N-(2-hydroxyethyl)-N-[2-[(1-oxooctyl)amino]ethyl]-β-alanine

Endpoint summary

Description of key information

Oral LD50 > 2000 mg a.i./kg bw; OECD TG 423 / Method B.1, rat; oral: gavage; RL1, GLP

Dermal LD50 > 2000 mg a.i./kg bw; OECD TG 402 / Method B.1, rat; RL1, GLP

Inhalation: no relevant route of 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:

2007-04-03 to 2007-04-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004

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

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
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: Body weight variation did not exceed+/- 20% of the sex mean
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per cage in labelled Macrolon cages (MIV type; height 18 cm.) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiaten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3 - 23.1°C
- Humidity (%): 31 - 63%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50.6%

MAXIMUM DOSE VOLUME APPLIED: 3.738 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: limit dose

Doses:

2024 mg a.i./kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality: Twice daily; Body weights: Days 1 (pre-administration), 8 and 15; clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No mortality occured.

Clinical signs:

other: Hunched posture was noted among the animals on Day 1.

Gross pathology:

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

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of Amphopropionate C8 in female Wistar rats was established to exceed 2000 mg a.i./kg body weight.

Executive summary:

In an acute oral toxicity study according to OECD Guideline 423 (2002) and EU Method B1., two groups of three fasted female young adult Wistar ratswere given a single oral dose of Amphopropionate C8 (50.6% a.i.) at the limit dose 2024 mg a.i./kg bw and were observed for14 days.

No mortality occurred. Hunched posture was noted among the animals on Day 1.

Oral LD50 females > 2000 mg a.i./kg bw

Based on these results, Amphopropionate C8 does not have to be classified and has no obligatory labelling requirement for oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

guideline study, GLP, RL1

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:

2007-05-09 to 2007-05-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: none
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage­enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiaten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Macrolon cages (MIV type).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.8 - 23.0°C
- Humidity (%): 39 - 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09 May 2007 To: 23 May 2007

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: 5x7 cm
- % coverage: 10%
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1 D), successively covered with aluminum foil and Caban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only

REMOVAL OF TEST SUBSTANCE
24 hours after application the dressings were removed and the skin cleaned of residual test substance using tap water

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3738 mL/kg; 2024 mg a.i./kg bw
- Concentration (if solution): 50.6%
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2024 mg a.i./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: Mortality: Twice daily; Body weights: Days 1 (pre-administration), 8 and 15; clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No mortality occurred.

Clinical signs:

other: Lethargy, flat posture, piloerection (head), chromodacryorrhoea (snout) and/or ptosis was noted among the animals. The animals had recovered from the symptoms between Days 2 and 3. Focal erythema, scars, scales and/or scabs were seen in the treated skin-

Gross pathology:

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

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of Amphopropionate C8 in Wistar rats was established to exceed 2000 mg a.i./kg body weight.

Executive summary:

In an acute dermal toxicity study according to OECD guideline 402 (1987) and EU Method B.3 (1992), groups of young adult Wistar rats (5 males and 5 females) were dermally exposed to Amphopropionate C8 (50.6% a.i.) for 24 hours to the limit dose of  2024 mg a.i./kg bw.  Animals then were observed for 14 days.

No mortality occurred. Lethargy, flat posture, piloerection (head), chromodacryorrhoea (snout) and/or ptosis was noted among the animals. The animals had recovered from the symptoms between Days 2 and 3. Focal erythema, scars, scales and/or scabs were seen in the treated skin-area of the females during the observation period.

 

Dermal LD50 Males    > 2000 mg/kg bw

                    Females > 2000 mg/kg bw

         

Based on these results, Amphopropionate C8 does not have to be classified and has no obligatory labelling requirement for dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

guideline study, GLP, RL1

Additional information

Acute oral toxicity

In an acute oral toxicity study according to OECD Guideline 423 (2002) and EU Method B1., two groups of three fasted female young adult Wistar ratswere given a single oral dose of Amphopropionate C8 (50.6% a.i.) at the limit dose 2024 mg a.i./kg bw and were observed for14 days.

No mortality occurred. Hunched posture was noted among the animals on Day 1.

 

Oral LD50 females > 2000 mg a.i./kg bw

 

Acute inhalation toxicity

Given that inhalation is not a relevant route of exposure, testing by the inhalation route is not necessary according to REACH Regulation Annex VIII 8.5.2 Column 2. Inhalation is not a relevant route of exposure to Amphopropionate C8. This applies to both workers and the general population and is due to the physicochemical properties of the substance and the nature of the products where it is used. Vaporisation needs not to be considered due to the substance’s low vapour pressure of <1.47E-03 Pa at 20°C. The generation of aerosols is excluded by technical means or product design. The substance is not used in spray applications. The most likely route of human exposure for workers and consumers is the dermal route. Results of laboratory animal studies show a low acute toxicity after oral and dermal exposure. Therefore the acute intrinsic toxic activity of the substance is considered to be low. The occurrence of a systemic toxicity relevant to humans after inhalation is unlikely and therefore the conduct of an acute inhalation toxicity study is unjustified.

 

Acute dermal toxicity

In an acute dermal toxicity study according to OECD guideline 402 (1987) and EU Method B.3 (1992), groups of young adult Wistar rats (5 males and 5 females) were dermally exposed to Amphopropionate C8 (50.6% a.i.) for 24 hours to the limit dose of 2024 mg a.i./kg bw.  Animals then were observed for 14 days.

No mortality occurred. Lethargy, flat posture, piloerection (head), chromodacryorrhoea (snout) and/or ptosis was noted among the animals. The animals had recovered from the symptoms between Days 2 and 3. Focal erythema, scars, scales and/or scabs were seen in the treated skin-area of the females during the observation period.

 

Dermal LD50 Males    > 2000 mg/kg bw

                   Females > 2000 mg/kg bw

There are no data gaps for the endpoint acute toxicity. No human data are available. However, there is no reason to believe that these results from rat would not be applicable to humans.

Justification for classification or non-classification

Based on the available data, Amphopropionate C8 does not have to be classified and has no obligatory labelling requirement for acute oral, dermal or inhalation toxicity according to Regulation (EC) No 1272/2008).