Morpholinium sulphamate

Endpoint summary

Description of key information

Morpholinium Sulphamate was tested for acute oral toxicity according to OECD Guideline 423/EU Method B.1 tris  in a single oral dose of 2000 mg/kg bw in female Crl:(WI)BR rats. No lethality was noted at single oral dose of 2000 mg/kg bw, thus the obtained LD50 value of the test item Morpholinium sulphamate was greater than 2000 mg/kg bw.
Testing for acute toxicity via the inhalation route was not applicable as data on acute oral and acute dermal toxicity were available. According to REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5 data for a maximum of two routes of exposure need to be provided.
Morpholinium Sulphamate was tested for acute dermal toxicity in a limit test in rats according to OECD Guideline 402/EU Method B.3. Under the experimental conditions, the acute dermal LD50 value of the test item Morpholinium sulphamate was greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 17 December 2001

Deviations:

no

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

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

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

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

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-11-22 to 2011-12-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 24 February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

adopted August, 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl(WI)Br

Sex:

male/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: 201-214 g (preliminary study); 230-243 g (males, main study); 221-247 g (females, main study)
- 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

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The back of animals was shaven (approximately 10 % of the total body surface area) 24 hours prior to the treatment. The test item was uniformly applied in a single dose to at least 10 % of the total body surface area throughout a 24-hour exposure period. Sterile gauze pads were placed on the skin of rats. These gauzes were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was wrapped with semi-occlusive plastic wrap for 24 hours. At the end of the exposure period, residual test item was removed, using body temperature water. The single administration, performed by dermal route, was followed by a 14-day observation period.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 animals per sex per dose

Control animals:

no

Details on study design:

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

Clinical Obersvations:
Animals were observed individually 1 h and 5 h after dosing, and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Body weight:
For the preliminary study, the body weights were recorded on day 0 (shortly before the treatment). For the main study, the body weight of all animals were recorded on day 0 (shortly before the treatment), on day 7 and on day 15 (with a precision of 1 g in main study).

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. The animals of preliminary study were humanely sacrificed at beginning of main study.

Statistics:

Not applicable

Preliminary study:

No mortality observed at the dose levels of 5, 50, 300 and 2000 mg/kg bw

Key result

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed.

Clinical signs:

other: No toxicologically relevant clinical signs were observable.

Body weight:

other body weight observations

Remarks:

The body weight development was undisturbed both in male and female animals.

Gross pathology:

none

Interpretation of results:

not classified

Conclusions:

In this acute dermal toxicity study with the test item Morpholinium Sulphamate no mortality occurred and the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Executive summary:

An acute dermal toxicity study was performed with test item morpholinium Sulphamate Crl:(WI)BR rats, in compliance with OECD Guideline No. 402, Directive 92/69 EEC B.3 and OPPTS 870.1200. A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to morpholinium sulphamate at 2000 mg/kg bw by dermal route. The test item was applied in its original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

The results of the study were summarised as follows: No mortality occurred during the study. Neither male nor female animals treated at 2000 mg/kg bw showed behavioural changes and no systemic toxic signs were noted during the study. The test item did not cause dermal irritation symptoms as erythema, oedema or other signs. The body weight development was undisturbed both in male and female animals. No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necropsy.

In this acute dermal toxicity study with the test item Morpholinium Sulphamate, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study.

Additional information

Acute oral toxicity:

In an 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 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. All organs of the animals treated with 2000 mg/kg bw dose proved to be free of treatment related gross pathological changes. 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).

Acute dermal toxicity:

An acute dermal toxicity study was performed with test item Morpholinium Sulphamate Crl:(WI)BR rats, in compliance with OECD Guideline No. 402, Directive 92/69 EEC B.3 and OPPTS 870.1200. A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to morpholinium sulphamate at 2000 mg/kg bw by dermal route. The test item was applied in its original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

No mortality occurred during the study. Neither male nor female animals treated at 2000 mg/kg bw showed behavioural changes and no systemic toxic signs were noted during the study. The test item did not cause dermal irritation symptoms as erythema, oedema or other signs. The body weight development was undisturbed both in male and female animals. No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necropsy. In this acute dermal toxicity study with the test item Morpholinium Sulphamate, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Acute inhalation toxicity:

Testing for acute toxicity via the inhalation route was not applicable as data on acute oral and acute dermal toxicity were available. According to REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5 data for a maximum of two routes are required.

Justification for selection of acute toxicity – oral endpoint
Only one GLP and guideline compliant study available.

Justification for selection of acute toxicity – dermal endpoint
Only one GLP and guideline compliant study available.

Justification for classification or non-classification

Based on the results obtained, the test substance was not classified and labelled for acute toxicity, according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) No 2022/692.