Reaction products of neodecanoic acid and titanium (IV) isopropoxide

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:

The study was performed between 20 October 2009 and 01 December 2009.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of GLP inspection: 28 January 2010 Date of Signature on GLP certificate: 26 November 2009

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
Harlan UK Limited, Bicester, Oxon, UK.

- Age at study initiation:
At the start of the study the animals were eight to twelve weeks of age.

- Weight at study initiation:
The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).

- Fasting period before study:
overnight fast immediately before dosing

- Housing:
The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.

- Diet (e.g. ad libitum):
(2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed ad libitum throughout the study.

- Water (e.g. ad libitum):free access to mains drinking water

- Acclimation period:acclimatisation period of at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
19 to 25°C

- Humidity (%):
30 to 70%

- Air changes (per hr):
The rate of air exchange was at least fifteen changes per hour.

- Photoperiod (hrs dark / hrs light):
lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.


IN-LIFE DATES: From: Day 1 To: Day 14

Route of administration:

oral: gavage

Vehicle:

arachis oil

Remarks:

Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
For the purpose of the study the test material was freshly prepared, as required, as a solution in arachis oil BP to give dose levels of 300 and 2000mg/kg bodyweight.

- Amount of vehicle (if gavage):
Not stated

- Justification for choice of vehicle:
Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

- Lot/batch no. (if required):
Not stated

- Purity:
Not stated


MAXIMUM DOSE VOLUME APPLIED:
10ml/kg


DOSAGE PREPARATION (if unusual):
Not applicable

CLASS METHOD (if applicable)

- Rationale for the selection of the starting dose:
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.

Doses:

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a solution in arachis oil BP, at a dose level of 2000 mg/kg bodyweight. Based on the results of this, a further group of four fasted females was given a single oral dose of test material, as a solution in arachis oil BP, at a dose level of 300 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

No. of animals per sex per dose:

EXAMPLE:
5 females at 300 mg/kg
5 females at 2000 mg/kg
EXAMPLE:

Control animals:

no

Details on study design:

- Duration of observation period following administration:
14 days

- Frequency of observations and weighing:
Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

- Necropsy of survivors performed:
Yes

- Other examinations performed:
Clinical signs, body weight.

Preliminary study:

A sighting test sighting test at dose levels of 300 mg/kg and 2000 mg/kg was performed.

Sex:

female

Dose descriptor:

LD50

Effect level:

300 - 2 000 mg/kg bw

Mortality:

300 mg/kg: There were no deaths.

2000 mg/kg: Four animals treated at a dose level of 2000 mg/kg were humanely killed two hours after dosing.

Clinical signs:

other: 300 mg/kg: Increased salivation was noted in one animal during the day of dosing. No other signs of systemic toxicity were noted. 2000 mg/kg: Signs of systemic toxicity noted were ataxia, lethargy, pilo-erection, splayed gait, prostration, decreased r

Gross pathology:

300 mg/kg: No abnormalities were noted at necropsy.

2000 mg/kg: Yellow liquid present in the stomach was noted at necropsy of animals that were humanely killed during the study. No abnormalities were noted at necropsy of the animal that was killed at the end of the study.

Other findings:

- Organ weights:
EXAMPLE: Not recorded

- Histopathology: N/A


- Potential target organs:
EXAMPLE: Not recorded

- Other observations:
EXAMPLE: None

Table1              Individual Clinical Observations and Mortality Data - 2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	AWs		ALP	A	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Female	PrRdRlLWs	PrRdRlLWs	CoRdRlWsX*
	3-1 Female	PrRdRlLWs	PrRdRlLWs	CoRdRlWsX*
	3-2 Female	PrRdRlLWs	PrRdRlLWs	CoRdRlWsX*
	3-3 Female	PrRdRlLWs	PrRdRlLWs	CoRdRlWsX*

0= No signs of systemic toxicity

A= Ataxia

L = Lethargy

P = Pilo-erection

Ws = Splayed gait

Pr = Prostration

Rd = Decreased respiratory rate

Rl = Laboured respiration

Co = Comatose

X* = Animal humanely killed

Table2              Individual Bodyweights and Bodyweight Changes - 2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight (g) at Death	Bodyweight Gain (g) During Week
		0	7	14		1	2
2000	2-0 Female	203	209	221		6	12
	3-0 Female	184	-	-	184	-	-
	3-1 Female	180	-	-	176	-	-
	3-2 Female	181	-	-	181	-	-
	3-3 Female	165	-	-	163	-	-

 

Table3              Individual Necropsy Findings - 2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	2-0 Female	Killed Day 14	No abnormalities detected
	3-0 Female	Humanely killed Day 0	Stomach: yellow liquid present
	3-1 Female	Humanely killed Day 0	Stomach: yellow liquid present
	3-2 Female	Humanely killed Day 0	Stomach: yellow liquid present
	3-3 Female	Humanely killed Day 0	Stomach: yellow liquid present

