Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

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Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to internationally accepted guidelines.
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Ace Animals, Boyertown, PA; born the weeks of 10/27 through 12/01/96- Age at study initiation: approx. 6 to 10 weeks- Weight at study initiation: 217 -299 grams for males and 202 - 288 grams for females- Fasting period before study: 16-20 hours prior to dosing- Housing: 5/sex/cage- Diet (e.g. ad libitum): Fresh Purina Rat Chow (Diet #5012) - Water (e.g. ad libitum): tap waterThe animal room, reserved exclusively for rats on acute tests, was temperature controlled, had a 12 hour light/dark cycle, and was kept clean and vermin free. ENVIRONMENTAL CONDITIONS- Temperature (°C):- Humidity (%):- Air changes (per hr):- Photoperiod (hrs dark / hrs light):IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test article was mixed with distilled water to make dosing by gavage possible. The dose was based on the sample weight as calculated from the specific gravity. A single dose was administered orally by syringe and dosing needle at a dose level of 1500 mg/kg. Since compound related mortality occurred, additional dose levels were tested.
Doses:
500, 750, 1000, 1500 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
In Vivo - Animals were observed 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for mortality. Body weights were recorded immediately pretest, weekly, at death and at termination in the survivors. Post Mortem - All animals were examined for gross pathology. Abnormal tissues were preserved in 10% buffered formalin for possible future microscopic examination.
Statistics:
The LD50 and 95% Confidence Limits were calculated by the method of Litchfield J.T. Jr., & F. Wilcoxon JPET 96:99.
Sex:
male
Dose descriptor:
LD50
Effect level:
1 400 mg/kg bw
Based on:
test mat.
Remarks:
Expressed as Suttocide A (Powder)
95% CL:
>= 782 - <= 2 504
Sex:
female
Dose descriptor:
LD50
Effect level:
940 mg/kg bw
Based on:
test mat.
Remarks:
Expressed as Suttocide A (Powder)
95% CL:
>= 785 - <= 1 125
Mortality:
Dose mg/kgTreated M/FDead M/F5005/51/07505/50/010005/51/315005/55/5
Clinical signs:
Predeath physical signs included lethargy, diarrhea, piloerection, dyspnea, flaccid muscle tone, ataxia, prostration, ptosis, coma, negative righting reflex and wetness of the anogenital area. Physical signs noted in the animals which survived included lethargy, piloerection, diarrhea, soiling of the anogenital area, emaciation, ataxia, dyspnea, wetness of the anogenital area, brown staining of the nose/mouth area, black discoloration of the distal portion of the tail and loss of the distal portion of the tail.
Body weight:
Body weight changes of survivors dosed at 500 mg/kg were normal. Instances of weight loss were noted in some survivors of the other dose groups.
Gross pathology:
Necropsy results of th/! animals which died during the study revealed abnormalities of the lungs, liver, thymus and gastrointestinal tract, as well as wetness and red or brown staining of the nose/mouth area and soiling or wetness of the anogenital area. Necropsy results of the animals which survived the study were generally normal. The loss of the distal portion of the tail was noted in two survivors dosed at 1000 mg/kg.
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The LD50 for single oral exposure is between 300 and 2000 mg/kg bw for both male and female rats. This means that Suttocide® A should be classified as Acute oral tox. cat. 4.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
940 mg/kg bw
Quality of whole database:
In three different studies the LD50 values ranged between 940 and 1400 mg/kg bw.

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
May, 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP study according to internationally accepted guidelines. This study is not considered as the key study because a part of the report copy was badly readable. However, the most relevant parts were still readable and could be copied in this robust summary.
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Hilltop Lab Animals, Scottdale, PA, USA- Quarantine period of at least one week- Weight at study initiation: 200 - 254 grams for males and females- Housing: 1 /cage in suspended cages. - Diet (e.g. ad libitum): Fresh Purina Rat Chow (Diet #5012)- Water (e.g. ad libitum): tap water- Acclimation: 7 to 24 days- Room temperature 70 - 74 dF
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Dosing: Exposure Levels (mg/L): 4.90; 5.92; 6.91Five male and five female rats were exposed to Suttocide® A in water, in an inhalation chamber for four-and-a-half hour. Following exposure the animals were returned to individual housing and observed for 14 days. Chamber Conditions: Temp. Range ( °F) : 69 - 71Humidity (% RH): 33-35; 55-80; 56-88Compressed air (lpm): 19 - 20Diluent air (lpm): 29.7-30.9; 30.5-30.9; 30.4-31.6Total air (lpm): 49 - 51100% equilibrium was eached within 10 minutes
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4.5 h
Concentrations:
Actual concentration was determined gravimetrically during exposure:4.90 +/- 0.20; 5.92 +/- 0.09 and 6.91 +/- 0.18, resp.. Particle size analyses revealed a mass mean aerodynamic diameter of 2.4 to 2.6 microns with a geometric standard deviation of 1.67 to 1.77.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Type and Frequency of Observations:- In Vivo - Animals were observed at hourly intervals during exposure, at one hour post exposure and once daily thereafter for 14 days for signs of toxicity and pharmacological effects. The animals were observed twice daily for mortality. Body weights were recorded pretest, weekly, at death and at termination in the survivors. - Post Mortem: All animals were examined for gross pathology.
Statistics:
LD50 calculation by probit analysis.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
6 mg/L air
Based on:
test mat.
95% CL:
>= 5.26 - <= 6.85
Exp. duration:
4.5 h
Mortality:
4.90 mg/L : one rat died by day 2, all others survived the 14-day observation period5.92 mg/L : seven out of ten rats died during the first 24 h, the others survived the 14-day observation period6.91 mg/L : seven out of ten rats died during the first 24 h, the others survived the 14-day observation period
Clinical signs:
other: Physical signs: reduced movement, hunched posture, lethargy, irregular respiration, facial staining and gasping. After 9 to 10 days, surviving rats recovered.
Body weight:
Body weight loss was observed during the first two days following exposure, thereafter body weights of the surviving rats recovered.
Gross pathology:
Necropsy results were normal except for edematous lungs in rats exposed to the higher concentrations.
Interpretation of results:
relatively harmless
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The Acute Inhalation by single exposure LC50 of Suttocide A, 50% Solution was 6.00 mg/L with 98%- Confidence Limits of 6.85 mg/L (upper) and 5.26 mg/L (lower). The LC50 for males was 5.80 mg/L with 95% Confidence Limits of 6.03 mg/L (upper) and 5.58 mg/L (lower). The data did not permit calculation of the LC50 for females but was estimated to be 6.20 mg/L.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
3 000 mg/m³
Quality of whole database:
Both studies used in this dossier for the acute inhalation endpoint had been performed under GLP according to internationally accepted guidelines.

