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Evaluation of subchronic repeated administration toxicity of ammonium nitrate in rats

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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.

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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

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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.

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Authors and Affiliations

  1. Department of Pathology, Inhalation Toxicity Research Center, Chemicals Toxicity Research Bureau, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency, 30, Expo-ro 339beon-gil, Yuseong-gu, Daejeon, 34122, Republic of Korea

    Mi Ju Lee, Yong Hyun Chung, Hye Yeon Choi & Hyo-Geun Cha

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  1. Mi Ju Lee
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  2. Yong Hyun Chung
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  3. Hye Yeon Choi
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  4. Hyo-Geun Cha
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Correspondence to Mi Ju Lee.

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Lee, M.J., Chung, Y.H., Choi, H.Y. et al. Evaluation of subchronic repeated administration toxicity of ammonium nitrate in rats. Toxicol Res. 36, 115–122 (2020). https://doi.org/10.1007/s43188-019-00022-4

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  • DOI: https://doi.org/10.1007/s43188-019-00022-4

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