2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar-heptyl ar',ar''-Me derivs.

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity: dermal

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

1972

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study is considered to be reliability 3 since it was performed at Industrial Biotest Laboratories prior to the implementation of GLP and during a time period where the conduct, quality and reliability of studies performed at this lab was brought into question.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1972

Report date:

1972

Materials and methods

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar-heptyl ar',ar''-Me derivs.

EC Number:

296-120-8

EC Name:

2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar-heptyl ar',ar''-Me derivs.

Cas Number:

92257-31-3

Molecular formula:

Not applicable

IUPAC Name:

2-​Naphthalenol, 1-​[2-​[4-​(2-​phenyldiazenyl)​phenyl]​diazenyl]​-​, ar-​heptyl ar',​ar''-​Me derivatives *

Test material form:

not specified

Test animals

Species:

mouse

Strain:

Swiss

Sex:

female

Details on test animals or test system and environmental conditions:

Experimental Animals:
Young adult female Swiss white mice of the Charles River CD-i strain were used in this investigation. The animals were selected for use in this test following a pretest observation and physical examination.

Organization of Groups:
Eight hundred mice divided into one control (C) and seven test groups (7 different test materials) of 100 each were utilized. The animals were housed ten to a cage in standard laboratory cages. Water was supplied in bottles with stainless steel drinking tubes. Feed was offered ad libitum.

Administration / exposure

Route of administration:

dermal

Vehicle:

not specified

Details on exposure:

Dosage:
Following a two-week laboratory observation period, the compound application was begun. The material was applied with a camel hair brush to the back of each animal three times weekly for the duration of the test using a different brush for each group. Prior to dosing, the hair was removed from the site with an electric clipper utilizing a #40 surgical blade. The animals were dosed three times per week for a period of 78 consecutive weeks.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

78 consecutive weeks.

Frequency of treatment:

3 times per week.

Post exposure period:

None

Doses / concentrations

Remarks:

Doses / Concentrations:
15 mg/mouse
Basis:
other: test material

No. of animals per sex per dose:

100

Control animals:

yes, concurrent no treatment

Details on study design:

Organization of Groups:
Eight hundred mice divided into one control (C) and seven test groups (7 different test materials) of 100 each were utilized.

Examinations

Observations and examinations performed and frequency:

Observations:
The animals were observed daily. Any untoward behavioral reactions or changes on the skin of the mice were noted. Separate records were kept on each mouse containing pertinent data regarding dates, skin reactions, dosage and quantity of material applied. After a suspected papilloma reached one mm in diameter, it was measured and its size recorded weekly.

Sacrifice and pathology:

An autopsy was performed on All animals. The skin, internal organs and carcass were fixed in 10 percent buffered formalin. All skin lesions were examined histologically using hematoxylin arid eosin stain.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

26 animals died in the Automate Red B group. There was 74% survival.

Mortality:

mortality observed, treatment-related

Description (incidence):

26 animals died in the Automate Red B group. There was 74% survival.

Body weight and weight changes:

not examined

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:

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 examined

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

The hair and skin of animals in the Automate Red B group became red upon application of test material. The majority of animals in this group showed a light orange coloration of internal fatty tissue.

Histopathological findings: neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Low incidence of spontaneous tumor (mammary) and a rather high incidence of lymphosarcomas (also a spontaneous tumor).

Details on results:

Mortality and Reactions:
No abnormal behavioral reactions or signs of systemic toxicity were noted. No growths were noted in the control group or the Automate Red B test group. The hair and skin of animals in the Automate Red B group became red upon application of test material. The majority of animals in the Automate Red Bgroup showed a light orange coloration of internal fatty tissue.

Histopathological Examination:
Histological examination of the organs and tissues of the treated mice revealed a low incidence of spontaneous tumors (mammary) and a rather high incidence of lymphosarcomas (also a spontaneous tumor). Since these were present in the control group, it was concluded that these are not related to an effect of the compound.

Applicant's summary and conclusion

Conclusions:

A carcinogenicity study was conducted in 100 Swiss white mice with Automate Red B and 100 control mice. The test compound was applied to the skin of the backs at a dose of 15 mg/mouse. This dose was applied three times weekly for 18 months. The control animals received nothing. No dermal lesions were observed in the test group. No abnormal behavioral reactions or signs of systemic toxicity were noted. No growths were noted in the control group or the Automate Red B test group. The hair and skin of animals in the Automate Red B group became red upon application of test material. The majority of animals in the Automate Red B group showed a light orange coloration of internal fatty tissue. Survival was 74% in the test group and 76% in the control group. Histological examination of the organs and tissues of the treated mice revealed a low incidence of spontaneous tumors (mammary) and a rather high incidence of lymphosarcomas (also a spontaneous tumor). Since these were present in the control group, it was concluded that these are not related to an effect of the compound.

Executive summary:

A carcinogenicity study was conducted in 100 Swiss white mice with Automate Red B and 100 control mice. The test compound was applied to the skin of the backs at a dose of 15 mg/mouse. This dose was applied three times weekly for 18 months. The control animals received nothing. No dermal lesions were observed in the test group. No abnormal behavioral reactions or signs of systemic toxicity were noted. No growths were noted in the control group or the Automate Red B test group. The hair and skin of animals in the Automate Red B group became red upon application of test material. The majority of animals in the Automate Red B group showed a light orange coloration of internal fatty tissue. Survival was 74% in the test group and 76% in the control group. Histological examination of the organs and tissues of the treated mice revealed a low incidence of spontaneous tumors (mammary) and a rather high incidence of lymphosarcomas (also a spontaneous tumor). Since these were present in the control group, it was concluded that these are not related to an effect of the compound.