Diphosphoric acid, compd. with piperazine (1:1)

Endpoint summary

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:

11 March to 25 March 2003

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)

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

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: Wistar outbred rat; Crl:(WI) WU BR
Supplier: Charles River, Germany
Sex and age: females, ca 7-8 weeks old upon arrival
Date of arrival: 26 February 2003
Quarantine/acclimatization: 13 days
Caging: a maximum of six animals per macrolon cage
Lighting: 12 hours light/12 hours dark cycle
Temperature during testing: 22± 3°C.
Relative humidity during testing: 30-70%. Upper limit incidentally up to 100%, because of meteorological circumstances and/or wet cleaning of the animal room.
Ventilation: ca 10 air changes/hour
Diet/water: standard laboratory diet ad libitum. Each batch of this diet is analysed by the supplier (SDS Special Diets services, Whitham, England) for the nutrients and contaminants and the results are kept available in the archives. Tap water (N.V. Hydron MiddenNederland) ad libitum. Results of routine physical, chemical and microbiological examination of drinking water as conducted by the supplier are kept available in the archives. The results of diet and water analyses were considered acceptable for this study.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The animals were dosed with a 10 ml/kg body weight of a 200 mg/ml aqueous suspension of the test substance in order to obtain the 2000 mg/kg dose level.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 animals

Control animals:

no

Details on study design:

The study was started with treatment of three females with a dose level of 2000 mg/kg body weight. Since none of the animals died during the following hours, the test was continued with the same dosing of another three females. The animals were dosed with a 10 ml/kg body weight of a 200 mg/ml aqueous suspension of the test substance in order to obtain the 2000 mg/kg dose level. The exact amount of the test substance to be dosed was calculated for each animal individually and administered by means of a syringe, equipped with an oral gavage. Prior to dosing, the animals had fasted overnight.
Approximately 4 hours after dosing, they had access to food again. The animals were observed for mortality up to 14 days after treatment.

Observation and measurements
Clinical signs: All visible reactions to treatment were recorded, including type, severity, onset and duration. Observations were made within 1 hour and within 4 hours after dosing, and subsequently in surviving animals at least once daily throughout an observation period of 14 days.
Body weights: The body weight of each animal was recorded immediately before dosing on day 0, and of the surviving animals on days 3, 7 and 14 of the study.
Termination of the study: At the end of the observation period, on day 14 of the study, all surviving animals were killed with carbon dioxide and examined for external changes. Next, the abdomen and the thorax of each animal was opened and examined for gross pathological changes.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the 14-day study period.

Clinical signs:

other: No clinical signs was observed during the 14-day study period.

Gross pathology:

Examination at necropsy of the animals did not reveal distinct treatment-related gross alterations.

Other findings:

No further findings investigated in this study.

Table 1

Acute oral toxicity of T-1063FM in rats; individual and mean bodyweights, dose amounts applied and mortality

 

Animal no.	Dose (ml) applied^1	Bodyweights (g) recorded on day:				Mortality^2
		0	3	7	14
2000 mg/kg (first group)
35	1.7	173	183	187	202	-
37	1.7	175	191	197	210	-
39	1.8	176	191	198	214	-
Mean bodyweight		175	188	194	209	0/3
(second group)
101	1.7	167	181	189	204	-
103	1.7	172	190	198	212	-
105	1.8	180	195	205	212	-
Mean bodyweight		173	189	197	209	0/3

¹2000 mg/kg; dose of 10 ml/kg bodyweight of a 200 mg/ml aqueous suspension of the test substance

²- = animal survived; + = animal died

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Since all animals survived the 2000 mg/kg dose level, the oral LD50 of T-1063FM is considered to be higher than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

11 March to 25 March 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species: Wistar outbred rat; Crl:(WI) WU BR
Supplier: Charles River, Germany
Sex and age: males and females, ca 7-8 weeks old upon arrival
Date of arrival: 26 February 2003
Quarantine/acclimatization: 13 days
Caging: a maximum of five animals per macrolon cage; individual housing during dermal exposure
Lighting: 12 hours light/12 hours dark cycle
Temperature during testing: 22 ± 3°C.
Relative humidity during testing: 30-70%. Upper limit incidentally up to 100%, because of meteorological circumstances and/or wet cleaning of the animal room.
Ventilation: ca 10 air changes/hour
Diet/water: standard laboratory diet ad libitum. Each batch of this diet is analysed by the supplier (SDS Special Diets services, Whitham, England) for the nutrients and contaminants and the results are kept available in the archives. Tap water (N.V. Hydron MiddenNederland) ad libitum. Results of routine physical, chemical and microbiological examination of drinking water as conducted by the supplier are kept available in the archives. The results of diet and water analyses were considered acceptable for this study.

