Table 1

Basic study information and summary of tumour incidences in males (unless otherwise indicated) in the studies taken into consideration by EU authorities

Study (year) duration (months)Species/strainTumour typeDoses (mg/kg body wt.)
--------------------------------
Number of tumours observed		P values (two-tailed) for trend test/pairwise comparison (significant values in bold)
Lankas (1981)
(26 months)		Rat/SDPancreatic carcinoma0—3—10.3—31.5
-------------------------
0—0—0—1		0.0496/1.000 (Fisher’s)
Stout & Ruecker (1990)
(24 months)		Rat/SDPancreatic islet cell adenoma0—89—362—940
-------------------------
1—8—5—7		0.1687/0.062 (Fisher’s)
Liver cell adenoma0—89—362—940
-------------------------
2—2—3—7		0.0171/0.162 (Fisher’s)
Liver cell adenoma and carcinoma0—89—362—940
-------------------------
5—4—4—9		0.0752/0.392 (Fisher’s)
Thyroid C-cell adenoma in females0—89—362—940
-------------------------
2—2—6—6		0.0435/0.168*
Knezevich and Hogan (1983)
(24 months)		Mouse/Crl:CD-1, Charles River WilmingtonLymphoreticular neoplasms†0—157—814—4841
-------------------------
2—5—4—2		No significant difference; no details given in CLH Report
Renal carcinoma0—157—814—4841
-------------------------
0—0—1—2		0.0370/0.495 (Fisher’s)
Renal adenoma and carcinoma0—157—814—4841
-------------------------
1—0—1—3		0.0339/0.617 (Fisher’s)
Atkinson et al (1993)
(24 months)		Mouse/Crl:CD-1, Charles River PortageMalignant  lymphoma‡0—100—300—1000
---------------------------
4—2—1—6		No meaningful statistics possible due to incomplete histopathology, but significant in trend test
Haemangiosarcoma0—100—300—1000
---------------------------
0—0—0—4		0.0004/0.059 (Fisher’s)
Sugimoto (1997)
(18 months)		Mouse/Crj:CD-1Malignant lymphoma0—165—838—4348
----------------------------
2—2—0—6		0.0085/0.269 (Fisher’s)
Haemangiosarcoma0—165—838—4348
-------------------------
0—0—0—2		0.0078/0.495 (Fisher’s)
Renal tubular adenoma0—165—838—4348
-------------------------
0—0—0—2		0.0078/0.495 (Fisher’s)
Kumar (2001)
(18 months)		Mouse/Swiss AlbinoMalignant lymphoma0—15—151—1460
--------------------------
10—15—16—19		0.0655/0.077§(Fisher’s)
Malignant lymphoma in females0—15—151—1460
--------------------------
18—20—19—25		0.068/0.225§ (Fisher’s)
Renal tubular adenoma0—15—151—1460
--------------------------
0—0—1—2		0.0390/0.495 (Fisher’s)
Wood et al (2009)
(18 months)		Mouse/Crl:CD-1Malignant lymphoma0—71—234—810
-------------------------
0—1—2—5		0.0037/0.067 (χ2)

  • A p value of <0.05  is considered statistically significant; p values for pairwise comparisons are for high-dose vs control group. Two-tailed tests were used. Number of animals per group and sex, in most cases 50, ranged from 43 to 60 in the different studies. Only the  seven studies with significant findings are depicted in the table.

  • *Own calculation, not given in [13].

  • ↵†No specification of malignant lymphoma.

  • ‡The incidences shown are only from lymph nodes with macroscopic changes.13

  • §Statistically significant in pairwise comparison in the Z-test (used in the original study report).