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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Study period:
start of study: 1949
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
A study of the Physiological Effects of Carbon Black. II. Skin Contact
Author:
Nau CA, Neal J, Stembridge V
Year:
1958
Bibliographic source:
A.M.A. Arch. Industr. Health 18, 511-520.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Carbon blacks were suspended in mineral oil, cottonseed oil, cooking oil or water with 1% carboxymethyl cellulose. The backs of the test animals were painted with a brush three times per week with 20% emulsions of the designated carbon blacks, benzene extracts thereof or extracted carbon black for 12-18 months. Additional groups were treatd with known carcinogens (methylcholanthrene, 3,4-benzpyrene). The negative controls were treated with the corresponding vehicle.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Oil furnace black (fast extrusion furnace), thermal combustion black (medium thermal), channel black (medium processing); one of the typical fast extrusion furnace oil carbon blacks and the channel black were extracted with hot redistilled benzene for 48 hours using a Soxhlet extractor, dried and the extracted furncace black tested in the same vehicles as the whole carbons; the benzene extracts of furnace and channel blacks were also tested, as well as pure carcinogens (methylcholanthrene, 3,4-benzpyrene)
- Substance type: technical products (whole carbon blacks) and pure active substances
- Physical state: solids and liquids (extracts)
- Analytical purity: not reported
- Impurities (identity and concentrations): benzene extractables from 0.00% (channel black), 0.17% (oil furnace black) to 1.05% (thermal combustion black)
- Composition of test material, percentage of components: not reported
- Storage condition of test material: not reported

Test animals

Species:
mouse
Strain:
other: CFW white and C3H brown
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not reported
- Age at study initiation: 6-10 weeks
- Weight at study initiation: not reported
- Fasting period before study: not reported
- Housing: the mice were kept in Monel pans - 10 to each pan in air-conditioned quarters
- Diet (e.g. ad libitum): Purina Dog Chow ad lib.
- Water (e.g. ad libitum): ad lib.
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25.5
- Humidity (%): 55
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported


IN-LIFE DATES: From: 1949 To: not reported

Administration / exposure

Type of coverage:
open
Vehicle:
other: 1% aqueous carboxymethyl cellulose, cottonseed oil, cooking oil or mineral oil
Details on exposure:
TEST SITE
- Area of exposure: up to the middle of the unshaven back from the base of the tail to the neck
- % coverage: not reported
- Type of wrap if used: none used
- Time intervals for shavings or clipplings: unshaven


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


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): the weight of the material applied to 10 mice was determined, and this value was divided by the number of mice painted. Fairly consistent results for each application were obtained (no quantities reported)
- Concentration (if solution): 20% mixtures/emulsions
- Constant volume or concentration used: yes
- For solids, paste formed: not reported


VEHICLE
- Justification for use and choice of vehicle (if other than water): not reported
- Amount(s) applied (volume or weight with unit): not reported
- Concentration (if solution): 20%
- Lot/batch no. (if required): not reported
- Purity: not reported


USE OF RESTRAINERS FOR PREVENTING INGESTION: not reported
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No details reported
Duration of treatment / exposure:
12-18 months
Frequency of treatment:
3 times/week
Doses / concentrations
Remarks:
Doses / Concentrations:
20% carbon black suspensions in cottonseed oil, mineral oil, cooking oil or in 1% aqueous carboxymethylcellulose
Basis:
other: concentration
No. of animals per sex per dose:
10-40 mice / group (sex not always specified)
Control animals:
yes, concurrent no treatment
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: not reported
- Rationale for animal assignment (if not random): not reported
- Rationale for selecting satellite groups: no satellite groups used
- Section schedule rationale (if not random): animals found to show abnormal signs were isolated and killed at such time as was deemed desirable, and a complete gross and microscopic pathological examination was made of all organs and tisues. Mice found dead on routine checking were studied in the same manner
Positive control:
Groups painted with known carcinogens (methylcholanthrene, 3,4-benzpyrene (in 1% benzene solutions, water or oil suspension)

