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Description of key information

2-Phenoxyethanol displayed low acute oral toxicity in rats.
2-Phenoxyethanol displayed very low acute dermal toxicity tested in rats and rabbits.
2-Phenoxyethanol displayed no effects following inhalation exposure in 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was performed
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2-phenoxyethanol (technical grade)
- Physical state: colourless liquid
- Analytical purity: ca. 80% 2-phenoxyethanol
- Composition of test material, percentage of components: 2-phenoxyethanol, (ca. 80% 2-phenoxyethanol, ca. 18% monophenyldiglycol, ca. 0.5% monophenyltriglycol)
- Lot/batch No.: substance number: 82/135
- Expiration date of the lot/batch: May 1983
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Germany
- Age at study initiation: ca. 12 weeks
- Weight at study initiation (mean): 188 g (males), 180 g (females)
- Fasting period before study: 16 h, but water was available
- Diet (e.g. ad libitum): conventional laboratory
- Water (e.g. ad libitum): drinking water
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 6.81, 14.70, 31.60, 50.00 %
- Amount of vehicle (if gavage): 10 mL/kg b.w.
- Other: 0.5 % aqueous carboxymethyl cellulose solution
Doses:
681, 1470, 3160, and 5000 mg/kg b.w.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (once daily)
Sex:
female
Dose descriptor:
LD50
Effect level:
1 840 mg/kg bw
95% CL:
1 010 - 2 960
Sex:
male
Dose descriptor:
LD50
Effect level:
4 070 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 740 mg/kg bw
95% CL:
1 910 - 4 050
Mortality:
All animals dosed with 681 mg/kg b.w. survived the 14 d observation period. All males survived a treatment of 1470 mg/kg b.w., whereas 2 out of 5 female rats died. At a dose level of 3160 mg/kg b.w., 2 males and 4 females died, respectively. At the highest dose level 3 male and all female animals died. In all treatment groups, the latest time point where death occurred was observation day 1. Generally females were more susceptible to 2-phenoxyethanol compared to males.
Increasing dose resulted in increased mortality.
Clinical signs:
Dyspnoea; apathy; abnormal position; staggering; atony; deficiency in pain and cornea reflex; coma-like state; spastic gait; rough fur; exsiccosis; exophthalmoses; general poor condition
Gross pathology:
Animals that died during the study course revealed following signs at necropsy:
Congestion; lungs which were slightly inflated; sporadically reddened glandular stomach

Dose [mg/kg b.w.]

Number of dead/
all animals were investigated

Time of death

 

Observations

 

Males

681

0

--

dyspnoea; apathy; abnormal position; staggering; atony; paresis

1470

0

--

dyspnoea; apathy; abnormal position; staggering; atony; deficiency in pain and cornea reflex; coma-like state;

3160

2

1 d

dyspnoea; apathy; abnormal position; staggering; atony; deficiency in pain and cornea reflex; coma-like state;

5000

3

1 d

dyspnoea; apathy; abnormal position; staggering; atony; deficiency in pain and cornea reflex; coma-like state; spastic gait; rough fur; exsiccosis; exophthalmoses; general poor condition

LD50value

4070 mg/kg b.w.

 

Females

681

0

--

dyspnoea; apathy; abnormal position; staggering; atony; paresis

1470

2

1 d

dyspnoea; apathy; abnormal position; staggering; atony; deficiency in pain and cornea reflex; coma-like state;

3160

4

1 d

dyspnoea; apathy; abnormal position; staggering; atony; deficiency in pain and cornea reflex; coma-like state;

5000

5

1 h (3 animals); 1 d (2 animals)

dyspnoea; apathy; abnormal position; staggering; atony; deficiency in pain and cornea reflex; coma-like state; exsiccosis; exophthalmoses; general poor condition

LD50value

1840 mg/kg b.w.

