Pitch, coal tar, high-temp., < 1% 4- to 5-membered condensed ring aromatic hydrocarbons

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Biochemical effects of manufactured gas plant residue following ingestion by B6C3F1 mice

Author:

Weyand EH, Wu Y, Patel S, Goldstein L

Year:

1994

Bibliographic source:

J Toxicol Environ Health 42, 89-107

Reference 2

Reference Type:

publication

Title:

Urinary excretion and DNA binding of coal tar components in B6C3F1 mice following ingestion

Author:

Weyand EH, Wu Y, Patel S, Taylor BB, Mauro DM

Year:

1991

Bibliographic source:

Chem. Res. Toxicol. 4, 466-473

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

no full examination protocol: hematology, urinalysis are lacking

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Coal tar

Molecular formula:

not applicalbe

IUPAC Name:

Coal tar

Test material form:

liquid: viscous

Details on test material:

- Substance type: organic

Specific details on test material used for the study:

- Name of test material (as cited in study report): manufactured gas plant residue, MGP (= Coal-tar sample C in Weyand et al. 1991)
- Physical state: viscous liquid at room temperature
- Source: Electric Power Research Institute, Palo Alto
- Production: by-product from coal gasification of East Coast coal feedstock

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Wilmington/Mass
- Age at study initiation: 49 - 56 d
- Weight at study initiation: 23 - 24 g (m); 17 - 18 g (f) (estimated from Report, Fig. 1
- Fasting period before study: none
- Housing:
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- controlled conditions: no details
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: water and gelling agent

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): 1x
- Preparation of the diet (basal gel diet): 3020 mL of boiling water was blended with 100 g of a gelling agent (not specified) for 1 min,
then 1948 g dry food added and blending continued for additionakl 2-3 min.
- Mixing appropriate amounts: Aliquots of MPG was added, followed by homogenisation (2-3 min).
The food blends were cooled down in bar molds.
- Storage temperature of food: packaged into plastic bags and stored at -20 °C

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

94 d and 185 d

Frequency of treatment:

continuous

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.05 other: % (w/w) in diet (nominal)

Remarks:

51 / 42 mg/kg bw/day (males / females) actual dose ingested

Doses / concentrations 2

Dose / conc.:

0.25 other: % (w/w) in diet (nominal)

Remarks:

251 / 196 mg/kg bw/day (males / females) actual dose ingested

Doses / concentrations 3

Dose / conc.:

0.5 other: % (w/w) in diet (nominal)

Remarks:

462 / 344 mg/kg bw/day (males / females) actual dose ingested

No. of animals per sex per dose:

12 (94 d)
12 (185 d)

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: previous range finding and acceptance (palatability) testing

Positive control:

Benzo[a]pyrene (BaP): 0.005 % in diet

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes, no details

DETAILED CLINICAL OBSERVATIONS: Yes, no details

BODY WEIGHT: Yes
- Time schedule for examinations: throughout (see Report, Fig. 1)

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/mouse/day: Yes, per mouse

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No (bone marrow was examined, 94 d and 185 d)

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 94 d or 185 d
- How many animals: 12 per group
- Parameters: glucose, creatine, BUN, protein, Asp-aminotransferase, ala-aminotransferase, alk. phosphatase

URINALYSIS: No data on standard parameters /
Chemical analysis of PAH metabolites in male mice over time (1-OH-pyrene + 3-OH-BaP)

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, all organs after 94 d and 185 d
HISTOPATHOLOGY: Yes, in in 10 animals per sex of the 0.5% group, BaP and control group (after 94 d and 185 d)

Other examinations:

DNA adducts in lung and forestomach

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not specified

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
no mortality

BODY WEIGHT AND WEIGHT GAIN (estimated from Report, Fig. 1)
Dose-related decrease, exception 0.05% (females):
0.25% (males): significant decrease in body weight of 10 - 12 % at 94 d and 185 d, respectively, as compared to the control
0.50 % (males): significant decrease in body weight of ~22 and ~15 % at 94 d and 185 d, respectively, as compared to the control
0.05% (female): significant increase in body weight of ~16 % at 94 d and 185 d, respectively, as compared to the control
0.50 % (female): significant decrease in body weight of ~20 % at 94 d and 185 d, respectively, as compared to the control


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study) [Report, Tab. 1]
Dose-related decrease as compared to the untreated control / increase for the 0.05 % female group

Changes in body-weight development may be partly explained by the differences in food consumption.


HISTOPATHOLOGY: NON-NEOPLASTIC
After 94 d. lesions observed included minimally to moderate vacuolisation of hepatocytes, increased hematopoietic cell proliferation
in spleens, modest hyperplasia of granulocytic cells in the bone marrow of the femur, and cytoplasmic alteration of the olfactory epithelial cells.

After 185 d, microscopic lesions observed included irregular cytoplasmic vacuoles in hepatocytes, infiltration of lymphoid cells in various tissues, and changes in the olfactory epithelial cells of the nose.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
After 185 d, a squamous cell carcinoma was present in the forestomach of one male (0.5 %),
one squamous papilloma was found in the forestomach of a female.

The effects were sporadic and not considered treatment-related.

Effect levels

1

Key result

Dose descriptor:

NOAEL

Remarks:

(highest tested dose)

Effect level:

0.5 other: % in diet (nominal), 462/344 mg/kg bw/day (males/females) actual dose ingested;

Based on:

test mat.

Basis for effect level:

other: no effects observed related to specific systemic toxicity

2

Key result

Dose descriptor:

NOAEL

Effect level:

0.25 other: % in diet (nominal), 251/196 mg/kg bw/day (males/females) actual dose ingested;

Based on:

test mat.

Basis for effect level:

other: body weight

Target system / organ toxicity

Critical effects observed:

not specified