2-(2,4-diaminophenoxy)ethanol dihydrochloride

Endpoint summary

Description of key information

Under the experimental conditions, the LD50 of the test item was close to 1000 mg/kg bw since a single dose of 1000 mg/kg induced death in 1/5 male and 3/5 female 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:

1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed according to OECD guideline 401 and in compliance to GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

other: Single dose acute toxicity study

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa Credo, France
- Age at study initiation: ~6 weeks old
- Weight at study initiation: 195+/-3g for males and 156+/-6g for females
- Fasting period before study: ~18 hours before dosing
- Housing: Polycarbonate cages (48cm x 27cm x 20cm)
- Diet (e.g. ad libitum): All animals had free access to A04C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France)
- Water (e.g. ad libitum): Drinking water filtered by FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: At least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-2
- Humidity (%): 30-70
- Air changes (per hr): ~12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: On day 15 (1998-07-09) all surviving animals were killed by carbondioxide asphyxiation

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10w/v%
- Amount of vehicle (if gavage): <10 ml/kg
- Justification for choice of vehicle: solubility
- Lot/batch no. (if required): 0101297 (test item)
- Purity: 99.6% (test item)

Doses:

1000 mg/kg bw

No. of animals per sex per dose:

One group of 5 males and 5 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: 30min, 1, 2, 4, 6hours, days 2-15 (clinical signs); days 1, 8, 15 (weighing)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination of main organs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 000 mg/kg bw

Based on:

test mat.

Mortality:

A single dose of 1000 mg/kg bw induced death in 1/5 male and 3/5 female rats.

Clinical signs:

other: Hypoactivity or sedation and piloerection were noted in all animals on day 1. Lateral recumbency and tonic-clonic convulsions were also observed in two animals on day 1, one of these animals was found dead a few hours later. One male and two females were

Gross pathology:

No apparent abnormalities were observed at necropsy in all animals.

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions, the LD50 of the test item was close to 1000 mg/kg bw since a single dose of 1000 mg/kg induced death in 1/5 male and 3/5 female rats.

Executive summary:

The acute oral toxicity of the substance was assessed according to OECD 401 in compliance to GLP. Under the experimental conditions, the LD50 of the test item was close to 1000 mg/kg bw. In accordance with Directive 67/548 and Regulation (EC) No 1272/2008 the substance is classified as harmful if swallowed.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

For level 10-100 tpy, under REACh, a second route, after the oral should be tested for the acute toxicity: inhalation or dermal route.

Considering the form of the substance: a solid powder. Inhalation could be considered. The particle size distribution of the test item 2-(2,4-diaminophenoxy)ethanol dihydrochloride was determined using a Malvern Instruments Laser Particle Sizer with a dry powder feed system. The median particle diameter was calculated to be 39µm (> 5µm). Hence, the exposure by inhalation of the powder form is expected to be very low. Furthermore, the substance is formulated in cosmetic whitout sprayed application, any toxicological relevance of air-born particles/droplets is not expected. The dermal route should be considered for the second route of exposure under REACh regulation.

The dermal route should be considered for the second route of exposure under REACh regulation. Since 2009, the performance of animal tests for those chemicals which are intended to be used in cosmetic products (like this hair dye) is not any longer allowed in the EU. To avoid any negative impact on the intentional use of this chemical, to avoid unnecessary additional animal tests and due to the unlikelihood to get more severe labelling on acute toxicity, any additional testing on acute toxicity was avoided. A route to route extrapolation is proposed from oral route to dermal route: To assess the acute dermal toxicity of 2,4-Diaminophenoxyethanol dihydrochloride, a route to route extrapolation was proposed: Study used for the determination of acute toxicity of 2,4-Diaminophenoxyethanol dihydrochloride: Acute Oral Toxicity study result (X. Manciaux. 2952: Acute Oral Toxicity in Rats. CIT Study No. 17303 TAR, 1998) LD50 oral: Under the experimental conditions, the LD50 of the test item was close to 1000 mg/kg bw since a single dose of 1000 mg/kg induced death in 1/5 male and 3/5 female rats. 1000mg/kg bw in the rat. Toxicokinetic study results in Sprague Dawley rats: Dose levels: Bioavailability, assuming 50% Oral (default value recommended by Dermal dosing: 1.1 % Extrapolation from oral to dermal: LD 50 oral: 1000 mg/kg bw Oral Bioavailability = 50% Determination of the correction factor oral vs. inhalation route: 50% oral vs. 1.1% dermal = 45.45 LD50 calc dermal: 1000 mg/kg bw x 45.45 = 45 450 mg/kg bw

Justification for classification or non-classification

The acute oral toxicity of the substance was assessed according to OECD 401 in compliance to GLP. Under the experimental conditions, the LD50 of the test item was close to 1000 mg/kg bw. In accordance with Directive 67/548 and Regulation (EC) No 1272/2008 the substance is classified as harmful if swallowed.