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Administrative data

Description of key information

Acute toxicity: Oral

LD50 was estimated to be 790 mg/kg bw when rat were orally exposed with 2,3-dimethylphenol.

Acute toxicity: Inhalation

LD50 was considered to be > 85.5 mg/m3when Fischer 344 male rat were exposed to saturated vapors of 2,3-dimethylphenol for 4 h.

Acute toxicity: dermal

LD50 was estimated to be 987 mg/kg bw when Vienna White male and female rabbit were dermally exposed with 2,3-dimethylphenol.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
Data is from Authoritative data base
Qualifier:
according to
Guideline:
other: Prediction
Principles of method if other than guideline:
Prediction is done by using Danish (Q)SAR
GLP compliance:
not specified
Test type:
other: Prediction
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report):2,3 –xylenol
- Molecular formula (if other than submission substance):C8H10O
- Molecular weight (if other than submission substance):122.166 g/mol
- Smiles notation (if other than submission substance):c1(c(cccc1O)C)C
- InChl (if other than submission substance): 1S/C8H10O/c1-6-4-3-5-8(9)7(6)2/h3-5,9H,1-2H3
- Substance type: organic
- Physical state: solid
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
not specified
Doses:
790 mg/kg
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
790 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50 % mortality observed
Mortality:
not specified
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified

Predicted data is in Domain: Reliability index- 0.74

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LD50 was estimated to be 790 mg/kg bw when rat were orally exposed with 2,3-dimethylphenol.
Executive summary:

In a prediction done by SSS (2017) using the Danish (Q)SAR with log kow as the primary descriptor, the acute oral toxicity was estimated for 2,3-dimethylphenol. The LD50 was estimated to be 790 mg/kg bw when rat were orally exposed with 2,3-dimethylphenol.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
790 mg/kg bw
Quality of whole database:
Data is from Registry of Toxic Effects of Chemical Substances (RTECS) Database

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:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from NTRL report
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Acute inhalation toxicity study of 2,3-dimethylphenol in male Fischer rats
GLP compliance:
not specified
Test type:
other: no data
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2,3-Dimethylphenol (Synoynm: 2,3-xylenol)
- Molecular formula (if other than submission substance): C8H10O
- Molecular weight (if other than submission substance): 122.17 g/mole
- Substance type: Organic
- Physical state: Solid
Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories in Wilmington, MA
- Age at study initiation: No data available
- Weight at study initiation: 200 to 250g
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): 12 h light (beginning at 6 a.m.) and 12 h darkness

IN-LIFE DATES: From: October 1985 To: February 1986
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No data availableGENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: ptexiglas chamber
- Exposure chamber volume: 120-L
- Method of holding animals in test chamber: cage drawer system
- Source and rate of air: chamber was controlled by metering air through a column packed with pulverized
- Method of conditioning air:
- System of generating particulates/aerosols:
- Method of particle size determination: A Miran 1A infrared analyzer (Foxboro) was used to monitor the concentration stability and w~ile the actual concentration of DMPwas determined by GC analysis of impinger samples collected in water. The GC detector peak areas were compared to DMPstandards in water.
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used: A Miran 1A infrared analyzer (Foxboro) was used to monitor the concentration stability of DMP in the chamber, w~ile the actual concentration of DMPwas determined by GC analysis of impinger samples collected in water. The GC detector peak areas were compared to DMPstandards in water.
- Samples taken from breathing zone: no

VEHICLE
- Composition of vehicle (if applicable): air
- Concentration of test material in vehicle (if applicable):85.5 mg/m3
- Justification of choice of vehicle: air
- Lot/batch no. (if required):
- Purity:

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:No data available
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): No data available

