Amines, N-C10-16-alkyltrimethylenedi-, reaction products with chloroacetic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1996

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Amines, N-C10–C16-alkyltrimethylenedi-, reaction products with chloroacetic acid

Cas Number:

139734-65-9

Molecular formula:

Not applicable (UVCB substance)

IUPAC Name:

Amines, N-C10–C16-alkyltrimethylenedi-, reaction products with chloroacetic acid

Details on test material:

- Name of test material: DOPA-Glycinate

Test animals

Species:

rat

Strain:

other: Wistar outbred rat / Crl: (WI) WU BR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: 9 – 10 weeks
- Weight at study initiation: 167 – 177 g
- Fasting period before study: yes, overnight
- Diet: standard laboratory diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 13 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL aqueous suspension of the test substance

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Only a single dose level of 300 mg/kg bw of the test substance was examined. Because the test material has been verified as corrosive to skin, any treatment of the animals with standard dose of 2000 mg/kg bw was anticipated to result in extreme pain and distress to the animals. Moreover, the corrosive and surface active effect of the test substance on the gastro-intestinal tract would prevent a meaningful evaluation of the systemic toxic properties

Doses:

300 mg/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: Observations of clinical signs within 1 hour and within 4 hours after dosing and subsequently in surviving animals at least once daily throughout an observation period of 14 days; body weight was recorded immediately before dosing on day 0, and of the surviving animals on days 3, 7 and 14 of the study
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

500 mg/kg bw

Based on:

act. ingr.

Mortality:

One female was found dead on day 1, 27 hours after dosing, showing sluggishness, encrusted nose, piloerection and a soiled fur prior to its death. No other mortality was observed during the study.

Clinical signs:

other: Clinical signs generally observed after dosing consisted of sluggishness, vocalization, encrustated nose and piloerection.

Body weight:

other body weight observations

Remarks:

Apart from a slight dip in body weight on day 3, the surviving animals gained weight during the 14-day study. The one animal found dead showed body weight lass.

Gross pathology:

Examination at necropsy of the animals did not reveal distinct treatment-related gross alterations.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 (rat, female) of the registration substance was determined to be between 300 and 2000 mg a.i/kg bw. According to the criteria laid down in Regulation (EC) No 1272/2008 as well as the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations the registration substance is classified for Acute oral toxicity, Category 4.

Executive summary:

The acute oral toxicity of the registration substance (99.4% a.i.) was tested in female Wistar rats according to EC method B.1 tris (1996) and OECD guideline 423 (2001). Two groups of 3 female rats received 300 mg/kg bw of test substance by gavage. After exposure the animals were observed for clinical signs, mortality, body weight and gross pathology for 14 days.

One female was found dead on day 1, 27 hours after dosing, showing sluggishness, encrusted nose, piloerection and a soiled fur prior to its death. No other mortality was observed during the study.

Clinical signs generally observed after dosing consisted of sluggishness, vocalization, encrustated nose and piloerection.

Over the 14 day study period the surviving animals gained weight, apart from a light reduction in body weight on day 3. The one animal found dead showed body weight loss.

Examination at necropsy of the animals did not reveal distinct treatment-related gross alterations.

Since 5 out of 6 animals survived the 300 mg/kg bw application of the test substance, the LD50 is estimated to be between 300 and 2000 mg/kg bw. A 2000 mg/kg bw dose level was not examined because of the corrosivity of the test material. The LD50 cut-off is 500 mg/kg bw.