Phosphoric acid, mono and bis-linear butyl esters, potassium salts

Endpoint summary

Description of key information

Oral toxicity: Approximate lethal dose (ALD) 18,000 mg/kg bw and LD50 20,371 mg/kg bw in the rat (pre-GLP investigations).

Dermal toxicity: Effect level > 2000 mg/kg bw in the rat based on cholinesterase activity in red blood cells and plasma (pre-GLP investigation)

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:

weight of evidence

Study period:

09 April 1981 to 24 June 2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The approximate lethal dose (ALD) of test material was determined following administration of two dose levels to groups of ten rats by gavage.

GLP compliance:

no

Remarks:

pre-GLP

Test type:

other: lethal dose

Limit test:

yes

Specific details on test material used for the study:

- Lot: 124

Species:

rat

Strain:

other: Crl:CD

Sex:

male

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- The test material was administered as received to groups of 10 young adult Crl:CD rats in a single dose.
- Surviving rats were weighed and observed during a 14-day recovery period and then sacrificed.

Doses:

18,000 mg/kg bw and 25,000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- The purpose of the study was to determine an LD50 for the test material and use it as a range-finder in determining a safe level for a cholinesterase response study.
- After exhausting the test material, it was decided by the submitter to terminate the LD50 study and an approximate lethal dose (ALD) was determined.

Key result

Sex:

male

Dose descriptor:

other: approximate lethal dose

Effect level:

18 000 mg/kg bw

Based on:

test mat.

Mortality:

- Two out of ten animals died in the 18,000 mg/kg dose group
- Eight out of ten animals died in the 25,000 mg/kg dose group
- Deaths occurred within one day after dosing

Clinical signs:

- Wet and stained perineal area
- Stained face
- Diarrhoea
- Weakness
- Salivation in animals receiving 18,000 mg/kg

Body weight:

- Initial weight loss at both dose levels

Gross pathology:

Not investigated

Dose (mg/kg)	Average body weight (g)	Suspension (%)	Average dose (mL)	Density	Mortality ratio
25,000	245	100 (as received)	5.06	1.21	8/10
18,000	243	100 (as received)	3.61		2/10

Interpretation of results:

GHS criteria not met

Conclusions:

The approximate lethal dose was determined to be 18,000 mg/kg and the material was considered to have very low toxicity when administered orally to young adult male Crl:CD rats in single doses.

Executive summary:

The approximate lethal dose (ALD) was investigated by administering 18,000 mg/kg bw and 25,000 mg/kg bw of test material to separate groups of ten male rats by gavage in a single dose under pre-GLP conditions. Mortality was observed within one day of dosing (8/10 animals in the 25,000 mg/kg group and 2/10 animals in the 18,000 mg/kg group). Clinical signs observed were wet and stained perineal area, stained face, diarrhoea and weakness at both dose levels and salivation at 18,000 mg/kg. Initial weight loss was seen at both dose levels. The approximate lethal dose was determined to be 18,000 mg/kg and the material was considered to have very low toxicity when administered orally to young adult male Crl:CD rats in single doses.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The LD50 of the test material was determined following administration of three dose levels to groups of 10 rats by gavage.

GLP compliance:

no

Remarks:

pre-GLP

Test type:

other: Oral LD50 test

Limit test:

yes

Specific details on test material used for the study:

- Lot: 20

Species:

rat

Strain:

other: ChR:CD

Sex:

male

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- The test material was administered as received to three groups of young adult male Chr:CD rats in a single dose by gavage (10 animals per dose).
- Surviving animals were sacrificed 14 days later.

Doses:

17000, 20000 and 25000 mg/kg bw

No. of animals per sex per dose:

Ten

Control animals:

no

Statistics:

- The LD50 value was calculated from mortality data using the method of DJ Finney (Probit analysis, 2nd Ed, 1952, Cambridge University Press).

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

20 371 mg/kg bw

Based on:

test mat.

