Ethyl 5-sulphamoyl-o-anisate

Endpoint summary

Description of key information

Acute oral toxicity:

Key study: OECD 423 and EU method B.1 tris. GLP study. The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat.

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:

October 18, 2016 - November 3, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: JANVIER LABS (53940 Legenest St. Isle - France)
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks old
- Weight at study initiation: 203.8 ± 5.8
- Fasting period before study: overnight
- Housing: Groups of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage was installed in conventional air conditioned animal husbandry.
- Diet (e.g. ad libitum): Foodstuff (ENVIGO -2016) ad libitum
- Water (e.g. ad libitum): Tap-water from public distribution system ad libitum. Microbiological and chemical analyses of the water were carried out once every six months by Bureau Veritas- Eurofins (France)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19ºC - 25ºC
- Humidity (%): 30% - 70%
- Air changes (per hr): 10 changes/hour
- Photoperiod (hrs dark / hrs light): 12 h light (7 - 19 h) / 12 h darkness

IN-LIFE DATES: From: 18 october 2016 To: 3 November 2016

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle: DMSO produced the most suitable formulation at the requested concentration.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/Kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Without preliminary information. The selected starting dose is 2000 mg/kg body weight.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6

Control animals:

yes

Remarks:

Control group refer to a control study performed from 20 September 2016 to 04 October 2016

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Systemic observations at 30 min, 1h, 3h, 4h, 24h, 48h after adminitrationand daily during 14 days. Weighing= D0 (just before administering the test item) then on D2, D7, and D14.
- Necropsy of survivors performed: yes. At termination, macroscopic observation was observed. Macroscopic observations were entered on individual autopsy sheets. Only those organs likely to be modified in cases of acute toxicity were examined. Parameters examined: Oesophagus, Stomach, Duodenum, Jejunum, Ileon, Caecum, Colon, Rectum, Spleen, Liver, Thymus, Trachea, Lungs, Heart, Kidneys, Urinary Bladder, Ovaries, Uterus, Treatment Area, Adrenals and Pancreas.
- Other examinations performed:
Clinical signs: Spontaneous activity, Preyer's reflex (noise), Respiratory rate, Convulsions, Tremors, Body temperature, Muscle tone, Palpebral opening, Pupil appearance, Salivation, Lachrymation, Righting reflex, Back hair appearance, Mortality.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: A decrease in spontaneous activity (1/6), associated with piloerection (1/6), an increase of salivation (2/6), and myosis (3/6), was noted during the first hours of the test. The animals recovered a normal behaviour between days 1 and 2.

Gross pathology:

The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Clinical observations: observation data sheets (Tables 1 to 4).

Body weight evolution: Table 5.

Macroscopical examinations: necropsy data sheets (Tables 6 and 7).

 

Table 1. Observation data sheet.

OBSERVATIONS:	FEMALES			FEMALES
T0 + 30 minutes	Rf 0526	Rf 0527	Rf 0528	Rf 0539	Rf 0540	Rf 0541
Spontaneous activity	N	N	N	N	N	N
Preyer’s réflex (noise)	N	N	N	N	N	N
Repiratory rate	N	N	N	N	N	N
convulsions	N	N	N	N	N	N
tremors	N	N	N	N	N	N
Body temperature	N	N	N	N	N	N
Muscle tone	N	N	N	N	N	N
Palpebral opening	N	N	N	N	N	N
Pupil appearance	Ms	Ms	Ms	N	N	N
Salivation	A	A	N	N	N	N
Lachrymation	N	N	N	N	N	N
Ringhting reflex	N	N	N	N	N	N
Back hair appearance	N	N	N	N	N	N
MORTALITY	0	0	0	0	0	0
Remarks	Rf0526: noisy breathing at T0 + 1 hour			None

N: Normal

Ms: Myosis

A: Increased

Table 2. Observation data sheet.

OBSERVATIONS:	FEMALES			FEMALES
T0 + 1 hour T0 + 3 hours T0 + 4 hours	Rf 0526	Rf 0527	Rf 0528	Rf 0539	Rf 0540	Rf 0541
Spontaneous activity	N	N	N	N	N	N
Preyer’s réflex (noise)	N	N	N	N	N	N
Repiratory rate	N	N	N	N	N	N
convulsions	N	N	N	N	N	N
tremors	N	N	N	N	N	N
Body temperature	N	N	N	N	N	N
Muscle tone	N	N	N	N	N	N
Palpebral opening	N	N	N	N	N	N
Pupil appearance	Ms	N	Ms	N	N	N
Salivation	N	N	N	N	N	N
Lachrymation	N	N	N	N	N	N
Ringhting reflex	N	N	N	N	N	N
Back hair appearance	N	N	N	N	N	N
MORTALITY	0	0	0	0	0	0
Remarks	Rf0526: noisy breathing			None

N: Normal

Ms: Myosis

Table 3. Observation data sheet.

OBSERVATIONS:	FEMALES			FEMALES
D1	Rf 0526	Rf 0527	Rf 0528	Rf 0539	Rf 0540	Rf 0541
Spontaneous activity	D	N	N	N	N	N
Preyer’s réflex (noise)	N	N	N	N	N	N
Repiratory rate	N	N	N	N	N	N
convulsions	N	N	N	N	N	N
tremors	N	N	N	N	N	N
Body temperature	N	N	N	N	N	N
Muscle tone	N	N	N	N	N	N
Palpebral opening	N	N	N	N	N	N
Pupil appearance	N	N	N	N	N	N
Salivation	N	N	N	N	N	N
Lachrymation	N	N	N	N	N	N
Ringhting reflex	N	N	N	N	N	N
Back hair appearance	Pi	N	N	N	N	N
MORTALITY	0	0	0	0	0	0
Remarks	None			None

N: Normal

Pi: Piloerection

D: Decreased

Table 4. Observation data sheet.

