Registration Dossier

Administrative data

Description of key information

Based on Analogue approach (3 -phenoxyphenol), the oral LD50 is determined to be equal to 1 600 mg/kg bw for 4 -phenoxyphenol.

An acute dermal toxicity study performed according to OECD 402 resulted in an LD50 of > 2 000 mg/kg bw.

On the basis of the rules for adaptation in Column 2 of the REACH Annex VIII, no inhalation acute toxicity was performed. Furthermore based on the OECD n°110 test showing that the majority of the particule size (92.3%) was between 45 and 125 µm, there is no alveolar fraction and systemic effect after inhalation is not expected.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The hypothesis is that 4-phenoxyphenol and 3-phenoxyphenol have the same behaviour for the acute toxicity.

2. ANALOGUE APPROACH JUSTIFICATION
According the position of polar group (-OH), it can be considered than the para and meta phenoxyphenol are the same breakdown process in the organism and they have the same order of magnitude of responsiveness.
This approach is justified by dermal acute toxicity : both isomers are the same magnitude of toxicological effect (> 2000 mg/kgbw)
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across: supporting information
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 1 600 mg/kg bw
Based on:
other: 3-phenoxyphenol
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The approximative LD50 (rat) for 4-PhenxyPhenol, per oral, is determined as equal that LD50 for 3-phenoxyphenol : 1 600 mg/kgbw.
Executive summary:

The approximative LD50 (rat) for 4-PhenxyPhenol, per oral, is determined as equal that LD50 for 3-phenoxyphenol : 1 600 mg/kgbw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 600 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
The rules for adaptation in Column 2 of the REACH Annex VIII state that, “in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 [inhalation and dermal acute toxicity] shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. If there is only one route of exposure, information for only that route need be provided”. The rules for adaptation also state that, “Testing by the dermal route is appropriate if…inhalation of the substance is unlikely…”. As oral and dermal routes of exposure are more relevant, testing for acute inhalation toxicity is therefore waived based on this information.Furthermore on the basis of the OECD n° 110 test the majority of the particle size (92.3%) was between 45 and 125 µm. Therefore there is no alveolar fraction and systemic effect after inhalation is not expected.
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Batch n°20180328
- Expiration date of the lot/batch:28 March 2019

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: Yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: JANVIER LABS (53940 Le Genest St Isle – France)
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 - 9 weeks old
- Weight at study initiation: 219.3 g +/- 8 g (mean)
- Housing: individual cage
- Diet :ad libitum (ENVIGO 2016)
- Water : ad libitum (tap-water from public distribution system - Microbiological and chemical analyses of the water were carried out once every 6 months)
- Acclimation period: Yes - Five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C to 25°C
- Humidity (%): 30% to 70%
- Air changes (per hr): ten changes cycles per hour
- Photoperiod (hrs dark / hrs light): 12h dark / 12h light
Type of coverage:
open
Vehicle:
DMSO
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10%
- Type of wrap if used: wides hypoallergenic microporeTM adhesive tape from 3M

REMOVAL OF TEST SUBSTANCE
- Washing : Yes (distiled water)

TEST MATERIAL
- Amount(s) applied: 1.006 g with 5 ml of DMSO or 2.006 g with 10 mL of DMSO

VEHICLE
- Amount(s) applied: 10 mL/kgbw
Duration of exposure:
24 hours
Doses:
2 000 mg/kgbw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0, 2, 7 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (spontaneous activity, preer's reflex, respiratory rate, convlusions, tremors, body temperature, muscle tone, palpebral opening, pupil appearance, salivation, lachrymation, righting reflex), body weight, Auopsy (oesophagus, stomach, duodenum, jejunum, ileon, caecum, colon, rectum, spleen, liver, thymus, trachea, lungs, heart, kidneys, urinary bladder, ovarie, uterus, skin, adrenals, pancrease), only organs presenting macroscopic anomalies can be removed and preserved in view to microscopic examination.
- These observations were compared to historical control data
Statistics:
Mean and standard deviation
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
No systemic clinical sign
Body weight:
The body weight evolution of the animals remained normal throughout the study.
Gross pathology:
No gross pathology

Body weight and weight gain in grams

 Females D0  D2  D2 -D0  D7  D7 -D0  D14  D14 -D0 
Female n°1  211  233  22  253  42  282  71 
 Female n°2 220 229  254  34  271  51 
 Female n°3 227  241  14  263  36  271  44 
 MEAN 219.3  234.3  15.0  256.7  37.3  274.7  55.3 
 Standard deviation 8.0  6.1  6.6  5.5  4.2  6.4  14.0 
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test item Paraphenoxyphenol is higher than 2000 mg/ kg body weight by dermal route in the rat.
Executive summary:

In accordance with the OECD guideline n° 402, the 4 -Paraphenoxyphenol was applied, as supplied, onto the intact skin of 3 female Sprague Dawley rats at the dose of 2000 mg/kg body weight.

No mortality occurred during the study. No systemic clinical sign related to the administration of the test item was observed. The body weight evolution of the animals remained normal throughout the study. The macroscopic examination of the animals at the end of the study did not reveal treatment-related changes.

In conclusion, the LD50 of the test item Paraphenoxyphenol is higher than 2000 mg/ kg body weight by dermal route in the rat. The test item Paraphenoxyphenol does not have to be classified in accordance with the Regulation 1272/2008 on classification, labelling and packaging of substances and mixtures.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification

Based on the available data, 4 -phenoxyphenol is classified, according to the CLP Regulation, H302 (oral acute toxicity, Cat. 4 - Harmful if swallowed).