95% CL:

>= 17 276 - <= 24 252

Remarks on result:

other:

Remarks:

slope 9.96

Mortality:

- Two out of ten animals died in the 17,000 mg/kg dose group
- Five out of ten animals died in the 20,000 mg/kg dose group
- Eight out of ten animals died in the 25,000 mg/kg dose group

Clinical signs:

- Clinical signs at 17,000 mg/kg were wet and bloody perineal area and diarrhoea for two days after dosing and wet and stained perineal area on the third day after dosing.
- Clinical signs in the 20,000 mg/kg dose group were salivation on the day of dosing, wet and blood-stained perineal area, diarrhoea, chromodacryorrhea and stained mouth for two days after dosing and congestion on the seventh day after dosing.
- Clinical signs in the 25,000 mg/kg dose group were belly-to-cage posture and laboured breathing on the day of dosing, wet and/or stained perineal area and congestion on the first and fourth day after dosing, salivation, nose bleeding and diarrhoea on the day after dosing, and weakness on the second day after dosing.

Body weight:

- Weight loss was observed in all dose groups for 1 to 7 days after dosing.

Gross pathology:

Not investigated.

Dose (mg/kg)	Average body weight (g)	Solution (%)	Average dose (mL)*	Mortality ratio
25,000	249	As received	6.23	8/10
20,000	247	As received	4.93	5/10
17,000	241	As received	4.10	2/10

* Administered as a divided dose

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value was calculated to be 20,371 mg/kg and the material was considered to have very low toxicity when administered orally to young adult male ChR:CD rats in single doses.

Executive summary:

The LD50 value was established by administering 17,000 mg/kg bw, 20,000 mg/kg bw and 25,000 mg/kg bw of test material to separate groups of ten male rats by gavage in a single dose under pre-GLP conditions. Mortality was observed (8/10 animals in the 25,000 mg/kg group, 5/10 animals in the 20,000 mg/kg bw group and 2/10 animals in the 17,000 mg/kg group). Weight loss was seen for 1 to 7 days after dosing in all groups. Clinical signs observed were wet and bloody perineal area and diarrhoea for two days after dosing and wet and stained perineal area on the third day after dosing (17,000 mg/kg bw), salivation on the day of dosing, wet and blood-stained perineal area, diarrhoea, chromodacryorrhea and stained mouth for two days after dosing and congestion on the seventh day after dosing (20, 000 mg/kg bw) and belly-to-cage posture and laboured breathing on the day of dosing, wet and/or stained perineal area and congestion on the first and fourth day after dosing, salivation, nose bleeding and diarrhoea on the day after dosing, and weakness on the second day after dosing (25,000 mg/kg bw). The LD50 value was calculated to be 20,371 mg/kg and the material was considered to have very low toxicity when administered orally to young adult male ChR:CD rats in single doses.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

07 June 1982 to 09 June 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

Test material was applied to the shaved backs of ten rats and the effect was determined via blood cell pathology and plasma cholinesterase.

GLP compliance:

no

Remarks:

pre-GLP

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

- Lot 109

Species:

rat

Strain:

other: Crl:CD

Sex:

male

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

- The backs of 10 male rats were shaved over their backs and collared prior to treatment.
- Animals were approximately equal weight.
- Animals were treated topically with 2 g/kg of test material.
- A second group of rats were not treated and served as controls.
- Twenty four hours after treatment, half of each group of animals were sent to clinical pathology for cholinesterase determinations in red blood cells and plasma.
- Forty eight hours after treatment, the other half of each group of animals were examined in the same manner.
- All rats were sacrificed after the determinations were made.

Duration of exposure:

24 or 48 hours

Doses:

2 g/kg

No. of animals per sex per dose:

10

Control animals:

yes, concurrent no treatment

Key result

Sex:

male

Dose descriptor:

other: effect level

Effect level:

> 2 other: g/kg

Based on:

test mat.

Remarks on result:

other: based on cholinesterase level

Remarks:

no effects in red blood cells or plasma

Mortality:

No unplanned animal deaths were reported

Clinical signs:

No clinical signs were observed

Body weight:

No weight losses were observed

Gross pathology:

Not investigated

Other findings:

No inhibition of cholinesterase activity occurred in the red blood cells or plasma of treated animals.

