Tetrakis(hydroxymethyl)phosphonium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

end 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to recognized guidelines, with acceptable restrictions. GLP not stated.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no necropsies were performed

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetrakis(hydroxymethyl)phosphonium chloride

EC Number:

204-707-7

EC Name:

Tetrakis(hydroxymethyl)phosphonium chloride

Cas Number:

124-64-1

Molecular formula:

C4H12O4P.Cl

IUPAC Name:

tetrakis(hydroxymethyl)phosphonium chloride

Details on test material:

- Name of test material (as cited in study report): Tetrakis(hydroxymethyl)phosphonium chloride (THPC) from Aceto Chemical Company (Flushing, New York)
- Analytical purity: 75 % (determined by iodate-thiosulfate titration, elemental analysi, and thin -layer chromatographic analyses)
- Storage condition of test material: 23°C
- Lot/batch No.: ON2
No other data

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)
- Age at study initiation: 7 week-old
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: five per cage (Polycarbonate (Lab Products, Inc., Rochelle Park, NJ). Bedding: Absorb-Dri (Lab Products, Inc. Garfield, NJ)
- Diet: Purina 5001 Lab Chow, pelleted (Ralston Purina, St. Louis, MO); available ad libitum
- Water: Freely available; automatic watering system (Edstrom Industries, Waterford, W)
- Acclimation period: 17 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 40-60
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs fluorescent light


IN-LIFE DATES: From: 30 october 1978 To: 13 november 1978

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: deionized water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg

Doses:

75, 150, 300, 600 or 1,200 mg/kg

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 2 x day
- Necropsy of survivors performed: no
- Other examinations performed: no

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

185 mg/kg bw

Based on:

act. ingr.

95% CL:

141 - 242

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

161 mg/kg bw

Based on:

act. ingr.

95% CL:

115 - 224

Mortality:

All male and female rats that received 600 or 1200 mg/kg THPC and all males that received 300 mg/kg THPC were dead by day 2.
At 150 mg/kg, 1/5 (male) and 2/5 (female) died.

Clinical signs:

other: Surviving rats of each sex that received 150 mg/kg had reddish fluid around the nostrils by day 3 and labored breathing.

Gross pathology:

Necropsies were not performed.

Any other information on results incl. tables

Table 1: Number of animals dead and time range within which mortality occurred

	Mortality (# dead/ total)
Dose mg/kg bw	male	female	combined	Time range of deaths (days)
75	0/5	0/5	0/10	-
150	1/5	2/5	3/10	(1 -4)
300	5/5	5/5	10/10	(2 -13)
600	5/5	5/5	10/10	2
1200	5/5	5/5	10/10	2

All male and female rats that received 600 or 1,200 mg/kg THPC and all males that received 300 mg/kg THPC were dead by day 2. Surviving rats of each sex that received 150 mg/kg had reddish fluid around the nostrils by day 3 and labored breathing. Final weights were not recorded. Necropsies were not performed.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of this test, THPC is classified as Acute toxicity Category 3 according to regulation (EC) 1272/2008.

Executive summary:

In a single-administration studies (NTP, 1987), groups of five F344/N rats of each sex were administered a single dose of 75, 150, 300, 600 or 1200 mg/kg THPC in deionized water by gavage. Animals were observed for 14 days. All male and female rats that received 600 or 1200 mg/kg THPC and all males that received 300 mg/kg THPC were dead by day 2. At 150 mg/kg bw, one male and two females died. Surviving rats of each sex that received 150 mg/kg had reddish fluid around the nostrils by day 3 and labored breathing. Final weights were not recorded. Necropsies were not performed.

Oral LD50 females is 161 mg/kg bw (115 -224) and oral LD50 males is 185 mg/kg (141 -242).

THPC is classified toxic by ingestion according to EU criteria and Acute toxicity Category 3 according to regulation (EC) 1272/2008, based on the male and female LD50.

This acute oral study is classified as acceptable and satisfies the guideline requirement for an acute oral study in the rats.