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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Peer-reviewed, non-GLP study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Deviations:
not specified
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
The ammonium sulfamate used was a white crystalline, hygroscopic, solid having the following characteristics: purity, 99%;moisture, 0.5%; iron, 100 ppm (maximum); m.p., 130°C; solubility, extremely soluble in water and moderately soluble in glycerol, glycol and formamide.

Test animals

Species:
rat
Strain:
other: ITRC derived albino
Sex:
female

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
90 days
Frequency of treatment:
Continual (drinking water) 6 days/week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
100 mg/kg/day
Basis:
nominal in water
Remarks:
Doses / Concentrations:
250 mg/kg/day
Basis:
nominal in water
Remarks:
Doses / Concentrations:
500 mg/kg/day
Basis:
nominal in water
No. of animals per sex per dose:
20
Control animals:
yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
Throughout the period of observation, the general condition and health of all rats remained apparently good.
Mortality:
mortality observed, non-treatment-related
Description (incidence):
One rat each from the adult (group 3) and male weanling (group 4) died on day 64 and day 76 of the experiment respectively due to bronchopneumonia.
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
There was no significant difference in the mean body weight of control or treated animals during or at the end of observation period. However, adult rats of group 4 started to lag behind in weight gain after 45-day period. By the end of 90 days the body weight of this group was significantly (P < 0.05) less than the weight of the controls
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
In general the food intake relative to body weight gradually decreased in all groups of rats as the ex'periment progressed. While there was no noticeable difference in case of adults, the food intake was significantly (P < 0.05) less by the weanlings (group 4), both males and females, as compared to the controls (Table II).
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Description (incidence and severity):
Water intake increased generally in all groups of rats. The weanlings (group 4), males as well as females, drank significantly (P< 0.01) more water than the controls
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Description (incidence and severity):
Haematological examination conducted at 30, 60 and 90 days revealed no significant changes.
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
There was no significant difference in the relative organ weights of all groups of animals as compared to controls.
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
In the histological examination, organs in all groups of animals appeared normal.
Histopathological findings: neoplastic:
not examined
Other effects:
not examined

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
food consumption and compound intake

Target system / organ toxicity

Key result
Critical effects observed:
not specified
Lowest effective dose / conc.:
500 mg/kg bw/day (nominal)
System:
other:
Organ:
not specified

Any other information on results incl. tables

Mean values of body weights of rats given daily oral doses of 100-500 mg/kg of ammonium sulfamate for 90 days

 

Body weights are means of 20 rats on 1st, 15th and 30th day, 14 rats on 45th and 60thday and 8 rats on 90th day.

 

Dose level

(mg/kg)

Body weight (g) at day

0a

15

30

45

60

90

Adult females

0

188

190

199

212

214

222

100

179

198

201

206

215

218

250

184

189

193

203

210

215b

500

180

188

196

210

195c

186c

Weanling males

0

47

94

141

168

178

212

100

37

89

135

159

177

206

250

40

87

140

165

169

209a

500

38

92

133

155

180

216b

Weanling females

0

48

91

118

138

147

152

100

42

86

115

127

144

148

250

46

89

107

132

150

156

500

42

85

111

129

140

155

a First day of feeding.

b Means of 7 rats.

c Differ significantly from those of controls, P < 0.05.

Mean values of food consumption of rats given daily oral doses of 100 -500mg/kg of ammonium sulfamate for 90 days

Food consumptions are means of 20 rats on1st, 15th and 30th day, 14 rats on 45th and 60th day and 8 rats on 90 th day. Food consumption was measured over the 24 -h period preceding the day shown.

 

Dose level (mg/kg)

Food consumption (g/rat/day) at day

Mean food consumption (g/rat/day)

0a

15

30

45

60

75

90

Adult females

0

12.5

12.2

12

11.8

11.5

11

10.7

11.5

100

12

11.8

11.8

11.4

11

10.7

10.5

11.2

250

12.8

12.4

12

11.7

11.4

11

10.7 b

11.5

500

12.6

12

11.7

11.5

11.5

11.1

10.8

11.4

Weanling males

0

14.2

14

13.8

13.5

13.5

13.1

13

13.5

100

14.5

14.2

13.9

13.6

13.1

12.8

12.8

13.4

250

14.8

14.5

14.2

13.9

13.5

13

12.6

13.6

500

14.6

14

12.5

10.2

8.5

6.3

5.4b

9.5c

Weanling females

0

13.5

13.1

12.8

12.6

12.2

12.2

11.9

12.5

100

13

13.4

13

12.6

12.3

11.8

11.5

12.4

250

13.6

13

12.7

12.5

12.2

12

12

12.4

500

13.2

12.8

11.5

10.1

9

8.6

6.8

9.8c

aFirstday offeeding.

b Meansof7rats.

c Differsignificantlyfromthoseofcontrols,p<0.05.

 

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study, the No Observed Adverse Effect Level (NOAEL) in rats exposed to the ammonium salt of sulphamidic acid orally for 90 days is 500 mg/kg bw/day.
Executive summary:

A 90-day study involving administration of 0 (group 1), 100 (group 2), 250 (group 3) and 500 mg/kg (group 4) of ammonium sulfamate to rats 6 days a week was carried out. No adverse effect was observed in respect of appearance, behaviour or survival of animals. No significant difference in the body weights of rats was observed except in case of adult rats (group 4) where the body weight was significantly less than the controls after the end of 60 days. In all the groups, food intake gradually reduced whereas water intake increased as the experiment proceeded. No significant change in relative organ weights were noticed in all groups of rats. Haematological examination conducted at 30, 60 and 90 days revealed non-significant increase in the neutrophils in the adults and male weanling rats (group 4) after 90 days. In the histological examination, organs in all the groups of animals appeared normal except that the liver of 1 rat in adults (group 4) showed slight fatty degenerative changes after 90 days. The No Observed Adverse Effect Level (NOAEL) was 500 mg/kg bw/day.