Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: Non-guideline acute oral toxicity of 4 solid, crystalline xylenol isomers including 2,5-xylenol was studied in white mice, albino rats, and rabbits, result: LD50 values of 383 ± 36 (S.E.), 444 ± 26, and 938 mg/kg bw were calculated for white mice, albino rats and rabbits, respectively.

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline available
Principles of method if other than guideline:
The acute toxicity of 4 solid, crystalline xylenol isomers including 2,5-xylenol was studied in white mice, albino rats, and rabbits. A single dose of the substances was administered by mouth in the form of finely dispersed aqueous suspensions. The animals were kept under clinical observation for 15 days. Data on rat and mice mortality were processed statistically by probit analysis as modified by Prozorovsky (1962). LD50 for rabbits was determined by the method of Deichmann and Le Blanc (1943).
GLP compliance:
no
Test type:
other: not specified
Limit test:
no
Species:
rat
Strain:
other: albino rats
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
water
Details on oral exposure:
A single dose of 2,5-xylenol was administered by mouth in the form of a finely dispersed aqueous suspension of the solid, cristalline material.
Doses:
not specified
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
The acute toxicity of 2,5-xylenol was studied in white mice, albino rats, and rabbits. A single dose of the substance was administered by mouth in the form of a finely dispersed aqueous suspension of the solid, cristalline material. The animals were kept under clinical observation for 15 days.
Statistics:
Mortality data of rats and mice were processed statistically by probit analysis as modified by Prozorovsky; LD50 for rabbits was determined by the method of Deichmann and Le Blanc (1943).

References:

Deichmann W, LeBlanc T (1943) Determination of the approximate lethal dose with about 6 animals. J Ind Hyp Toxicol 25, 415-417.
Prozorovsky VB (1962) Application of a method of least squares for probit-analysis of the lethality curves // Farmakol. i toksikol. - 1962. -N9l. - P. 115-120 (in Russian).
Key result
Sex:
not specified
Dose descriptor:
LD50
Remarks:
species: rat
Effect level:
ca. 444 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
S:E. 26 mg/kg bw
Mortality:
Most of the animals with acute poisoning died within 24 hours of administration.
Clinical signs:
The clinical picture was similar in all the species of laboratory animals investigated (and for all of the 4 isomers considered). The clinical signs of acute poisoning were dyspnea, disturbance of motor coordination, a rapid advent of clonic spasms, and an asymmetrical body position.
Body weight:
not specified
Gross pathology:
no data

Species

LD50-values (mg/kg bw ± standard error if indicated)

White mice

383 ± 36

Albino rats

444 ± 26

Rabbits

938

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
2,5-Xylenol showed slight acute oral toxicity, with a rat LD50 value of 444 ± 26 (S.E.) mg per kg body weight.
Executive summary:

The acute toxicity of 4 solid, crystalline xylenol isomers including 2,5-xylenol was studied in white mice, albino rats, and rabbits in accordance with international accepted scientific methods. No guideline was followed. A single dose of the substances was administered by mouth in the form of finely dispersed aqueous suspensions. The animals were kept under clinical observation for 15 days. Data on rat and mice mortality were processed statistically by probit analysis as modified by Prozorovsky (1962).  LD50 for rabbits was determined by the method of Deichmann and Le Blanc (1943). The clinical picture was similar in all the species of laboratory animals investigated (and for all the isomers considered). The clinical signs of acute poisoning were dyspnea, disturbance of motor coordination, a rapid advent of clonic spasms, and an asymmetrical body position. Most of the animals with acute poisoning died within 24 hours of administration.

Based on the study results, LD50values of 383 ±36 (S.E.), 444 ± 26, and 938 mg/kg bw were calculated for white mice, albino rats and rabbits, respectively.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
444 mg/kg bw
Quality of whole database:
The quality of the database is adequate to support a risk assessment of the chemical.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute oral toxicity

In the key study the acute toxicity of 4 solid, crystalline xylenol isomers including 2,5-xylenol was studied in white mice, albino rats, and rabbits (KS_Acute toxicity: oral_rat_Maazik 1968). A single dose of the substances was administered by mouth in the form of finely dispersed aqueous suspensions. The animals were kept under clinical observation for 15 days. Data on rat and mice mortality were processed statistically by probit analysis as modified by Prozorovsky (1962).  LD50 for rabbits was determined by the method of Deichmann and Le Blanc (1943). The clinical picture was similar in all the species of laboratory animals investigated (and for all of the 4 isomers considered). The clinical signs of acute poisoning were dyspnea, disturbance of motor coordination, a rapid advent of clonic spasms, and an asymmetrical body position. Most of the animals with acute poisoning died within 24 hours of administration. Based on the study results, LD50 values of 383±36 (S.E.), 444±26, and 938 mg/kg bw were calculated for white mice, albino rats and rabbits, respectively.

In an early published supporting study conducted by Lamson and Brown (1934), the acute oral toxicity of a series of n-alkyl-m-cresols with antihelmintic properties was experimentally determined in white rats. For 2,5-xylenol (identified as n-methyl-m-cresol), a rat LD50 value of 0.73 cm3 of the test material per kg body weight was obtained. Given the approximate density of 0.97 g per cm3 at 20 °C, the result is corresponding to an LD50value of 708.1 mg/kg body weight.

Due to harmonised classification as skin corrosion 1B, acute toxicity studies do not generally need to be conducted according to information requirements specified in Annex VII to Regulation (EC) No 1907/2006. Data already existent for the test item is considered sufficient for risk assessment.

Acute inhalation toxicity

Due to harmonised classification as skin corrosion 1B, acute toxicity studies do not generally need to be conducted according to information requirements specified in Annex VII to Regulation (EC) No 1907/2006.

Acute dermal toxicity

Due to harmonised classification as skin corrosion 1B, acute toxicity studies do not generally need to be conducted according to information requirements specified in Annex VII to Regulation (EC) No 1907/2006.

Justification for classification or non-classification

Present data on the acute toxicity of 2,5-xylenol would lead to classification in Category 4 for acute oral toxicity (H302) according to CLP criteria. Taking into account the harmonised classification as agreed in Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation), classification as Acute Tox. 3 for oral and dermal toxicity (H301 +H311) is proposed.