Phenol, 4,4'-(1-methylethylidene)bis-, oligomer with (chloromethyl)oxirane and ethylenediamine, reaction products with carbon disulphide, potassium salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Single dose; 14 day observation

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Justification for type of information:

Performed to guidelines, 2018
Material tested included butanol, monoethylene glycol and water at ca 50% actives. The solvents and water were not possible to remove under conditions that would not otherwise cause stability problems. The solvents and water are not stabilisers, but the temperatures needed to remove cause instability.
Freeze drying is not possible in view of the solvents, water and amines in the substance forming azoetropes.
In view of the mortality seen in three out of four animals at the top dose, a reduced dose of 300 mg/kg of the material supplied was tested. It is accepted that for REACH, a dose of 600 mg/kg (300 mg/kg actives) should have been tested, but as the data is also needed for US regulatory purposes and for classification of the material as supplied, the dose levels were aimed at the material as supplied.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phenol, 4,4'-(1-methylethylidene)bis-, oligomer with (chloromethyl)oxirane and ethylenediamine, reaction products with carbon disulphide, potassium salts

EC Number:

600-775-0

Cas Number:

1067676-04-3

IUPAC Name:

Phenol, 4,4'-(1-methylethylidene)bis-, oligomer with (chloromethyl)oxirane and ethylenediamine, reaction products with carbon disulphide, potassium salts

Test material form:

liquid

Details on test material:

Technical grade, CA 50% in water

Specific details on test material used for the study:

Batch: Lot#102-17 filtered
Purity: Not a neat substance the average activity is 48.66%
Physical state / Appearance orange liquid
Expiry Date: 01 May 2019
Storage Conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

At the start of the study the animals were 8 to 12 weeks of age. The body weight variation did not exceed ±20% of the mean body weight of any previously treated animals

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

For the 300 mg/kg dose level the test item was freshly prepared as required, as a solution in distilled water.
For the 2000 mg/kg dose level the test item was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.

Doses:

Initial sightighting 300 mg/kg and 2000 mg/kg on material as supplied (ca 150 and 1000 mg/kg actives)
Main dose 2000 mg/kg (1000 mg/kg acitves), but mortality noted in this group, even though animal used in sighting study survived.
Further treatment of 300 mg/kg (ca 150 mg/kg actives) to confirm no adverse effect level

No. of animals per sex per dose:

Four females in main groups.

Control animals:

no

Results and discussion

Preliminary study:

The single females treated with 300 and 2000 mg/kg survived (150 and 1000 mg/kg actives) and at 2000 mg/kg, minimal clincial signs seen (hunched posture for 2 hours post dosing)

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

ca. 1 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: Estimated

Remarks:

Two out of 5 animals survived dose of 2000 mg/kg material supplied (ca 1000 mg/kg actives)

Effect levels 2

Sex:

female

Dose descriptor:

other: NOAEL

Effect level:

ca. 150 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: Five out of five animals showed no adverse effects (other than short term hunched posture) at 150 mg/kg actives (300 mg/kg as supplied)

Mortality:

Three animals treated at a dose level of 2000 mg/kg were found dead on Day 0. There were no deaths noted at a dose level of 300 mg/kg.
Deaths were within 2 hours of treatment.

Clinical signs:

other: Signs of systemic toxicity noted in the animals that were found dead during the study were hunched posture, ataxia, lethargy, loss of righting reflex, decreased respiratory rate and labored respiration. Signs of systemic toxicity noted in the surviving an

Gross pathology:

Abnormally red lungs, dark liver, dark kidneys and reddened gastric mucosa were noted at necropsy of animals treated at a dose level of 2000 mg/kg that died during the study. There were no abnormalities noted at necropsy of the surviving animals treated at a dose level of 2000 mg/kg. There were no abnormalities noted at necropsy of animals treated at a dose level of 300 mg/kg.

Other findings:

No other significant findings

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg (150 - 1000 mg/kg expressed as actives).

Material tested included butanol, monoethylene glycol and water at ca 50% actives. The solvents and water were not possible to remove under conditions that would not otherwise cause stability problems. The solvents and water are not stabilisers, but the temperatures needed to remove cause instability.
Freeze drying is not possible in view of the solvents, water and amines in the substance forming azoetropes.

In view of the mortality seen in three out of four animals at the top dose, a reduced dose of 300 mg/kg of the material supplied was tested. It is accepted that for REACH, a dose of 600 mg/kg (300 mg/kg actives) should have been tested, but as the data is also needed for US regulatory purposes and for classification of the material as supplied, the dose levels were aimed at the material as supplied.

The survival of 2 of the 5 animals that received the top dose of 1000 mg/kg actives (2000 mg/kg as supplied) and the absence of any effect at 150 mg/kg actives (300 mg/kg as supplied) would suggest GHS Acute Tox 4. Testing another group at 300 mg/kg actives is not justifed.