Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
liquid: viscous

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Animals were received from Charles River, Raleigh NC and Stone Ridge NY, on 02 Mar 2017 and
15 Mar 2017. Following an acclimation period of at least five days, three healthy male and six healthy, non-pregnant and nulliparous female Sprague Dawley rats were assigned to treatment groups without conscious bias.
The animals were born 04 Jan 2017 and 23 Jan 2017. The pretest body weight range was
206 - 221 grams for males and 199 - 243 grams for females. The weight variation of the animals used did not exceed ±20% of the mean body weight of the previously dosed animals within a sex.
The animals were identified by cage notation and indelible body marks, and housed in suspended wire cages; five per sex per cage prior to dosing and three per sex per cage following dosing. Absorbent paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rat Chow (Diet No. 5012) was freely available except for 16-20 hours prior to dosing. Water was available ad libitum. The animal room, reserved exclusively for rats on acute tests, was temperature controlled, had a 12-hour light/dark cycle, and was kept clean and vermin free.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test article was used as received and the dose was based on the sample weight as calculated from the specific gravity. A single dose was administered orally by syringe and dosing needle at a dose level of 2000 mg/kg to three female rats. A dose level of 300 mg/kg was administered to three female and three male rats.
Doses:
2000 mg/kg/bw and 300 mg/kg/bw
No. of animals per sex per dose:
3 females were dosed 2000 mg/kg/bw
3 females and 3 males were dosed 300 mg/kg/bw
Control animals:
no
Details on study design:
Dosing
The test article was used as received and the dose was based on the sample weight as calculated from the specific gravity. A single dose was administered orally by syringe and dosing needle at a dose level of 2000 mg/kg to three female rats. A dose level of 300 mg/kg was administered to three female and three male rats.
Type and Frequency of Observations
In Vivo - Animals were observed at 15 minutes, 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects and twice daily for mortality. Body weights were recorded immediately pretest, weekly, at death and at termination in the survivors.
Post Mortem – All animals were humanely sacrificed using CO2 and were examined for gross pathology following study termination.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All three female rats died within one hour following a single 2000 mg/kg oral dose.
Two female and two male rats survived following a single 300 mg/kg oral dose. One female and one male rat died by Day 1.
Clinical signs:
2000 mg/kg
Prior to death, abnormal physical signs including dyspnea and wetness of the nose-mouth area were observed.
300 mg/kg
Abnormal physical signs including wetness of the nose/mouth area and piloerection were observed among the surviving animals. Wetness of the nose/mouth area, anogenital area wet with red fluid, lethargy, sagging eyelids, dyspnea, and piloerection were observed among the two decedents.
Body weight:
2000 mg/kg
Terminal body weight loss was observed among all three animals.
300 mg/kg
The four surviving animals gained body weight by study termination. Terminal body weight loss was observed among two decedents.
Gross pathology:
2000 mg/kg
The gross necropsy revealed red staining of the nose/mouth area, yellow staining of the anogenital area, dark areas on the liver, red areas on the lungs, and abnormalities of the gastrointestinal tract.
300 mg/kg
The gross necropsy of the survivors revealed no observable abnormalities. Red and yellow staining of the nose/mouth area, red staining of the anogenital area, darker than normal lungs, dark areas on the liver, and abnormalities of the gastrointestinal tract were observed among the two decedents.

Applicant's summary and conclusion

Conclusions:
The oral LD50 of test material benzylated polyamine is greater than 300 mg/kg but less than 2000 mg/kg of body weight in rats.
Executive summary:

The objective of the test was to determine the potential for oral toxicity using the Acute Toxic Class Determination. This study was designed to comply with the standards set forth in the current OECD Guidelines for the Testing of Chemicals, Guideline 423. Guideline 423 is referred to in OPPTS 870.1000 as an acceptable method to assess lethality within a dose range.

Initially, three healthy female Sprague Dawley rats were dosed orally with Benzylated Polyamine at 2000 mg/kg. Since the animals died, an additional three healthy females were dosed at 300 mg/kg. There was one death at this level, so an additional three males were dosed as a confirmatory group at 300 mg/kg. The rats were observed at 15 minutes, 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects, and twice daily for mortality. Body weights were recorded immediately pretest, weekly, at death and at termination in the survivors. All animals were examined for gross pathology. The test article was assigned to a toxic category based on the mortality response noted.