Table4              Individual Clinical Observations and Mortality Data -300mg/kg

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
300	1-0 Female	S	S	S	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0= No signs of systemic toxicity

S = Increased salivation

Table5              Individual Bodyweights and Bodyweight Changes-300mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
300	1-0 Female	176	185	198	9	13
	4-0 Female	179	188	196	9	8
	4-1 Female	173	182	190	9	8
	4-2 Female	173	178	183	5	5
	4-3 Female	170	179	184	9	5

Table6              Individual Necropsy Findings-300mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
300	1-0 Female	Killed Day 14	No abnormalities detected
	4-0 Female	Killed Day 14	No abnormalities detected
	4-1 Female	Killed Day 14	No abnormalities detected
	4-2 Female	Killed Day 14	No abnormalities detected
	4-3 Female	Killed Day 14	No abnormalities detected

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information: The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be in the range of 300 2000 mg/kg bodyweight (Globally Harmonised Classification System  Category 4).

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be in the range of 300 2000 mg/kg bodyweight (Globally Harmonised Classification System - Category 4).

Executive summary:

Introduction. The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

        OECD Guidelines for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (2001)

      Method B1 bisAcute Toxicity (Oral) of CommissionRegulation (EC) No. 440/2008

Method. Following a sighting test at dose levels of 300 mg/kg and2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as asolutioninarachis oil BP, at a dose level of 2000 mg/kg bodyweight. Based on the results of this, a further group of four fasted females was given a single oral dose of test material, as asolutioninarachis oil BP, at a dose level of 300 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. Four animals treated at a dose level of 2000 mg/kg were humanely killed two hours after dosing. There were no deaths noted at a dose level of 300 mg/kg.

Clinical Observations. Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were ataxia, lethargy, pilo-erection, splayed gait, prostration, decreased respiratory rate and laboured respiration. Four animals treated at a dose level of 2000 mg/kg were comatose two hours after dosing. The surviving animal treated at a dose level of 2000 mg/kg appeared normal one day after dosing. Increased salivation was noted in one animal treated at a dose level of 300 mg/kg. No other signs of systemic toxicity were noted in animals treated at a dose level of 300 mg/kg.

Bodyweight. Surviving animals showed expected gains in bodyweight.

Necropsy. Yellow liquid present in the stomach was noted at necropsy of animals treated at a dose level of 2000 mg/kg that were humanely killed during the study. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Conclusion. The acute oral median lethal dose (LD₅₀) of the test material in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg bodyweight (Globally Harmonised Classification System-Category 4).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

The study is GLP compliant and has a 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:

The study was performed between 01 April 2010 and 15 April 2010.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

The sequence of dosing may not always follow the Test Guideline as shown in the schematic diagram in attachment 1. It is Company Policy to minimisethe number of animals used on each study in accordance with UK Government Home Office guidelines.

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of GLP inspection: 18 May 2010 Date of Signature on GLP certificate: 26 November 2009

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:

Test Animals:
Animals: Rat, HsdRccHan: WIST

Rationale: Recognized by international guidelines as a recommended test system.

Breeder: Harlan Laboratories UK Limited, Bicester, Oxon, UK.

Number of Animals per Group: 5 males and 5 females

Total number of Animals: 5 males and 5 females

Age when treated: At the start of the study the animals weighed at least 200g, and were eight to twelve weeks of age. The weight variation did not exceed ± 20% of the mean weight for each sex.

Identification: After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.

Acclimatization: At least 5 days under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

Environmental Conditions:
Conditions:
The temperature and relative humidity were within the range of 19 to 21 cC and 45 to 56% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Accommodation:
The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.

Diet:
Free access food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study. The diet was routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

Water:
Free access to mains drinking water was allowed throughout the study. The drinking
water was routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10 % of the total body surface.

Using available information on the toxicity of the test material, a single group of animals was treated as follows:

Dose Level Specific Gravity Dose Volume Number of Rats
(mg/kg) (ml/kg) Male Female
2000 1.070 1.87 5 5

The calculated volume of test material, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body
surface area) using a graduated syringe. A piece of surgical gauze, approximately 10 cm x 8 cm in size, was placed over the treatment area and semi-occluded with a piece of self adhesive bandage. The animals were caged individually for the 24 hour exposure period. Shortly after dosing the
dressings were examined to ensure that they were securely in place.

After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened
with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.


Rationale: Dermal administration was used as this is one possible route of human exposure during manufacture, handling and use of the test item.

Duration of exposure:

24 hours

Doses:

2000 mg /kg body weight

No. of animals per sex per dose:

5 Example:

Control animals:

not required

Details on study design:

After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened
with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourte The animals were returned to group housing for the remainder of the study period.

After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and
scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the
Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth) 4

Oedema Formation

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Any other skin reactions, if present were also recorded.

Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.

At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external
examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were
retained.

