JICOSH was closed in 2008. For further information, please contact JISHA.
JICOSH Home > Guidelines > Standards for Investigation by Carcinogenicity Studies

Standards for Investigation by Carcinogenicity Studies

(LSB Notification No.144   dated March 11, 1997)

In Japanese

1. Test Method
The administration method of carcinogenicity studies shall be selected in consideration of the physicochemical properties of the test substance and the route through which the test substance is exposed to human bodies.

2. Test Animals
(1)  Animals used in carcinogenicity studies shall be rodents of two or more species such as rats, mice, etc. of the age around 6 weeks having uniform body weights.
(2) The number of animals used in carcinogenicity studies shall be at least 50 males and 50 females per one group.

3. Administered Groups and Control Groups
(1) The number of administered groups in carcinogenicity studies shall be 3 or more, respectively for male and female.
(2) A control group shall be established in the carcinogenicity studies in addition to the administered groups.

4. Dose Levels of the Test substance
The dose levels of the test substance in the carcinogenicity studies shall conform to that set forth below.
(1) The dose levels shall be determined on the basis of the results of short-term tests carried out in advance for one to three months.
(2) The highest dose level shall be the level at which normal life span of the test animals is not changed due to causes other than tumors, and the enough level at which minimum toxic signs are observed.

5. Administration Period
The administration period in the carcinogenicity studies shall be 18 months or more for mice and 24 months or more for rats.

6. Observation and Measurement
(1) General conditions and body weight shall be observed at proper intervals for all the cases of each group.
(2) Food consumption shall be measured with proper frequency.
(3) When the test substance is added in drinking water for administration, the water consumption shall be measured with proper frequency.
(4) All the animals used for the studies (including those that died and were sacrificed during the studies) shall be necropsied, and macroscopic and histopathological examinations on organs and tissues shall be performed.
At the time of sacrifice, blood samples shall be obtained as required and tested on appropriate items in consideration of the toxicity of the test substance.
(5) The histopathological examination shall be carried out on the following organs and tissues:
Skin, mammary gland, lymph node, salivary gland, breastbone, vertebra or thighbone (including marrow), thymus, nasal cavity, nasopharynx, throat, airway, lung and bronchial tube, heart, thyroid gland and parathyroid gland, tongue, esophagus, stomach, small intestine, large intestine, liver, pancreas, spleen, kidney, adrenal gland, bladder, seminal vesicle, prostate gland, epididymis, testis, ovary, womb, vagina, eyeball, brain, pituitary gland, spinal cord, and other organs and tissues with macroscopic changes.