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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: 90-day oral toxicity study
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to internationally accepted guidelines.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: EPA OPP 82-1 (90-Day Oral Toxicity)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Suttocide®A, the CTFA Adopted Name of Sodium Hydroxymethylglycinate- Lot/batch No.: Not specified- Purity: Not specified, but analytical studies were carried out over a twelve week period to determine whether 2%-Suttocide A solutions used in the 90 Day Oral Gavage Study at Food and Drug Research Laboratories, Inc. were stable.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
90 days
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:10, 40, 160 mg/kg bwBasis:actual ingested
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
CAGE SIDE/CLINICAL OBSERVATIONS: Yes - Time schedule: daily two mortality checks five hours apart, once daily for external signs of toxicity- Cage side observations checked in table were included (Appendix III of the study report).BODY WEIGHT and FOOD CONSUMPTION: Yes - Time schedule for examinations: measured prior to initiation of the study (day -1), weekly thereafter, and at the time of necropsy. - Food consumption: measured weekly. - Food efficiency: Yes OPHTHALMOSCOPIC EXAMINATION: Yes - Time schedule for examinations: on all rats prior to initiation of the study and on all rats after 13 weeks of dosing. - The eyes of all rats were examined by indirect ophthalmoscopy after pupil dilation with 1% Tropica-mide. CLINICAL LABORATORY STUDIES: Yes- Blood samples for hematology and clinical chemistry determinations and urine samples for urine analysis were collected after 6 and 13 weeks of dosing from all animals.- Blood was drawn from the periorbi tal plexus (orbital sinus puncture) under light ether anesthesia. - Animals were fasted overnight prior to blood collection.* HAEMATOLOGY: Yes- Parameters: hemoglobin; hematocrit; erythrocyte count; total and differential leucocyte counts platelet count. * CLINICAL CHEMISTRY: Yes- Parameters: urea nitrogen; glutamic pyruvic transaminase (GPT) glutamic oxaloacetic transaminase (GOT) calcium; phosphorus; chloride; sodium; potassium; glucose; total bilirubin; albumin; globulin; total protein ; creatinine * URINALYSIS: Yes - Parameters: appearance; specific gravity; occult blood; protein; pH; bilirubin; urobilinogen; ketones; glucose; microscopic examination of sediment
Oestrous cyclicity (parental animals):
Not examined
Sperm parameters (parental animals):
Not examined
Litter observations:
Not applicable
Postmortem examinations (parental animals):
SACRIFICE- Male animals: All surviving animals - Maternal animals: All surviving animals GROSS NECROPSY- Gross necropsy HISTOPATHOLOGY / ORGAN WEIGHTS- Microscopic examination of paraffin embedded hema-toxylin and eosin stained tissue sections (3-5 microns) was performed on the following organs and tissues from all rats in the high dosage and control groups which were sacrificed at termination and from one rat that died during the course of the study: ovaries testes thyroid (both lobes) and parathyroidsadrenal glands liver spleen aorta stomach uterus cerebellular cortexpancreas thymus esophagus pituitary gland brain-medulla/pons heart rectum urinary bladder intestine, small (duodenum, jejunum, ileum) salivary gland (submaxillary) intestine, large (cecum, colon) sciatic nerve all gross lesionkidneys lung with mainstem bronchi lymph node (mesenteric)
Postmortem examinations (offspring):
Not applicable
Statistics:
Continuous data (body weight, food consumption, clinical parameters, absolute and relative organ weights) were analyzed using analysis of variance (Snedecor and Cochran, 1967). Differences between groups were identified using the Least Significant Difference test. Pathology inci- dence data were analyzed using Fisher's Exact test. For all statistical analyses, significance was juagea at the level of pi 0.05.
Reproductive indices:
Not applicable
Offspring viability indices:
Not applicable

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
not examined

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
160 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: overall effects: clinical signs; mortality; body weight; food consumption; food efficiency; ophthalmoscopic examination; haematology; clinical chemistry; urinalysis; gross pathology; organ weights; histopathology
Remarks on result:
other: Generation: juvenile to adult in a 90-day study (migrated information)

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
not examined

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
not examined

Effect levels (P1)

Remarks on result:
not measured/tested

Results: F1 generation

General toxicity (F1)

Clinical signs:
not examined
Mortality / viability:
not examined
Body weight and weight changes:
not examined
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings:
not examined

Effect levels (F1)

Remarks on result:
not measured/tested

Results: F2 generation

Effect levels (F2)

Remarks on result:
not measured/tested

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Oral administration (via gavage) of Suttocide A for 90 consecutive days to Sprague-Dawley rats at levels of 10, 40 and 160 mg/kg body weight did not result in any significant toxicological or histopathological effects which were treatment related. This includes examination of both testes and uteri of exposed male and female rats, respectively.