Dimethyl phosphonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (no GLP study, no environmental conditions reported, body weights not recorded, fasting period too short). However, according to OECD SIDS a reliability of 1 was given.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Toxicology and carcinogenesis studies of dimethyl hydrogen phosphite (CAS No. 868-85-9) in F344/N rats and B6C3F1 mice (gavage studies)

Author:

National Toxicology Program (NTP)

Year:

1985

Bibliographic source:

Technical Report Series No. 287, NIH Publication, No. 86-2543, 1 - 179

Reference 2

Reference Type:

secondary source

Title:

Dimethyl phosphonate - CAS No: 868-85-9 - SIDS Initial Assessment Report.

Author:

OECD

Year:

2004

Bibliographic source:

UNEP Publications

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(no GLP study, no environmental conditions reported, body weights not recorded).

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl phosphonate

EC Number:

212-783-8

EC Name:

Dimethyl phosphonate

Cas Number:

868-85-9

Molecular formula:

C2H7O3P

IUPAC Name:

dimethyl phosphonate

Details on test material:

- Name of test material (as cited in study report): dimethyl hydrogen phosphite
- Analytical purity: 96%
- Lot/batch No.: DM113077

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories (Portage, MI, USA)
- Age at study initiation: 6 weeks.
- Fasting period before study: yes. Rats were fasted overnight before dosing.
- Housing: 5 animals per cage. Cage: Polycarbonate (Lab Products, Inc., Garfield, NJ, USA).
- Diet (e.g. ad libitum): Purina Lab Chow meal (St. Louis, MO, USA); available ad libitum (except during fasting period).
- Water (e.g. ad libitum): Acidified with HCl (pH 2.6) tap water; available ad libitum.
- Acclimation period: 2 weeks.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 259.03, 378.85, 556.82, 817.62, 1200.00 mg/mL
- Justification for choice of vehicle: the vehicle was chosen because of the potential of the test substance for chemical hydrolysis in water.
- Amount of vehicle (if gavage): 5.675 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 5.675 mL/kg bw

DOSAGE PREPARATION: Appropriate amounts of dimethyl hydrogen phosphite and corn oil were added by pipette to test tube; mixture was shaken for 1 min; mixtures were resuspended before dosing.

Doses:

1470, 2150, 3160, 4640, 6810 mg/kg bw.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: observed immediately after dosing, 1 h and 4 h later, and 1 X d thereafter for 14 d.
- Necropsy of survivors performed: yes.
- Other examinations performed: clinical signs, necropsy.

Statistics:

The LD50 values as determined by the Spearman-Karber method (Finney, 1978. Statistical Method in Biological Assay, 3rd ed. New York: MacMillan
Publishing Co, pp. 394-401).

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

3 283 mg/kg bw

Based on:

test mat.

95% CL:

2 729 - 3 949

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

3 040 mg/kg bw

Based on:

test mat.

95% CL:

2 527 - 3 656

Mortality:

Number of deaths among male animals at each dose:
- 1470 mg/kg bw: 0/5
- 2150 mg/kg bw: 0/5
- 3160 mg/kg bw : 2/5
- 4640 mg/kg bw : 5/5
- 6810 mg/kg bw : 5/5

Number of deaths among female animals at each dose:
- 1470 mg/kg bw: 0/5
- 2150 mg/kg bw: 0/5
- 3160 mg/kg bw: 3/5
- 4640 mg/kg bw: 5/5
- 6810 mg/kg bw: 5/5

Clinical signs:

other: At dose >= 3160 mg/kg bw the following symtomps were observed: inactivity, weakness, shallow breathing.

Gross pathology:

No data

Other findings:

- Other observations: at a dose >= 3160 mg/kg bw: gas was found in the stomach and/or intestine.

Any other information on results incl. tables

Table 1. Survival of rats in the single-administration gavage studies of dimethyl hydrogen phosphite (a)

	Dose (mg/kg)	Survival (b)
MALE
	1470	5/5
	2150	5/5
	3160	3/5
	4640	0/5
	6810	0/5
FEMALE
	1470	5/5
	2170	5/5
	3160	2/5
	4640	0/5
	6810	0/5

(a) Body weights were not recorded.

(b) Number surviving/number initially in the group; all deaths occurred on day 1.

Based on the study results and according to DSD-DPD and CLP classification criteria, the test substance is not to be classified.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Executive summary:

The oral LD50 of dimethyl phosphonate was determined by acute oral toxicity study conducted with a method similar to OECD guideline 401 with deviations (no GLP study, environmental conditions not reported; body weights not recorded; fasting period too short). The LD50 of dimethyl phosphonate was calculated to be 3040 mg/kg bw in female Fischer 344 rats (95% confidence limits of 2627-3656 mg/kg) and 3283 mg/kg bw in male rats (95% confidence limits of 2729-3949 mg/kg). Clinical signs of toxicity, which have been observed after oral administration of dimethyl phosphonate, were inactivity, weakness, prostration and shallow breathing in rats. Based on the study results, the test substance is not to be classified.