Amines, C16-18 (even numbered)-alkyl , salts with phosphoric acid, mono- and di-C16-18 (even numbered) alkyl esters

Endpoint summary

Description of key information

The acute oral toxicity of the substance was investigated during a GLP-compliant study conducted in accordance with the OECD Testing Guideline 423. No mortality was observed at up to 2,000 mg/kg bw.
In accordance with Annex VIII, Column 2, it is not required to investigate the toxicity of the substance following an acute exposure via inhalation as it is not a relevant route of exposure.
In accordance with Annex VIII, Column 2, it is not required to investigate the toxicity of the substance following an acute exposure via the dermal route as the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure.

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:

23 June 2020 - 21 July 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF)

Version / remarks:

2000 including most recent revisions

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately 8-10 weeks old
- Weight at study initiation: 146 to 194 g.
- Fasting period before study: Yes; O/n (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of test item. Water was available.
- Housing: animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages containing sterilized wooden fibers as bedding material equipped with water bottles.
- Animal enrichment: animals were provided with paper, except when interrupted by study procedures/activities.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum. The feed was analyzed by the supplier for nutritional components and environmental
contaminants.
- Water: Municipal tap water, ad libitum. Periodic analysis of the water was performed.
- Contaminants: It is considered that there were no known contaminants in the feed or water that would interfere with the objectives of the study.
- Acclimation period: at least 5 days
- Microbiological status: SPF

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C (target range); 21°C (actual daily mean)
- Humidity (%): 40 to 70% (target range); 41 to 73% (actual daily mean)
- Air changes (per hr): Ten or greater air changes per hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 30 June 2020 To: 21 July 2020

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Supplier: Sigma-Aldrich, Steinheim, Germany
- Justification for choice of vehicle: Trial preparations were performed to select the suitable vehicle and to establish a suitable formulation procedure. These trials were not performed as part of this study and these preparations were not used for dosing.
- Specific gravity: 0.92

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

CLASS METHOD
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Group 1: 3 females
Group 2: 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days; Animals were observed twice daily for general health and mortality.
- Frequency of observations: Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter.
- Frequency of weighing: Day 1 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was performed.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture was noted for three animals on Day 1. No clinical signs were observed in the other animals.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of an acute oral study, performed according to OECD guideline 423 and in
accordance with GLP principles, the oral LD50 value of Amines, C16-18 (even numbered)-alkyl , salts with phosphoric acid, mono- and di-C16-18 (even numbered) alkyl esters in Wistar Han rats was determined to exceed 2000 mg/kg bodyweight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. As a consequence, Amines, C16-18 (even numbered)-alkyl , salts with phosphoric acid, mono- and di-C16-18 (even numbered) alkyl esters does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Executive summary:

An acute oral study was performed according to OECD guideline 423 and in accordance with GLP principles, six female rats were exposed at test item concentration of 2000 mg/kg bodyweight and observed for 14 days. No mortality occurred. Hunched posture was noted for three animals on Day 1. No clinical signs were observed in the other animals. The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of Amines, C16-18 (even numbered)-alkyl , salts with phosphoric acid, mono- and di-C16-18 (even numbered) alkyl esters in Wistar Han rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. Based on these results, Amines, C16-18 (even numbered)-alkyl , salts with phosphoric acid, mono- and di-C16-18 (even numbered) alkyl esters does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

A GLP-compliant study was conducted in accordance with the OECD Testing Guideline 423.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

An acute oral study was performed according to OECD guideline 423 and in accordance with GLP principles, six female rats were exposed at test item concentration of 2000 mg/kg bodyweight and observed for 14 days. No mortality occurred. Hunched posture was noted for three animals on Day 1. No clinical signs were observed in the other animals. The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of Amines, C16-18 (even numbered)-alkyl , salts with phosphoric acid, mono- and di-C16-18 (even numbered) alkyl esters in Wistar Han rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. Based on these results, Amines, C16-18 (even numbered)-alkyl , salts with phosphoric acid, mono- and di-C16-18 (even numbered) alkyl esters does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

 

Acute inhalation toxicity

A study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

 

Acute dermal toxicity

A study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure.

Justification for classification or non-classification

No mortaility was observed following a single exposure to the substance at up to 2,000 mg/kg bw, therefore, it does not meet the criteria for classification as Acute Tox in accordance with Regulation (EC) No 1272/2008. No testing was required for the inhalation and dermal routes of exposure in accordance with REACH.