Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OTS 798.1175 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Remarks:
testing lab.
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of the test substance used in the study report: C-01650 (4-HAP)
purity: 99.97%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Body weight range approximately 190-350 g at pre-fast. Animal weights fell within 20% of the group mean.
Acclimation period: 7 days
Animal identification: Each animal was assigned a unique and individual number. This number was permanently indicated on the animal with an ear tag.
Animals were housed separately from any other species and individually housed in stainless steel, wire mesh bottom cages.
Temperature: 64 - 79°F; humidity 30 - 70%; light: 12/12 light/dark cycle.
Fresh certified rodent feed was provided ad libitum, except feed was withheld the night prior to dosing; fresh potable water was provided ad libitum.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test substance homogeneized in corn oil was administered orally to five male and five female animals at each of the following dose levelst 1.0, 2.0, and 5.0 g/kg. The 5.0 g/kg dose level was administered initially and based upon the mortality noted in this dose group, the remaining dose levels were administered subsequently in order of decreasing concentration. A vehicle control group consisting of five male and five female rate were dosed with corn oil. The control animals were dosed concurrently with the 5.0 g/kg animals. Individual dosing volumes were adjusted to 1 ml/100 g body weight, based upon the animal's fasted body weight.
The animals were randomly selected by a computer randomization programn based on their prefasted body weights. The animals were fasted the night immediately prior to dosing.
Doses:
1000, 2000, 5000 mg/kg
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
Observations were made hourly for the first 4 hours immediately after dosing and twice daily (a.m. and p.m.) for the next 13 days for a total of 14 days of observation.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 240 mg/kg bw
Mortality:
Control: 0; 1000 mg/kg: 0; 2000 mg/kg: 3/5 males and 3/5 females; 5000 mg/kg: 4/5 males and 5/5 females
All animals died within 24 hours.
Clinical signs:
8 of the 5000 mg/kg dose group animals, 10 of the 2000 mg/kg dose group animals and 8 of the 1000 mg/kg dose group animals exhibited one or more of the following observations during their respective 14 day observation periods: oral discharge, nasal discharge, ocular discharge, alopecia, abnormal respiration, tremors, abnormal stools, lethargy and/or moribundity.
Seven of the vehicle control. animals appeared normal throughout the study period. Two of the animals exhibited abnormal stool on day 0 and an additional animal exhibited stained coat on days 3-9 of the study period.
Body weight:
All of the animals within the treatment groups, which survived the 14-day study period, gained weight by the end of the study.
All of the vehicle control animals had gained weight by the end of the study.
Gross pathology:
All animals that survived the study period were euthanized by CO2. All animals at the conclusion of the study and those that died on study were subjected to a post-mortem examination. Gross necropsy observations included fluid in one or more of the following organs: stomach, duodenum, jejunum and/or ileum as well as external observations. One animal from the 2000 mg/kg dose group was missing the left testicle. The missing testicle is considered to be a genetic anomaly.

Applicant's summary and conclusion