Phosphoric Acid, Esters with Alcohols, C11-14 iso, C13-rich

Endpoint summary

Description of key information

Acute oral toxicity was assessed in an OECD 423 study for a read-across substance, Phosphoric acid, 2-ethylhexl ester; the LD₅₀was 2500 mg/kg bw - Category 5 acute toxicity (GHS).

 

Acute inhalation and dermal toxicity studies were waived based on skin corrosivity.

 

The test material contains between 20 - 40% of the parent alcohol Alcohols, C11-14-iso-, C13-rich (EC 271-235-6). In consideration of this, in the REACH registration for that substance the acute LD/LC₅₀were:

Oral LD₅₀is greater than 2000 mg/kg.

Dermal LD₅₀is greater than 2000 mg/kg.

Inhalation LC₅₀is greater than 12.2 ppm.

 

These data illustrate the very low acute toxicity of this category of substances.

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:

experimental study

Adequacy of study:

key study

Study period:

30 June 2011 and 26 July 2011

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Female Wistar (RccHan#:WIST) strain rats were supplied by Harlan Labo
ratories UK Ltd., Oxon, UK.- Age at study initiation: Eight to twelve weeks of age- Weight at study
initiation: 158 - 183 g - Fasting period before study: Overnight fast immediately before dosing and for
approximately three to four hours after dosing- Housing: The animals were housed in groups of three
in suspended solid floor polypropylene cages furnished with woodflakes.- Diet (e.g. ad libitum): Food
(2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed
throughout the study.- Water (e.g. ad libitum): Free access to mains drinking water was allowed throu
ghout the study.- Acclimation period: At least five days.ENVIRONMENTAL CONDITIONS- Tempera
ture (°C): Set to achieve limits of 19 to 25°C - Humidity (%): Set to achieve limits of 30 to 70%- Air
changes (per hr): 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.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE- Concentration in vehicle: 30 mg/ml or 200 mg/mlMAXIMUM DOSE VOLUME APPLIED:
10 ml/kgDOSAGE PREPARATION: The test item was freshly prepared, as required, as a solution at t
he appropriate concentration in distilled water. The test item 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 item, 300 mg/kg was chosen as the starting dose.

Doses:

300 mg/kg and 2000 mg/kg

No. of animals per sex per dose:

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

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 recor
ded prior to dosing and seven and fourteen days after treatment or at death.- Necropsy of survivors
performed: yes; 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:

2 500 mg/kg bw

Based on:

test mat.

Mortality:

Individual mortality data are given in Table 1.One animal treated at a dose level of 2000 mg/kg was
found dead two days after dosing.

Clinical signs:

Individual clinical observations are given in Table 2 and Table 3.Signs of systemic toxicity noted in
one animal treated at a dose level of 2000 mg/kg were increased salivation, red/brown staining ar
ound the snout and noisy respiration. There were no other signs of systemic toxicity noted.

Body weight:

Individual bodyweights and weekly bodyweight changes are given in Table 4 and Table 5.The s
urviving animals showed expected gains in bodyweight over the study period.

Gross pathology:

Individual necropsy findings are given in Table 6 and Table 7.Abnormalities noted at necropsy of the
animal that died during the study were patchy pallor of the liver, dark spleen, dark kidneys and h
aemorrhage of the gastric mucosa. No other abnormalities were noted at necropsy of animals that we
re killed at the end of the study.

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	1	0	0	0	0	0	0	1/3

Table 2: Individual Clinical Observations - 300 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
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

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	SSs	SSs	S	Rn	Rn	Rn	Rn	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	X
	3-2 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           

Rn = Noisy respiration

S = Increased salivation

Ss = Red/brown staining around the snout

X = Animal dead

Table 4: Individual Bodyweights and Weekly Bodyweight Changes - 300 mg/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	177	203	210	26	7
	1-1 Female	158	173	180	15	7
	1-2 Female	183	210	220	27	10

Table 5: Individual Bodyweights and Weekly 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	177	182	193		5	11
	2-1 Female	171	174	189		3	15
	2-2 Female	169	177	191		8	14
	3-0 Female	162	177	183		15	6
	3-1 Female	158	-	-	150	-	-
	3-2 Female	168	174	180		6	6

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	Found Dead Day 2	Liver: patchy pallor Spleen: dark Kidneys: dark Gastric mucosa: haemorrhagic
	3-2 Female	Killed Day 14	No abnormalities detected

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was approx imately 2500 mg/kg bodyweight (Globally Harmonised Classification System - Category 5, >2000 -5000 mg/kg bodyweight).

Executive summary:

Introduction.

The study was performed to assess the acute oral toxicity of the test item following a single oral

administration in the Wistar strain rat. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 423 “Acute Oral Toxicity – Acute Toxic Class

Method” (adopted 17 December 2001) - Method B1 tris Acute Toxicity (Oral) of CommissionRegulation (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 bodyweight. Based on the results from this dose level further groups of fasted females were treated at

a dose level 2000 mg/kg bodyweight. Dosing was performed sequentially. The test item was administered orally as a solution in distilled water. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality.

One animal treated at a dose level of 2000 mg/kg was found dead two days after dosing.

Clinical Observations.

Signs of systemic toxicity noted in one animal treated at a dose level of 2000 mg/kg were increased salivation, red/brown staining around the snout and noisy respiration. There were no other signs of systemic toxicity noted.

Bodyweight.

The surviving animals showed expected gains in bodyweight over the study period.

Necropsy.

Abnormalities noted at necropsy of the animal that died during the study were patchy pallor of the liver,

dark spleen, dark kidneys and haemorrhage of the gastric mucosa. No other 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 item in the female Wistar strain rat was

approximately 2500 mg/kg bodyweight (Globally Harmonised Classification System ‑ Category 5,

>2000 ‑ 5000 mg/kg bodyweight).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across hypothesis proposed is that the organism is not exposed to common compounds but rather, because of structural similarity, that different compounds have similar toxicological and fate properties. In this case the ECHA Read-Across Assessment Framework (RAAF) Scenario 2 is used.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source: Phosphoric acid, 2-ethylhexyl ester [EC 235-741-0; CAS 12645-31-7]
Target: Phosphoric Acid, Esters with Alcohols, C11-14 iso, C13-rich [EC not yet assigned; CAS not assigned]
3. ANALOGUE APPROACH JUSTIFICATION
The acute oral toxicity of the Source substances is very low with an LD50 value of greater than 2500 mg/kg bw. In addition, the alcohol constituent, Alcohols, C11-14-iso-, C13-rich, has a reported LD50>2000 mg/kg bw. Structural and chemical similarities in the Source and Target molecules suggests that these molecules are likely to be of very low acute oral systemic toxicity. The predicted acute oral toxicity of the Target would likely be an LD50 of greater than 2000 mg/kg bw.
4. DATA MATRIX
Please refer to attached justification.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Interpretation of results:

Category 5 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 500 mg/kg bw

Quality of whole database:

Adequate

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The acute oral median lethal dose (LD₅₀) of the test item in the female Wistar strain rat was approximately 2500 mg/kg bodyweight (Globally Harmonised Classification System - Category 5, >2000 -5000 mg/kg bodyweight).

The test material contains between 20 - 40% of the parent alcohol Alcohols, C11-14-iso-, C13-rich (EC 271-235-6). In consideration of this, in the REACH registration for that substance the acute LD/LC₅₀were:

Oral LD₅₀is greater than 2000 mg/kg.

Dermal LD₅₀is greater than 2000 mg/kg.

Inhalation LC₅₀is greater than 12.2 ppm.

 

These data serve to emphasise the very low acute toxicity of this category of substances