Reaction mass of hexadecyl dihydrogen phosphate and dihexadecyl hydrogen phosphate

Endpoint summary

Description of key information

Acute toxicity after single oral application was tested in rats, which received 16000 mg/kg bw/d. All animals survived until the end of the study without showing any signs of systemic toxicity. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. At necropsy, no macroscopic findings were observed. The LD50 value for acute oral toxicity is > 16000 mg/kg bw.
A single dermal application of Dihexadecyl hydrogen phosphate to 20 rats (10 males and 10 females) at a dose of 2000 mg/kg bw was associated with no mortality and neither signs of irritation. The dermal LD50 was determined to be > 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:

Aug - Sept 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP conform study with design equivalent to guideline; sufficient reporting

Qualifier:

equivalent or similar 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:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK Ltd., Huntingdon, England
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 109 - 150 g
- Fasting before dosing: overnight prior to and approx. 4 h after dosing
- Housing: in groups by sex in metal cages with wire mesh floors
- Diet (e.g. ad libitum): standard laboratory rodent diet (Labsure LAD 1), ad libitum
- Water (e.g. ad libitum): water, ad libitum
- Acclimation period: min. 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23°C
- Humidity (%): 62%
- Air changes (per hr): approx. 15/h
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 30.8. To: 13.9.1985

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 80% (w/v)
- Amount of vehicle (if gavage): 20 mL/kg

Doses:

16000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Animals were observed soon after dosing; then at frequent intervals for the remainder of day 1. On subsequent days the animals were observed at least once in the morning and once at the end of the experimental day. Individual body weights were taken on days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (see above), body weight (see above)

Statistics:

none

Preliminary study:

A trial test was carried out by dosing two male and two female rats at 16000 mg/kg bw. The results of the preliminary study indicated that the acute median lethal oral dose of the test item was in excess of 16000 mg/kg bw.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 000 mg/kg bw

Mortality:

no mortalities occurred.

Clinical signs:

other: Piloerection only was observed in the rats treated at 16000 mg/kg bw with the test substance. A similar reaction was not seen in control animals. Recovery of test animals as judged by external appearance and behaviour was apparently complete by day 3.

Gross pathology:

No effects

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The median lethal dose of Dihexadecyl hydrogen phosphate (LD50) greater than 16000 mg per kg body weight. Based on the result of this study the test substance is not subject for labelling and classification requirements according to regulatory requirements.

Executive summary:

Dihexadecyl hydrogen phosphate was tested for its acute toxic properties in rats via oral route. No animal died or showed clinical symptoms/macroscopic anomalies after application of 16000 mg/kg bw.

Therefore, the median lethal dose of Dihexadecyl hydrogen phosphate (LD50) was greater than 16000 mg per kg body weight. Based on the result of this study the test item is not subject for labelling and classification requirements according to regulatory requirements.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

16 000 mg/kg bw

Quality of whole database:

1 (reliable without restrictions)

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:

Aug - Sept 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP conform study, equivalent to guideline; sufficient reporting

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK Ltd., Huntingdon, England
- Age at study initiation: 8 -11 weeks
- Weight at study initiation: 200 - 256 g
- Housing: indivividually in metal cages with wire mesh floors
- Diet (e.g. ad libitum): standard laboratory diet (Labsure LAD 1), ad libitum
- Water (e.g. ad libitum): water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23°C
- Humidity (%): 63%
- Air changes (per hr): 15/h
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21.8. To: 4.9.1985

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 5x5 cm
- % coverage: 100%
- Type of wrap if used: The treated area was covered with gauze which was held in place with an impermeable dressing encircled firmly around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water (40-40°C) and blotted dry with absorbent paper
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw (as 80% (w/v) paste in distilled water
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 2.5 mL/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Animals were observed soon after dosing; then at frequent intervals for the remainder of day1. On subsequent days the animals were observed at least once in the morning and once at the end of the experimental day. Individual body weights of rats were mearsured on days 1, 4, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
other: Treated areas of skin were examined daily for signs of dermal irritation and assessed.

Statistics:

none

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no mortalities.

Clinical signs:

other: No signs of toxicity observed.

Gross pathology:

No effects

Other findings:

No dermal reactions.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Under the conditions of the present study, single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with no mortality and neither signs of toxicity nor signs of irritation.The dermal LD50 was determined to be > 2000 mg / kg body weight.

Executive summary:

Under the conditions of the present study, single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with no mortality and neither signs of toxicity nor signs of irritation.The dermal LD50 was determined to be > 2000 mg / kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

1 (reliable without restrictions)

Additional information

Based on the results of an oral toxicity study and an acute dermal toxicity study the LD₅₀values for acute oral and dermal toxicity was determined to be > 16000 and > 2000mg/kg bw, respectively.
In accordance with REACH “Column 2” in Annex VIII there is sufficient weight of evidence from several independent sources of information leading to the conclusion that Reaction mass of dihexadecyl hydrogen phosphate and hexadecyl dihydrogen phosphate does not exert systemic toxic effects after acute inhalation exposure and thus does not have to be classified, because

- the LD50 value for acute oral toxicity of Dihexadecyl hydrogen phosphate is > 16000 mg/kg bw,

- the LD50 value for acute dermal toxicity of Dihexadecyl hydrogen phosphate is > 2000 mg/kg bw and

- inhalation is very unlikely to occur, taking into account the physical state of the substance.

Therefore, and for animal welfare reasons, it is concluded that testing of acute inhalation toxicity of Reaction mass of dihexadecyl hydrogen phosphate and hexadecyl dihydrogen phosphate is not scientifically necessary.

Justification for selection of acute toxicity – oral endpoint
GLP conform study with design equivalent to guideline; sufficient reporting

Justification for selection of acute toxicity – inhalation endpoint
n.a.

Justification for selection of acute toxicity – dermal endpoint
GLP conform study, equivalent to guideline; sufficient reporting

Justification for classification or non-classification

Due to the results described in the acute oral and dermal toxicity studies (LD₅₀oral/dermal in rats > 16000 and > 2000 mg/kg bw, respectively)Reaction mass of dihexadecyl hydrogen phosphate and hexadecyl dihydrogen phosphatedoes not have to be classified as acute orally and dermally toxic. Based on the substance's physico-chemical properties no higher systemically exposure via inhalation is expected to occur than that tested in the course of the oral and dermal toxicity studies. Therefore,Reaction mass of dihexadecyl hydrogen phosphate and hexadecyl dihydrogen phosphatedoes not have to be classified as acute toxic.