Morpholinium sulphamate

Acute Toxicity: dermal

Administrative data

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

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:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 24 February 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 3

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

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:

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

Administration / exposure

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

Results and discussion

Preliminary study:

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

Effect levels

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

Applicant's summary and conclusion

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.