Registration Dossier

Administrative data

Description of key information

ORAL
An acute oral study was performed using methodology similar to that outlined in OECD 401 and identified an LD50 in rats of 1470 mg/kg.

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:
other: Study was conducted in methods comparable to OECD guideline 401. However, animal acclimation information was not provided. Animals were only fasted for 3-4 hours before dosing. Body weight results are not provided in the report.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Animal acclimation information was not provided. Animals were only fasted for 3-4 hours before dosing. Body weight results are not provided in the report.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 207 to 326 grams
- Fasting period before study: Food was withheld from the animals for a period of three to four hours prior to dosing.
- Housing: Following intubation, the animals were housed by groups in metal cages.
- Diet: ad libitum
- Water: ad libitum


Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 or 20% weight/volume solution
Doses:
100, 215, 464, 1000, 2150, and 4640 mg/kg bw
No. of animals per sex per dose:
five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Animals were closely observed for mortality and toxic effects at the following intervals after compound administration: immediately; at one, four, and 24 hours; and once daily thereafter for a total of 14 days. At the end of the observation period, the surviving animals were weighed, sacrificed by cerebral concussion, and necropsied.
- Necropsy of survivors performed: yes. At the end of the observation period, the surviving animals were weighed, sacrificed by cerebral concussion, and necropsied. Necropsies were also performed on the animals that succumbed during the course of the study.
- Other examinations performed: clinical signs
Statistics:
Statistical analysis of the mortality data was conducted by the method by Thompson, W.R., Bact. Rev., 11, 115, 1947, utilizing the tables of Horn, H. J., Biometrics, 12, 311, 1956.
Sex:
male
Dose descriptor:
LD50
Effect level:
1 470 mg/kg bw
Based on:
test mat.
Mortality:
All animals in the 100, 215, 464, and 1000 mg/kg bw dose groups survived the 14 day study period. In the 2150 mg/kg bw dose group, three animals died 1 hour after treatment, one animal died 24 hours after treatment, and one animal died 2 days after treatment. In the 4640 mg/kg dose group, all animals died 1 hour after treatment.
Clinical signs:
No clinical signs were observed in animals in the 100 mg/kg dose group. The principle clinical signs for animals in the 215, 464, and 1000 mg/kg bw groups were depression and flushed appearance, labored respiration and ataxia (1000 mg/kg dose level only). The onset of signs started within one hour after treatment, complete recovery in all animals was observed within 48 hours.
For animals in the 2150 and 4640 groups, depression, flushed appearance, lacrimation, exophthalmos, salivation, slow labored respiration, ataxia, sprawling of the limbs, depressed righting and placement reflexes, prostration, coma, and death were observed.
Body weight:
no data
Gross pathology:
No necropsy findings were observed in the 100, 215, 464, or 1000 mg/kg bw dose groups.
At the 2150 and 4640 mg/kg bw dose level, congestion of the lungs, liver, spleen, kidney, and adrenals; gastrointestinal inflammation and apparent sloughing of stomach mucosa were observed.
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of 2,6-xylenol for adult male Sprague-Dawley rats is 1470 mg/kg body weight based on the results of this study.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 470 mg/kg bw
Quality of whole database:
The key study was conducted prior to the adoption of GLP using methodology equivalent to that outlined in a standardised guideline and was well reported. The data was awarded a reliability score of 2 in accordance with the criteria for assessing data quality set forth by Klimisch et al. (1997).
The supporting study was cited by secondary sources and the peer review of data unknown, therefore the data was awarded a reliability score of 4 in accordance with the criteria for assessing data quality set forth by Klimisch et al. (1997). The quality of the database is therefore considered to be fair.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Supporting information was available in the form of data originally published in grey literature and subsequently disseminated by the European Chemicals Bureau. The data was awarded a reliability score of 4 in accordance with the criteria for assessing data quality set forth by Klimisch et al. (1997) due to the limited methodology and study details available. The quality of the database is therefore considered to be adequate.

