Reaction mass of 2,2',2''-nitrilotriethanol and disodium succinate and sodium acetate and sodium bromide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-11-06 to 2013-01-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: study according to OECD TG 423 (2011) and EU Method B1 tris (2008) and under GLP

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

The sequence of the dosing may not always follow the test guideline. It is Company Policy to minimise the number of animals used in accordance with UK Government Home Office guidelines. The sequence of testing does not affect the final classification.

Test guideline 2

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:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction Mass of CXN1-55

IUPAC Name:

Reaction Mass of CXN1-55

Details on test material:

- Name of test material (as cited in study report): Reaction mass of CXN1-55- Substance type: multi-constituent substance- Physical state: Paste- Stability under test conditions: substance considered stable under normal ambient conditions- Storage condition of test material: at room temperature at 20 ± 5 °C, in the dark.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: female Wistar (RccHanTM:WIST) strain rats from Harlan Laboratories UL Ltd., Oxon, UK- Age at study initiation: 8-12 weeks- Weight at study initiation: interval of ± 20 % of the eman initial body weight of the first treated group- Fasting period before study: overnight immediately before dosing and for approx. 3-4 hours after dosing- Housing: in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.- Diet (e.g. ad libitum): with the exception of the fasting period ad libitum, 2014C Teklad Gobal Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK)- Water: with the exception of the fasting period ad libitum- Acclimation period: at least five daysENVIRONMENTAL CONDITIONS- Temperature (°C): 19-25 ° C- Humidity (%): 30-70 %- Air changes (per hr): at least 15 per hour- Photoperiod: 12 hours continuous light (06.00-18:00) and 12 hours darkIN-LIFE DATES: From: 2012-11-06 To: 2012-12-06

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: destilled water

Details on oral exposure:

VEHICLE: destilled waterMAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weightDOSAGE PREPARATION (if unusual): 10 mL/kg body weightCLASS METHOD (if applicable)- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 300 mg/kg body weight was chosen as starting dose in order to minimise the number of animals.

Doses:

300 and 2000 mg/kg body weight

No. of animals per sex per dose:

3 for 300 mg/kg body weight6 for 2000 mg/kg body weight

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days- Frequency of observations and weighing: 0.5, 1, 2 and 4 hours after dosing at day 0, afterwards daily- Necropsy of survivors performed: yes- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: clinical observations

Statistics:

Using the mortality data, an estimate of the acute oral median lethal dose (LD50) was made using the testing procedure diagram.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths in any dose group (see Table 1).

Clinical signs:

other: No signs of systemic toxicity (Table 2).

Gross pathology:

No abnormalities were found at necropsy (Table 4).

Other findings:

No other findings.

Any other information on results incl. tables

Table 1 Mortality Data

Dose Level mg/kg	Sex	Number of treated animals	Deaths during day of dosing (hours)				Deaths during period after dosing (days)
			1	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
300	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2000	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2000	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Table 2 Individual Clinical Observations

Dose Level mg/kg	Animal number and sex		Effects noted after dosing (hours)				Effects noted during period after dosing (days)
			1	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
	1-0 Female		0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
300	1-1 Female		0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-2 Female		0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-0 Female		0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2000	2-1 Female		0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female		0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Female		0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2000	3-1 Female		0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Female		0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Table 3 Individual Body Weight

Dose Level mg/kg	Animal number and sex		Body weight (g) at Day			Body weight gain (g) during week
			0	7	14	1	2
	1-0 Female		166	178	219	12	41
300	1-1 Female		153	164	195	11	31
	1-2 Female		154	170	198	16	28
	2-0 Female		166	194	206	28	12
2000	2-1 Female		160	179	192	19	13
	2-2 Female		167	189	198	22	9
	3-0 Female		155	184	196	29	12
2000	3-1 Female		162	192	202	30	10
	3-2 Female		160	190	200	30	10

Table 4 Individual Necropsy Findings

Dose Level mg/kg	Animal number and sex		Time of Death	Macroscopic observations
	1-0 Female		Killed Day 14	No abnormalities detected
300	1-1 Female		Killed Day 14	No abnormalities detected
	1-2 Female		Killed Day 14	No abnormalities detected
	2-0 Female		Killed Day 14	No abnormalities detected
2000	2-1 Female		Killed Day 14	No abnormalities detected
	2-2 Female		Killed Day 14	No abnormalities detected
	3-0 Female		Killed Day 14	No abnormalities detected
2000	3-1 Female		Killed Day 14	No abnormalities detected
	3-2 Female		Killed Day 14	No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

In a reliable, valid and conclusive study according to OECD TG 423 and EU Method B1 tris, the acute oral median lethal dose (LD50) of the test item Reaction Mass of CNX1-55 in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight .Unclassified according to the Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

This valid, reliable and conclusive study was performed to assess the actute oral toxicity of the test item Reaction Mass of CNX1 -55 following a single oral administration in the Wistar strain rat. The testing was performed in accordance with UK GLP standards. The method was designed to be compatible with the OECD Guidelines for the Testing of Chemicals No. 423 "Acute Oral Toxicity - Acute Toxic Class Method" (adopted 17 December 2001) and Method B1 tris Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008.

Method: A group of three fasted females was treated with the test item at a dose level of 300 mg/kg body weight. Based on the results from this dose level firther groups of fasted females were treated at a dose level of 2000 mg/kg body weight. Dosing was performed sequentially. The test item was administered orally as a solution in destilled water. Clinical signs and body development were monitored during the study. all animals were subjected to gross necropsy.

Mortality: Threre were no deaths observed in any dose group.

Clinical observations: There were no signs of systemic toxicity.

Body weight: All animals showed expected gains in body weight over the study period.

Necropsy: No abnormalities were noted at necropsy.

Conclusion: The acute oral median lethal dose (LD50) of the test item Reaction Mass of CNX1-55 in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures - Unclassified.