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Administrative data

Description of key information

Acute toxicity potential of 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol was evaluated by oral route by two studies in rat. The first study considered as key (OECD 401) indicates that oral LD50 is higher than 2000 mg/kg and the second that LD50 is equal to 6400 mg/kg. The acute inhalation toxicity to rats was determined following OECD 403 at achieved concentrations of 0.021 mg/l (nominal) and no deaths or abnormalities were recorded. There was no data for dermal acute 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted by GLP accredited laboratory using OECD Guideline 401.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
At the start of the main study, the males weighed 154 - 180 g, and the females 126 - 136 g, were approximately five to eight weeks old.
The animal room was maintained at a temperature of 19 - 22°C and relatve humidity of 46 - 58%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Exposure period of 14 days
Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
5
Control animals:
not specified
Preliminary study:
A range-finding study was conducted using 1 female and 1 male rats to establish the dose regime. The dose level was 2000 mg/kg, the concentration was 200 mg/ml and the dose volume was 10 mg/kg. Overt signs or deaths were observed 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 5 days. There were no deaths or clinical signs of toxicity. Based on this information, a dose level of 2000 mg/kg bodyweight was selected for the main study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was recorded.
Clinical signs:
Common signs of hunched posture were noted with additional signs of ataxia, lethargy and decreased respiratory rate.
Animals recovered one day after dosing except for two males which appeared normal throughout the study.
Body weight:
All animals showed expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
not classified
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be > 2000 mg/kg bodyweight.
Executive summary:

The acute oral toxicity of the test substance to Sprague-Dawley rats was determined in accordance with the OECD Guideline for Testing of Chemicals 401. The rats were exposed to a dose of 2000 mg/kg bw of the test substance via oral gavage route. No mortality was observed and the acute oral median lethal dose (LD50) of the test material was found to be > 2000 mg/kg bodyweight. The test substance is not classified for acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
two acute oral toxicity studies were available and indicate the low acute toxicity of the substance.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was conducted using OECD Testing Guideline 403.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(Inhalation hazard test described in the Annex V; adopted 1981)
Deviations:
yes
Remarks:
not GLP study
Principles of method if other than guideline:
Standardized test method (BASF-Test): The test was performed in principle as described in OECD test guideline 403. It demonstrates the toxicity of an atmosphere saturated with vapours of the volatile components of a test substance at 20°C. Young adult laboratory rats, 3 per sex, were exposed sequentially to the vapours generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 8 h. The exposure was subsequently repeated in the same manner. No analytical determination of the atmosphere concentrations was performed. The nominal concentration was calculated as quotient of the amount of test substance weight loss during exposure, and the amount of air used during exposure. Group-wise documentation of clinical signs was performed over a 7 day study period. Body weight of groups was determined before the start of the study and at the end of the observation period.
GLP compliance:
no
Test type:
other: inhalation risk test
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

Rats were exposed for 8 h to a vapour saturated atmosphere. Vapour was generated by bubbling 200 l/h air through the liquid substance column (volume ca. 50 ml) of about 5 cm above a fritted glass disc in a glass cylinder. The air pressure was 754 mm Hg. Temperature in the exposure chamber was 20°C. Concentration was stated in the raw data to be 0.021 mg/l in the case of the 8 h exposure.

TEST ATMOSPHERE

Brief description of analytical method used: no analytics performed
Samples taken from breathing zone: no



Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
No verification of the concentration was performed. Nominal concentration: 0.021 mg/L
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
Duration of observation period following administration: 7 days
Frequency of observations and weighing: group wise documentation on working days
Necropsy of survivors performed: yes
Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
other: IHT
Effect level:
0.021 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
other: No mortality.
Mortality:
No mortality observed.
Clinical signs:
other: No abnormality detected.
Gross pathology:
No abnormality detected.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The Inhalation Hazard Test was given as 0.021 mg/l (air). No deaths or abnormalities were recorded. The substance vapours were not toxic at the maximum achieveable test concentrations.
Executive summary:

The acute inhalation toxicity of the test substance to rats (strain not specified) was determined in accordance with the OECD Guideline for Testing of Chemicals 403. The rat was exposed to a whole body dose, nominally stated as 0.021 mg/l. The Inhalation Hazard Test was given as 0.021 mg/l (air). No deaths or abnormalities were recorded. The substance vapours were not toxic at the maximum achievable test concentrations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
21 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Quality of whole database:
The results of the acute inhalation study are coherent with the physico-chemical properties of the substance.

Additional information

Acute oral toxxicity :

Two acute oral toxicity studies are available with 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol.

The first study (Safepharm Laboratories Limited 1994) has been performed according to OECD 401. Five animals/sex were given 2000 mg/kg BW of 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol and observed for 14 days. No mortality was observed; common signs of toxicity (hunched posture, ataxia, lethargy and decreased respiratory rate) were noted but disappeared one day after dosing. The LD(50) was considered to be > 2000 mg/kg bw.

The second one (BASF 1970) is also based on an OECD 401 protocol but without GLP Standards.

Ten rats/sex/dose were treated by gavage at the dose-levels of 200, 1600, 3200, 4000, 5000 and 6400 mg/kg bw and observed for a 7-day period. No mortality or clinical signs were observed up to 4000 mg/kg bw.

The acute oral median lethal dose LD(50) of the test material was found to be 6400 mg/kg.

Acute inhalation toxicity :

The acute inhalation toxicity of 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol

to rats (strain not specified) was determined in accordance with the OECD Guideline for Testing of Chemicals 403. The rats (2 animals/sex) were exposed to a whole body dose, nominally stated as 0.021 mg/l. No deaths or abnormalities were recorded. The substance vapours were not toxic at the maximum achievable test concentrations.

Justification for classification or non-classification

Acute oral and inhalation toxicity studies with rats are available with 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol. No mortality was noted up to 4000 mg/kg bw by oral route or at the maximum achievable concentration of 0.021 mg/l by inhalation.

Based on these results, 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol does not have to be classified and has no obligatory labelling requirement for acute oral, inhalation and dermal toxicity according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.