1,2-Ethanediamine, N1-(2-aminoethyl)-, 2-hydroxy-2-phenylethyl and stearyl derivs.

Endpoint summary

Description of key information

The acute oral median lethal dose (LD50) of FAT 92'267/A in rats of both sexes, observed over a period of 15 days, was estimated to be greater than 2000 mg/kg.

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:

3 April 1991 to 24 April 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material:
EN 3.86

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the dark at room temperature
- Stability under storage conditions: stable for at least 2 hours in water
- Stability under test conditions: unknown

Species:

rat

Strain:

Wistar

Remarks:

Hanlbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wölferstrasse 4, CH-4414 Füllinsdorf
- Age at study initiation: Males: 8 weeks and females: 10 weeks
- Weight at study initiation: Males: 182-209 g and females: 173-182 g
- Fasting period before study: Fasted for 16 to 22 hours before gavage.
- Housing: Groups of five in Makrolon type-3 cages with standard softwood bedding.
- Diet: Pelleted standard Kliba 343, Batch 83/91 rat maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst) available ad libitum.
- Water: Community tap water from Füllinsdorf, available ad libitum.
- Acclimation period: One week under laboratory conditions, after veterinary examination.
- Identification: By unique cage number and corresponding color-coded spots on the tail.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): Air conditioned with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light / 12 hours dark and music during the light period.

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on oral exposure:

The animals received a single dose of the test article on a mg/kg body weight base by oral gavage after being fasted for 16 to 22 hours (access to water was not interrupted). Food was again presented approximately 3 hours after dosing. Application Volume: 10 ml at 2000 mg/kg.
Rationale: The oral administration was used because this is one possible route of human exposure during manufacture, handling and use of the test article.

Doses:

2000 mg/kg.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Observations mortality/ Viability: Four times during test day 1 and daily during days 2-15
- Observations body weight: Test days 1 (pre-administartion), 8 and 15.
- Necropsy of survivors performed: yes. All animals were euthanized by intraperitoneal injection of sodium pentobarbitone.
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

The LOGIT-Model could not be applied to the observed rates and death. The toxicity was estimated without use of a statistical model.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities were observed.

Clinical signs:

other: There were no clinical signs were observed except sedated, hunched posture, ruffled fur in one male animal on day one.

Gross pathology:

No obvious macroscopical organ findings noted.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of FAT 92267/A in rats of both sexes was estimated to be greater than 2000 mg/kg.

Executive summary:

The acute oral toxicity study was carried out to assess the toxicological profile of FAT 92267/A when administered to rats by single oral gavage, with an observation period of 15 days according to OECD Guidelines 401 and EU method B.1. The experiment was done on five males and 5 females rats. The test article FAT 92267/A was administered to rats of both sexes by oral gavage, at a single dose of 2000 mg/kg. There were no mortality found. There were no clinical signs were observed except sedated, hunched posture, ruffled fur in one male animal on day one. The body weight gain of the animals was not affected by the test article treatment throughout the entire study period. There were no obvious macroscopical organ findings noted. Based on the study results, the acute oral median lethal dose (LD50) of FAT 92267/A in rats of both sexes, observed over a period of 15 days, was estimated to be greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

OECD guideline and GLP compliance study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity: oral

The acute oral toxicity study was carried out to assess the toxicological profile of FAT 92267/A when administered to rats by single oral gavage, with an observation period of 15 days according to OECD Guidelines 401 and EU method B.1. The experiment was done on five males and 5 females rats. The test article FAT 92267/A was administered to rats of both sexes by oral gavage, at a single dose of 2000 mg/kg. No mortality was found. There were no clinical signs were observed except sedated, hunched posture, ruffled fur in one male animal on day one. The body weight gain of the animals was not affected by the test article treatment throughout the entire study period. There were no obvious macroscopical organ findings noted. Based on the study results, the acute oral median lethal dose (LD50) of FAT 92267/A in rats of both sexes, observed over a period of 15 days, was estimated to be greater than 2000 mg/kg.

Acute toxicity: inhalation

Currently no study to assess the acute inhalation toxicity potential of FAT 92267 is available. Based on column 2, ‘Specific rules for adaptation from column 1’ of the table given in REACH Annex VII, the study on acute inhalation toxicity only needs to be conducted if an exposure via inhalation is to be expected. FAT 92267 is used as an intermediate only and as such will be used in closed processes. Hence, the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur. The chemical showed low toxicity potential in the available acute oral toxicity study (LD₅₀: >2000 mg/kg bw), with no mortality or systemic toxicity being seen, hence it does not need to be classified as STOT SE, further supporting the conclusion that it is expected to have low toxicity via the inhalation route. Taking, the above information into consideration, the inhalation toxicity test for FAT 92267 was considered scientifically not necessary.

Acute toxicity: dermal

Currently no study to assess the acute dermal toxicity potential of FAT 92267 is available. Based on column 2, ‘Specific rules for adaptation from column 1’ of the table given in REACH Annex VII, the study on acute dermal toxicity only needs to be conducted if an exposure via dermal route is to be expected. FAT 92267 is used as an intermediate only and as such will be used in closed processes. Hence, the use of this substance will not result to dermal exposure of the workers. The chemical showed low toxicity potential in the available acute oral toxicity study (LD₅₀: >2000 mg/kg bw), with no mortality or systemic toxicity being seen, hence it does not need to be classified as STOT SE,Similarly, absence of systemic toxicity in skin irritation and sensitisation studies, further supports the conclusion that no adverse effects are expected for the chemical via the dermal route. Further experience with similar chemical substances has demonstrated that it is very unlikely that toxicity related to the intrinsic properties of the chemical only show up upon dermal exposure and not after systemic application. Taking into consideration the above arguments, low toxicity is expected on acute dermal exposure ofFAT 92267 and testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

Based on the observed LD₅₀ of >2000 mg/kg bw in the acute oral toxicity study, the test substance does not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.