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parameters (decreased pH, specific gravity and colour intensity; increased urine volume; presence
of crystalline hydroxyatrazine sediments) were observed at 400 ppm.
Necropsy of rats at interim and decedent rats at 400 ppm revealed discoloration and enlargement
of renal lymph nodes and calculi, cysts, dilated pelvis and rough pitted surface of the kidney.
Additionally, in males calculi and thickened walls were recorded in the urinary bladder. Absolute and
relative kidney weights were increased in males (+19% and +50%) and females (+10% and +51%)
at 400 ppm at 12 months only.
Treatment-related histopathological changes in the kidneys were noted at 200 ppm and greater
at all killing intervals and included the deposition of crystalline material within collecting ducts, renal
pelvises and occasional distal tubules (summarized in Table 19 as “dilatation with crystal deposits”).
Tubules and collecting ducts that contained the crystalline material were dilated and either devoid of
epithelium or lined by hyperplastic tubular epithelium. The tubular changes were often accompanied
by acute intratubular inflammatory infiltration and by thickening and fibrosis of the papillary interstitium.
In kidneys that contained pelvic aggregates of the crystalline material, multifocal transitional
cell erosion and/or ulceration of the renal transitional epithelium was noted.
In the renal papillae, swelling and increased eosinophilia of interstitial cells, which was accompanied
by the interstitial accumulation of a hyaline basophilic material (acidic sulfated mucosubstances
that make up the ground substance of the interstitial matrix) was significantly increased in
incidence/severity in males at 200 ppm and greater and in females at at 25 ppm and greater. However,
the toxicological significance of the minimal to moderate accumulation of this matrix in females at
25 ppm, in the absence of any other signs of renal damage or impaired renal function, was highly
questionable.
In males at 400 ppm and in females at 200 ppm and greater, papillary lesions were accompanied
by cortical changes consistent with chronic progressive nephropathy. These consisted of thickening
of tubular and glomerular basement membranes, tubular dilatation with accumulation of proteinaceous
material, chronic interstitial nephritis, hyaline droplet accumulation within proximal tubular
cells, pronounced glomerulosclerosis and infrequent tubular epithelial basophilia or hyperplasia.
In both sexes at 400 ppm, nephropathy was often accompanied by mineralization of renal
(tubular epithelia and basement membranes) as well as extrarenal (e.g. aorta, heart, and lungs) tissues
(metastatic mineralization).
There was no increase in the incidence of any tumour or decrease in any tumour-onset time that
was attributable to treatment.
Table 19. Relevant histopathological findings in the kidney of rats fed diets containing
hydroxyatrazine in a long-term study of toxicity
Finding
Dietary concentration (ppm)
Males
Females
0 10 25 200 400 0 10 25 200 400
Kidney, No. examined 79 69 70 70 80 79 70 68 69 80
Dilatation with crystal deposits 0 0 0 5** 79** 0 0 0 15** 78**
Nephropathy, progressive 75 67 64 65 80** 36 32 34 50** 79**
Papilla, accumulation, interstitial, matrix 4 3 2 32** 17 10 26* 26 0**
Papilla, fibrosis, interstitial 1 2 1 11** 80** 0 0 0 20** 79**
Pelvis, dilatation with crystal deposits 0 0 0 5 60** 0 0 0 9* 40**
From Chow & Hart (1995)
* p < 0.05; ** p < 0.01.
ATRAZINE 37–138 JMPR 2007