9-Octadecen-1-ol, (Z)-, phosphate

Endpoint summary

Description of key information

ORAL EXPOSURE:
The test item Reaction product of oleylalcohol with polyphosphoric acid did not induce mortality following a single oral administration to female rats at a dose of 2000 mg/kg bw. There were no toxic clinical signs or any other test item related effects. Body weights and body weight gain were not influenced by the test item during the study. Autopsy revealed no treatment related pathological changes.
RESPIRATORY EXPOSURE:
According to REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5 data for a maximum of two routes of exposure need to be provided. Testing for acute toxicity via the inhalation route was not required as data on acute oral and acute dermal toxicity were available. In addition, the vapour pressure of the high viscous liquid is expected to be very low.
DERMAL EXPOSURE:
In this acute dermal toxicity study with the test item Reaction product of oleylalcohol with polyphosphoric acid, the obtained acute dermal LD50 value was higher than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

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:

2013-03-19 to 2013-04-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: according to GLP, OECD and EC guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17th December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(Official Journal L 142, 31/05/2008)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

adopted December 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Species / Strain: Rat, Crl(WI)Br
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90.
- Age at study initiation: Young adult rats, 8 weeks old in group 1 and 2
- Body weight range at starting (first step): 181-194 g
- Body weight range at starting (second step): 187-198 g
- Fasting period before study: food but not water was withheld overnight
- Housing: 3 animals/sex/cage
- Diet: ad libitum (ssniff® SM R/M-Z+H complete diet)
- Water: ad libitum
- Acclimatisation time: 5 days in first step and 6 days in second step

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 10-15 air exchanges/hour by central air-condition system.
- Photoperiod: Artificial light, from 6 a.m. to 6 p.m.

Route of administration:

oral: gavage

Vehicle:

other: Helianthi annui oleum raffinatum

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 animals/group

Control animals:

no

Details on study design:

Testing Procedure
A single oral administration - followed by a fourteen-day observation period - was performed by gavage. The day before treatment the animals were fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment.

Dose Level
Starting dose was selected on the basis of the available information about the test item.
The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level. Therefore, treatment with 2000 mg/kg bw was repeated with further three female rats. Again, no animal died in the second step, thus, no further testing was required. The stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix 7) were met.
A single administration was performed by oral route and was followed by a
14-day observation period.

Observations
Mortality
Inspection for signs of morbidity and mortality were made twice daily at the beginning and end of the working day.
Clinical Observations
Animals were observed individually after dosing once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and once per day for 14 days thereafter. Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern.
Particular attention was directed to observation of tremors, convulsions,
salivation, diarrhoea, lethargy, sleep and coma.
Body weight
The body weight were recorded on day 0 (shortly before the treatment), on day 7 and on day 15 on all animals with a precision of 1 g.
Pathology
All animals were subjected to gross pathology. All animals were exsanguinated under isoflurane anaesthesia. After examination of the external appearance the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross pathological changes were recorded for each animal on the post mortem record sheets.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item Reaction product of oleylalcohol with polyphosphoric acid did not induce mortality following a single oral administration to female rats at a dose of 2000 mg/kg bw. All female rats survived the performed treatment until the end of the 14-day observation period.

Clinical signs:

other: No treatment related symptoms were observed throughout the treatment day and 14-day post-treatment period at any groups of the female animals.

Gross pathology:

All animals treated with 2000 mg/kg bw dose of test item survived until the
scheduled necropsy on Day 15.
No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

Other findings:

none

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item Reaction product of oleylalcohol with polyphosphoric acid did not induce mortality following a single oral administration to female rats at a dose of 2000 mg/kg bw. There were no toxic clinical signs or any other test item related effects. Body weights and body weight gain were not influenced by the test item during the study. Autopsy revealed no treatment related pathological changes.

Executive summary:

The method used is not intended to allow for the calculation of a precise LD₅₀value. However, for this acute oral toxicity study with the test item Reaction product of oleylalcohol with polyphosphoric acid in rats the determined LD₅₀is greater than 2000 mg/kg bw (LD₅₀≥ 2000 mg/kg bw).

The test item was ranked into classes of the current EU Regulation on classification, labelling and packaging (CLP) (EC) No 1272/2008 as below:

 Table 2:

Dose (mg/kg bw)	Mortality (dead/treated)	LD50 (mg/kg bw)	CLP
2000	0/6	above 2000	not classified

 

According to the current EU Regulation on classification, labelling and packaging (CLP) (EC) No 1272/2008 no classification is required for the test item Reaction product of oleylalcohol with polyphosphoric acid.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study with test item.

