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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
three-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP guideline study performed for and reviewed and validated by regulatory agencies (USEPA and USFDA)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1964
Report date:
1964

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPP 83-4 (Reproduction and Fertility Effects)
Deviations:
not specified
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
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:
not specified

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
female

Administration / exposure

Route of administration:
oral: feed
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
3 months per generation
Frequency of treatment:
Daily (feed)
Details on study schedule:
Ammonium sulfamate was fed to Ch-CD male and female rats, starting with 29-day old animals, for three months at levels of 0.0, 0.035, and 0.05% of an adequate nutritional diet (Purina Laboratory Chow). This equates to 0, 35 and 50 mg/kg bw/day. At the end of this time, a reproduction study was initiated within each group of 16 male and 16 female rats in which F1a and F1b litters were cast. Sixteen male and 16 female were selected from each of the three groups of the F1b generation and continued on their respective diets for approximately three months, at which time they were bred within groups to produce F2a and F2b litters. Two male and two female weanling rats (21 days old) from each of the five litters of the F2b generation of the groups that received 0.0 and 0.05% ammonium sulfamate in the diet were subjected to a histopathologic evaluation. In addition, 16 male and 16 female rats were selected from each of the three groups of the F2b generation and continued on their respective diets for approximately three months, at which time they were bred within groups to produce the F3a litter.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 35 and 50 mg/kg bw/day
Basis:
nominal in diet
No. of animals per sex per dose:
16
Control animals:
yes, concurrent no treatment

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
not examined
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
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Other effects:
not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed

Effect levels (P0)

Key result
Dose descriptor:
NOAEL
Effect level:
> 50 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
water consumption and compound intake
gross pathology
reproductive performance
Remarks on result:
other:

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
not examined
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
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Other effects:
not examined

Results: F1 generation

Effect levels (F1)

Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
sexual maturation
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
water consumption and compound intake
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic

Results: F2 generation

General toxicity (F2)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Other effects:
not examined

Effect levels (F2)

open allclose all
Key result
Dose descriptor:
NOAEL
Generation:
F2a
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
sexual maturation
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
water consumption and compound intake
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
Key result
Dose descriptor:
NOAEL
Generation:
F2b
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
sexual maturation
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
water consumption and compound intake
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Reproductive Indexes for Multi-Generation

Evaluation of Dietary Ammonium Sulfamate

Group

No. of Pregnancies

No. Pups
Born

(Average/litter)

No. Pups
Born Alive

(Average/litter)

Fertility
Index*

Gestation
Index

Viability
Index

Lactation
Index

F1a

0%

14/16

163 (11.6)

163 (11.6)

88

100

100

95

0.035%

14/17

177 (12.6)

173 (12.4)

88

100

97

95

0.050%

14/16

129 (10.8)

126 (10.5)

75

100

97

95

F1b

0%

15/16

192 (12.8)

190 (12.7)

94

100

97

89

0.035%

13/16

168 (12.9)

156 (12.0)

81

100

98

92

0.050%

11/16

144 (13.1)

144 (11.1)

69

100

99

98

F2a

0%

15/16

186 (12.4)

182 (12.1)

94

100

94

99

0.035%

13/16

144 (11.1)

144 (11.1)*

81

100

99

98

0.050%

14/16

184 (13.1)

172 (12.3)

88

93

91

98

F2b

0%

15/16

197 (13.1)

179 (12.0)

94

100

91

99

0.035%

14/16

186 (13.3)

185 (13.2)

81

100

99

99

0.050%

15/16

204 (13.6)

200 (13.3)

94

100

97

97

F3a

0%

11/16

127 (11.5)*

125 (11.4)

69

100

98

97

0.035%

12/16

118 (9.8)

115 (9.6)

75

100

96

96

0.050%

15/16

168 (11.2)

161 (10.7)

94

100

93

99

* One pup in an otherwise normal litter of 10 had hydrocephalus

 

Fertility Index: Percentage of matings resulting in pregnancy

Gestation Index: Percentage of pregnancies resulting in birth of live litters

Viability Index: Percentage of rats born that survived four days or longer

Lactation Index: Percentage of rats alive 4 days that survived the 21 day lactation period

Applicant's summary and conclusion

Conclusions:
The test substance did not demonstrate any adverse effects on the reproduction or lactation of rats under the condition of this multi-generation reproduction assay.
Executive summary:

Ammonium Sulfamate was fed to ChR rats at levels of 0.0, 0.035 and 0.05% of an adequate nutritional diet. A reproduction study through the F3a generation revealed no adverse effects of two dietary concentrations of the test substance upon the various reproductive and lactational indexes. Histopathologic examination of weanling animals from the control and test group receiving 0.05% ammonium sulfamate of the F2b generation revealed no abnormalities that could be contributed to the feeding of the test compound.