Dimethyl propylphosphonate

Endpoint summary

Description of key information

Valid studies for acute oral toxicity according OECD 401 and acute inhalation toxicity according OECD 403 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:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Five male and five female Wistar rats (176-188 g) received a single dose of 2000 mg/kg bw of dimethyl propylphophonate per gavage. The animals were observed for mortality, body weights and clinical signs through day 14. A gross necropsy was performed on animals sacrificed at the end of the 14 days observation period.

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female animals/dose

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

A dose of 2000 mg/kg bw caused a staggared gait, sedation, paresis of the hind limbs, ruffle fur, chromodacryorrhoe, haggard flanks, and crouch position.

Body weight gain was not influenced by male rats. The surviving female rats revealed a weight loss during the first observation week and one animal of both weeks.

One female rat died 3 days after the application of 2000 mg/kg bw of dimethyl propylphosphonate. The bladder was filled with blood and the intestines were filled with faces of hard consiscence.

One female rat killed after 14 days revealed a reddened intestine mucosa. All other animals were without finding at the gross necropsy.

Executive summary:

Five male and five female Wistar rats (176-188 g) received a single dose of 2000 mg/kg bw of dimethyl propylphosphonate

per gavage. The animals were observed for mortality, body weights and clinical signs through day 14. A gross necropsy was performed on animals sacrificed at the end of the 14 days observation period.

A dose of 2000 mg/kg bw caused a staggared gait, sedation, paresis of the hind limbs, ruffle fur, chromodacryorrhoe, haggard flanks, and crouch position. One female rat died 3 days after the application of 2000 mg/kg bw of dimethyl propylphosphonate.

The LD50 is > 2000 mg/kg bw (male and female rats) and was not exactly determined.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 001 mg/kg bw

Quality of whole database:

The materials/methods and results are described in detail und 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:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

One group of 3 male and 3 female Wistar rats was nose-only exposed to dimethyl propylphosphonate (DMPP) at an actual aerosol concentration of 5788 mg/m³ for 4 hours. The aerosol was generated neat without any vehicle. The animals were observed for mortality, weight and clinical signs through day 14. A gross necropsy was performed.

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5788 mg/m³

No. of animals per sex per dose:

control group: 5 male and 5 female rats
test group: 3 male and 3 female rats

Control animals:

yes

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 788 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

The maximum tested concentration was tolerated without mortality.

The following clinical signs were observed: bradypnea, labored breathing patterns, piloerection, motility reduced, atony, high-legged gait; lurching, hypothermia, decreased reflexes, and transient decrease in body weights. The lead pathodiagnostic effects were

suggestive of mild and rapidly reversible portal of entry-related effects (irregular and labored breathing patterns which were observed up to the first postexposure day).

Gross necropsy was unobtrusive.

The respirability of the aerosol was adequate to achieve the objective of study, i.e. the average mass median aerodynamic diameter (MMAD) was 4.6 µm, the average geometric standard deviation (GSD) was 1.8. Measures were made to maximize the respirability of aerosol; however, at the expense of the actual concentration. Due to the marginal evidence of mild upper respiratory tract irritation, further exposure at lower but more respirable aerosol does not seem to be justified scientifically nor on animal welfare reasons.

In summary, the aerosolized test substance (liquid aerosol) proved to have a low acute inhalation toxicity in rats.

Executive summary:

One group of 3 male and 3 female wistar rats was nose-only exposed to dimethyl propylphosphonate (DMPP) at an actual aerosol concentration of 5788 mg/m³ for 4 hours. The aerosol was generated neat without any vehicle. The animals were observed for mortality, weight and clinical signs through day 14. A gross necropsy was performed.

The maximum tested concentration was tolerated without mortality.

The following clinical signs were observed: bradypnea, labored breathing patterns, piloerection, motility reduced, atony, high-legged gait; lurching, hypothermia, decreased reflexes, and transient decrease in body weights. The lead pathodiagnostic effects were

suggestive of mild and rapidly reversible portal of entry-related effects (irregular and labored breathing patterns which were observed up to the first postexposure day). Gross necropsy was unobtrusive.

The acute LC50 (aerosol) of dimethyl propylphosphonate is > 5788 mg/m³ in male and female rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 788 mg/m³ air

Quality of whole database:

The materials/methods and results are described in detail und are sufficient for evaluation

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the acute oral toxicity study a dose of 2000 mg/kg bw caused a staggered gait, sedation, paresis of the hind limbs, ruffle fur, chromodacryorrhoe, haggard flanks, and crouch position. One female rat died 3 days after the application of 2000 mg/kg bw of the test substance. The LD50 is > 2000 mg/kg bw (male and female rats) and was not exactly determined.

In the acute inhalation toxicity study male and female Wistar rats were nose-only exposed to dimethyl propylphosphonate (DMPP) at an actual concentration of 5788 mg/m³ for 4 hours. The maximum tested concentration (5788 mg/m³) was tolerated without mortality.

The following clinical signs were observed: bradypnea, labored breathing patterns, piloerection, motility reduced, atony, high-legged gait; lurching, hypothermia, decreased reflexes, and transient decrease in body weights. The lead pathodiagnostic effects were suggestive of mild and rapidly reversible portal of entry-related effects (irregular and labored breathing patterns which were observed up to the first postexposure day). Gross necropsy was unobtrusive.

The acute LC50 (aerosol) of dimethyl propylphosphonate is > 5788 mg/m³ in male and female rats.

Justification for selection of acute toxicity – oral endpoint
only available study

Justification for selection of acute toxicity – inhalation endpoint
only available study

Justification for classification or non-classification

Due to the results of the acute oral toxicity study (LD50 > 2000 mg/kg bw) and the acute inhalation toxicity study (LC50 > 5788 mg/m³) a classification is not justified.