Registration Dossier

Administrative data

Description of key information

No experimental repeated-dose toxicity data is available on pitch, coal tar, high-temp. itself. A related coal-tar material containing also constituents present in CTPht produced no particular, treatment-related toxicity in male and female mice receiving the test material in the feed for up to 6 months. The NOAEL, 0.5 % in the diet, is estimated to correspond to approximately 400 mg/kg bw/d. Early not verifiable reports indicate that young pigs may have a significant lower tolerance to ingested coal-tar pitch or coal tar than the adult animals.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
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
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
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
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

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 additional 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
Dose / conc.:
0.05 other: % (w/w) in diet (nominal)
Remarks:
51 / 42 mg/kg bw/day (males / females) actual dose ingested
Dose / conc.:
0.25 other: % (w/w) in diet (nominal)
Remarks:
251 / 196 mg/kg bw/day (males / females) actual dose ingested
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
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 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
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
0.25% (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.
The effects were sporadic and not considered treatment-related.

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.
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.
Sex:
male/female
Basis for effect level:
other: no effects observed related to specific systemic toxicity
Key result
Dose descriptor:
NOEL
Effect level:
0.25 other: % in diet (nominal), 251/196 mg/kg bw/day (males/females) actual dose ingested;
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
Key result
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
400 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

Apart from one oral study of limited significance in pigs, no repeated-dose toxicity studies with pitch addressing effects other than carcinogenicity have been located. The subchronic feeding study in mice with coal-tar material (compared to pitch a worst case) indicates that more marked toxicity following long-term exposure to pitch is unlikely to occur.

Tars and pitches constitute a family of products that result from different distillation steps of coal (condensation products and distillation residues). Depending on distillation step and distillation temperature, constituents of the products and their portions are variable. But major components of all the distillation products and residues are condensed ring aromatic hydrocarbons in varying composition (i.e. polynuclear aromatic hydrocarbons). Major toxicological effects of these products will primarily be caused by the PAH fraction in the respective substances. Especially for toxicological endpoints that fall into the toxicological action profile of PAH, it is justified to use related tars and pitches as supporting substances to characterise potential effects of pitch, coal tar, high temp.


Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver

Justification for classification or non-classification

Pitch is not classifiable, as there was no evidence for specific target-organ effects at doses lower than 100 mg/kg bw/d (test material: coal tar).