Phosphoric acid, mono- and di-C16-18-alkyl esters

Endpoint summary

Description of key information

Acute oral toxicity No acute oral toxicity studies are available for Phosphoric acid, mono- and di- C16-18 (even numbered) alkyl esters. Relevant, reliable and adequate data are available for the closely related substances Potassium hexadecyl hydrogen phosphate, Hexadecyl dihydrogen phosphate and Dihexadecyl phosphate.  Oral LD50 for rat and mice, males and females is > 2000 mg/kg bw.  Acute dermal toxicity No acute dermal toxicity studies are available for Phosphoric acid, mono- and di- C16-18 (even numbered) alkyl esters. Relevant, reliable and adequate data are available for the closely related substances Dihexadecyl phosphate and Aluminium dicetyl phosphate (= Aluminium dihexadecyl phosphate). Dermal LD50 for rat and rabbit, males and females is > 2000 mg/kg bw   Acute inhalative toxicity According to REACH regulation, Annex VII, 8.5.2, an acute inhalation toxicity study is not required. Inhalation is no relevant route of exposure and testing by inhalation is not appropriate. Exposure of humans via inhalation is unlikely taking into account the possibility of exposure to aerosols, particles or droplets of an inhalable size.  

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 700 mg/kg bw

Quality of whole database:

Four relevant, reliable (Klimisch score = 2; reliable with restrictions due to read-across) and adequate read-across studies with similar results are available and no adverse effects were seen also for other routes at highest dose/conc. tested.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Three relevant, reliable (Klimisch score = 2; reliable with restrictions due to read-across) and adequate read-across studies with similar results are available and and no adverse effects also for other routes at highest dose/conc. tested

Additional information

Acute oral toxicity

No acute oral toxicity studies are available for Phosphoric acid, mono- and di- C16-18 (even numbered) alkyl esters. Relevant, reliable and adequate data are available for the closely related substances Potassium hexadecyl hydrogen phosphate, Hexadecyl dihydrogen phosphate and Dihexadecyl phosphate. A read across approach is considered appropriate as the registered UVCB substance contains mono- and dialkylesters of Phosphoric acid with predominantly C16 and C18 aliphatic alcohols. The difference in chain length between the C16 and C18 alkyl ester is not considered relevant for acute oral toxicity.

Four studies with RL 2 (reliable with restrictions) are available: one GLP study in rats with Potassium hexadecyl hydrogen phosphate, two non-GLP studies in rats with Hexadecyl dihydrogen phosphate, and Dihexadecyl phosphate and one non-GLP study in mice with Dihexadecyl phosphate.

In an acute oral toxicity study according to OECD Guideline 423 (Acute Oral Toxicity - Acute Toxic Class Method), adopted 17 December 2001 and EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method), 6 female fasted, 6 to 10 weeks old Hsd Sprague Dawley (SD) rats were given a single oral dose of Potassium hexadecyl hydrogen phosphate (100% a.i.) in sesame oil at a limit dose of 2000 mg/kg bw and observed for 14 days. There were no deaths. No signs of systemic toxicity were noted. All animals showed expected gains in bodyweight over the observation period. No abnormalities were noted at necropsy.

Oral LD50 females > 2000 mg/kg bw

In an acute oral toxicity study (no guideline followed), 5 week old Sprague-Dawley rats (10/sex) were given a single oral dose of Hexadecyl dihydrogen phosphate (97.5% a.i.) by gavage in distilled water at doses of 2350 and 4700 mg/kg bw and observed for 14 days.

In the 2350 mg/kg dose group 0/10 males and 1/10 females died. In the 4700 mg/kg bw dose group 2/10 males and 0/10 females died. Clinical signs observed were decreased locomotor activities, diarrhea and abdominal swelling by gas retention.

Oral LD50 rat, males and females > 4700 mg/kg bw

In an acute oral toxicity study according to notification No. 118 of the Pharmaceuticals Affairs Bureau, 15 Feb 1984, Toxicity Test Guideline (similar to OECD guideline 401) groups of fasted, 4 to 6 weeks old CFY (Sprague-Dawley origin) rats, 10/sex were given a single oral dose of Dihexadecyl phosphate (100% a.i.) in distilled water at doses of 0 (control) and 16.0 g/kg bw and observed for 14 days.

No mortality occurred. Piloerection was observed in all animals in the treated group, animals had recovered on day 3. No effects on body weight were observed. Terminal necropsy findings were normal.

