Reaction mass of Octadec-9-en-1-yl ammonium di-n-hexyl phosphorodithioate and Octadec-9-en-1-yl ammonium mono- and di-butylphosphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between February 5, 1985, and April 16, 1985.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Octadec-9-en-1-yl ammonium mono and di-butylphosphate

Molecular formula:

C22H48NO4P - C26H56NO4P

IUPAC Name:

Octadec-9-en-1-yl ammonium mono and di-butylphosphate

Constituent 2

Reference substance name:

Octadec-9-en-1-yl ammonium di-n-hexyl phosphorodithioate

Molecular formula:

C30H64NO2PS2

IUPAC Name:

Octadec-9-en-1-yl ammonium di-n-hexyl phosphorodithioate

Test material form:

liquid: viscous

Details on test material:

Material is a yellow viscous liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Y oung adult male and female Sprague-DawleyR Crl :coR ( SD) BR rats, supplied by Charles River Breeding Laboratories, Inc. , Wilmington, Massachusetts, were used in this study. Animals dosed in the 5. 0 g/kg screen were received on January 15, 1985, and allowed a conditioning
period of 21 days prior to dosing in our laboratory. Animals used in the LD50 determination arrived January 29, 1985, and were allowed a 42-day conditioning period prior to dosing. An additional dose level was tested in males which were allowed a 56-day conditioning period after arrival on February 5, 1985.

The males were 71 days of age and weighed 299-335 grams, and the females were 78 days of age and weighed 198-223 grams at the time of
dosing the oral screen. The males were 92 days of age and weighed 364-469 grams, and the females were 99 days of age and weighed 197-
257 grams at the time of dosing the LD50. Males in the additional LD5O dose group were 79 days of age and weighed 357-397 grams at the
time of dosing.

The animals were housed individually in wire-bottom cages in an airconditioned room. The temperature ranged from 20.2-24.0°c and the
relative humidity from 31.3-75 .7% during the study. The photoperiod consisted of a 12-hour light/dark cycle: lights on at 0630 and off at 1830. The animals had free access to Purina Laboratory Rodent ChowR 15001 and water except during the overnight period prior to dosing when only water was available.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test material was delivered neat; no special preparation was required.

Doses:

1.0, 1.7, 2.9, 3.6 and 5.0 g/kg

(1000, 1700, 2900, 3600 and 5000 mg/kg)

No. of animals per sex per dose:

5 males, 5 females per dose group

Control animals:

yes

Details on study design:

The animals were dosed approximately three to five hours after the onset of the light cycle. They were observed frequently for any physiological or behavioral abnormalities on the day of dosing and at least once each weekday morning and late afternoon for 13 days after treatment; on weekends, the animals were observed once daily. On Day 14, the animals were observed once prior to sacrifice.

Body Weights
The animals were weighed immediately prior to dosing and at 2, 7, and 14 days after treatment with the exception of males dosed on March 12, 1985, which were weighed on Day 3 rather than Day 2.

Statistics:

The LD50, slope, and 95% confidence limits were determined using the method of Berkson ( 1).

The mean body weights of the treated groups with three or more survivors were compared to those of the respective controls using one-way analysis of variance followed when significant by the least significance difference test (2).

(1) Berkson, J. Tables for use in estimating the normal distribution function by normit analysis. Biometrika, 44: 411-435, 1957.

(2) Sokal, R. R., and Rohlf, F. J. Biometry. Company, San Francisco, pp. 175-252, 1969.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

3 770 mg/kg bw

Based on:

test mat.

95% CL:

780 - 7 200

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

4 570 mg/kg bw

Based on:

test mat.

95% CL:

600 - 9 190

Mortality:

5/5 males in the 5000 mg/kg dose group died.
1/5 males in the 3600 mg/kg dose group died.

3/5 females in the 5800 mg/kg dose group died.
4/5 females in the 5000 mg/kg dose group died.
2/5 females in the 3200 mg/kg dose group died.

Clinical signs:

other: Signs of toxicity observed i n both survivors and animal s that died on study were sal ivation, diarrhea, reduced food intatke/no feces, decreased motor activity, ocular and nasal discharges, lacrimation, anogenital discharge and stain, discolored fur aro

Gross pathology:

Gross pathological changes observed at necropsy consisted of thin gastric walls with either enlargement of the stomach or hemorrhage, broken blood vessels, or discoloration of the gastric mucosa in animals dosed with 5 .0 or 5 .8 g/kg of XA 289M. Thickened or blanched intestinal walls, enlarged and darkened adrenal glands, mottled lungs, reddened pancreas, hollow kidneys, and/or alopecia were observed in animals at several dose levels.

Histopathological evaluation showed severe gastric necrosis and ulceration in one male and severe gastric hyperkeratosis in one female. Both animals were dosed at 5.0 g/kg; these lesions may have been compound-related. Other findings of gastritis, congestion of the adrenal glands, lungs, pancreas, and cecum, hydronephrosi s, and acute dermatitis were agonal or related to spontaneous disease.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU