Arsenic acid

Endpoint summary

Description of key information

Testing was performed for 2 years in rats and dogs with sodium arsenate. 
In rats, marked enlargement of the common bile duct was observed at 250 and 400 ppm and these levels also caused weight depression and decreased survival. Body weight was slightly reduced in both sexes at 125 ppm.  The NOAEL in rat for sodium arsenate is then 62.5 ppm equivalent to 3.1 mg/kg bw/day. 
In dogs, high dose groups showed no treatment-related systemic effects except for weight depression and mild anemia. Only microscopic finding related to treatment was the presence of granular, brownish, iron-positive, nonbirefringent pigment in the liver macrophages in all dogs at high dose groups but was seen only randomly below this level and was noted in one control animal. The NOAEL in dog for sodium arsenate is then 50 ppm equivalent to 1.25 mg/kg bw/day.
For the derivation of a key value for chemichal safety assessment of arsenic acid, carcinogenicity appears as the critical end-point with lowest NOAEL and will therefore be used to derive the DNEL. 

Additional information

In a 2 year study, sodium arsenate was administered through feed to groups of 50 weanling Osborne-Mendel rats/sex/dose at 400, 250, 125, 62.5 and 31.25 ppm. Main finding were a slight increase of leukocyte count in the females at the highest dosage throughout the experiment and in the males for the first year. No distinct differences in ratio of organ weight to body weight were noted. Marked enlargement of the common bile duct was observed at 250 and 400 ppm and these levels also caused weight depression and decreased survival. At 250 ppm, survival was slightly reduced, enlargement of the common bile duct (less pronounced) and reduced weight, particularly in females was observed. At 125, 62.5 and 31.25 ppm, arsenate did not cause common bile duct enlargement and did not affect survival. Body weight was slightly reduced in both sexes at 125 ppm. No carcinogenic effect could be detected. Histopathologically, enlarged common bile ducts showed hyperplasia of the glandular elements, focal necrosis and fibrosis. The NOAEL in rat for sodium arsenate is then 62.5 ppm equivalent to 3.1 mg/kg bw/day.

 

In the same study, sodium arsenate was administered through feed to groups of 6 Beagle dogs/sex/dose at 125, 50, 25 and 5 ppm. Only one of six dogs on the high level of arsenate died, and this one dog lost much weight. High dose groups showed no treatment-related systemic effects except for weight depression and mild anemia. No gross pathology was reported except for weight loss at the high level and traumatic brain hemorrhage in one dog. Only microscopic finding related to treatment was the presence of granular, brownish, iron-positive, nonbirefringent pigment in the liver macrophages in all dogs at high dose groups but was seen only randomly below this level and was noted in one control animal. The NOAEL in dog for sodium arsenate is then 50 ppm equivalent to 1.25 mg/kg bw/day.