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:

2013-03-19 to 2013-04-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: CLP and Guideline compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

, adopted 24th February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

, 31.05.2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

, adopted August, 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90.
- Age at study initiation: Young adult rats, females were nulliparous and non-pregnant
- Weight at study initiation: Male 230-248 g, Female 233-263 g
- Fasting period before study: food but not water was withheld overnight
- Housing during acclimasation: 3 animals/sex/cage and during the study: animals were housed individually
- Diet: ad libitum (ssniff® SM R/M-Z+H complete diet )
- Water: ad libitum
- Acclimation period: 5 days (males), 47 days (females)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 10-15 air exchanges/hour by central air-condition system.
- Photoperiod: Artificial light, from 6 a.m. to 6 p.m.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 10 % of the total body surface
- The vial with the test item was opened shortly before being moistened and applied.
- Type of wrap if used: sterile gauze pad below a semi-occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- residual test item was removed, using helianthi oleum raffinatum as an appropriate solvent
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: Limit test: 2000 mg/kg bw

Duration of exposure:

single administration for 24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the body weight of all animals were recorded on day 0 (shortly before the treatment), on day 7 and on day 15 (with a precision of 1 g)
- Necropsy of survivors performed: yes
- Other examinations performed: Animals were observed individually 1 h and 5 h after dosing, and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
All animals were subjected to gross pathology. All animals were exsanguinated under isoflurane anaesthesia on day 15. After examination of the external appearance the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross pathological changes were recorded for each animal on the post mortem record sheets.

Statistics:

not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality occured

Clinical signs:

other: General symptoms No behavioural changes or systemic toxic signs were noted during the study. Dermal irritation symptoms as erythema (redness), oedema and other signs were observed on the treatment site. The very slight (score 1) redness, well defined (sc

Gross pathology:

All animals survived until the scheduled necropsy on Day 15.
Slight hydrometra was observed in one female and moderate hydrometra was found in two females. Hydrometra was an indication for the sexual cycle of female animals and is a frequent observation in experimental rats with no toxicological meaning.
No macroscopic alterations due to the systemic toxic effects of the test item were found.

Other findings:

none

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In this acute dermal toxicity study with the test item Reaction product of oleylalcohol with polyphosphoric acid, the obtained acute dermal LD50 value was higher than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Executive summary:

A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to Reaction product of oleylalcohol with polyphosphoric acid at 2000 mg/kg bw by dermal route. The test item was applied in its original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

 The results of the study were summarised as follows:

No mortality occurred during the study.

Dose	2000 mg/kg bw
Male	5
Mortality	0/5
Female	5
Mortality	0/5

 

Neither male nor female animals treated at 2000 mg/kg bw showed behavioural changes and no systemic toxic signs were noted during the study.

The test item caused dermal irritation symptoms as slight to severe erythema, slight oedema and other signs as wounds, crusting and desquamation between Day 1 and Day 14 in males and between Day 1 and Day 11 in females.

Very slight body weight variations were observed in two females during first week and also in one out of the two females during second week.

The body weight development was undisturbed in all male animals.

No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necropsy.

In this acute dermal toxicity study with the test item Reaction product of oleylalcohol with polyphosphoric acid, the obtained acute dermal LD50 value was higher than 2000 mg/kg bw in male and female Crl:(WI)BRrats.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study with test item.

Additional information

Oral:

The method used is not intended to allow for the calculation of a precise LD₅₀value. However, for this acute oral toxicity study with the test item Reaction product of oleylalcohol with polyphosphoric acid in rats the determined LD₅₀is higher than 2000 mg/kg bw (LD₅₀≥ 2000 mg/kg bw). According to the current EU Regulation on classification, labelling and packaging (CLP) (EC) No 1272/2008 no classification for the test item

Reaction product of oleylalcohol with polyphosphoric acid.

Inhalation:

According to REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5 data for a maximum of two routes of exposure need to be provided. Testing for acute toxicity via the inhalation route was not required as data on acute oral and acute dermal toxicity were available. In addition, the vapour pressure of the high viscous liquid is expected to be very low.

Dermal:

A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to Reaction product of oleylalcohol with polyphosphoric acid at 2000 mg/kg bw by dermal route. The test item was applied in its original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

Neither male nor female animals treated at 2000 mg/kg bw showed behavioural changes and no systemic toxic signs were noted during the study.

No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necropsy.

In this acute dermal toxicity study with the test item Reaction product of oleylalcohol with polyphosphoric acid, the obtained acute dermal LD50 value was higher than 2000 mg/kg bw in male and female Crl:(WI)BRrats.

Justification for selection of acute toxicity – oral endpoint
Most reliable study

Justification for selection of acute toxicity – dermal endpoint
Most reliable study

Justification for classification or non-classification

According to the results from the oral toxicity study and dermal toxicity study, the LD 50 obtained for the test item was found to be above 2000 mg/kg bw. Therefore according to current EU Regulation on classification, labelling and packaging (CLP) (EC) No 1272/2008 no classification is required for the test item Reaction product of oleylalcohol with polyphosphoric acid.