 

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
CLP: acute toxicity Cat. 4
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 840 mg/kg bw

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
Study period:
06 Sep 2005 - 17 Feb 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
other: OECD 412
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht, Mainz
Test type:
other: sub-acute inhalation toxicity
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2-phenoxyethanol
- Physical state: liquid/ colourless, clear
- Analytical purity: > 99.9 core peak-area% (GC)
- Lot/batch No.: 41183068E0
- Expiration date of the lot/batch:
- Stability under test conditions: The stability under storage conditions over the exposure period was guaranteed by the sponsor and the sponsor holds the responsibility
- Storage condition of test material: room temperature, under N2, in the dark
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany
- Age at study initiation: about 7 weeks
- Weight at study initiation: males: ca. 227 g, females: ca. 163 g
- Housing: animals were housed singly in makrolon-wire cages (type MD III, Becker & Co., Castrop-Rauxel, FRG (floor area about 800 cm²)
- Diet (e.g. ad libitum): milled mouse/rat laboratory diet “GLP”, (Provimi Kliba SA, Kaiseraugst, Basel Switzerland)
- Water (e.g. ad libitum): tap water
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 06 Sep 2005 To: 28 Sep 2005
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Generator systems:
- Continuous infusion pumps PERFUSOR (B. Braun) for test group 1
- Piston metering pumps (Sarstedt DESAGA) for test group 2 and 3
- Two-component atomizers (stainless steel, Schlick mod. 970)
- Glass mixing stages (BASF)
- Glass cyclonic separators (BASF)

Generation procedure:
For each concentration the test substance was supplied to a two-component atomizer at a constant rate by means of a metering pump. The aerosol was generated with compressed air in a mixing stage with conditioned dilution air and passed via the cyclonic separator into the inhalation system. Due to the vapor pressure of the test substance, in all test groups mixtures of vapor and liquid aerosol are tested. The theoretical vapor concentration is up to 40 mg/m3.

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.)
The target concentration of 40 mg/m3 in test group 1 was the saturation vapor concentration. At this concentration, part of the test substance might condensate in the atmosphere, thus liquid aerosols might be formed. To demonstrate the aerosol formation, two cascade impactor measurements were carried out. These resulted in MMADs between 2.9 and 3.7 μm with GSDs of 4.3 and 4.5. The amount of test substance that was trapped by the cascade impactor was approximately 20 % of that measured in the atmosphere, which was in the expected range for condensation effect. Due to the long sampling time (150 min), the condensation on the cascade stages during the sampling period might be much more pronounced in this group than in the other groups. Therefore, the particle size measurements in test group 1 were considered not to reflect the real particle size distribution, but to describe the liquid aerosol formation in the test atmosphere.
Cascade impactor measurements in the test groups 2 and 3 resulted in MMADs between 0.5 and 1.3 μm that were well within the respirable range. The calculated mass fractions of particles below 3 μm aerodynamic size ranged between 72.0 and 85.2%. The EACD (effective aerodynamic cut-off diameter 50%) of the last impactor stage is 1.2 μm. MMAD values below 1.2 μm are gained by extrapolation outside the effective measuring range of the impactor. Therefore the real value may lie between the calculated one and 1.2 μm.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
> 6 h
Remarks on duration:
6 hours per day, 5 days per week for 14 days (10 exposures)
Concentrations:
0, 40, 200, 1000 mg/m³ (nominal)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days exposure period without post exposure observation period
- Frequency of observations and weighing: once each working day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: examination of blood
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 000 mg/m³ air (nominal)
Mortality:
No deaths were recorded throughout the study up to and including the maximal dose.
Clinical signs:
other: In none of the test groups clinical signs of toxicity were observed.
Body weight:
Treatment related influence on body weight development or food consumption was found in the high concentration group on study day 7.
Gross pathology:
Clinical pathology examinations revealed no treatment-related changes in either males or females. 14 days of aerosol inhalation of the test substance led to histopathologic findings in the respiratory tract. The respiratory epithelium in the nasal cavity was the target tissue in high and mid concentration males and females. In the very anterior part signs of degeneration and metaplasia were noted, whereas in the more posterior parts hyperplasia was observed. Inflammatory cell infiltrates were seen in the mid and top concentration groups as a reaction to treatment. These findings are thought to be substance-related and the top concentration groups were slightly more affected. In the larynx (level I) in the area of the very sensitive epithelium at the base of the epiglottis, three male animals of the high concentration group showed a minimal to slight hyperplasia of the respiratory epithelium. This finding is also considered to be substance-related.
Other findings:
- Organ weights: In males of the mid and top concentration the absolute lung weight (up to 20.4%) and in males of the top concentration the relative lung weight (up to 19.3%) were statistically significantly increased.
- Histopathology: In the lungs there was an increase in thickness of small and terminal bronchi and increased numbers of mucous cells in larger bronchi of mid and top concentration males and females.
- Potential target organs: upper respiratory tract
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
1 000 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
other: Draft IRLG (Interagency Regulatory Liaison Group) Guidelines for Selected Acute Toxicity Tests (August. 1979)
Deviations:
no
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was performed
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2-phenoxyethanol, "Cosmetical grade"
- Physical state: liquid
- Analytical purity: Not given, however assumed to be ca. 92% 2-phenoxyethanol, ca. 8% Diethylenglykolmonophenylether (cosmetical grade)
- Lot/batch No.: sample number: 2219-93
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Plummers Rabbit Ranch
- Weight at study initiation: 2500- 2780 g
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5-5.6 mL
Duration of exposure:
24 h
Doses:
2 mL/kg (corresponding to 2214 mg/kg bw; based on a density of 1.107 g/mL)
No. of animals per sex per dose:
4
Control animals:
no
Details on study design:
Test was performed on abraded skin only.
- Duration of observation period following administration: 14 days
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 214 mg/kg bw
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 214 mg/kg bw

