Paraffin waxes and Hydrocarbon waxes, chloro

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Paraffin waxes and Hydrocarbon waxes, chloro

EC Number:

264-150-0

EC Name:

Paraffin waxes and Hydrocarbon waxes, chloro

Cas Number:

63449-39-8

Molecular formula:

C18H33Cl5 C18H30Cl8 C20H36Cl6 C20H33Cl9 C25H45Cl7 C25H42Cl10 C25H29C23 C30H53Cl9 C30H49Cl13 C30H35Cl27

IUPAC Name:

Paraffin waxes and Hydrocarbon waxes (C18 and longer), chloro

Test material form:

solid

Remarks:

waxy solid

Details on test material:

C20-30, 70% Cl (solid) (unstabilized). Electrofine S70.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The appropriate amount of the test material was ground with 1000 grams of Certified Rodent Chow #5002.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

100 gram samples from the top, middle, and bottom of the batches were tested for homgeneity of test article dispersion prior to use.

Duration of treatment / exposure:

13-weeks

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
100, 900, 3750 mg/kg/day
Basis:
nominal in diet

No. of animals per sex per dose:

15

Control animals:

yes, concurrent vehicle

Details on study design:

.

Positive control:

No

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations checked included: signs of overt toxicity, morbidity and mortality.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: A detailed examination took place before the study was terminated.

BODY WEIGHT: Yes
- Time schedule for examinations: Individual body weights were recorded on days 0 and 5.

FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Daily

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, All rats received a post mortem examination at the termination of the study.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

mortality observed, non-treatment-related

Description (incidence):

All mortalities were due to blood sampling procedures

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

slightly reduced mean body weight gain in 3750 mg/kg/day males (high concentration of non-nutritive test article may have influenced).

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

indications of increased mean food consumption at 3750 mg/kg/day (high concentration of non-nutritive test article may have influenced).

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

slightly elevated liver transaminase levels at 3750 mg/kg/day (females)

Urinalysis findings:

effects observed, treatment-related

Description (incidence and severity):

A general tendency of reduced urine volume with corresponding increases in specific gravity at 3750 mg/kg/day (particularly for males).

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

liver weight increase at 3750 mg/kg/day (females)

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

hypertrophy and cytoplasmic fat vacuolation in liver at 3750 mg/kg/day

Details on results:

There were no significant changes in appearance or behavior. Four deaths, including 2 control females, occurred following blood sample collection and were not considered treatment related.

There was evidence of an effect on the liver at 3750 mg/kg/day with slight changed in alanine and aspartate aminotransferase and alkaline phosphate levels, increased liver weights, oil red "O" staining, cytoplasmic fat vacuolation and hepatocellular hypertrophy.

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

900 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed

2

Dose descriptor:

LOAEL

Effect level:

3 750 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

histopathology: non-neoplastic

organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:

yes

Lowest effective dose / conc.:

3 750 mg/kg bw/day (nominal)

System:

hepatobiliary

Organ:

liver

Treatment related:

yes

Dose response relationship:

yes

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

The NOAEL from this study is 900 mg/kg/day for both male and female rats. Effects, primarily in the liver, were noted at 3750 mg/kg/day.

Executive summary:

The NOAEL from this study is 900 mg/kg/day for both male and female rats. Effects, primarily in the liver, were noted at 3750 mg/kg/day.