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

At the end of the acclimatization period, the hair was removed from the back and flanks of the animals using electric clippers in a way as to avoid abrasions. The next day, the test material was applied to the clipped area of 5 male and 5 female rats by weight in one dose level of 2000 mg of the test substance per kg body weight. For this purpose, the animals were dosed with a 4 ml/kg body weight of a 500 mg/ml aqueous suspension of the test substance in order to obtain the 2000 mg/kg dose level. The weight variation of the animals did not exceed plus or minus 20% of the mean body weight at the start of the study. The amount of the test material was calculated for each animal individually and distributed in a thin layer over an area of intact skin, measuring at least 4 x 5 cm. For each animal, the exposure area was at least 20 cm2, i.e. at least 10% of the total body surface of the animals. The exposed area was covered by a gauze, which was fixed to the application site by means of adhesive tape and the entire trunk of the rat was wrapped with a tape to maintain the test patch in position and to retard evaporation of volatile substances. During the exposure period the animals were housed individually. After an exposure period of circa 24 hours the materials and residues of the material applied were removed with water. The animals were observed for mortality up to 14 days after treatment.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

Observation and measurements
Clinical signs: All visible reactions to treatment were recorded, including type, severity, onset and duration. Observations were made within 1 hour and within 4 hours after dosing, and subsequently in surviving animals at least once daily throughout an observation period of 14 days.
Body weights: The body weight of each animal was recorded immediately before dosing on day 0, and of the surviving animals on days 3, 7 and 14 of the study.
Dermal reactions: The skin reactions were evaluated by the method of Draize et al. (J. Pharmacol. Exp. Ther. 82 (1944) 377-390). Skin readings were made on day 1 after substance removal, and in surviving animals on days 3, 7, and 14 of the study.
Termination of the study: At the end of the observation period, on day 14 of the study, all surviving animals were killed with carbon dioxide and examined for external changes. Next, the abdomen and the thorax of each animal was opened and examined for gross pathological changes.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the 14-day study period.

Clinical signs:

other: No clinical signs were observed during the 14-day study period.

Gross pathology:

Examination at necropsy of the animals did not reveal distinct treatment-related gross alterations.

Other findings:

No signs of skin irritation were observed during the 14-day observation period.

Table 1

Acute dermal toxicity of T-1063FM in rats; individual and mean bodyweights, dose amounts applied, and mortality

Animal no.	Dose (ml) applied^1	Bodyweights (g) recorded on day:				Motrality^2
		0	3	7	14
2000 mg/kg Males
2	1.1	267	268	285	317	-
4	1.1	274	274	287	319	-
6	1.0	261	263	276	298	-
8	1.1	265	259	273	300	-
10	1.1	272	275	286	318	-
Mean bodyweight		268	268	281	310	0/5
Females
1	0.80	201	202	210	216	-
3	0.74	185	185	192	212	-
5	0.74	185	185	192	205	-
7	0.77	192	187	195	227	-
9	0.78	194	192	197	213	-
Mean bodyweight		191	190	197	215	0/5

¹2000 mg/kg; dose of 4 ml/kg bodyweight of a 500 mg/ml aqueous suspension of the test suspension

²- = animal survived; + = animal died

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Since all animals survived the 2000 mg/kg dose level, the dermal LD50 of T-1063FM is considered to be higher than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

In both, the acute oral and the acute dermal toxicity studies, all animals survived the limit dose of 2000 mg/kg b.w. Therefore, classification of T-1063 FM for acute oral or dermal toxicity is not required according to REGULATION (EC) 1272/2008. Also classification for acute inhalation toxicity is not required based on the arguments as provided in the waiver of the respective study.