Additional information

Oral:

In an oral toxicity study according to OECD 401 (BASF AG, 1982), 2 -phenoxyethanol has a low acute oral toxicity in the rodent species rat (LD50 female approximately 1840 mg/kg bw). Generally males were less susceptible to 2-phenoxyethanol than females (LD50 male 4070 mg/kg). However the purity of the test substance was only 80%. In another oral toxicity study conducted according to OECD 401 (Sasol, 1983), the LD50 value for male and female rats was determined to be 1850 mg/kg bw. The purity of the test substance was > 99%.

However, these observations were contradictory to the observations made in less reliable studies. Administration of high oral doses to rats induced dyspnoea, apathy, abnormal position, staggering, atony, deficiency in pain and cornea reflex, coma like state, spastic gait, rough fur, exsiccosis, exophthalmoses and general poor condition.

Dermal:

There are two dermal acute toxicity studies with only basic data given. Based on these studies

2-phenoxyethanol has a low dermal toxicity: In rats, acute dermal toxicity was tested up to a concentration of 24575 mg/kg bw. In this test, mortalities occurred 21 to 48 h post-dosing (no further details given) (Davies 1970). The LD50 in rat was calculated to be 14391 mg/kg bw.

In rabbits, no mortality was noted at the limit dose of 2.0 mL/kg bw (corresponding to 2214 mg/kg bw) tested on abraded skin only (Doyle 1980). The only effect observed in two rabbits was a local erythema and desquamation at the dosing site, which was reversible within 3 days after dosing. Desquamation was observed in one rabbit from observation days 3-14. Thus, the LD50 was > 2214 mg/kg bw.

Inhalation: Several acute Inhalation Risk Tests (IRT) of minor relevance were available. Rats were exposed to saturated vapour for 7 or 8 hours, respectively (BASF AG 1963, Union Carbide Corp., 1982). If the vapour pressure of 0.014 hPa, respectively 0.01 hPa both at 20°Care taken into account, this corresponds to an atmospheric concentration of 80 resp. 57 mg/m3by calculation. No deaths or clinical signs were observed. The low inhalation toxicity of 2-phenoxyethanol in rat was confirmed by a Guideline subacute aerosol inhalation study performed according to GLP (BASF AG, 2007). No mortalities were seen in rats head/nose only exposed up to 1000 mg/m³ for 14 days (6 hours per day, 5 days per week). No deaths were recorded and in none of the test groups were clinical signs of toxicity observed throughout the study up to and including the maximal dose (LC50 1000 mg/m³).

If one looks at analytically measured concentrations in the 14 day inhalation study in rats, the calculated values are in line with the 14 day NOAEC of 40 mg/m3(nominal) respectively 48 mg/m3analytically determined. At this concentration the vapour fraction was about 80% and the rest was aerosol.This allows the conclusion that the LC50 of phenoxyethanol vapour is clearly above the saturated vapour concentration at room temperature after a single 8 hour exposure and even if exposure is prolonged to 14 days.

Justification for classification or non-classification

Acute oral toxicity:

CLP: Cat. 4 / EU: Xn R22

Acute dermal toxicity:

CLP: not classified / EU: not classified

Acute inhalation toxicity: (testing up to 1000 mg/m3 displayed no effects)

CLP: not classified / EU: not classified