Phosphoric acid, mono- and di-decyl ester, compd. with 2,2',2''-nitrilotris[ethanol]

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From September 20, 2011 to October 11, 2011

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA study

Justification for type of information:

Refer to the section 13 of IUCLID dataset for details on the read across justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

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:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: At the start of the study the animals were eight to twelve weeks of age
- Weight at study initiation: The bodyweights fell within an interval of ±20% of the mean initial bodyweight of the first treated group
- Fasting period before study: overnight fast
- Housing: The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): Free access
- Water (e.g. ad libitum): Free access
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL or 200 mg/mL

- DOSAGE PREPARATION (if unusual): The test substance was freshly prepared, as required, as a suspension at the appropriate concentration in distilled water. The test substance was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on the toxicity of the test substance, 300 mg/kg was chosen as the starting dose.

Doses:

300 mg/kg bw and 2000 mg/kg bw

No. of animals per sex per dose:

3 females at 300 mg/kg bw 6 females at 2000 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days. Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% confidence limits not given in study report.

Mortality:

No mortality

Clinical signs:

Hunched posture and pilo erection were noted in one animal treated at a dose level of 2000 mg/kg. There were no other signs of systemic toxicity.

Body weight:

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

Gross pathology:

No abnormalities were noted at necropsy.

Table 1: Mortality Data

Dose Level mg/kg	Sex	Number of Animals Treated	Deaths During Day of Dosing (Hours)				Deaths During Period After Dosing (Days)								Deaths
			½	1	2	4	1	2	3	4	5	6	7	8-14
300	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3
2000	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3
	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3

Table 2: Individual Clinical Observations - 300 mg/kg bw

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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	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

0 = No signs of systemic toxicity

Table 3: Individual Clinical Observations - 2000 mg/kg bw

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	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
	3-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	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	HP	HP	HP	H	0	0	0	0	0	0	0	0	0	0

0 =     No signs of systemic toxicity

H =     Hunched posture

P =     Pilo-erection

Table 4: Individual Bodyweights and Weekly Bodyweight Changes - 300 mg/kg bw

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	150	165	168	15	3
	1-1 Female	156	171	174	15	3
	1-2 Female	168	181	183	13	2

Table 5: Individual Bodyweights and Weekly Bodyweight Changes - 2000 mg/kg bw

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	2-0 Female	173	184	196	11	12
	2-1 Female	175	189	200	14	11
	2-2 Female	160	171	194	11	23
	3-0 Female	187	190	195	3	5
	3-1 Female	170	177	180	7	3
	3-2 Female	175	178	186	3	8

Table 6              Individual Necropsy Findings - 300 mg/kg

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

Table 7              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
	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
	3-1 Female	Killed Day 14	No abnormalities detected
	3-2 Female	Killed Day 14	No abnormalities detected

Interpretation of results:

other: CLP criteria not met

Conclusions:

Under the study conditions, the rat oral LD50 for the test substance was considered to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, phosphoric acid, mono- and di-C6 -10 -alkyl ester, according to OECD Guideline 423, EU Method B.1 tris and EPA OPPTS 870.1100, in compliance with GLP. A group of three fasted females was treated with the test substance at a dose level of 300 mg/kg bw. This was followed by a further group of three fasted females at a dose level of 2000 mg/kg bw. Based on the results from this dose level a further group of three fasted females was treated at a dose level of 2000 mg/kg bw. Dosing was performed sequentially. Animals were subjected to daily observations and weekly determinations of body weight. Macroscopic examination was performed after terminal sacrifice. Hunched posture and/or piloerection were noted for three animals on Day 1 only. The mean body weight gain over the study period was considered to be normal. Finally, no abnormalities were found at macroscopic post mortem examination. Under the study conditions, the acute oral LD50 of the test substance was considered to be >2000 mg/kg bw (Sanders, 2012).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From November 28, 1965 to January 04, 1966

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Refer to section 13 for details on the read-across justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

The acute oral toxicitiy of the test substance was assessed in rats.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2 % (200 ccm/kg) and 20 % (all other dose levels) (v/v)
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: test substance is readily soluble in water

Doses:

200, 1600, 3200, 4000, 5000, 6400 mg/kg bw

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 d
- Frequency of observations and weighing: daily on working day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

6 400 mg/kg bw

Based on:

test mat.

