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Evaluation of subchronic repeated administration toxicity of ammonium nitrate in rats

  • Mi Ju LeeEmail author
  • Yong Hyun Chung
  • Hye Yeon Choi
  • Hyo-Geun Cha
Original Article
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Abstract

Ammonium nitrate is a chemical mostly used in agriculture and munitions to produce fertilizers and explosives, respectively. Its annual production and consumption exceed ten million tons. Despite is diverse uses, large production and consumption, and occupational risk, information on the toxicity that results from oral exposure to ammonium nitrate is limited. In this study, the safety of ammonium nitrate was therefore evaluated by observing its subchronic toxicity in rats. Ammonium nitrate (0, 100, 300 and 1000 mg/kg/day) was orally administered by gavage to rats at 5 times/week for 13 weeks. Reversibility of the effects of 1000 mg/kg/day was assessed in rats after 2 weeks. Mortality, clinical signs, body weight, and food consumption were monitored. Hematology, serum chemistry, urinalysis, organ weight, necropsy, and histopathology were performed. Salivation was intermittently observed in both sexes receiving 300 and 1000 mg/kg/day ammonium nitrate, which normalized 2 weeks post-treatment. Urine volume increased in both sexes receiving 1000 mg/kg/day ammonium nitrate. Urine pH decreased in both sexes of all dosing groups when compared with the concurrent control group. Urinary changes normalized 2 weeks post-treatment. Blood urea nitrogen levels increased in males receiving 1000 mg/kg/day, but normalized 2 weeks later. Potassium level in males and sodium and chloride levels in both sexes receiving 1000 mg/kg/day ammonium nitrate decreased, but normalized 2 weeks later. Hypertrophy of zona glomerulosa in the adrenals was observed in both sexes receiving 1000 mg/kg/day and in females receiving 300 mg/kg/day ammonium nitrate. After a 2-week recovery period, the same lesion was observed in one female receiving 1000 mg/kg/day ammonium nitrate. Our results indicate that ammonium nitrate induces reversible salivation, increases BUN levels, induces acidic diuresis with decreases in sodium, potassium, and chloride levels, and induces ZG hypertrophy. These results shed light on the toxicity profile of ammonium nitrate.

Keywords

Ammonium nitrate 13-Week repeated toxicity 2-Week recovery Reversible changes 

Abbreviations

LD50

50% lethal dose

APTT

Activated partial thromboplastin time

ALT

Alanine aminotransferase

Alb

Albumin

A/G

Albumin/globulin ratio

ALP

Alkaline phosphatase

AST

Aspartate aminotransferase

BUN

Blood urea nitrogen

Ca

Calcium

Cl

Chloride

Crea

Creatinine

Glu

Glucose

HCT

Hematocrit

H&E

Hematoxylin and eosin

HGB

Hemoglobin concentration

LDH

Lactate dehydrogenase

LYM

Lymphocyte

MCH

Mean cell hemoglobin

MCHC

Mean cell hemoglobin concentration

MCV

Mean cell volume

NEU

Neutrophil

ANOVA

One-way analysis of variance

P

Phosphorus

PLT

Platelet count

K

Potassium

PT

Prothrombin time

Reti

Reticulocyte count

Na

Sodium

T-Bili

Total bilirubin

T-Chol

Total cholesterol

RBC

Total erythrocyte count

WBC

Total leukocyte count

TP

Total protein

TG

Triglyceride

ZG

Zona glomerulosa

GGT

γ-Glutamyl transpeptidase

Notes

Acknowledgements

This work was supported by the Korea Occupational Safety and Health Agency, Ministry of Labor, Republic of Korea, and a Grant-in-Aid for chemical hazard assessment.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Korean Society of Toxicology 2019

Authors and Affiliations

  • Mi Ju Lee
    • 1
    Email author
  • Yong Hyun Chung
    • 1
  • Hye Yeon Choi
    • 1
  • Hyo-Geun Cha
    • 1
  1. 1.Department of Pathology, Inhalation Toxicity Research Center, Chemicals Toxicity Research Bureau, Occupational Safety and Health Research InstituteKorea Occupational Safety and Health AgencyDaejeonRepublic of Korea

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