Reaction product of a ((2S)-2, 6-diaminohexanoic acid hydrochloride salt, phosphonic acid and methanal) with a 1,2-disubstituted alkane and sodium hydroxide.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study meets generally accepted scientific principles, but was not conducted in compliance with GLP.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1967

Report date:

1967

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Conducted prior to the adoption of OECD test guidelines.

Deviations:

yes

Remarks:

Limited detail on test substance, and methodology.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Details on test material:

Anhydrous ATMP SR 450
Sample number 225
Tested as aqueous solution (25% active acid). It has been confirmed by Solutia (email, J. DiLoreto to P. Fisk, 13/06/03) that doses were corrected for purity.

NB: Test substance described in the study report as Aminotri(methyl phosphonic anhydride). Solutia have confirmed (email, A Aarts to R Wildey, 07/04/2003) that 'anhydrous' is what is meant and not 'anhydride'.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: Males: 230 - 250 g. Females: 210 - 225 g.
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data


IN-LIFE DATES: No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: No data.

Doses:

2000, 2510, 3160 and 3980 mg/kg bw (as a 25 % aqueous solution).

No. of animals per sex per dose:

Two or three depending on dose (five in total/dose).

Control animals:

no

Details on study design:

- Duration of observation period following administration: No data, but at least four days.
- Frequency of observations and weighing: Not stated
- Necropsy of survivors performed: No
- Other examinations performed: clinical signs, and gross pathology.

Statistics:

LD50 calculated by a modification of the method of E.J. de Beer (no further detail, calculation not presented).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 910 mg/kg bw

95% CL:

>= 2 530 - <= 3 345

Mortality:

No deaths at the lowest dose of 2000 mg/kg bw. There were one, two and five deaths in the 2510, 3160 and 3980 mg/kg bw groups, respectively. Survival time was several hours to four days, with most death occurring "overnight" (it is not clear if this means the night after the dosing).

Clinical signs:

Weakness in one to two hours with diarrhoea, salivation and tremors.

Body weight:

Body weights do not appear to have been measured apart from prior to dosing.

Gross pathology:

Inflammation of the gastrointestinal mucosa as well as liver and renal hyperaemia.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a well conducted acute oral study (reliability score 2), conducted using a protocol similar to the now deleted OECD 401, but not to GLP, an LD50 of 2910 mg/kg bw was determined for Dequest 2000 in the rat.

Executive summary:

Dequest 2000 was administered to Sprague-Dawley rats (two or three per sex depending on dose; five total) as aqueous solutions at doses of 2000, 2510, 3160 and 3980 mg/kg bw, by oral gavage. Observations were made for clinical signs and the viscera of the animals that died were examined macroscopically. There were 0, 1, 2 and 5 deaths, respectively. Survival time was several hours to four days with most deaths occurring "overnight". Toxic symptoms included weakness in one to two hours with diarrhoea, salivation and tremors. At macroscopic examination inflammation of the gastrointestinal mucosa as well as renal and liver hyperaemia were observed. The LD₅₀ for the test substance was calculated to be 2910 mg/kg bw.