Morpholinium sulphamate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-09-22 to 2011-10-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17 December 2001

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

adopted, December 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Morpholinium sulphamate

EC Number:

258-061-6

EC Name:

Morpholinium sulphamate

Cas Number:

52636-67-6

Molecular formula:

C4H9NO.H3NO3S

IUPAC Name:

morpholin-4-ium sulfamate

Test material form:

solid: crystalline

Test animals

Species:

rat

Strain:

other: CrL(WI)Br

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90.
- Age at study initiation: Young adult rats, 8 weeks old;
- Weight at study initiation: 197-203 g (first step); 169-211 g (second step);
- Fasting period before study: 24 hours;
- Housing: Type II polypropylene/polycarbonate; rat type cages with a solid floor, stainless steel wire covers and self-feeding baskets; 3 animals/sex/cage;
- Diet: ssniff® SM R/M-Z+H complete diet produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum;
- Water: tap water from watering bottles ad libitum;
- Acclimation period: 5 days in first step and 6 days in second step;

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C;
- Humidity: 30 - 70 %;
- Air changes: 8-12 air exchanges/hour by central air-condition system;
- Photoperiod: Artificial light, from 6 am to 6 pm

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Salsol A

Details on oral exposure:

A single oral administration - followed by a fourteen-day observation period - was performed by gavage. The day before treatment the animals were fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment.

Doses:

The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. A single administration was performed by oral route and was followed by a 14-day observation period. No animal died in the first step at 2000 mg/kg bw dose level. Therefore, treatment with 2000 mg/kg bw was repeated on further three female rats. Again, no animal died in the second step, thus, no further testing was required. The stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix 7) were met.

No. of animals per sex per dose:

3 + 3 females per dose (2000 mg/kg bw)

Control animals:

no

Details on study design:

Testing Procedure
A single oral administration - followed by a fourteen-day observation period - was performed by gavage. The day before treatment the animals were
fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment.

Dose Level
Starting dose was selected on the basis of the available information about the test item.
The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 were met.
A single administration will be performed by oral route and will be followed by a 14-day observation period.

Mortality
Inspection for signs of morbidity and mortality were made twice daily at the beginning and end of the working day.

Clinical Observations
Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Body weight
The body weight were recorded on day 0 (shortly before the treatment), at day 7 and at day 15 on all animals with a precision of 1 g.

Pathology
All animals were subjected to gross pathology. All animals were exsanguinated under isoflurane anaesthesia. After examination of the external appearance the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross pathological changes were recorded for each animal on the post mortem record sheets.

Statistics:

Not applicable

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item Morpholinium Sulphamate did not induce mortality following a single oral administration to female rats at a dose of 2000 mg/kg bw. All female rats survived the performed treatment until the end of the 14-day observation period.

Clinical signs:

other: In group 1, treated with the test item at a dose of 2000 mg/kg bw, excretion of unusually yellow coloured urine (6 cases of 57 observations) was observable. This symptom (score +3; +2) occurred in all animals. This symptom was observed between Day 1 and D

Body weight:

other body weight observations

Remarks:

The body weight development was normal in all animals

Gross pathology:

All animals treated with 2000 mg/kg bw dose of test item survived until the scheduled necropsy on Day 15. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

Other findings:

NA

Applicant's summary and conclusion

Interpretation of results:

not classified

Conclusions:

No lethality was noted following oral administration of a single dose of 2000 mg/kg bw. For this acute oral toxicity study with the test item Morpholinium Sulphamate in rats the determined LD50 is greater than 2000 mg/kg bw (LD50 ≥ 2000 mg/kg bw).

Executive summary:

In this acute oral toxicity study, two groups of female rats (Crl(WI)Br) were given a single oral dose of the test item Morpholinium Sulphamate at a concentration of 2000 mg/kg bw. The starting dose was selected on the basis of the available information about the test item. The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level. Therefore, treatment with 2000 mg/kg bw was repeated on further three female rats. Again, no animal died in the second step, thus no further testing was required. The stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix 7) were met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment.

Gross pathological examination was carried out on the 15th day after the treatment.

 

Lethality, Clinical symptoms and Body weight:

No lethality was noted following oral administration of a single dose of 2000 mg/kg bw. In the first treatment step, yellow coloured urine was observed in animals on Day 1 and Day 2. In the second treatment step, yellow coloured urine was observed in animals on Day 1 and Day 2.The body weight development was normal in all animals.

 

Gross pathology:

Altogether 6 animals were sacrificed scheduled during the study. All organs of the animals treated with 2000 mg/kg bw dose proved to be free of treatment related gross pathological changes.

 

Evaluation:

The method used is not intended to allow for the calculation of a precise LD50 value. However, for this acute oral toxicity study with the test item Morpholinium Sulphamate in rats the determined LD50 is greater than 2000 mg/kg bw (LD50 ≥ 2000 mg/kg bw).