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Toxicological information

Repeated dose toxicity: oral

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Administrative data

sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented, scientifically acceptable study

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
not specified
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
Name of the test substance used in the study report: C-800 (= 4-HAP)
100% active ingredient

Test animals

Details on test animals or test system and environmental conditions:
Age of animals at receipt: 28 days
Age of animals at initiation of treatment: 49 days
Body weights: males 214; females 168 g
Animals were acclimated for 21 days. All animals were examined by the staff veterinarian during the acclimation period.
Each rat was identified with a metal ear tag bearing its unique Bio/-dynamics, Inc. animal number. If the tag was lost, ilt was replaced and/or the rat was toe-clipped for identification. In addition, each cage was provided with a cage card, which was color-coded for dose level identification and contained the project number, animal number, sex and dose-group information.
The rats were doubly housed in elevated stailness steel wire mesh cages during the first week of the acclimation period and indivdually housed thereafter.
Standard laboratory diet (fresh food presented weekly); water was available ad libitum.
Environmental conditions: 12 hour light/dark cycle (7 a.m. - 7 p.m.) via automatic timer; temperature (64 - 76°F) and humidity (27 - 79%) were monitored and recorded twice daily.

Administration / exposure

Route of administration:
oral: gavage
corn oil
Details on oral exposure:
Appropriate amounts of the test substance were suspended in the vehicle twice weekly to yield dose levels of 5, 15 and 45 mg/kg/day at a constant dose volume of 5 ml/kg/dose. Individual doses were adjusted by most recent weekly body weight. Control animals were administered the vehlcle at the same dose volume.
Samples of the prepared suspensions were taken after each preparation for the first 4 weeks of the study and during weeks 8 and 13. Samples were analyzed for concentration of test substance for the first mix/week at the following intervals: weeks 1-4, 8 and 13. Prior to test substance administration, samples were taken for homogeneity and stability analyses.
Analytical verification of doses or concentrations:
Duration of treatment / exposure:
90 days
Frequency of treatment:
daily (7 days per week) through the day prior to necropsy
Doses / concentrations
Doses / Concentrations:
5, 15, 45 mg/kg
actual ingested
No. of animals per sex per dose:
Control animals:
yes, concurrent vehicle


Observations and examinations performed and frequency:
Physical observations, ophthalmoscopic examinations, body weight and food consumption measurements were performed on all animals, hematology, clinical chemistry and urinalyses were performed on 10 animals/sex/group at selected intervals during the treatment period.
Sacrifice and pathology:
After approximately 3 months of treatment, all survivors were sacrificed, selected organs were weighed and organ/body and organ/brain weight ratios
calculated. Complete gross post mortem examinations, were conducted for all animals. Hlstopathological evaluation of selected tissues were conducted on all animals.

Results and discussion

Results of examinations

Details on results:
One mid-dose treated female was sacrificed moribund on Test-Day 57. A control male was found dead on Test Day 12. A total of 7 other animals distributed across the groups were considered accidental deaths. These animals showed evidence of intubation trauma and their deaths were not considered treatment-related.
Physical observations noted in the treated males and females were of the type commonly seen in laboratory rats and did not appear to be treatment-
related. Several (1-3) male animals in the control and most treated groups exhibited chromodacryorrhea, and/or lacrimation at one or more observation intervals. These findings were not considered treatment-related.
There were no findings noted at the terminal ophthalomoscopic examination which were considered treatment-related.
The mean body weights of the males and females in all treated groups were comparable to or slightly exceeded their respective corresponding control values. There were no indications of treatment-related effects in any of the mean body weight data.
Mean food consumption values were slightly elevated In the high-dose-group males during the later weeks of the study (Weeks 8-12). A similar effect was not evident in the high-dose treated females. While in some cases the increased food consumption values noted in the treated animals were statistically significant, the increases were slight, were generally not dose-related and were not considered indicative of significant toxicity.

Hematology: There was a suggestion from this study that the test substance may have a simliar effect at higher doses than were employed in this study. At Month 1 1/2 there was a dose-related increase in reticulocytes in males and females but no statistically significant differences were recorded. No trends occurred at month 3 in either sex in animals given the test substance. It is concluded that administration of up to 45 mg/kg/day produced no significant effects.
Urinalysis data for the treated male and female rats were unremarkable. There were no findings which were suggestive of a treatment-related response.
Pathology: There were no treatment-related effects noted in the tissues examined.

Effect levels

Dose descriptor:
Effect level:
45 mg/kg bw/day (nominal)
Basis for effect level:
other: overall effects

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

There were-no adverse treatment-related effects noted in animals receiving the test substance on mortality, physical observations, ophthalmology, body weight data, clinical chemistry or urinalysis parameters evaluated.