Rationale: Dermal administration was used as this is one possible route of human exposure during manufacture, handling and use of the test item.

Statistics:

No statistical analysis was performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed during the course of the study. There were no signs of dermal irritation.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Other findings:

None.

Table1              Individual Clinical Observations and Mortality Data

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Initiation of Exposure (Hours)				Effects Noted After Initiation of Exposure (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-1 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-2 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-3 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-4 Male	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
	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
	2-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-4 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Table2              Individual Dermal Reactions - Males

Dose Level mg/kg	Animal Number and Sex	Observation	Effects Noted After Initiation of Exposure (Days)
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Male	Erythema	0	0	1	1	1	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	Br	Br	Br	0	0	0	0	0	0	0	0	0
	1-1 Male	Erythema	0	0	1	1	1	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	Br	Br	Br	Br	0	0	0	0	0	0	0	0
	1-2 Male	Erythema	0	0	1	1	1	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	Br	Br	Br	Br	0	0	0	0	0	0	0	0
	1-3 Male	Erythema	0	0	1	1	1	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	Br	Br	Br	0	0	0	0	0	0	0	0	0
	1-4 Male	Erythema	0	0	1	1	1	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	Br	Br	Br	0	0	0	0	0	0	0	0	0

Table3              Individual Dermal Reactions - Females

Dose Level mg/kg	Animal Number and Sex	Observation	Effects Noted After Initiation of Exposure (Days)
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	Erythema	0	0	1	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	Br	Br	Br	0	0	0	0	0	0	0	0	0
	2-1 Female	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	Erythema	0	0	1	1	1	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-3 Female	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-4 Female	Erythema	0	0	1	1	1	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	Br	Br	Br	0	0	0	0	0	0	0	0	0

0= No signs of systemic toxicity

0= No reactions           Br = Light brown discolouration of the epidermis

0= No reactions           Br = Light brown discolouration of the epidermis

Table4              Individual Bodyweights and Weekly Bodyweight Changes

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Change (g) During Week
		0	7	14	1	2
2000	1-0 Male	251	278	296	27	18
	1-1 Male	260	289	302	29	13
	1-2 Male	234	249	259	15	10
	1-3 Male	248	273	286	25	13
	1-4 Male	244	268	283	24	15
	2-0 Female	204	210	212	6	2
	2-1 Female	211	215	218	4	3
	2-2 Female	200	201	209	1	8
	2-3 Female	217	221	229	4	8
	2-4 Female	201	203	209	2	6

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

Introduction. 

The study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. 

Method. 

A group of ten animals (five males and five females) was given a single, 24‑hour, semi‑occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. 

There were no deaths.

Clinical Observations. 

There were no signs of systemic toxicity.

Dermal Irritation. 

Very slight erythema was noted at the test sites of all males and three females. Light brown discolouration of the epidermis was also noted at the test sites of all males and two females. No signs of dermal irritation were noted in two females.

Bodyweight. 

All animals showed expected gains in bodyweight over the study period.

Necropsy. 

No abnormalities were noted at necropsy.

Conclusion. 

The acute dermal median lethal dose (LD₅₀) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The study is GLP compliant and has a Klimisch score of 1

Additional information

The test substance was found to be harmful in an acute oral toxicity tests in rats with an LD50 in the range of >300 and <2000 mg/kg bw. Mortalities were reported in all females (4/4) in the group treated with 2000 mg/kg bw. Associated signs of toxicity were seen and included ataxia, lethargy, pilo-erection, splayed gait, decreased respiratory rate and laboured respiration. No signs of systemic toxicity (other than increased salivation) were observed in animals treated at 300 mg/kg/bw. There were no mortalities in any of the females at this dose.

 

The test substance was found to be of low toxicity in an acute dermal toxicity test in rats (LD50 >2000 mg/kg bw). Effects were limited to very slight erythema observed in 5/5 males and 3/5 females, which persisted up to 4-5 days after treatment. In addition, light brown discolouration of the epidermis was observed in 5.5 males and 2/5 females. No mortalities or signs of systemic toxicity were reported.

The test substance is not volatile (vapour pressure 1.4 x 10^-1Pa at 25ºC; boiling point >495 ºK) and would not pose an inhalation hazard under normal conditions of use. Under normal conditions of uses there is minimal potential for formation of mists / aerosols and blending operations occur with low energy mixing and in closed systems. In addition, the acute toxicity of the test substance has been assessed by the oral and dermal routes of exposure, which are the main exposure routes. Results of in-vitro irritation studies indicate that the liquid material is irritating to both skin and eyes (see appropriate sections). It is possible that the material will be irritating to the respiratory tract epithelial tissue if significant exposure were to occur. 

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

The test data support classification of the registered substance as acutely toxic via ingestion (Category 4), but not via the dermal route, according to the criteria laid down in Regulation (EC) No 1272/2008 (i.e. CLP)