Compound	Strain	Duration	Equivalent doses of sodium or potassium nitrite	NOAEL	Main observed effects	Reference
Subchronic toxicity studies
Sodium nitrite and potassium nitrite	Wistar rats	13 weeks	Sodium nitrite = 7.3, 219 mg/kg bw per day Potassium nitrite = 1.1, 2.2, 4.5, 9, 270 mg/kg bw per day	Sodium nitrite = 7.3 mg/kg bw per day Potassium nitrite = 9 mg/kg bw per day	♂ ➚ Methaemoglobin ♀ Hypertrophy zona glomerulosa adrenal glands ➘ Plasma aldosterone and corticosterone ♀ ➚ Methaemoglobin	Til et al. (1997)
Sodium nitrite	B6C3F1 mice	14 weeks	90, 190, 345, 650, 990 mg/kg bw per day ♂ 120, 240, 445, 840, 1,230 mg/kg bw per day♀	345 mg/kg bw per day ♂ 240 mg/kg bw per day ♀	♂ ➚ Extramedullary haematopoiesis ♀➚ Extramedullary haematopoiesis	NTP (2001)
Sodium nitrite	F344/N rats	14 weeks	30, 55, 115, 200, 310 mg/kg bw per day ♂ 40, 80, 130, 225, 345 mg/kg bw per day ♀	115 mg/kg bw per day ♂ 130 mg/kg bw per day ♀	♂➚ Methaemoglobin, reticulocytes, cell volume, cell haemoglobin ♀➚ Methaemoglobin, hematocrit, cell volume, cell haemoglobin	NTP (2001)
Potassium nitrate	Wistar rats	11 days	211 mg/kg bw per day ♂	NI	➘ Blood pressure	Vleeming et al., 1997
Sodium nitrite	2K1C Wistar rats	6 weeks	5.6, 61, 85 mg/kg bw per day ♂	NI	➘ Systolic blood pressure, ➚ NO levels	Montenegro et al. (2011)
Sodium nitrite	Albino rats	3 months	80 mg/kg bw per day ♂	NI	➚ Plasma glucose, AST, ALT, ALP, bilirubin, urea, creatinine;➘ total protein	Hassan et al. (2009, 2010)
Sodium nitrite	F344 rats	7 days	240 mg/kg bw per day ♂	NI		Okasaki et al. (2006)
Chronic toxicity and carcinogenicity studies
Sodium nitrite	Male rats (strain not specified)	14 months	100 mg/kg bw	NI	➚ Methaemoglobin,➚ GSH in red blood cells,;➘plasma vitamin E	Chow and Hong (1980)
Sodium nitrite	F344 rats	104 weeks treatment (120 weeks follow‐up)	62.5, 125 mg/kg bw per day♂, ♀	125 mg/kg bw per day	No statistically significant effects	Maekawa et al. (1982)
Sodium nitrite	B6C3F1 mice	104–105 weeks	60, 120, 220 mg/kg bw per day ♂ 45, 90, 165 mg/kg bw per day ♀	220 mg/kg bw per day ♂ 165 mg/kg bw per day ♀	No statistically significant effects	NTP (2001)
Sodium nitrite	F344/N rats	104–105 weeks	35, 70, 130 mg/kg bw per day ♂ 40, 80, 150 mg/kg bw per day ♀	130 mg/kg bw per day ♂ 150 mg/kg bw per day ♀	♂♀➚ Methaemoglobin; blood plasma nitrite at highest dose ♂♀➚ incidence of minimal stomach hyperplasia at highest dose tested	NTP (2001)
Sodium nitrite	Rats (strain not specified)	104 weeks treatment (120 weeks follow‐up)	NI	NI	➚ Methaemoglobin; dilated bronchi infiltrated with lymphocytes; foci and fibrosis in heart coronaries thin and dilated	Shuval and Gruener (1972)
Others studies
Sodium nitrite + fish meal	F344 rats	104 weeks	6 mg/kg bw per day ♀, ♂	NI	➚ Incidence of atypical renal tubules at the highest fish meal tested	Furukawa et al. (2000)
Sodium nitrite + ascorbic acid + butylated hydroxyanisole	F344 rats ♂	42 weeks	45, 90, 180 mg/kg bw per day	NI	➚ Incidence of squamous cell carcinomas and forestomach hyperplasia when given together with ascorbic acid. No statistically significant effects alone	Okasaki et al. (2006)
