Potassium hexadecyl hydrogen phosphate

Endpoint summary

Description of key information

Potassium hexadecyl hydrogen phosphate was tested for acute toxicity by the oral and dermal routes while performance of a toxicity study by the inhalation route was waived. The studies revealed a LD50 (oral) value of > 5000 mg/kg bw and a LD50 (dermal) of > 2000 mg/kg bw.

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:

1987-06-02 until 1987-06-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Ibm: RORO (SPF), also known as Fü-albino SPF rat

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: about 6 weeks
- Weight at study initiation: female 114-117 g; male 116-124 g
- Fasting period before study: 18 hours
- Housing:
- Diet: NAFAG standard rat maintenance diet, No. 850 (cubic), ad libitum
- Water : tap water, ad libitum
- Acclimatisation period: seven days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 20-24°C
- Humidity: 45-65 %
- Air changes: air-conditioned room
- Photoperiod : 12/12 hrs dark / hrs light

Route of administration:

oral: gavage

Vehicle:

other: Standard Suspending Vehicle (SSV), please see below in " Details on oral exposure"

Details on oral exposure:

VEHICLE
The test article was suspended in Standard Suspending Vehicle (SSV)
1000 mL SSV contain:
5 g sodium carboxy methyl cellulose of median viscosity,
4 mL Tween 80,
5 mL benzylalcohol pro analysis,
9 g sodium-chloride pro analysis,
aqua destillata ad 1000 mL.

- Amount of vehicle: 10 mL/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: daily for clinical signs and weighing on day 1, 4, 8, 11, 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (respiratory distress, crust around nose, hunched posture, crust around eyes, exitability), body weight, histopathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No compound-related deaths occurred. One male was found dead early in the morning of day 8. This case of death was considered to be a result of an application injury. This male rat showed a marked respiratory distress and a marked loss of weight. The histopathological examination of the lung of this animal revealed aspiration pneumonia.

Clinical signs:

other: The main symptom was respiratory distress seen in 3 males and 1 female. This symptom developed in consequence of aspiration of a little test suspension. The other findings were of no toxicological significance.

Gross pathology:

In the urinary bladder of male rat 2694, gritty contents were observed. This finding was of a spontaneous nature. No other macroscopic organ changes were seen.

Other findings:

Histopathology: Bronchopneumonia caused the respiratory distress and itself was caused by aspiration of test suspension (by the male rat that died at day 8).

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions the LD50 value determined in rats was greater than 5000 mg/kg bw.

Executive summary:

Five male and 5 female Fü-albino SPF rats were randomly selected for an acute oral toxicity study. Fasted rats were given a single dose of the test substance suspended in SSV (Standard Suspended Vehicle) by gavage at a dose level of 5000 mg/kg bw. They were observed for 15 days for toxic signs, mortality and body weight changes. All rats were examined for gross lesions.

The LD50 value determined for the test substance in rats was greater than 5000 mg/kg bw. No compound-related deaths occurred. No compound-related incompatibility reactions were observed. No compound-related effect on body weight development appeared. No compound-related gross or microscopic lesions were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

OECD TG 401

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:

other:

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:

1987-06-01 until 1987-06-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals, Paragraph 81-2: "Acute dermal toxicity study"; U.S. Environmental Protection Agency, Office of Pesticide and Toxic Substances, Washington, D.C., November, 1982

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Ibm: RORO (SPF), also known as Fü-albino SPF rat

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: about 8 weeks
- Weight at study initiation: female 162-186 g; male 244-278 g
- Housing: The rats were individually kept
- Diet: NAFAG standard rat maintenance diet, No. 850 (cubic), ad libitum
- Water : tap water, ad libitum
- Acclimatisation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20-24°C
- Humidity: 45-65 %
- Air changes: air-conditioned room
- Photoperiod : 12/12 hrs dark / hrs light

Type of coverage:

occlusive

Vehicle:

other: the test article was moistened with water

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: about 10 % of the total body surface area
- Type of wrap if used: The application site of all rats was covered with an occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: the dressing was removed and the skin was cleaned with lukewarm water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg bw
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex

Details on study design:

- Duration of observation period following administration: 16 days
- Frequency of observations and weighing: weighing recorded on days 1(immediately before treatment), 5, 9, 12, and 17. Clinical signs were examined every day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (behaviour, vivacity, signs of injury, local skin reactions, signs of sickness and abnormality), body weight, and in autopsy a gross examination was performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred.

