National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/16218

Abstract for IMM98003 - Dichloroacetic Acid (CASRN 79-43-6)

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see http://ntp.niehs.nih.gov/ntp/htdocs/levels/09-3566%20NTP-ITOX-R1.pdf). The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.

NTP Study Number: IMM98003

Disinfection by-products (DBPs) are contaminants found in drinking water. DBPs are formed as by-products as a result of the chlorination/ozination process used to purify water to acceptable drinking water standards. The potential effects of drinking water contaminants to affect adversely the immune system is a concern of both the Environmental Protection Agency (EPA) and the National Institute of Environmental Health Sciences (NIEHS). Several drinking water DBPs have been identified and selected for evaluation of their potential effects on the immune system in a joint project between the EPA and the NIEHS.

The National Toxicology Program (NTP) requested that a dose range-finding study be performed in order to establish the potential effects of dichloroacetic acid (DCA) on the immune system and to determine doses that could be used in a full immunotoxicology study. These studies were conducted in female B6C3F1 mice. The animals were exposed to DCA based on the concentration of the test article in the drinking water. Five DCA concentrations of 125, 250, 500, 1000 and 2000 mg/L for 28 days were utilized. The national average for DCA in finished drinking water is 12.4 µg/l. DCA solutions were prepared fresh every two weeks in tap water and stored refrigerated. The in-life phase of these studies was carried out between 10 April 1998 and 26 May 1998.

The baseline toxicology studies are summarized in Table ES-1. There were few notable changes among the standard toxicological parameters that were assessed with the exception of a dose-related increase in liver weight and decreases in reticulocytes counts.

The immunological studies are summarized in Table ES-2. In contrast to the toxicological effects observed, DCA, at the doses administered, had virtually no effect on the various immunological endpoints evaluated.

In summary, based on the results of this range-finding study, further investigation of the effect of DCA on the immune system appears unwarranted. As a disinfection by-product, human exposure to DCA can occur from the drinking water; however, the immune system does not appear to be a major target organ for DCA.

 

Table ES-1
SUMMARY TABLE FOR TOXICOLOGY STUDIES
RF-DCA-28-1M-DW

Body Weight
Parameter Results Maximum
Effect
Dose Comment
Day 1 No Effect
 

 

 
Day 8 No Effect
 

 

 
Day 15 No Effect
 

 

 
Day 22 No Effect
 

 

 
Day 29 No Effect
 

 

 
Weight Changes
Parameter Results Maximum
Effect
Dose Comment
Day 8-1 No Effect
 

 

 
Day 15-1 No Effect
 

 

 
Day 22-1 No Effect
 

 

 
Day 29-1 No Effect
 

 

 
Pathology
Parameter Results Maximum
Effect
Dose Comment
Gross Pathology No Effect
 

 

 
Histopathology Not Conducted
 

 

 
Organ Weights
 

 

 

 
Liver Increase 41% 2000 ml/L Abs. Bdy Wgt
% Bdy Wgt
Spleen No Effect
 

 

 
Lungs No Effect
 

 

 
Thymus No Effect
 

 

 
Kidney No Effect
 

 

 
Hematology
Parameter Results Maximum
Effect
Dose Comment
RBCs No Effect
 

 

 
Hemoglobin Decrease 6% 2000 mg/L
 
Hematocrit Decrease 4% 2000 mg/L
 
MCV Decrease 3% 2000 mg/L
 
MCH Decrease 5% 2000 mg/L
 
MCHC Decrease 2% 125 mg/L
2000 mg/L

 
Platelets No Effect
 

 

 
Reticulocytes Decrease 25% 1000 mg/kg
 
Leukocytes No Effect
 

 

 
% Lymphocytes No Effect
 

 

 
% Neutrophils No Effect
 

 

 
% Eosinophils No Effect
 

 

 
Abs Lymphocytes No Effect
 

 

 
Abs Neutrophils Increase 108% 2000 mg/L
 
Abs Eosinophils No Effect
 

 

 


Table ES-2
SUMMARY TABLE FOR IMMUNOLOGY STUDIES
RF-DCA-28-1M-DW

Surface Makers (Absolute Values)
Parameter Results Maximum
Effect
Dose Comment
Ig+ No Effect
 

 

 
CD3+ No Effect
 

 

 
CD4+CD8- No Effect
 

 

 
CD4-CD8+ No Effect
 

 

 
CD4+CD8+ No Effect
 

 

 
NK1.1+CD3- No Effect
 

 

 
Mac-3+ No Effect
 

 

 
IgM Humoral Immune Response to Sheep Erythrocytes
Parameter Results Maximum
Effect
Dose Comment
IgM AFC Response No Effect
 

 

 
Serum Titer No Effect
 

 

 
Mixed Leukocyte Response
Parameter Results Maximum
Effect
Dose Comment
Responders Only No Effect
 

 

 
Responders + Stimulators No Effect
 

 

 
Macrophage
Parameter Results Maximum
Effect
Dose Comment
PEC Activity without MAF No Effect
 

 

 
PEC Activity with MAF No Effect
 

 

 
NK Cell Activity
Parameter Results Maximum
Effect
Dose Comment
NK Cell Activity No Effect
 

 

 

Report Date: July 2002

NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.