Bis(2-ethylhexyl) hydrogen phosphate

Endpoint summary

Description of key information

Several acute oral and dermal toxicity studies are available for bis(2-ethylhexyl) hydrogen phosphate. For acute inhalation toxicity an inhalation hazard test was conducted with bis(2-ethylhexyl) hydrogen phosphate. 

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:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: secondary literature

Principles of method if other than guideline:

Five groups of 5 male and 5 female Wistar rats received per gavage a single dose of 500, 880, 1260, 2000 or 3000 mg/kg bw of undiluted bis(2-ethylhexyl) hydrogen phosphate. The animals were observed for mortality, body weight and clinical signs through day 14. Necropsy was carried out on animals sacrifieced at the end of the observation period.

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

500, 880, 1260, 2000 or 3000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female animals/dose

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 400 mg/kg bw

Based on:

test mat.

Mortality: dose       m       f

500       1/5       0/5

880       0/5       1/5

1260       2/5       2/5

2000       1/5       4/5

3000       5/5       5/5

Executive summary:

Five groups of 5 male and 5 female Wistar rats received per gavage a single dose of 500, 880, 1260, 2000 or 3000 mg/kg bw of undiluted bis(2-ethylhexyl) hydrogen phosphate. The animals were observed for mortality, body weight and clinical signs through day 14. Necropsy was carried out on animals sacrificed at the end of the observation period.

LD50 = 1400 mg/kg bw (rat, male + female)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 400 mg/kg bw

Quality of whole database:

The materials/methods and results are described sufficient for evaluation.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: insufficient documented

Principles of method if other than guideline:

Groups of 6 male or female rats were exposed to concentrated vapour of bis(2-ethylhexyl) hydrogen phosphate for up to 8 hours.

GLP compliance:

no

Test type:

other: inhalation hazard test

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Analytical verification of test atmosphere concentrations:

no

Concentrations:

Rats were exposed to concentrated vapour of the test substance - but no analytical data were presented in the publication.
A saturated chamber atmosphere has a concentration of 1300 mg/m³ according the BUA report no 172.

No. of animals per sex per dose:

6 male or six female animals/exposure period

Control animals:

no

Sex:

not specified

Dose descriptor:

LC0

Effect level:

> 1 300 mg/m³ air (nominal)

Based on:

test mat.

Exp. duration:

8 h

After an exposure of 8 hours in a concentrated vapours atmosphere no animals died within 14 days.

Executive summary:

No animals died within 14 days after an exposure of 8 hours in a concentrated test atmosphere.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

1 300 mg/m³ air

Quality of whole database:

Inhalation hazard test. No animals died within 14 days after an exposure of 8 hours in a concentrated test atmosphere.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable and sufficient documented

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Bis(2-ethylhexyl) hydrogen phosphate was administered undiluted at a dose level of 2000 mg/kg bw to 3 male and 3 female New Zealand rabbits. Bis(2-ethylhexyl) hydrogen phosphate was applied under gauze (8 ply) and occlusive rubber for 24 hours. The animals were observed for mortality, body weight and clinical signs.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2 male and 1 female rat with abradded skin
1 male and 2 female rats with intact skin

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

There were no deaths after administration of bis(2-ethylhexyl) hydrogen phosphate. There was no significant change in body weights after 14 days. No toxic signs were observed. Bis(2-ethylhexyl) hydrogen phosphate elicited signs of severe irritation in all animals. Eschar and severe edema were observed and persisted through the study.

Executive summary:

Bis(2-ethylhexyl) hydrogen phosphate was administered undiluted at a dose level of 2000 mg/kg bw to 3 male and 3 female New Zealand rabbits. Bis(2-ethylhexyl) hydrogen phosphate was applied under gauze (8 ply) and occlusive rubber for 24 hours. The animals were observed for mortality, body weight and clinical signs.

There were no deaths after administration of the test compound. There was no significant change in body weights after 14 days. No toxic signs were observed. Bis(2-ethylhexyl) hydrogen phosphate elicited signs of severe irritation in all animals. Eschar and severe edema were observed and persisted through the study. A dermal LD50 > 2000 mg/kg bw was determined.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The materials/methods and results are described in detail und are sufficient for evaluation.

Additional information

In the acute oral study by Smyth et al. for male Wistar rats a LD50 of 4742 mg/kg bw was found (Smyth HF et al., 1962). In the study by D'Aleo on 2 doses (500 and 5000 mg/kg bw) were applied (D'Aleo CJ, 1982). In the high dose group all animals died whereas in the low dose group all animals survived. Therefore the LD50 is between 500 and 5000 mg/kg bw. In the study by Lewis using male and female wistar rats, a LD50 of 1400 mg/kg bw was determined (Lewis CA, 1977). The female rats seem to have a lower tolerance against bis(2-ethylhexyl) hydrogen phosphate than male rats.

Two studies were conducted on rabbbits to determine the acute dermal toxicity for bis(2-ethylhexyl) hydrogen phosphate. Smyth et al., found a LD50 = 1200 mg/kg bw (Smyth HF et al., 1962). In the study by D'Aleo a LD50 > 2000 mg/kg bw was found (D'Aleo CJ, 1982).

For the determination of the acute inhalation toxicity an inhalation hazard test was conducted. None of the animals exposed for 8 hours to the test atmosphere died within 14 days. A concentrated test atmosphere corresponds with a concentration of 1300 mg/m³ of bis(2-ethylhexyl) hydrogen phosphate in air (BUA Report No. 172).

Justification for selection of acute toxicity – oral endpoint
Several acute oral toxicity studies are available for bis(2-ethylhexyl) hydrogen phosphate. By a weight of evidence consideration for acute oral toxicity a LD50 of 1400 (found in the study by Lewis) seems adequate for male and female rats.

Justification for selection of acute toxicity – inhalation endpoint
The only available study was used

Justification for selection of acute toxicity – dermal endpoint
Two studies were conducted on rabbbits to determine the acute dermal toxicity of bis(2-ethylhexyl) hydrogen phosphate. In the dermal toxicity studies a LD50 = 1200 mg/kg bw (Smyth HF et al., 1962) and a LD50 > 2000 mg/kg bw (D'Aleo CJ, 1982) were found. The study from D'Aleo was scientifically acceptable and suffient documented and is therefore used as key study.

Justification for classification or non-classification

By a weight of evidence consideration for acute oral toxicity a LD50 of 1400 (found in the study by Lewis) seems adequate for male and female rats. A classification as Xn, R22 (harmful if swallowed) (GHS: Acute Tox.4; H302) is justified.

In the dermal toxicity studies a LD50 = 1200 mg/kg bw (Smyth HF et al., 1962) and a LD50 > 2000 mg/kg bw (D'Aleo CJ, 1982) were found. The study from D'Aleo was scientifically acceptable and suffient documented and is therefore used as key study. A classification is based on this study not justifed.

Due to the results of of the inhalation hazard test a classification seems not justified as no animals died in a concentrated test atmosphere after an exposure of 8 hours.