OBSERVATIONS:	FEMALES			FEMALES
D2 to D14	Rf 0526	Rf 0527	Rf 0528	Rf 0539	Rf 0540	Rf 0541
Spontaneous activity	N	N	N	N	N	N
Preyer’s réflex (noise)	N	N	N	N	N	N
Repiratory rate	N	N	N	N	N	N
convulsions	N	N	N	N	N	N
tremors	N	N	N	N	N	N
Body temperature	N	N	N	N	N	N
Muscle tone	N	N	N	N	N	N
Palpebral opening	N	N	N	N	N	N
Pupil appearance	N	N	N	N	N	N
Salivation	N	N	N	N	N	N
Lachrymation	N	N	N	N	N	N
Ringhting reflex	N	N	N	N	N	N
Back hair appearance	N	N	N	N	N	N
MORTALITY	0	0	0	0	0	0
Remarks	None			None

N: Normal

Table 5. Body weight and weight gain in grams.

FEMALES	D0	D2			D2-D0	D7	D7-D0		D14	D14-D0
Rf 0526	201	209			8	228	27		248	47
Rf 0527	213	224			11	239	26		250	37
Rf 0528	198	209			11	212	14		230	32
Rf 0539	199	232			33	245	46		271	72
Rf 0540	204	221			17	239	35		254	50
Rf 0541	208	231			23	246	38		266	58
MEAN	203.8	221.0			17.2	234.8	31.00		253.2	49.3
Standard deviation	5.8		10.2	9.4		12.9	11.1	14.5			14.5

 

 

Table 6. Necropsy data sheet of rats Rf0526 to Rf0528 (2 November 2016)

 

Found dead:	Euthanasia: X	At term: X
GENERAL APPEARANCE BEFORE AUTOPSY: Normal
	Observed Organs	Observations
* OESOPHAGUS	X	N.t.R.
* STOMACH	X	N.t.R.
* DUODENUM	X	N.t.R.
* JEJUNUM	X	N.t.R.
* ILEON	X	N.t.R.
* CAECUM	X	N.t.R.
* COLON	X	N.t.R.
* RECTUM	X	N.t.R.
* SPLEEN	X	N.t.R.
* LIVER	X	N.t.R.
* THYMUS	X	N.t.R.
* TRACHEA	X	N.t.R.
* LUNGS	X	N.t.R.
* HEART	X	N.t.R.
* KIDNEYS	X	N.t.R.
* URINARY BLADDER	X	N.t.R.
* OVARIES	X	N.t.R.
* UTERUS	X	N.t.R.
* TREATMENT AREA	-	-
* ADRENALS	X	N.t.R.
* PANCREAS	X	N.t.R.
PARTICULARS. None

N.t.R.: Nothing to report

Table 7. Necropsy data sheet of rats Rf0539 to Rf0541 (3 November 2016)

 

Found dead:	Euthanasia: X	At term: X
GENERAL APPEARANCE BEFORE AUTOPSY: Normal
	Observed Organs	Observations
* OESOPHAGUS	X	N.t.R.
* STOMACH	X	N.t.R.
* DUODENUM	X	N.t.R.
* JEJUNUM	X	N.t.R.
* ILEON	X	N.t.R.
* CAECUM	X	N.t.R.
* COLON	X	N.t.R.
* RECTUM	X	N.t.R.
* SPLEEN	X	N.t.R.
* LIVER	X	N.t.R.
* THYMUS	X	N.t.R.
* TRACHEA	X	N.t.R.
* LUNGS	X	N.t.R.
* HEART	X	N.t.R.
* KIDNEYS	X	N.t.R.
* URINARY BLADDER	X	N.t.R.
* OVARIES	X	N.t.R.
* UTERUS	X	N.t.R.
* TREATMENT AREA	-	-
* ADRENALS	X	N.t.R.
* PANCREAS	X	N.t.R.
PARTICULARS. None

N.t.R.: Nothing to report

 

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat.

Executive summary:

The acute oral toxicity of the test ite has been tested in accordance with OECD 423 and EU method B.1 tris, following GLP. The test item was administered to a group of 6 female Sprague-Dawley rats at the dose of 2000 mg/kg body weight by oral gavage. No mortality occurred during the study and the body weight evolution of the animals remained normal during the study. A decrease in spontaneous activity (1/6), associated with piloerection (1/6), an increase of salivation (2/6), and myosis (3/6), was noted during the first hours of the test. The animals recovered a normal behaviour between days 1 and 2. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes. No other signs of systemic toxicity were noted. The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off of the test item may be considered to be higher than 5000 mg/kg body weight by oral route in the rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

Key study: The acute oral toxicity of the test ite has been tested in accordance with OECD 423 and EU method B.1 tris, following GLP. The test item was administered to a group of 6 female Sprague-Dawley rats at the dose of 2000 mg/kg body weight by oral gavage.No mortality occurred during the study and the body weight evolution of the animals remained normal during the study. A decrease in spontaneous activity (1/6), associated with piloerection (1/6), an increase of salivation (2/6), and myosis (3/6), was noted during the first hours of the test. The animals recovered a normal behaviour between days 1 and 2. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes. No other signs of systemic toxicity were noted. The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off of the test item may be considered to be higher than 5000 mg/kg body weight by oral route in the rat.

Justification for classification or non-classification

Based on available information (LD50>2000 mg/kg bw), the substance is not classified for acute toxicity according to CLP Regulation (EC) no. 1272/2008.