Additional information

Acute Oral Toxicity

In the key study, the potential of the test material to cause acute toxicity via the oral route was investigated using methodology comparable to that outlined in the standardised guideline OECD 401.

Male Sprague-Dawley rats were exposed to concentrations of 100, 215, 464, 1000, 2150 and 4640 mg/kg bw in corn oil (5 rats per dose level). Animals were closely observed for mortality and toxic effects immediately, 1, 4 and 24 hours after test material administration, and once daily thereafter for a total of 14 days. Animals were also observed for clinical signs. At the end of the observation period, the surviving animals were weighed, sacrificed by cerebral concussion, and necropsied. Necropsies were also performed on the animals that succumbed during the course of the study.

All animals in the 100, 215, 464, and 1000 mg/kg bw dose groups survived the 14 day study period. In the 2150 mg/kg bw dose group, three animals died 1 hour after treatment, one animal died 24 hours after treatment, and one animal died 2 days after treatment. In the 4640 mg/kg dose group, all animals died 1 hour after treatment.

No clinical signs were observed in animals in the 100 mg/kg dose group. The principle clinical signs for animals in the 215, 464, and 1000 mg/kg bw groups were depression and flushed appearance, labored respiration and ataxia (1000 mg/kg dose level only). The onset of signs started within one hour after treatment, complete recovery in all animals was observed within 48 hours. For animals in the 2150 and 4640 groups, depression, flushed appearance, lacrimation, exophthalmos, salivation, slow labored respiration, ataxia, sprawling of the limbs, depressed righting and placement reflexes, prostration, coma, and death were observed.

No necropsy findings were observed in the 100, 215, 464, or 1000 mg/kg bw dose groups. At the 2150 and 4640 mg/kg bw dose level, congestion of the lungs, liver, spleen, kidney, and adrenals and gastrointestinal inflammation and apparent sloughing of stomach mucosa were observed.

Under the conditions of this study, the acute oral LD50 was 1470 mg/kg body weight.

The supporting information provided is based on a literature reference cited by secondary sources; the peer review status of the data is unknown. No details on methodology and results were available. 

This study was included in the dossier due to the fact that it served as the basis for the harmonized classification of 2,6-xylenol for acute oral toxicity.

Under the conditions of this study, the acute oral LD50 was determined to be 296 mg/kg bw in the rat.

Acute Inhalation Toxicity

In accordance with section 8.5 of Column 2 of Annex VIII, acute toxicity studies generally do not need to be conducted if the substance is classified as corrosive to the skin. As 2,6-Xylenol is classified as corrosive to the skin, it is considered that testing the acute toxicity via the inhalation route is not appropriate.

Acute Dermal Toxicity

In accordance with section 8.5 of Column 2 of Annex VIII, acute toxicity studies generally do not need to be conducted if the substance is classified as corrosive to the skin. As 2,6-Xylenol is classified as corrosive to the skin, it is considered that testing the acute toxicity via the dermal route is not appropriate.

Supporting information was available for this endpoint; however very limited methodology and study details were available. A dermal LD50 of 1000 mg/kg in the rabbit was identified in the literature, but it was from a secondary source and could not be confirmed.


Justification for selection of acute toxicity – oral endpoint
This study was selected as key on the basis that it was deemed to be the more reliable of the two available studies.

Justification for selection of acute toxicity – dermal endpoint
No key study was selected on the basis that this endpoint was waived.

Justification for classification or non-classification

In accordance with Annex VI, Regulation (EC) No. 1272/2008, the substance requires classification with respect to acute toxicity via the oral route as Category 3 (H301: Toxic if swallowed) and the dermal route as Category 3 (H311: Toxic in contact with skin).

With regard to the available data, in accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance would require classification with respect to acute toxicity via the oral route as Acute Tox Category 4 (H302: Harmful if swallowed) on the basis of an LD50 of 1470 mg/kg bw.