N-(2-nitrophenyl)phosphoric triamide

Endpoint summary

Description of key information

Acute oral toxicity:

LD50 > 2000 mg/kg bw.

Acute dermal toxicity:

LD50 > 2000 mg/kg bw.

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:

2004-10-27 - 2004-08-24

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)

Version / remarks:

OECD 423 (2001)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

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.

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.

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP-compliant and has Klimisch score 1.

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:

2004-08-24 - 2004-10-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The GLP study was conducted according to an internationally accepted guideline. All study parameters are based on the specific guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

Approximately 24 hours before administration the fur was removed by shaving from the dorsal area (6x6 cm) of the trunk. Only animals with healthy intact skin were used. 0.2 g / 100 g body weight

Individual doses were adjusted according to the recorded body weight.

The test item was moistened with deionised water, applied to the shaved skin area and covered with a layer of a gaze patch and then with aluminium foil (6.5 x 6.5 cm). This patch was held in contact with the skin by occlusive dressing (Elastoplast, Beiersdorf AG), single administration on September 07, 2004, 9.25 - 9.59 a.m. After 24 hours the patch was removed and the application area was cleaned with water without altering the integrity of the epidermis.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 male and 5 female animals

Control animals:

not required

Details on study design:

Observations

The animals were observed over a period of 14 days after administration of the test item.

Mortality

Animals were observed for mortality and morbidity continuously on the day of administration and once daily thereafter (in the morning).

Clinical Observations

The animals were monitored for general clinical condition continuously on the day of administration and once daily thereafter (in the morning).

The following signs were given predominant consideration: changes in skin, fur, eyes and mucous membranes; gait and posture; respiratory, circulatory, autonomic and central nervous system; occurrence of secretions and excretions; presence of clonic or tonic movements and stereotypies or bizarre behaviour.

Skin of the Administration Area

Animals were observed for erythema and/or oedema at the skin of the administration area one hour after patch removal and once daily thereafter (in the morning).

Body Weight Gain

Body weights were recorded on the day of administration and on days 7 and 14 thereafter.

Pathology

At the end of the observation period all animals were killed by CO2 inhalation.

All animals were examined externally. The cranial, thoracic and abdominal cavities were then opened and examined macroscopically.

Statistics:

Body weights and body weight gain:

Calculation of group mean values and standard deviations.

Comparison with historical control data.

Preliminary study:

None of the animals died after a single dermal administration of 2000 mg/kg b.w. AL(2-NitrophenyI)phosphoric triamide.
Clinical signs were not observed during the observation period.
Except for a slightly yellowish discolouring not any alteration of the skin at the administration area was observed.
The body weight gain of the animals was not affected by the test item. No pathological findings were observed at necropsy.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: None of the animals showed alterations of the general state of well-being during the course of investigation.

Gross pathology:

There were no macroscopic pathological findings in the animals.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 of N-(2-Nitrophenyl)phosphoric triamide in the rat is > 2000 mg/kg b.w.

Executive summary:

Acute dermal toxicity of N-(2 -Nitrophenylphosphoric triamide was tested in 5 male and 5 female Charles River Wistar rats according to OECD guideline 402. The test item was applied at a single dose of 2000 mg/kg body weight to a shaved dorsal area of the trunk of the animals and was then covered with a gauze patch which was held in contact with the skin with an occlusive dressing. Exposure was for 24 hours. Animals were examined for mortality, clinical signs, alterations of the administration area, body weight gain and pathological alterations of organs at the end of a 14-day observation period, None of the animals died during the course of the investigation. The LD50 dermal rat is > 2000 mg/kg b.w. Clinical signs were not observed during the observation period. Except for a slightly yellowish discolouring not any alteration of the skin at the administration area was observed. The body weight gain of the animals was not affected by the test item. No pathological findings were observed at necropsy.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP-compliant and has Klimisch score 1.

Additional information

Acute oral toxicity:

The LD50 (oral, rat) of N-(2-Nitrophenyl)phosphoric triamide was investigated in a GLP-study according to OECD guideline 423. The LD50 is > 2000 mg/kg bw.

Acute dermal toxicity:

The acute dermal toxicity of N-(2-Nitrophenyl)phosphoric triamide was investigated in a GLP-study according to OECD guideline 402. The LD50 is > 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint

Only one study available.

Justification for selection of acute toxicity – dermal endpoint

Only one study available.

Justification for classification or non-classification

Acute oral toxicity:

The respective criteria are not met.

The estimated LD50 of > 2000 mg/kg bw. is above the treshold for hazard category 4 (2000 mg/kg bw).

N-(2-Nitrophenyl)phosphoric triamide

is therefore not classified for acute oral toxicity.

Acute toxicity via the dermal route:

The respective criteria are not met. The estimated LD50 of > 2000 mg/kg bw. is above

the treshold for hazard category 4 (2000 mg/kg bw).

N-(2-Nitrophenyl)phosphoric triamide

is therefore not classified for acute dermal toxicity.

Acute toxicity via the inhalation route:

The dermal route is considered as the major route of exposure for N-(2-Nitrophenyl)posphoric triamide. In addition, as determined by the particle size distribution study, very few particles (4.14 %) are smaller than the respirable particle size of 10 μm. In conclusion further testing on vertebrate animals is not justified, thus the substance will be not classified for acute inhalation toxicity.