Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study apparently meeting scientific standards, documentation insufficient for assessment

Data source

Reference
Reference Type:
publication
Title:
Coal tar pitch poisoning in pigs
Author:
Graham R, Hester HR, Henderson JA
Year:
1940
Bibliographic source:
J. Amer. Vet. Med. Assoc., 96, 135-140

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Feeding study using non-standard animals (pigs), study stimulated by outbreaks of an uncommon disease among grazing young pigs in USA farms.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: powdered or liquid
Details on test material:
- Name of test material (as cited in study report): powdered clay-target remnants
- original source: coal-tar pitch
- Substance type: organic
- Physical state: solid

Test animals

Species:
pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: 9 weeks
- Weight at study initiation: no data
- Fasting period before study: no
- Diet: ad libitum
- Water: ad libitum:


ENVIRONMENTAL CONDITIONS
no data

Administration / exposure

Route of administration:
other: oral: feed or in capsules
Details on oral exposure:
DIET PREPARATION
Experiment A (specified in Report):
- Mixing appropriate amounts with (Type of food): no data on amount / grain ration consisting of ground yellow corn,
ground oats, wheat middlings, soybean oil meal, tankage, bonemeal and cod-liver oil
- Total dose amounted to 57 g/animal

FOLLOW-UP STUDIES:

Experiment B and C = modification of A, including cross control with lead shot

Experiment D:
Coal tar administered in capsules for 5 successive days
Dose: 3 g/d for 5 successive days (3 animals)
3 g/d for 2 successive days (2 animals)



Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Experiment A (pitch): 5 days
Experiment D (tar): 5 and 2 days
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
Experiment A: 15 and 6g/day per animal (pitch)
Basis:
other: 15 g/d (diet, 3 d), 6 g/d (capsule, 2 d)
Remarks:
Doses / Concentrations:
Experiment B: 15 and 6g/day per animal (pitch) plus 5 g/d of lead shot
Basis:

Remarks:
Doses / Concentrations:
Experiment D: 3 g/day per animal (coal tar)
Basis:
other: 15 g in total for 5 d, administered by capsule
No. of animals per sex per dose:
Experiment A: 5 per group
Experiment D: 3 and 2 per group
Control animals:
yes, concurrent no treatment
Details on study design:
Post-exposure period: =< 20 days

Examinations

Sacrifice and pathology:
GROSS PATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Death within 8 to 20 days
Mortality:
mortality observed, treatment-related
Description (incidence):
Death within 8 to 20 days
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
liver degeneration, jaundice
Details on results:
EXPERIMENT A (coal-tar pitch from remnants of clay pigeons):

CLINICAL SIGNS AND MORTALITY
Death of all 5 animals within 8 to 20 d after dosing for 5 d

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Inappetence for food on day 4: refusal of food intake (all 5 animals),
Note: Therefore, dosing was continued by applying the TS in capsules for another 2 days

GROSS PATHOLOGY
LIVER CHANGES  including JAUNDICE, and  MARKED DEGENERATION, or EDEMA of the VISCERAL LYMPH NODES, and 
EXCESSIVE  SEROUS ABDOMINAL FLUID in 4/5 pigs.  In the remaining animal, no gross hepatic changes. 
--------------------------------------

EXPERIMENT B (coal-tar pitch from remnants of clay pigeons plus lead shot):

CLINICAL SIGNS AND MORTALITY
Death of 4/5 animals within 8 to 22 d after dosing for 5 d

GROSS PATHOLOGY
Characteristic LIVER CHANGES in 4/5 pigs comparable to effects found in Experiment A.  In the remaining animal, no gross hepatic changes.
================================


For COMPARISON
EXPERIMENT D (coal tar):

CLINICAL SIGNS AND MORTALITY
Group 1: Death 10 to 18 d
Group 2: Death after 38 d of one animal, one surviver until sacrifica after 60 d

GROSS PATHOLOGY
Group 1: LIVER CHANGES: MARKED DEGENERATION in all 3 animals (no further data)
Group 2: In succumbed animal, no gross hepatic changes, pseudomelanosis of the entire colon. 
In survivor, no gross hepatic changes, extensive moist proliferative dermatitis of unknown origin


DIET CONTROL group
No gross pathology changes were seen.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The experimental observations of liver degeneration resembled the historical fatal cases of young pigs grazing on farmland, while adult pigs obviously remained unaffected.

Applicant's summary and conclusion

Executive summary:

Outbreaks of coal tar pitch poisoning in grazing swine and pigs resulting in mortality and histological liver changes, reported in the 1920s and 1930s, instigated experiments in which groups of 9-week-old pigs were orally (diet and/or capsule) given powdered clay pigeon remnants (consisting of CTP, finely ground limestone, calcimine), powdered clay pigeon plus lead, or commercial CTP (not further specified, no results data). Two additional groups given lead and a normal diet, respectively, were included.

In the first group (n=5) given a total dose of 57 g powdered remnants during five subsequent days, all animals died within eight to 20 days. At autopsy, jaundice, excessive serous fluid in the abdomen, oedematous visceral lymph nodes, and marked degenerative

liver changes were found in four out of five animals. In the remaining fifth animal, there were no gross liver effects.

Treatment with a total dose of 57 g of powdered remnants together with a total dose of 25 g of lead (exposure period: 5 days) caused the death of four out of five animals within 22 days. At autopsy, animals showed hepatic lesions. No such lesions were seen in the surviving animal sacrificed after 60 days.

In the last experimental group, liquid coal tar was administered by capsule at doses of 3 g/day, for five (n=3) or two (n=2) days. All three animals dosed for five days died within 10 to 18 days showing diffuse degenerative changes in the liver. One of the pigs dosed for two days died (at day 38). At autopsy, there were no gross liver lesions, but pseudomelanosis of the entire colon was seen.

In the remaining animal sacrificed after 60 days, an extensive moist, proliferative dermatitis of unknown origin, but no liver changes were reported. No gross pathology changes were seen in the diet-control group. In the animals given lead alone, one out of five animals died within 30 days showing a marked haemorrhagic gastritis. No gross lesions were reported in the surviving animals

(according to NL 2009: Annex V transition dossier on coal-tar pitch).