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:No data available
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
85.5 mg/m3
No. of animals per sex per dose:
5 male animals
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rat were weighed and observed at 1, 2, 4, 7 and 14 days post exposure
- Necropsy of survivors performed: no data available
- Other examinations performed: Mortality, clinical signs, body weight and gross pathology were examined.
Statistics:
No data available
Preliminary study:
No data available
Sex:
male
Dose descriptor:
LC50
Effect level:
> 85.5 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No mortality observed
Mortality:
No mortality was observed in treated male rat at 85.5 mg/m3
Clinical signs:
other: No data available
Body weight:
At 85.5 mg/m3 Body weight gain observed in exposed rats compared favorably with weight gains of the control rats
Gross pathology:
At 85.5 mg/m3 No exposure-related lesions were observed.
Other findings:
No data available
Interpretation of results:
other: not classified
Conclusions:
LD50 was considered to be > 85.5 mg/m3 when Fischer 344 male rat were exposed to saturated vapors of 2,3-dimethylphenol for 4 h.
Executive summary:

In a acute inhalation toxicity study, Fischer 344 male rat were exposed to saturated vapors of 2,3-dimethylphenol for 4 h in a clear, 120-L ptexiglas chamber. No mortality was observed in treated male rat at 85.5 mg/m3. No effect on body weight gain and no gross lesions were observed in treated rats as compared to control. Therefore, LD50 was considered to be > 85.5 mg/m3when Fischer 344 male rat were exposed to saturated vapors of 2,3-dimethylphenol for 4 h.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
85.5 mg/m³
Quality of whole database:
Data is from NTRL report

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
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): 2,3-Dimethylphenol (Synoynm: 2,3-xylenol)
- Molecular formula (if other than submission substance): C8H10O
- Molecular weight (if other than submission substance): 122.17 g/mole
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
Vienna White
Sex:
male/female
Details on test animals and environmental conditions:
No data available
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
No data available
Duration of exposure:
24 h
Doses:
987 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
No data available
Statistics:
No data available
Preliminary study:
No data available
Sex:
male/female
Dose descriptor:
LD50
Effect level:
987 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50 % mortality observed
Mortality:
No data available
Clinical signs:
No data available
Body weight:
No data available
Gross pathology:
No data available
Other findings:
No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and "m" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Phenols (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Aryl AND Phenol by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Overlapping groups AND Phenol by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.06

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.94

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
LD50 was estimated to be 987 mg/kg bw when Vienna White male and female rabbit were dermally exposed with 2,3-dimethylphenol.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2,3-dimethylphenol. The LD50 was estimated to be 987 mg/kg bw when Vienna White male and female rabbit were dermally exposed with 2,3-dimethylphenol.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
987 mg/kg bw
Quality of whole database:
Data is Klinisch 2 and from OECD QSAR toolbox

Additional information

Acute oral toxicity:

In different studies, 2,3-dimethylphenol has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in mice and rats for 2,3-dimethylphenol. The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the Danish (Q)SAR with log kow as the primary descriptor, the acute oral toxicity was estimated for 2,3-dimethylphenol. The LD50 was estimated to be 790 mg/kg bw when rat were orally exposed with 2,3-dimethylphenol.

In another prediction done by SSS (2017) using the Danish (Q)SAR with log kow as the primary descriptor, the acute oral toxicity was estimated for 2,3-dimethylphenol. The LD50 was estimated to be 660 mg/kg bw when mice were orally exposed with 2,3-dimethylphenol.

Also further supported experimental study given by RTECS (Registry of Toxic Effects of Chemical Substances, 2016), rat were treated with 2,3-dimethylphenol orally. 50 % mortality were observed in treated rat at 562 mg/kg bw. Therefore, LD50 was considered to be 562 mg/kg bw when rats were treated with 2,3-dimethylphenol orally.

This further supported by experimental study given by RTECS (Registry of Toxic Effects of Chemical Substances, 2016), Mice were treated with 2,3-dimethylphenol orally. 50 % mortality were observed in treated mice at 302 mg/kg bw. Therefore, LD50 was considered to be 302 mg/kg bw when mice were treated with 2,3-dimethylphenol orally.

Further supported by study summarized by European Food Safety Authority (EFSA) (EFSA Journal 2011; 9(5):1990), rat were treated with 2,3-dimethylphenol in the concentration of 5000 mg/kg bw. 50 % mortality was observed in treated rat at 5000 mg/kg bw. Therefore, LD50 was considered to be < 5000 mg/kg bw when rat were treated with 2,3-dimethylphenol orally.