Sodium nitrite + ascorbic acid + MNNG	F344 rats	12 weeks	240 mg/kg bw per day ♂	NI	No statistically significant effects	Kuroiwa et al. (2007)
Reproduction toxicity studies
Sodium nitrite	CD‐1 mice	10 weeks	180 mg/kg bw per day	NI	Significant reduction in offspring numbers No effects observed on reproductive parameters measured	Anderson et al. (1978)
Sodium nitrite	CD‐1 mice	RACB (two generation – reproduction toxicity study)	Task 1 = 20, 40, 70, 140, 260 mg/kg bw per day Task 2 = 131, 273, 437 mg/kg bw per day ♂; 123, 254, 412 mg/kg bw per day ♀ Task 4 = 433 mg/kg bw per day ♂; 556 mg/kg bw per day ♀	Task 1: 260 mg/kg bw per day Task 2: 437 mg/kg bw per day ♂; 412 mg/kg bw per day♀ Task 4: 433 mg/kg bw per day♂ 556 mg/kg bw per day ♀	No statistically significant effects	NTP (1990)
Reproduction end‐points examined in subchronic toxicity studies
Sodium nitrite	B6C3F1 mice	90, 190, 345, 990 mg/kg bw per day ♂; 120, 240, 445, 1230 mg/kg bw per day ♀	14 weeks	990 mg/kg bw per day ♂; 240 mg/kg bw per day ♀	♂➚ testicular degeneration ♀ ➚ oestrous cycle length	NTP (2001)
Sodium nitrite	F344/N	30, 115, 310 mg/kg bw per day ♂; 40, 130, 345 mg/kg bw per day ♀	14 weeks	30 mg/kg bw per day ♂; 345 mg/kg bw per day ♀	♂ ➘ sperm motility at two highest doses	NTP (2001)
Developmental toxicity studies
Sodium nitrite	Pregnant albino CD‐1 mice	From (GD) 6–15	Via gavage with 0, 0.2, 1.1, 5.0 or 23.0 mg sodium nitrite/kg bw per day	Highest dose tested	No adverse effects for dams and fetuses	FDA (1972a)
Potassium nitrite	Pregnant albino CD‐1 mice	From (GD) 6–15	Via gavage with 0, 0.3, 1.5, 7.0 or 32.0 mg potassium nitrite/kg bw per day	Highest dose tested	No adverse effects for dams and fetuses	FDA (1972b)
Sodium nitrite	Pregnant albino Wistar rats	From (GD) 6–15	via gavage with 0, 0.1, 0.5, 3.0, 10.0 mg sodium nitrite/kg bw per day	3.0 mg/kg bw per day	Slight effect on skeletal retardation	FDA (1972a)
Potassium nitrite	Pregnant albino Wistar rats	From (GD) 6–15	via gavage with 0, 0.1, 0.5, 3.0, 10.0 mg sodium nitrite/kg bw per day	3.0 mg/kg bw per day	Slight effect on skeletal retardation	FDA (1972b)
Sodium nitrite	Pregnant Golden hamsters	From (GD) 6–10	via gavage 0, 0.2, 1.1, 5.0 or 23.0 mg sodium nitrite/kg bw per day	Highest dose tested	No adverse effects for dams and fetuses	FDA (1972a)
Potassium nitrite	Pregnant Golden hamsters	From (GD) 6 – 10	via gavage with 0, 0.3, 1.5, 7.0 or 32.0 mg potassium nitrite/kg bw per day	Highest dose tested	No adverse effects for dams and fetuses	FDA (1972b)
Sodium nitrite	Dutch belted rabbits	From (GD) 6–18	via gavage with 0, 0.2, 1.1, 5.0 or 23.0 mg sodium nitrite/kg bw per day		High mortality rates (not relevant for risk assessment)	FDA (1972a)
Potassium nitrite	Dutch belted rabbits	From (GD) 6–18	via gavage with 0, 0.2, 1.1, 5.0 or 23.0 mg sodium nitrite/kg bw per day		High mortality rates (not relevant for risk assessment)	FDA (1972b)

AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase.