AMMONIUM SULFATE CAS NÂ°: 7783-20-2

More documents

Recommendations

Info

OECD SIDS AMMONIUM SULFATE 3.1.5 Repeated Dose Toxicity Studies in Animals Inhalation The repeated dose toxicity after inhalation of ammonium sulfate aerosols was studied in rats, guinea pigs, and hamsters, using non-standard protocols. In most of the studies the animals were pretreated with intratracheal instillations, only one concentration was tested, the test protocol was not validated, the scope of the examinations was limited or the animals were examined not immediately after the last exposure, so only one study is considered to be sufficiently reliable. In a 14-day inhalation study, 10 male rats were exposed to an ammonium sulfate aerosol for 8 hours/day at a concentration of 300 mg/m 3 (count mean particle diameter: 1 - 2 µm). The concentration used was determined on the basis of a preliminary study with rats, which were exposed for 3 consecutive days to the maximum attainable concentration of ammonium sulfate (1000 - 1200 mg/m 3 ; 8 hours/day; count mean particle diameter: 2 - 3 µm). No adverse effects were noted in this pre-test. In the main study, arterial blood gases were measured after 1, 3, 7, and 14 days. Pulmonary function tests were performed after 14 days of exposure and histological examinations were performed at the end of the exposure period. The exposure did not result in any significant changes in lung morphology, lung volumes, and arterial blood gases. The histological examinations did not reveal any changes in the trachea, bronchial lymph nodes, and lungs and the exposure had no adverse effects on body weight. A NOEL of 300 mg/m 3 for toxicity to the lower respiratory tract can be deduced from the study (Pepelko, Mattox and Cohen, 1980). In an inhalation study consisting of two separate experiments with 160 male hamsters, in the ammonium sulfate group and control group, resp, the incidence or severity of pneumonitis or pulmonary fibrosis was not significantly increased after 15 weeks of exposure (6 hours/day, 5 days/week) to approximately 0.2 mg ammonium sulfate/m 3 . The animals were examined after 2 years. Also, no significant pathological changes of organs were observed. This inhalation did increase the incidence of emphysema as examined microscopically but not the severity. The increase in emphysema incidence was not statistically significant (9.0 vs 15.2 %; EPA, 1978). Another publication of this study described an increase in emphysema incidence, which is however of doubtful statistical significance. It was based on only 80 animals per group (8.6 vs 16.1 %; Godleski et al., 1984). Due to the higher number of animals used, the EPA results are more reliable and 0.2 mg ammonium sulfate/m 3 cannot be regarded as a LOAEL. However it seems not acceptable to take 0.2 mg/m 3 as the NOAEL from this study because the animals were not examined immediately after exposure but only after 2 years. Studies in animals pre-treated with intratracheal instillations: Loscutoff et al. (1985) exposed 27 - 29 male Sprague-Dawley rats/group for 5 or 20 days (6 hours/day, 5 days/week) to approximately 1 mg/m³ of ammonium sulfate aerosol (MMAD: 0.42 µm) after receiving an intratracheal instillation of saline. The exposure resulted in an increased residual volume and functional residual capacity indicative of a mild pulmonary emphysema. In a further study, 20 Sprague-Dawley rats were exposed for 20 days (6 hours/day, 5 days/week) to approximately 1.03 mg/m³ of ammonium sulfate aerosol (MMAD: 0.42 µm) after receiving an intratracheal instillation of saline or elastase. The exposure resulted in a measurable degree of enlargement of alveoli, alveolar ducts and sacs (Busch et al., 1984). These changes may be indicative of beginning lung emphysema; clear changes were, however, only found in elastase pretreated animals. 20 UNEP PUBLICATIONS
OECD SIDS AMMONIUM SULFATE A similar study was carried out with 15 Hartley guinea pigs, exposed for 20 days (6 hours/day, 5 days/week) to approximately 1.03 mg/m³ of an ammonium sulfate aerosol (MMAD: 0.42 µm) after receiving an intratracheal instillation of saline. The exposure resulted in an apparent alteration in the secretory activity characterized by hypertrophy and hyperplasia of non-ciliated epithelial cells, with an increased number of secretory granules per cell. Changes comparable to those in the rat study were not seen (Busch et al., 1984). The reported changes may be seen as signs of an inflammatory response. In another study, the examination of the lung function of 29 Hartley guinea pigs exposed for 5 or 20 days (6 hours/day, 5 days/week) to approximately 1 mg/m³ of ammonium sulfate aerosol (MMAD: 0.42 µm) after receiving an intratracheal