Clinical signs:

other: After removing of occlusive dressing, reddish maculae became visible on the application site of 3 female rats. These reddish maculae had disappeared at week 2 of the observation period. No other incompatibility reactions appeared.

Gross pathology:

With the exception of 2 bulbous nodules in the left-hand uterus horn in 1 female rat, which were formed by proliferative processes and considered to be accidental findings without relation to treatment, no gross findings were seen.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 > 2000 mg/kg bw

Executive summary:

Five male and 5 female Fü-albino SPF rats were randomly selected for an acute dermal toxicity study. The animals were treated by dermal application of a single dose of 2000 mg/kg of the test substance moistened with water to a shaven area of skin (approximately 10% of the total body surface) on their backs. The application site of all rats was covered with an occlusive dressing which was fixed with elastic adhesive bandages. After 24 hours, the test item was removed with lukewarm water and the skin was inspected whether the treatment caused skin reactions. During 16 days, all animals were observed for toxic signs including mortality and body weight changes. At the end of the study, all rats were examined for gross lesions. No deaths occurred. The LD50 value determined was greater than 2000 mg/kg bw. With the exception of reddish maculae on the application site of 3 female rats, no incompatibility reactions appeared. No effect on the body weight development was observed. No treatment-related gross lesions were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Scientifically well documented study

Additional information

Acute toxicity oral

Five male and 5 female Fü-albino SPF rats were randomly selected for an acute oral toxicity study (key study). Fasted rats were given a single dose of the test substance suspended in SSV (Standard Suspending Vehicle) by gavage at a dose level of 5000 mg/kg bw. They were observed for 15 days for toxic signs, mortality and body weight changes. All rats were examined for gross lesions.

The LD50 value determined for the test substance in rats was greater than 5000 mg/kg bw. No compound-related deaths occurred. No compound-related incompatibility reactions were observed. No compound-related effect on body weight development appeared. No compound-related gross or microscopic lesions were observed.

Results of another study performed with the test substance in female rats supported the results detailed above. In this supporting study, the LD50 obtained was above 2000 mg/kg bw, no mortality nor symptoms occurred. Development of body weight was not impaired and no animal showed any macroscopically visible changes.

Acute toxicity inhalation

According to REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5, data for a maximum of two routes of exposure are required. Data on acute oral and acute dermal toxicity were available. Data on acute toxicity via the inhalation route were not provided. Of the three possible exposure routes, exposure to humans through the inhalation route is not likely, taking in account the nature of the substance. The vapour pressure of potassium hexadecyl hydrogen phosphate is very low (2.89 E-3 Pa at 25°C) based on a vapour pressure study (see section 4.6 ). Further, exposure to potassium hexadecyl hydrogen phosphate via inhalation is not likely as the particles are not inhalable (L50 = 213 µm) based on the results of a granulometry study (see section 4.5).

Acute toxicity dermal

Five male and 5 female Fü-albino SPF rats were randomly selected for an acute dermal toxicity study. The animals were treated dermally with a single dose of 2000 mg/kg of the test substance moistened with water to a shaven area of skin (approximately 10% of the total body surface) on their backs. The application site of all rats was covered with an occlusive dressing which was fixed with elastic adhesive bandages. After 24 hours, the test item was removed with lukewarm water and the skin was inspected whether the treatment caused skin reactions. During 16 days, all animals were observed for toxic signs including mortality and body weight changes. At the end of the study, all rats were examined for gross lesions.

No deaths occurred. The LD50 value determined was greater than 2000 mg/kg bw. With the exception of reddish maculae on the application site of 3 female rats, no incompatibility reactions appeared. No effect on the body weight development was observed. No treatment-related gross lesions were observed.

Justification for classification or non-classification

Based on the results obtained, potassium hexadecyl hydrogen phosphate was not classified and labelled for acute toxicity, according to Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.