Interpretation of results:

GHS criteria not met

Conclusions:

Rats treated dermally with 2 g/kg of test material showed no change in cholinesterase activity that could be attributed to the test material and no clinical signs or weight losses were observed.

Executive summary:

Dermal toxicity was investigated in male Crl-CD rats under pre-GLP conditions. Ten male rats of approximately equal weight were selected, the animals were shaved over their backs and collared prior to treatment. Test item (2 g/kg) was applied topically to one group of 10 animals and a second group of 10 animals was not treated and acted as controls. Twenty four hours after treatment, half of each group was sent to clinical pathology for cholinesterase determinations in red blood cells and plasma. Forty eight hours after treatment, the other half of each group was examined in the same manner. All rats were sacrificed after the determinations were made. Rats treated dermally with 2 g/kg of test material showed no change in cholinesterase activity that could be attributed to the test material and no clinical signs or weight losses were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Oral toxicity: Two pre-GLP studies are available that report complementary results. In the first study, the approximate lethal dose (ALD) was investigated by administering 18,000 mg/kg bw and 25,000 mg/kg bw of test material to separate groups of ten male rats by gavage in a single dose under pre-GLP conditions. Mortality was observed within one day of dosing (8/10 animals in the 25,000 mg/kg group and 2/10 animals in the 18,000 mg/kg bw group). Clinical signs observed were wet and stained perineal area, stained face, diarrhoea and weakness at both dose levels and salivation at 18,000 mg/kg bw. Initial weight loss was seen at both dose levels. The approximate lethal dose was determined to be 18,000 mg/kg bw and the material was considered to have very low toxicity when administered orally to young adult male Crl:CD rats in single doses. In the second study, the LD50 value was established by administering 17,000 mg/kg bw, 20,000 mg/kg bw and 25,000 mg/kg bw of test material to separate groups of ten male rats by gavage in a single dose under pre-GLP conditions. Mortality was observed (8/10 animals in the 25,000 mg/kg bw group, 5/10 animals in the 20,000 mg/kg bw group and 2/10 animals in the 17,000 mg/kg bw group). Weight loss was seen for 1 to 7 days after dosing in all groups. Clinical signs observed were wet and bloody perineal area and diarrhoea for two days after dosing and wet and stained perineal area on the third day after dosing (17,000 mg/kg bw), salivation on the day of dosing, wet and blood-stained perineal area, diarrhoea, chromodacryorrhea and stained mouth for two days after dosing and congestion on the seventh day after dosing (20, 000 mg/kg bw) and belly-to-cage posture and laboured breathing on the day of dosing, wet and/or stained perineal area and congestion on the first and fourth day after dosing, salivation, nose bleeding and diarrhoea on the day after dosing, and weakness on the second day after dosing (25,000 mg/kg bw). The LD50 value was calculated to be 20,371 mg/kg bw and the material was considered to have very low toxicity when administered orally to young adult male ChR:CD rats in single doses.

Dermal toxicity: One pre-GLP study is available in which dermal toxicity was investigated in male Crl-CD rats. Ten males of approximately equal weight were selected, the animals were shaved over their backs and collared prior to treatment. Test item (2 g/kg) was applied topically to one group of 10 animals and a second group of 10 animals was not treated and acted as controls. Twenty four hours after treatment, half of each group was sent to clinical pathology for cholinesterase determinations in red blood cells and plasma. Forty eight hours after treatment, the other half of each group was examined in the same manner. All rats were sacrificed after the determinations were made. Rats treated dermally with 2 g/kg of test material showed no change in cholinesterase activity that could be attributed to the test material and no clinical signs or weight losses were observed.

Justification for classification or non-classification

Oral toxicity: The approximate lethal dose (ALD) for the test material was found to be 18,000 mg/kg bw in the rat and those data are supported by an LD50 value of 20, 371 mg/kg bw in the rat. Classification for is therefore not required under the terms of Regulation (EC) No 1272/2008.

Dermal toxicity: No clinical signs or effects on cholinesterase activity were reported in the 48 hours following topical application of 2000 mg/kg test item to the backs of male rats. Classification for is therefore not required under the terms of Regulation (EC) No 1272/2008.