Mortality:

6400 mg/kg bw dosing group: 5/10 animals (2 males, 3 females) within 24 h no further deaths recorded.

Clinical signs:

200 mg/kg bw dosing group: slight agitation up to 4 hours following treatment..;
other dosing groups: unsteady, elevated respiration; anancasm to chew; apathy lasting for 1 or 2 days; reduced grooming;
All animals were without findings two days after dosing.

Gross pathology:

Organs without findings

Interpretation of results:

other: GHS criteria not met

Conclusions:

Under the study conditions, the acute oral LD50 of the substance in rats was determined to be 6400 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, 2,2',2''-nitrilotriethanol, similar to OECD Guideline 401.

Male and female Sprague-Dawley rats were administered the test substance by oral gavage at a doses of 0, 200, 1600, 3200, 4000, 5000 and 6400 mg/kg bw. Following administration, the animals were observed for 14 d and mortality, clinical signs and body weights were recorded daily. At the end of this period, rats were examined for macroscopic and microscopic abnormalities. At 6400 mg/kg bw mortality was observed in 5/10 animals (2 males, 3 females) within 24 h no further deaths recorded. No evidence of systemic toxicity was noted during the study period. Unsteady, elevated respiration and apathy lasting for 1 or 2 d in other doses were observed. No abnormalities were seen at necropsy of animals killed at the end of the study. Under the study conditions, the acute oral LD50 of the substance in rats was determined to be 6400 mg/kg bw (BASF, 1966).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral:

Study 1:

A study was conducted to determine the acute oral toxicity of the read across substance, phosphoric acid, mono- and di-C6 -10 -alkyl ester, according to OECD Guideline 423, EU Method B.1 tris and EPA OPPTS 870.1100, in compliance with GLP. A group of three fasted females was treated with the test substance at a dose level of 300 mg/kg bw. This was followed by a further group of three fasted females at a dose level of 2000 mg/kg bw. Based on the results from this dose level a further group of three fasted females was treated at a dose level of 2000 mg/kg bw. Dosing was performed sequentially. Animals were subjected to daily observations and weekly determinations of body weight. Macroscopic examination was performed after terminal sacrifice. Hunched posture and/or piloerection were noted for three animals on Day 1 only. The mean body weight gain over the study period was considered to be normal. Finally, no abnormalities were found at macroscopic post mortem examination. Under the study conditions, the acute oral LD50 of the test substance was considered to be >2000 mg/kg bw (Sanders, 2012).

Study 2:

A study was conducted to determine the acute oral toxicity of the read across substance, 2,2',2''-nitrilotriethanol, similar to OECD Guideline 401. Male and female Sprague-Dawley rats were administered the test substance by oral gavage at a doses of 0, 200, 1600, 3200, 4000, 5000 and 6400 mg/kg bw. Following administration, the animals were observed for 14 d and mortality, clinical signs and body weights were recorded daily. At the end of this period, rats were examined for macroscopic and microscopic abnormalities. At 6400 mg/kg bw mortality was observed in 5/10 animals (2 males, 3 females) within 24 h no further deaths recorded. No evidence of systemic toxicity was noted during the study period. Unsteady, elevated respiration and apathy lasting for 1 or 2 d in other doses were observed. No abnormalities were seen at necropsy of animals killed at the end of the study. Under the study conditions, the acute oral LD50 of the substance in rats was determined to be 6400 mg/kg bw (BASF, 1966).

Justification for classification or non-classification

Based on the results of the read across studies, Phosphoric acid, C6 -12 -alkyl esters, potassium salts, does not warrant classification for acute toxicity according to EU CLP (Regulation 1272/2008/EC) criteria.