N-(2-nitrophenyl)phosphoric triamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-10-27 - 2004-08-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

OECD 423 (2001)

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:

-

EC Number:

477-690-9

EC Name:

-

Cas Number:

874819-71-3

Molecular formula:

Hill formula: C6H9N4O3P CAS formula: C6H9N4O3P

IUPAC Name:

N-(diaminophosphoryl)-2-nitroaniline

Test material form:

solid: crystalline

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species / Strain: rat/WistarCrkWI BR
Rationale:The rat is a suitable rodent species for acute toxicity
studies and is acceptable to regulatory authorities.
Sex:female (nulliparous, non-pregnant)
Supplier:Charles River Wiga GmbH,
D-97320 Sulzfeld
Age at start of acclimatisation: approximately 8 weeks
Acclimatisation: 6 days before randomisation
Randomisation: Animals were assigned to cages according to random numbers one day prior to first administration.
The study room and cages were cleaned and disinfected before the animals arrived. During the study, the room and cages were cleaned at regular intervals. The animals were housed in groups of up to 3 to a cage (Makrolon® Type 3) during acclimatisation. From the randomisation until sacrificing a single animal was housed in a Makrolon® Type 3 cage.
Feed: ALTROMIN 1324. pelleted standard diet (ALTROMIN, D-32791 Lage/Lippe) Batch: 190904/1342 With the exception of overnight fasting before oral administration and until 3 hours after administration food was available ad libitum.
Bedding: ALTROMIN Type S8/15, granulated soft wood bedding Batch: 230604 Water: tap water, ad libitum (municipal supply) Makrolon® bottles, changed daily Environment: air conditioned temperature: 19 - 23 °C relative humidity: 30 - 65% Lighting: artificial light was set to give a cycle of 12 hours light and 12 hours dark; the light phase was from 6.30 a.m. - 6.30 p.m.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % (m/v) solution of Tylose MH 1000 in deionised water

Details on oral exposure:

Formulation of Test Item The test item was suspended after crushing with a pestle and mortar to a fine dust shortly before administration in a 0.5 % (m/v) solution of Tylose MH 1000 in deionised water by mixing and continuously mixed by a stirrer during the administration. The homogeneity was proved visually.
All doses are expressed in terms of test item as supplied.
Oral exposure: using a metal catheter and disposable plastic syringes

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

Volume of administration: 1 ml / 100 g body weight Individual doses were adjusted according to the recorded body weight.
Time of administration: single administration Animals 1-3: September 07, 2004; 7.19 - 7.23 a.m.
Animals 4-6: September 08, 2004; 7.13 - 7.15 a.m.
Fasting period: the night before administration and 3 hours after administration.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: Except for a yellow urine on the day of administration and the day thereafter clinical symptoms were not observed during the course of investigation. The body weight gain of the animals was slightly delayed.

Gross pathology:

Effects on organs:
No pathological findings were observed.

Any other information on results incl. tables

Hours or days p.a.	Clinical signs in animal No.
	1	2	3	4	5	6
1 h	-	-	-	0	0	0
2h	0	0	0	-	-	-
3 h	0	0	0	0	0	0
4h	yellow urine	yellow urine	yellow urine	-	-	-
6h	-	-	-	yellow urine	yellow urine	yellow urine
1 d	yellow urine	yellow urine	yellow urine	yellow urine	yellow urine	yellow urine
2 d	0	0	0	0	0	0
3 d	0	0	0	0	0	0
4d	0	0	0	0	0	0
5 d	0	0	0	0	0	0
6d	0	0	0	0	0	0
7d	0	0	0	0	0	0
8 d	0	0	0	0	0	0
9 d	0	0	0	0	0	0
10 d	0	0	0	0	0	0
11 d	0	0	0	0	0	0
12 d	0	0	0	0	0	0
13 d	0	0	0	0	0	0
14 d	0	0	0	0	0	0

Test group Dose	Animal No./ Symbol	Body weight [g|			Body weight increase [g]
		before ad­ministration	7 days p. a.	14 days p. a.	1st week	2nd week	total
2000	1	206	236	253	30	17	47
mg/kg b.w.	2	188	213	220	25	7	32
	3	186	212	227	26	15	41
	4	187	218	235	31	17	48
	5	191	206	222	15	16	31
	6	185	207	212	22	5	27
	X	190.5	215.3	228.2	24.8	12.8	37.7
	± s	7.9	11.0	14.4	5.8	5.4	8.9
	n	6	6	6	6	6	6

p.a. = post applicationem x = mean value + s = standard deviation n = number of values

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 (oral, rat) of N-(2-Nitrophenyl)phosphoric triamide is > 2000 mg/kg bw.

Executive summary:

The acute oral toxicity of N-(2-Nitrophenyl)phosphoric triamide was tested in 6 female Charles River Wistar rats according to OECD guideline 423. The test item was administered at the single dose of 2000 mg/kg body weight (Limit test) by gavage. All animals were examined for mortality, clinical signs and body weight gain. The pathological alterations of organs were examined at the end of a 14-day observation period. None of the animals died during the course of investigation. The LD50 (oral,rat) is > 2000 mg/kg bw.

Except for a yellow urine on the day of administration and the day thereafter clinical sy mptoms were not observed during the course of investigation. The body weight gain of the animals was slightly delayed. No pathological findings were observed.

The LD50 (oral, rat) of N-(2-Nitrophenyl)phosphoric triamide is > 2000 mg/kg bw.