instillation of saline revealed no adverse effect (Loscutoff et al., 1985). In a further study by the same working group (Smith et al., 1989), groups of rats were pre-treated intratracheally with either physiologic saline or porcine pancreatic elastase. Animals of each pretreatment group were exposed to filtered air (controls), or to 0.5 mg/m 3 ammonium sulfate for 5 hours/day and 5 days/week for 4 months (n = 15), 8 months (n = 15), or for 8 months plus 3 months recovery (n = 14), There were no signifycant differences in final body weights or in the investigated immunologic parameters measured after 4 months (spleen weight, mitogenic response of spleen cells, peripheral blood lymphocytes, distribution of T cells in the spleen). No differences were found in vital capacity, total lung capacity, time constant, CO 2 -diffusion capacity, residual volume, functional residual capacity, or N 2 -slope measured after 4 months. The quasistatic compliance was slightly, though significantly reduced. Main results from the saline-pretreated groups are summarized in the following table (results from elastase-pretreated animals are not included): Table 2: Morphological lung effects in saline-pretreated rats after exposure to ammonium sulfate for 4 months, 8 months, or 8 months plus 3 months recovery: number of animals with effect / total number of animals 4 months treatment 8 months treatment 8 months treatment plus 3 months recovery Air (NH 4 ) 2 SO4 Air (NH 4 ) 2 SO 4 Air (NH 4 ) 2 SO 4 Emphysema 2/15 0/15 0/13 2/15 2/13 4/14 Alveolar birefringence Bronchiolar epithelial hyperplasia NEC a counts (cells/standard area) Chord length Mean (mm) Median (mm) 8/15 0/15 9/13 15/15* 10/13 12/14 6/15 13/15* 0/13 0/15 0/13 0/14 27.7 32.7* 24.8 30.0* 26.4 25.9 4.66 4.29 a Nonciliated epithelial cells * p < 0.05 5.07* 4.47* 4.28 3.71 4.45 3.99 3.87 3.60 4.14* 3.92* UNEP PUBLICATIONS 21
Page 1 and 2: OECD SIDS AMMONIUM SULFATE FOREWORD
Page 3 and 4: OECD SIDS AMMONIUM SULFATE 10. Comm
Page 5 and 6: OECD SIDS AMMONIUM SULFATE Similarl
Page 7 and 8: OECD SIDS AMMONIUM SULFATE Consumer
Page 9 and 10: OECD SIDS AMMONIUM SULFATE 1.3 Phys
Page 11 and 12: OECD SIDS AMMONIUM SULFATE - in the
Page 13 and 14: OECD SIDS AMMONIUM SULFATE The inte
Page 15 and 16: OECD SIDS AMMONIUM SULFATE 228 µg/
Page 17 and 18: OECD SIDS AMMONIUM SULFATE also an
Page 19: OECD SIDS AMMONIUM SULFATE 3.1.3 Ir
Page 23 and 24: OECD SIDS AMMONIUM SULFATE diarrhoe
Page 25 and 26: OECD SIDS AMMONIUM SULFATE 3.1.8 To
Page 27 and 28: OECD SIDS AMMONIUM SULFATE oral exp
Page 29 and 30: OECD SIDS AMMONIUM SULFATE Table 3
Page 31 and 32: OECD SIDS AMMONIUM SULFATE No test
Page 33 and 34: OECD SIDS AMMONIUM SULFATE freshwat
Page 35 and 36: OECD SIDS AMMONIUM SULFATE Toxicity
Page 37 and 38: OECD SIDS AMMONIUM SULFATE Table 7
Page 39 and 40: OECD SIDS AMMONIUM SULFATE 6 REFERE
Page 41 and 42: OECD SIDS AMMONIUM SULFATE Gmelin (
Page 43 and 44: OECD SIDS AMMONIUM SULFATE Sato A,
Page 45 and 46: OECD SIDS AMMONIUM SULFATE I U C L
Page 47 and 48: OECD SIDS AMMONIUM SULFATE 1. GENER
Page 59 and 60: OECD SIDS AMMONIUM SULFATE 2. PHYSI
Page 65 and 66: OECD SIDS AMMONIUM SULFATE 3. ENVIR
Page 71 and 72:
OECD SIDS AMMONIUM SULFATE 3. ENVIR
Page 73 and 74:
Page 75 and 76:
Page 77 and 78:
OECD SIDS AMMONIUM SULFATE 4. ECOTO
Page 79 and 80:
Page 81 and 82:
Page 83 and 84:
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
Page 91 and 92:
Page 93 and 94:
Page 95 and 96:
Page 97 and 98:
Page 99 and 100:
Page 101 and 102:
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
Page 109 and 110:
Page 111 and 112:
Page 113 and 114:
Page 115 and 116:
Page 117 and 118:
Page 119 and 120:
Page 121 and 122:
Page 123 and 124:
Page 125 and 126:
Page 127 and 128:
Page 129 and 130:
Page 131 and 132:
Page 133 and 134:
Page 135 and 136:
Page 137 and 138:
Page 139 and 140:
Page 141 and 142:
Page 143 and 144:
OECD SIDS AMMONIUM SULFATE 5. TOXIC
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Page 157 and 158:
Page 159 and 160:
Page 161 and 162:
Page 163 and 164:
Page 165 and 166:
Page 167 and 168:
Page 169 and 170:
Page 171 and 172:
Page 173 and 174:
Page 175 and 176:
Page 177 and 178:
Page 179 and 180:
Page 181 and 182:
Page 183 and 184:
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
Page 195 and 196:
Page 197 and 198:
Page 199 and 200:
Page 201 and 202:
Page 203 and 204:
Page 205 and 206:
Page 207 and 208:
Page 209 and 210:
Page 211 and 212:
Page 213 and 214:
Page 215 and 216:
Page 217 and 218:
Page 219 and 220:
Page 221 and 222:
OECD SIDS AMMONIUM SULFATE 6. REFER
Page 223 and 224:
Page 225 and 226:
Page 227 and 228:
Page 229 and 230:
Page 231:
show all

AMMONIUM SULFATE CAS NÂ°: 7783-20-2

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?