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice each day

DETAILED CLINICAL OBSERVATIONS: No data

DERMAL IRRITATION: No data

BODY WEIGHT: No data

FOOD CONSUMPTION: No data

FOOD EFFICIENCY: No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes (all organs and tissues). Animals found to show abnormal signs were isolated and killed at such time as was deemed desirable, and a complete gross and microscopic pathological examination was made of all organs and tisues. Mice found dead on routine checking were studied in the same manner
HISTOPATHOLOGY: Yes (all organs and tissues). Animals found to show abnormal signs were isolated and killed at such time as was deemed desirable, and a complete gross and microscopic pathological examination was made of all organs and tisues. Mice found dead on routine checking were studied in the same manner
Other examinations:
Not reported
Statistics:
Not reported

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
not specified
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
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:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY
59 of 170 animals painted with whole carbon black were found dead during the course of the study (no details provided).
56 of 140 animals painted with extracted carbon black were found dead during the course of the study (no details provided).

ORGAN WEIGHTS
not reported

GROSS PATHOLOGY
Mice painted with medium processing channel black: 1 mesenteric tumour was found in a group of 20 female mice painted with carbon black in cooking oil; 1 mesenteric tumour was found in another group of 40 mice painted with carbon black in mineral oil.
No changes from the normal were found in the groups treated with extracted carbon black.

HISTOPATHOLOGY: NON-NEOPLASTIC
not reported

HISTOPATHOLOGY: NEOPLASTIC
The painting of whole carbon black of the fast extrusion furnace and medium thermal types produced no changes from the normal in C3H mice. There occurred, however, observable tumours (adenoma and lymphosarcoma) in a few mice painted with the medium processing channel black. These did not occur at the site of painting but primarily in the gastrointestinal tract. These tumours were: 1 diffuse lymphosarcoma and 1 lymphoblastic proliferation in spleen and lymph nodes of a CFW mouse in a group of 20 mice painted with the carbon black in cooking oil for 12 months; 1 lymphosarcoma of colon in a CFW mouse of a group of 20 painted with carbon black in cooking oil for 17 months; 1 squamous cell adenoma of stomach in a group of 40 C3H mice painted with the CMC-suspension for 18 months, 1 squamouscell adenoma of stomach in a group of 20 C3H mice painted with the CMC-suspension for 12 months (in this group benzene was applied as a local irritant before painting); and 1 lymposarcoma of the spleen in a CFW mouse of a group of 40, painted with carbon black in mineral oil for 13 months.
The painting of the extracted carbon black of the fast extrusion furnace type led to no changes from the normal in 128 mice; 2 CFW mice treated with the extracted carbon black in mineral oil for 12 months, had lymphosarcoma (lymph nodes and spleen).
The whole benzene extracts (in a water suspension or 1% benzene solution) were found to be carcinogenic except for the extract of the channel furnace type of carbon. Painting of the known "free" carcinogens methylcholanthrene and 3,4-benzpyrene produced skin cancer in a high percentage of the animals. When these carcinogens are adsorbed on carbon black, the incidence of skin cancer resulting from the skin application of the absorbed carcinogen was reduced or abolished.

HISTORICAL CONTROL DATA (if applicable): there were 13 mice in the control group of 943 mice which developed spontaneous malignant neoplasms (6 malignant skin neoplasms, 1 malignant spleen neoplasm, 6 malignant liver neoplasms)

Effect levels

Dose descriptor:
NOEL
Effect level:
20 other: %
Sex:
male/female
Basis for effect level:
other: gross pathology; histopathology;

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
Carbon blacks as manufactured produce no significant changes from the normal following skin contact. Carbon blacks have adsorbed components which, when free, and applied to the skin of mice, produce skin cancer. The adsorbed components, however, are ineffective as a carcinogen. Carbon blacks can adsorb effectively known carcinogens such as methylcholanthrene and 3,4-benzpyrene and by such adsorption do eliminate or reduce the carcinogenicity of these substances.
Executive summary:

In this study with limited documentation, no changes in organs or tissues of C3H mice were found after treating them three times per week with various types of carbon blacks (20% carbon black suspensions in cottonseed oil, mineral oil or in 1% aqueous carboxymethylcellulose, painted onto the animals’ backs) for 12 -18 months.