Distillates (petroleum), light hydrocracked

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-03-22 to 1988-06-24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable with restrictions because it is an acceptable and a well-documented study report.

Justification for type of information:

Concawe believes that dermal is the most relevant exposure route, and is sufficiently robust, to identify any potential hazards from repeated exposures to petroleum products to be able to adequately manage the potentially associated risks. Please see attached document for further justification.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

64741-49-7

Cas Number:

64741-49-7

IUPAC Name:

64741-49-7

Constituent 2

Reference substance name:

Vacuum Tower Overheads

IUPAC Name:

Vacuum Tower Overheads

Test material form:

other: low viscosity liquid hydrocarbon

Details on test material:

Name of test material (as cited in study report): Vacuum Tower Overheads (CAS# 64741-49-7)
No other test material information was provided.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Taconic, Germantown, New York
- Age at study initiation: approximately 29 days of age
- Weight at study initiation: not reported
- Fasting period before study:
- Housing: individually housed in suspended, stainless steel cages with wire mesh bottoms and fronts.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22 degrees Celsius
- Humidity (%): relative humidity
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: dorsal trunk
- % coverage: not reported
- Type of wrap if used: test site remained open
- Time intervals for shavings or clippings: 24 hours prior to dosing then once per week


REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported
- Time after start of exposure:


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): dependent on body weight of the animal
- Concentration (if solution):
- Constant volume or concentration used: within 10% accuracy


VEHICLE - no vehicle was used.


USE OF RESTRAINERS FOR PREVENTING INGESTION: yes - Elizabethan collars

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

Five days per week for 13 weeks

Doses / concentrations

Remarks:

Doses / Concentrations:
30, 125, and 500 mg/kg/day
Basis:
nominal per unit body weight

No. of animals per sex per dose:

10 male and 10 female per dose

Control animals:

yes, concurrent no treatment

Details on study design:

Dose selection rationale: Dose level chosen based on data obtained in studies with other similar substances such as Heavy Vacuum Gas Oil, Heavy Coker Gas Oil and Coker Light Gas Oil.
Rationale for animal assignment (if not random): Random

Positive control:

no positive controls were used.

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once daily


DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: scored weekly.


BODY WEIGHT: Yes
- Time schedule for examinations: Animals were weighed one week prior to dosing, immediately before dosing and weekly thereafter.


FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No


WATER CONSUMPTION: No


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: Yes
- Time schedule for collection of blood: during week 5 and 13.
- Anaesthetic used for blood collection: yes, with diethyl ether.
- Animals fasted: Yes
- How many animals: all surviving animals at week 5 and week 13
- Parameters checked in table [No.?] were examined. - red blood count, white blood cell differentials, mean corpuscular volume, mean corpuscular hemaglobin and mean corpuscular haemoglobin concentration.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: during weeks 5 and week 13
- Animals fasted: No data
- How many animals: all surviving animals at week 5 and week 13.
- Parameters checked in table [No.?] were examined. - sorbitol dehydrogenase, alanin aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, inorganic phosphorus, creatinine, calcium, chloride, triglycerides, albumin, potassium, sodium, total protein, uric acid, urea nitrogen, glucose, cholesterol.


URINALYSIS: Yes
- Time schedule for collection of urine:during weeks 5 and week 13
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. Check for appearance, bilirubin, blood, glucose, specific gravity, ketone, pH, protein, and urobilinogen.


OTHER: MORBIDITY and MORTALITY - twice daily at least six hours apart.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

Spermatozoa/spermatid evaluations were made on male rats. Body and organ weights were also obtained.

Statistics:

ANOVA F-tests were performed on quantitative data followed by Dunnett's test or Tukey's multiple range test. Differences were found to be statistically significant if p< 0.05.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

effects observed, treatment-related

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY - No animals died before scheduled sacrifice and necropsy. Slight erythema, flaking of the skin were observed in the treated groups during the dosing phase.


BODY WEIGHT AND WEIGHT GAIN - High-dose males weighed significantly less than control males during weeks 8 through week 13. High-dose females weighed significantly less than control females during week 11.

HAEMATOLOGY - adverse affects were seen in decrease of red blood counts, haemoglobin and hematocrit in high-dose animals.


CLINICAL CHEMISTRY - A linear relationship was found between dose and serum level for urea nitrogen, alanin aminotransferase, and cholesterol in males and cholesterol, albumin and calcium in females.


ORGAN WEIGHTS - Liver weights increased in males and females dosed at 125 and 500 mg/kg/day. A decrease in thymus weights was seen in males and females dosed at 500 mg/kg/day.

Effect levels

Dose descriptor:

NOAEL

Effect level:

30 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: clinical signs; body weight; haematology; clinical chemistry; organ weights

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The dermal application of Vacuum Tower Overheads was found to affect both haematology and serum parameters as well as the body, thymus and liver weights of exposed animals. The adverse effects on the thymus had been reported in other studies referenced in this study report.
The NOEL has been reported as 30 mg/kg/day

Executive summary:

In a 90 -day dermal toxicity study, Vacuum Tower Overheads were applied to the shaved skin of 30 young adult male and female Sprague-Dawley rats at dose levels 0, 30, 125, and 500 mg/kg/day for 5 days/week during a 90 -day period.

The dermal application of Vacuum Tower Overheads was found to affect both haematology and serum parameters as well as the body, thymus and liver weights of exposed animals. The adverse effects on the thymus had been reported in other studies referenced in this study report. No treatment-related effects were noted on examination of the weight of epididymides, ovaries, prostate, testes or uterus nor in the histopathology of the ovaries and testes nor in the number of epididymal sperm, sperm/g cauda epididymis, number of abnormal and normal sperm, number of testicular spermatids, and sperm/g testis.

The NOAEL has been reported as 30 mg/kg/day.

This study is classified as reliable with restrictions because it is an acceptable and a well-documented study report.