Thus, based on the above studies and predictions on 2,3-dimethylphenol, it can be concluded that LD50 value is less than 2000 mg/kg bw. Thus comparing this value with the criteria of CLP regulation, 2,3-dimethylphenol can be classified under “Category IV” for acute oral toxicity.

Acute inhalation toxicity:

In a study, 2,3-dimethylphenol has been investigated for acute inhalation toxicity to a greater or lesser extent. Study based on in vivo experiments in rodents, i.e. most commonly in rats for 2,3-dimethylphenol.

In a experimental study conducted by Kinkeadet al(National Technical Information Service. AAMRL-TR-87-021, APRIL 1987), Fischer 344 male rat were exposed to saturated vapors of 2,3-dimethylphenol for 4 h in a clear, 120-L ptexiglas chamber. No mortality was observed in treated male rat at 85.5 mg/m3. No effect on body weight gain and no gross lesions were observed in treated rats as compared to control. Therefore, LD50 was considered to be > 85.5 mg/m3when Fischer 344 male rat were exposed to saturated vapors of 2,3-dimethylphenol for 4 h.

Thus, based on the above studies and predictions on 2,3-dimethylphenol, it can be concluded that LD50 value is less than 20 mg/L. Thus, comparing this value with the criteria of CLP regulation, 2,3-dimethylphenol can be Not classified as acute inhalation toxicity.

Acute dermal toxicity:

In different studies, 2,3-dimethylphenol has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 2,3-dimethylphenol along with the study available on structurally similar read across substance p-Cresol (CAS no 106-44-5) and o-Cresol (CAS 95-48-7). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2,3-dimethylphenol. The LD50 was estimated to be 987 mg/kg bw when Vienna White male and female rabbit were dermally exposed with 2,3-dimethylphenol.

In another experimental study given by RTECS (Registry of Toxic Effects of Chemical Substances, 2016), mice were treated with 2,3-dimethylphenol dermally. 50 % mortality were observed in treated mice at 920 mg/kg bw. Therefore, LD50 was considered to be 920 mg/kg bw when mice were treated with 2,3-dimethylphenol dermally.

Also further supported by experimental study given by RTECS (Registry of Toxic Effects of Chemical Substances, 2016), rabbits were treated with 2,3-dimethylphenol dermally. 50 % mortality were observed in treated rabbits at 1040 mg/kg bw. Therefore, LD50 was considered to be 1040 mg/kg bw when rabbits were treated with 2,3-dimethylphenol dermally.

This is further supported by experimental study summarize by Cosmetics Ingredient Expert Review Panel (International Journal of Toxicology; Volume: 25 issue: 1_suppl, page(s): 29-127; 2006) on structurally similar read across substance p-Cresol (CAS no 106-44-5), rabbits were treated with p-Cresol applied on rabbits in the concentration of 300 mg/kg for 24 hours. 50 % Mortality was observed in treated rabbits. Therefore, LD50 was reported to be 300mg /kg bw when rabbits were treated with p-Cresol by dermal application for 24 hours.

Further supported by experimental study summarize by Cosmetics Ingredient Expert Review Panel (International Journal of Toxicology; Volume: 25 issue: 1_suppl, page(s): 29-127; 2006) on structurally similar read across substance o-Cresol (CAS 95-48-7), rabbits were treated with o-Cresol applied on rabbits in the concentration of 890 mg/kg. 50 % Mortality was observed in treated rabbits at 890 mg/kg bw. Therefore, LD50 was considered to be 890 mg /kg bw when rabbits were treated with o-Cresol by dermal application.

Thus, based on the above studies and predictions on 2,3-dimethylphenol and its read across substances, it can be concluded that LD50 value is < 1000 mg/kg bw. Thus comparing this value with the criteria of CLP regulation, 2,3-dimethylphenol can be classified under “Category III” for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on 2,3-dimethylphenol, it can be concluded that 2,3-dimethylphenol can be classified under “Category IV” for acute oral toxicity and “Category III” for acute dermal toxicity and not Classified for acute Inhalation toxicity .