Oral LD50 rat, males and females > 16000 mg/kg bw

In an acute oral toxicity study according to notification No. 118 of the Pharmaceuticals Affairs Bureau, 15 Feb 1984, Toxicity Test Guideline (similar to OECD guideline 401) groups of fasted, 4 to 6 weeks old CFLP mice (ICI Strain 1), 10/sex were given a single oral dose of Dihexadecyl phosphate (100% a.i.) in distilled water at doses of 0 (control) and 16.0 g/kg bw and observed for 14 days.

No mortality occurred. Piloerection was observed in all animals in the control and treated group, animals had recovered on day 2. No effects on body weight were observed. Terminal necropsy findings were normal.

Oral LD50 mouse, males and females > 16000 mg/kg bw

The overall oral LD50 for rat and mice (males and females) is > 2000 mg/kg bw.

Acute dermal toxicity

No acute dermal toxicity studies are available for Phosphoric acid, mono- and di- C16-18 (even numbered) alkyl esters. Relevant, reliable and adequate data are available for the closely related substances Aluminium dicetyl phosphate (= Aluminium dihexadecyl phosphate) and Dihexadecyl phosphate. A read across approach is considered appropriate as the registered UVCB substance contains mono- and dialkylesters of Phosphoric acid with predominantly C16 and C18 aliphatic alcohols. The difference in chain length between the C16 and C18 alkyl ester is not considered relevant for acute dermal toxicity.

The acute dermal toxicity of Aluminium dicetyl phosphate was tested in rats. Additionally, two studies assessing the acute dermal toxicity of Dihexadecyl phosphate are available: one in rats and one in rabbits.

In an acute dermal toxicity study according to OECD guideline 402 performed as limit test, groups of young adult Crl:CDR(SD) BR rats (5 male, 5 female) were dermally exposed to Aluminium dicetyl phosphate moistened with distilled water for 24 hours to 10% of body surface area at a dose of 2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD50 rat, males and females > 2000 mg/kg bw

No mortality occurred in this limit test. No clinical signs of toxicity were observed throughout the observation period. The skin at the application site showed no changes. No test substance related gross pathological changes were found in any animals.

In an acute dermal toxicity study performed comparable to a limit test (OECD guideline 402), 10 female and 10 male young adult rats were dermally exposed to Dihexadecyl phosphate for 24 hours to 10 % of body surface area at a dose of 2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD50 rat, males and females > 2000 mg/kg bw

No mortality occurred in this limit test. No clinical signs of toxicity were observed throughout the observation period. The skin at the application site showed no changes. No test substance related gross pathological changes were found in any animals.

In an acute dermal toxicity study performed comparable to a limit test (OECD guideline 402), 10 female and 10 male young adult rabbits were dermally exposed to Dihexadecyl phosphate for 24 hours to 10 % of body surface area at a dose of 2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD50 rabbit, males and females > 2000 mg/kg bw

No mortality occurred in this limit test. No substance related clinical signs of toxicity were observed throughout the observation period. The skin at the application site showed no changes. No test substance related gross pathological changes were found in any animals.

The overall oral LD50 for rat and rabbit (males and females) is > 2000 mg/kg bw.

Acute inhalative toxicity

Inhalation is no relevant route of exposure and testing by inhalation is not appropriate.

Exposure of humans via inhalation is unlikely taking into account the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Based on the available information, the acute toxicity of Phosphoric acid, mono- and di- C16-18 (even numbered) alkyl esters is low for oral and dermal routes of administration in rat, mice and rabbits. There are no data gaps in acute toxicity. Even though there is no information on acute inhalative toxicity, there is no reason to believe that the acute toxicity is higher for this route of exposure. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

Justification for selection of acute toxicity – oral endpoint
No single key study has been selected since all four weight-of-evidence studies showed no adverse effects.

Justification for selection of acute toxicity – inhalation endpoint
Inhalation is no relevant route of exposure and testing by inhalation is not appropriate. Exposure of humans via inhalation is unlikely taking into account the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for selection of acute toxicity – dermal endpoint
No single key study has been selected since all three weight-of-evidence studies showed no adverse effects up to the limit dose.

Justification for classification or non-classification

Acute oral toxicity

Based on relevant, reliable and adequate data of read-across studies with chemically related substances Phosphoric acid, mono- and di- C16-18 (even numbered) alkyl esters has not to be classified and labelled according to the CLP Regulation (EC) No 1272/2008 and Directive 67/548/EEC with respect to acute oral toxicity.

 

Acute dermal toxicity

Based on relevant, reliable and adequate data of read-across studies with chemically related substances Phosphoric acid, mono- and di- C16-18 (even numbered) alkyl esters do not need to be classified and labelled according to the CLP Regulation (EC) No 1272/2008 and Directive 67/548/EEC with respect to acute dermal toxicity.