Sulphamidic acid

Repeated dose toxicity: oral

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

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

not specified

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium sulphamidate

EC Number:

231-871-7

EC Name:

Ammonium sulphamidate

Cas Number:

7773-06-0

Molecular formula:

H3NO3S.H3N

IUPAC Name:

ammonium sulfamate

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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
100 mg/kg/day
Basis:
nominal in water

Doses / concentrations 2

Remarks:

Doses / Concentrations:
250 mg/kg/day
Basis:
nominal in water

Doses / concentrations 3

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 60^thday and 8 rats on 90th day.
Dose level (mg/kg)	Body weight (g) at day
	0^a	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	215^b
500	180	188	196	210	195^c	186^c
Weanling males
0	47	94	141	168	178	212
100	37	89	135	159	177	206
250	40	87	140	165	169	209^a
500	38	92	133	155	180	216^b
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)
	0^a	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	5.4^b	9.5^c
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	9.8^c
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.