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study accoring to internationally accepted guidelines
Qualifier:
according to
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Ace Animals, Boyertown, PA- Quarantine period of at least one week- Body weight range was 2.0 - 2.2 kg for males and 2.0 - 2.3 kg for females- Housing: The animals were identified by cage notation and a uniquely numbered metal eartag and housed 1/cage in suspended wire cages. Bedding was placed beneath the cages and changed at least three times/week. - Diet (e.g. ad libitum): Fresh Purina Rabbit Chow (Diet #5321) - Water (e.g. ad libitum): tap water- The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12 hour light/dark cycle, and was kept clean and vermin free.
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
The day prior to application of the test article, the dorsal area of the trunk of each animal was clipped free of hair. The prepared site was approximately 10% of the body surface and remained intact. A single dose of the test article was applied to the prepared site at a dose level of 2000 mg/kg. The dose was based on the dry weight. The test article was applied under a 4 layered surgical gauze patch measuring 1 O X 15 cm. The patch and test article were moistened with distilled water to enhance contact of the test article with the dose site. Gentle pressure was applied to the gauze to aid in the distribution of the test substance over the prepared site. The torso was wrapped with plastic which was secured with non-irritating tape. The test article remained in contact with the skin for 24 hours at which time the wrappings were removed. Residual test article was removed by gentle washing with distilled water.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived the 2000 mg/kg dermal application.
Clinical signs:
Instances of diarrhea and soiling of the anogenital area were noted during the observation period. Dermal reactions, well defined to moderate on day 1, were absent to severe on days 7 and 14.
Body weight:
Body weight changes were normal in 9/10 animals. One female lost weight during the first week of the study but gained normally by day 14.
Gross pathology:
Necropsy results were normal in 4/1 O animals. Treated skin abnormalities were noted in six animals.
Interpretation of results:
practically nontoxic
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The LD50 is greater than 2000 mg/kg of body weight.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Both studies support the key value, of which one was performed under GLP.

Additional information

Acute oral: In three different studies the LD50 values range between 940 and 1400 mg/kg bw. This means that Suttocide® A should be classified as Acute oral tox. cat. 4.

Acute inhalation: Based on two GLP studies, the LC50 of sodium hydroxymethyl glycinate exposed as a dust or aerosol corresponds with a value between 1.0 and 5.0 mg/L. This means that Suttocide® A should be classified as Acute inhalation tox. cat. 4.

Acute dermal: All animals survived the 2000 mg/kg dermal application in a GLP study. Instances of diarrhea and soiling of the anogenital area were noted during the observation period. Dermal reactions, well defined to moderate on day 1, were absent to severe on days 7 and 14. Body weight changes generally were normal.


Justification for selection of acute toxicity – oral endpoint
GLP study according to internationally accepted guidelines.

Justification for selection of acute toxicity – inhalation endpoint
The key study showed that the LC50 for rats exposed to sodium hydroxymethyl glycinate was > 2.3 mg/ml (2300 mg/m3). The supporting study delivered an actual LC50 for sodium hydroxymethyl glycinate in a 50% solution in water of 6.0 mg/ml, corresponding with 3.0 mg/L (3000 mg/m3).

Justification for classification or non-classification

The LD50 for single oral exposure is between the CLP limits of 300 and 2000 mg/kg bw for both male and female rats. For inhalation

the LC50 is between the CLP limits of 1.0 and 5.0 mg/L for dusts or aerosols. For the dermal route the LD50 exceeds the limits for classification according to CLP.