preceded death. All deaths occurred within 48 hours of exposure. Necropsy of decedents revealed dark red lungs. Microscopic investigation showed epithelial desquamation in the trachea and bronchi, resulting in bronchial and bronchiolar obstruction, with oedematous and haemorrhagic changes apparent in the alveoli. No findings were observed in survivors.

The acute (4 hour) inhalation LC50 of phosphoryl trichloride was found to be 0.303 mg/L in female rats under the conditions of this study.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

303 mg/m³ air

Quality of whole database:

Published study of good quality.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Older guideline-comparable study reported in summary form

Qualifier:

equivalent or similar to guideline

Guideline:

other: Class B poison test

GLP compliance:

no

Remarks:

: study pre-dates GLP

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Five rabbits (three male and two female) New Zealand albino rabbits in the weight range of between 1.9 kg and 2.5 kg were used in this experiment.

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

No details specified

Duration of exposure:

24 hour exposure

Doses:

Four dose levels were used in this study: 398, 631, 1000 and 1580 mg/kg bw.

No. of animals per sex per dose:

Three male and two females

Control animals:

no

Details on study design:

One male rabbit was administered with the 398 mg/kg bw dose, one female rabbit received the 631 mg/kg bw dose, one male and one female rabbit received the 1000 mg/kg bw dose and one male rabbit received the 1580 mg/kg bw dose.

Statistics:

No additional information

Preliminary study:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 000 mg/kg bw

Remarks on result:

other: 1/2 deaths at this dose level

Mortality:

No deaths were recorded at dose levels of 398 and 631 mg/kg bw, where as one death (1/2) was recorded at the 1000 mg/kg bw level and one death was recorded at the 1580 mg/kg bw level

Clinical signs:

other: Signs of toxicity were recorded as follows: weight loss (two to three days in survivors), increasing weakness, collapse and death

Gross pathology:

Lung and liver hyperaemia, enlarged gall bladder, kidney discolouration in one instance and gastrointestinal inflammation. After 14 days the viscera of the survivors appeared normal

Other findings:

No additional information

No deaths were recorded at dose levels of 398 and 631 mg/kg bw, where as one death (1/2) was recorded at the 1000 mg/kg bw level by day 4 and one death was recorded at the 1580 mg/kg bw level by day 2 after dosing. Signs of systemic toxicity (weight loss (in survivors), increasing weakness, collapse and death) were observed.

Dose level mg/kg bw	Average initial weight		Mortalities / Dosed			Time of Mortality
	Male	Female	Male	Female	Combined
398	2.5	-	0/1	-	0/1	-
631	-	2.0	-	0/1	0/1	-
1000	2.1	2.0	0/1	1/1	1/2	4 days
1580	1.9	-	1/1	-	1/1	2 days

Conclusions:

Based on the mortality of 1/2 animals at this dose level, the acute dermal LD50 value is estimated to be 1000 mg/kg bw.

Executive summary:

Phosphoryl trichloride was applied (occlusion and duration not specified) to five rabbits (three male and two female) at dose levels of 398 (1), 631 (1), 1000 (2) and 1580 mg/kg bw (1). Deaths occurred at the 1000 mg/kg bw (1/2) by day four after dosing, and 1580 mg/kg bw (1/1) by day 2 after dosing.

Based on the results of this study, the acute dermal LD50 of phosphoryl trichloride is estimated to be 1000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Quality of whole database:

Two older non-guidline studies are available. The information given in these studies are sufficient for evaluation.

Additional information

Acute oral toxicity

LD50 values in the range of 304-475 mg/kg bw (Molodkina, 1973) were reported. In an additional study (Terrell, 1977) the acute oral LD50 of phosphoryl trichloride was found to be 110 mg/kg bw in the rat whereas Birch (1978) reports an acute oral LD50 value of 36 mg/kg bw. The lower value reported in the Birch study may be a consequence of the administration of undiluted test substance, whereas vegetable/corn oil was used as a dosing vehicle in the other studies.

Acute inhalation toxicity

A good quality guideline-comparable published study (Weeks et al, 1964) reports 4-hour analytical LC50 values of 0.303 mg/L for female rats and 0.330 mg/L for male guinea pigs. An additional study (Marhold & Cizek, 1957) reports an estimated LC50 value of 0.20 mg/L.

Acute dermal toxicity

In the acute dermal toxicity study in the rabbit (Imlay, 1977) no deaths occurred at a dose level of 250 mg/kg bw (12 animals tested). However the single animal tested at 500 mg/kg bw died. On the basis of this study, the acute dermal LD50 is calculated to be between 250-500 mg/kg bw. An acute dermal LD50 of 1000 mg/kg bw is calculated based on the death of one of two animals at this dose level in an additional study (Birch, 1978).

Justification for selection of acute toxicity – oral endpoint
The oral LD50 was determined as 36 to 380 mg/kg bw for rats showing a very steep dose/mortality relation in individual studies. Phosphoryl trichloride is hydrolyzed in seconds or minutes in water or moist air forming hydrochloric acid and phosphoric acid.
The acute oral LD50 values of hydrochloric acid were determined to be 238-277 mg/kg bw for female rats and the acute oral LD50 of phosphoric acid was approximately 2000 mg/kg bw in rat. Therefore, on a weight-of-evidence consideration an acute oral LD50 of 380 mg/kg bw seems reasonable.

Justification for selection of acute toxicity – inhalation endpoint
A published study of good quality is used. The LD50 in rats and guinea pigs are close together. The 4h-LC50 of phosphoryl trichloride is 48.4 ppm (303 mg/m³) to 11.1 ppm (71 mg/m³) for rats and 52.5 ppm (335 mg/m³) for guinea pigs.

Justification for selection of acute toxicity – dermal endpoint
Two studies were available. In one study a LD50 > 250 mg/kg bw was found, whereas in the other study a LD50 of ca. 1000 mg/kg bw was calculated. No LD50 data were found for hydrochloric acid. The acute oral LD50 of phosphoric acid was approximately 2000 mg/kg bw in rat . Therefore, on a weight-of-evidence consideration, an acute dermal LD50 of 1000 mg/kg bw seems reasonable.

Justification for classification or non-classification

Phosphoryl trichloride is listed on Annex VI of Regulation (EC) No 1272/2008 with classifications as Acute Tox. 4*, H302: Harmful if swallowed and Acute Tox. 2*, H330: Fatal if inhaled. On a weight of evidence consideration of the available data this classification is justified.

Phosphoryl trichloride is listed on Annex VI of Regulation (EC) No 1272/2008 with classification as Skin corr. 1A, H314: Causes severe skin burns and eye damage and therefore an additional classification for dermal toxicity is not required.

 

Phosphoryl trichloride is hydrolyzed in seconds or minutes in water or moist air. Phosphoryl trichloride reacts with water forming hydrochloric acid and phosphoric acid.