Methylphosphonic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl phosphonic acid

Cas Number:

993-13-5

IUPAC Name:

Methyl phosphonic acid

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Methyl phosphonic acid (MPA)
- Analytical purity: 80 -84 %
- Impurities (identity and concentrations): methyl ester of MP
- Supplier: Prime Organics, Inc. (Woburn, MA)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Charles River Laboratories, Wilmington, MA
- Age at study initiation: about 7 weeks
- Weight at study initiation: 150 to 225 g
- Fasting period before study: over night
- Housing: individually, steel wire mesh cages
- Diet ad libitum
- Water ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Doses:

2000, 1750, 1500, 1000 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: prior to dosing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 888 mg/kg bw

95% CL:

1 462 - 2 438

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

2 005 mg/kg bw

Effect levels 3

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 760 mg/kg bw

Mortality:

At 2000 mg/kg bw all deaths occurred on day 1 of the study. At 1750 mg/kg bw, one female died on day 3, one male on day 2.
No adverse clinical signs were seen in any other dose groups.

2000 mg/kg bw: 4/5 males, 5/5 females (9/10)
1750 mg/kg bw: 1/5 males, 1/5 females (2/10)
1500 mg/kg bw 0/5 males, 0/5 females (0/10)
1000 mg/kg bw 0/5 males, 0/5 females (0/10)
0 mg/kg bw 0/5 males, 0/5 females (0/10)

Clinical signs:

other: At 2000 mg/kg bw, four males and five females were hypoactive and cold to touch with laboured breathing. In addition, three males and two females were observed with convulsions and one male was observed with tremors and redness around nose/eyes.

Gross pathology:

Upon necropsy, all animals treated with 2000 mg/kg bw had at lease one gross lesion noted, including a dilated stomach, (4 m/ 2 f), a dilated small and large intestine (3 m/ 3 f) kidney foci (1 m/ 1 f) and enlarged stomach (3 f). At 1750 mg/kg bw 4 m and 2 f had no gross lesions, 1 m had dilated stomach and dilated intestine filled with yellow liquid. Two females had pigmented ovaries and 1 f had a dilated thin-walled stomach filled with fluid and mucosa. as well as a tan liver focus. Ovary pigmentation was observed in 2 f that had not died and in the male that died the stomach was dilated and fluid-filled, with a thin wall , mucus covering and black pigment. The small intestine was dilated and filled with yellow fluid and the liver exhibited a tan lateral lobe focus. At 1500 mg/kg, one female had bilateral red ovary pigmentation. At 1000 mg/kg no gross lesions were observed.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 was determined to be 1888 mg/kg bw (females: 1760 mg/kg bw; males: 2005 mg/kg bw).

Executive summary:

The acute oral toxicity of methylphosphonic acid was evaluated in a study conducted according to guideline EPA.OPPTS 870. 1100. For each treatment group 5 males and five females were randomly assigned to treatment and control groups. Animals were administered the test article or vehicle control via oral gavage following an overnight fasting period. The following doses were used: 2000, 1750, 1500, 1000 mg/kg bw. At 2000 mg/kg bw all deaths occurred on day 1 of the study. At 1750 mg/kg bw, one female died on day 3, one male on day 2. No deaths occurred in any other dose groups. Based on the findings of the study, the LD50 was determined to be 1888 mg/kg bw (females: 1760 mg/kg bw; males: 2005 mg/kg bw).