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.