Indole

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1953

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

WHO report

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Kaiser, K. (1953) Investigations on the carcinogenic activity of indole in rats. Zeitschrift Krebsforschung, 59, 488–495.

GLP compliance:

no

Test material

Test material information

1

Reference substance name:

Indole

EC Number:

204-420-7

EC Name:

Indole

Cas Number:

120-72-9

Molecular formula:

C8H7N

IUPAC Name:

1H-indole

Test material form:

solid

Test animals

Species:

rat

Strain:

other: Strain W

Details on species / strain selection:

Groups of five male and twenty female strain W rats were maintained on a diet providing indole at a dose of 0 or 100 mg/kg bw per day for 460 days, followed by a 30-day period of no treatment to examine the possible reversibility of any
treatment-related effects.

Sex:

male/female

Details on test animals or test system and environmental conditions:

Groups of five male and twenty female strain W rats were maintained on a diet providing indole at a dose of 0 or 100 mg/kg bw per day for 460 days, followed by a 30-day period of no treatment to examine the possible reversibility of any
treatment-related effects.

Administration / exposure

Route of administration:

oral: feed

Duration of treatment / exposure:

Groups of five male and twenty female strain W rats were maintained on a diet providing indole at a dose of 0 or 100 mg/kg bw per day for 460 days, followed by a 30-day period of no treatment to examine the possible reversibility of any
treatment-related effects. Following the reversibility period, treatment with a diet providing indole at a dose of 200 mg/kg bw per day was continued for 100 additional days.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

100 mg/kg bw (total dose)

Doses / concentrations 2

Dose / conc.:

0 mg/kg bw (total dose)

Doses / concentrations 3

Dose / conc.:

200 mg/kg bw (total dose)

No. of animals per sex per dose:

Groups of five male and twenty female strain W rats were maintained on a diet

Control animals:

yes

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Animals were monitored every 2 weeks for food consumption, body weight,
survival and haematological effects. At necropsy, liver, kidney, and spleen were examined microscopically. Rats maintained on a diet supplemented with indole showed a 20% reduction in body-weight gain compared with controls. The
haematological profile obtained for the first 460 days revealed slightly reduced concentrations of haemoglobin and erythrocyte counts compared with thoseof the controls (i.e. haemoglobin, 15.2 versus 13.8 g Hb/100 ml blood; and erythrocyte count, 8 versus 6.4 million cells/ml blood, respectively), which were reversible upon cessation of treatment. By day 460, the leukocyte counts reached twice their
original values, which the authors stated were still within the normal range of values for rats. No leukaemia or other tumours attributable to administration of indole were observed in the animals. The average life expectancy of the rats was not altered by the inclusion of indole in the diet. Except for indications of moderate reversible anaemia, no other adverse effects were reported (Kaiser, 1953).

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Animals were monitored every 2 weeks for food consumption, body weight,
survival and haematological effects. At necropsy, liver, kidney, and spleen were examined microscopically. Rats maintained on a diet supplemented with indole showed a 20% reduction in body-weight gain compared with controls.

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Animals were monitored every 2 weeks for food consumption, body weight,
survival and haematological effects. At necropsy, liver, kidney, and spleen were examined microscopically. Rats maintained on a diet supplemented with indole showed a 20% reduction in body-weight gain compared with controls. The
haematological profile obtained for the first 460 days revealed slightly reduced concentrations of haemoglobin and erythrocyte counts compared with thoseof the controls (i.e. haemoglobin, 15.2 versus 13.8 g Hb/100 ml blood; and erythrocyte count, 8 versus 6.4 million cells/ml blood, respectively), which were reversible upon cessation of treatment. By day 460, the leukocyte counts reached twice their
original values, which the authors stated were still within the normal range of values for rats. No leukaemia or other tumours attributable to administration of indole were observed in the animals. The average life expectancy of the rats was not altered by the inclusion of indole in the diet. Except for indications of moderate reversible anaemia, no other adverse effects were reported (Kaiser, 1953).

Effect levels

Key result

Dose descriptor:

NOEL

Effect level:

< 100 mg/kg bw (total dose)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

haematology

mortality

Remarks on result:

not determinable due to adverse toxic effects at highest dose / concentration tested

Target system / organ toxicity

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

100 mg/kg bw (total dose)

System:

haematopoietic

Organ:

kidney

liver

spleen

Treatment related:

yes

Dose response relationship:

yes

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

590 days NOEL is l < 100 mg/kg bw/day determined by WHO report. .

Executive summary:

Groups of five male and twenty female strain W rats were maintained on a diet providing indole at a dose of 0 or 100 mg/kg bw per day for 460 days, followed by a 30-day period of no treatment to examine the possible reversibility of any

 treatment-related effects. Following the reversibility period, treatment with a diet providing indole at a dose of 200 mg/kg bw per day was continued for 100 additional days. A concurrent control group was maintained, but was not described.

 Animals were monitored every 2 weeks for food consumption, body weight,

 survival and haematological effects. At necropsy, liver, kidney, and spleen were examined microscopically. Rats maintained on a diet supplemented with indole showed a 20% reduction in body-weight gain compared with controls. The

 haematological profile obtained for the first 460 days revealed slightly reduced concentrations of haemoglobin and erythrocyte counts compared with thoseof the controls (i.e. haemoglobin, 15.2 versus 13.8 g Hb/100 ml blood; and erythrocyte count, 8 versus 6.4 million cells/ml blood, respectively), which were reversible upon cessation of treatment. By day 460, the leukocyte counts reached twice their

 original values, which the authors stated were still within the normal range of values for rats. No leukaemia or other tumours attributable to administration of indole were observed in the animals. The average life expectancy of the rats was not altered by the inclusion of indole in the diet. Except for indications of moderate reversible anaemia, no other adverse effects were reported (Kaiser, 1953).