Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 March to 9 August 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study in accordance with internationally recognised guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: The study was designed to evaluate the acute toxicity of PEP-36 following a single oral dose to rats according to Environmental Protection Agency, Toxic Substances Control Act Test Guidelines, 40 CFR Part 798, Subpart B, 1985.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): PEP-36
- Physical state: White powder
- Purity: 100%
- Date received: 24 March 1987
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: a reputable animal supplier
- Age at study initiation: not specified
- Weight at study initiation: initial body weights of the males ranged from 259.9 to 281.0 g, and initial body weights of the females ranged from 251.5 to 270.5 g.
- Fasting period before study: no
- Housing: elevated wire-mesh cages
- Diet: certified rodent diet, ad libitum (except for overnight prior to dosing)
- Water (e.g. ad libitum):
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

IN-LIFE DATES: From: To: 21 April 1987 to 21 May 1987

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: not reported
- Amount of vehicle (if gavage): 10 ml per kg
- Justification for choice of vehicle: not reported

Doses:
Range finding: 50, 100, 1000, 2500,and 5000 mg/kg of body weight,
Main study: 5000 mg/kg of body weight
No. of animals per sex per dose:
Range finding study: 1
Main study: 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations:
Toxic and pharmacologic effects: 1, 2, 4, 24 and 48 hours post dose (range finding); 1, 2 and 4 hours post dose and once daily
thereafter to 14 days (main study).
Weighing: prior to test material administration, on Day 7, and at termination
Mortality/moribundity: daily
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:
All animals survived and gained weight from initiation to termination. Clinical observations consisted of urine stains and soft feces through to the 48 hour interval. No observable gross pathology findings were noted in any of these animals at time of necropsy.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
Male: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Soft faeces (2/10) without toxicological significance. Colored urine, 3/10 reversible at day 2.

No other signs related to treatment were observed.
Body weight:
All the animals gained weight from initiation to termination.
Gross pathology:
Effects on organs:
Liver discoloration (3/10) and discoloration of the kidneys (2/10). Abnormal content in the intestines in 2 females and 4 males.


Intestines containing a yellow liquid (3/10) or red (2/10)
or paste (1/10)

Any other information on results incl. tables

In the Single Dose Study (5000 mg/kg of body weight), clinical observations consisted of urine stains and soft faeces. No observable gross pathology findings were noted in two males and one female; while, observable gross pathology findings in the remaining animals involved the liver and kidneys (discolored) and intestines (abnormal contents).

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon the results of the study, the acute oral LD50 was estimated to be greater than 5000 mg/kg of body weight in male and female and combined male and female rats.