N,N’-di[3-(p-toluene sulfonyl)oxy]phenyl urea

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

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:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

December 17, 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Crj: CD(SD)

Remarks:

Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CRL, Japan
- Females: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 200.1g (sighting study); 194.8 - 210.7g (main study)
- Fasting period before study: 17 - 19 hours
- Housing: hanging stainless steel cages with mesh floors; barrier-system animal rooms
- Historical data:
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week
- Method of randomisation in assigning animals to test and control groups: not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25°C 
- Humidity (%): 40 - 70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12hrs dark / 12hrs light

Route of administration:

oral: gavage

Vehicle:

olive oil

Remarks:

The substance was suspended in olive oil at a concentration of 20% (w/v)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% (w/v)
- Amount of vehicle (if gavage): 20mL
- Justification for choice of vehicle: the test substance would not dissolve in purified water. Vehicle is commonly used in general toxicity studies

DOSAGE VOLUME: 10 mL/kg

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

sighting study: 1 female/dose
main study: 4 female/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed continuously for 10 minutes after administration, then 30 minutes, then 3 hours. From Day 1 to Day 14 the animals were observed once each morning.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: yes
- Other examinations performed: gross necropsy. External surfaces of the body, all orifices, subcutis, cranial, thoracic, abdominal and pelvic cavities with their contents were observed.

Statistics:

None

Preliminary study:

No evidence of toxicity or mortality was observed in the sighting study.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other:

Body weight:

lower than 10% body weight loss

Remarks:

No body weight loss was observed. See Table 4 below

Gross pathology:

No treatment-related effects observed.

Table 3: Clinical signs

Study	Dose (mg/kg)	Animal no.	Day after administration
			0				1	2	3	4	5	6	7	8	9	10	11	12	13	14
			(min)			(hr)
			^0a)-5	5-10	30	3
Sighting	2000	1	-	-	-	MS	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Main		2	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
		3	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
		4	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
		5	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

^{a) immediately after dose administration} 

^{- no abnormalities detected}

^{MS: mucous stool}

Table 4: Body weight

Study	Dose (mg/kg)	Animal No.	Body weight (g)
			Day after administration
			initial	1^a)	7^a)	14^a)
Sighting	2000	1	200.1	226.8 (26.7)	251.2 (24.4)	265.1 (13.9)
Main		2	195.1	213.5 (18.4)	239.7 (26.2)	253.0 (13.3)
		3	194.8	213.8 (19.0)	239.7 (25.9)	258.0 (18.3)
		4	199.7	218.5 (18.8)	221.3 (2.8)	250.5 (29.2)
		5	210.7	234.8 (24.1)	254.9 (20.1)	280.4 (25.5)

a) figues in parentheses indicate difference from previous body weight

Table 5: Historical data: Frequency of mucous stool after administration of olive oil to starved Crl:CD (SD)

Sign	Sex	No. of occurances/no. of dosed animals
Mucous stool	Female	38/135

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality or treatment-related effects were observed during the study. The LD50 value was determined to be >2000 mg/kg.