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Description of key information

Following single oral treatment of rats LD50 is 242 mg/kg bw. Follwing dermal application to rabbits the LD50 was 2050 mg/kg bw. Clinical signs included hypoactivity, salivation, tremors and convulsions. The skin of dermal treated rabbits show additionally severe erythema and burns.
The databases on acute inhalation toxicity of m-cresol in animals is very limited and does not allow final conclusion.

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: no information on strain used , no information on statistical evaluation given
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Method: single application by gavage, 5 rats/dose group, 4 doses, undiluted liquid, time of recovery: up to 14 days, observations for signs of toxicity, necropsy at the end of the observation time.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
no data
Route of administration:
oral: gavage
Vehicle:
other: none
Details on oral exposure:
no further data
Doses:
147, 215, 316, 464 mg/kg bw.
No. of animals per sex per dose:
5 males/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily; weighing at the beginning and at the end
:
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross autopsy of survivors and decedents
Statistics:
yes, method not described
Preliminary study:
no data
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 242 mg/kg bw
95% CL:
>= 190 - <= 308
Remarks on result:
other: Clinical signs included hypoactivity, salivation, tremors and convulsions
Mortality:
see section"remarks on results including tables and figures".
Clinical signs:
other: onset: 0-4 hours: hypoactivity, tremor, convulsions salivation, prostration death (see section"remarks on results including tables and figures").
Gross pathology:
survivors: no significant findings
decedents: inflammation of the gastrointesinal tract, hyperemia of lungs, liver, kidneys
see section"remarks on results including tables and figures"
Other findings:
no further data

dosage onset of sympt. mortality mortality
mg/kg bw 0-4 hrs 0-4hrs day3 day6 day7 cumulat.
147        S 0/5
215        S 1/5 1/5 2/5
316        S 3/5 1/5 4/5
464        S 4/5 1/5 5/5

S=signs of intoxication: Hypoactivity, H tremors, convulsions, salivation, prostration
survivors: recovery within observation time, gross necropsy: no significant findings
decedents, gross necropsy: inflammation of the gastrointestinal tract, hyperemia of lungs, liver and kidneys.

Interpretation of results:
Category 3 based on GHS criteria
Executive summary:

Single oral application of undiluted testsubstance by gavage to 5 rats/dose group and an observation time up to 14 days resulted in an LD50 value of 242 mg/kg bw.

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

Acute toxicity: via inhalation route

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no information about strain used, statistical evaluation not given
Principles of method if other than guideline:
5 rabbits/dose, 4 doses, exposure time not mentioned, up to 14 days post exposure observation time.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.29 -2.67 kg
Type of coverage:
not specified
Vehicle:
other: none
Details on dermal exposure:
no further data
Duration of exposure:
no data
Doses:
1000, 1470, 2150, 3160 mg/kg bw.
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Necropsy of survivors and decedents performed: yes
- Other examinations performed: clinical signs,
Statistics:
yes, method not given.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
2 050 mg/kg bw
95% CL:
>= 1 590 - <= 2 650
Remarks on result:
other: Clinical signs included hypoactivity, salivation, tremors and convulsions; the treated skin showed severe erythema and burns.
Mortality:
see section "remarks on results"
Clinical signs:
other: see section " remarks on results including tables and figures"
Gross pathology:
see sedtion " remarks on results including tables and figures"
Other findings:
no data

Dosage onset of symp. mortality mortality
mg/kg 4-12 hrs 12-24 hrs day3 cumulative

100       0 0/5
147       0 0/5
215       0 S 4/5 4/5
316       0 S 4/5 4/5

S = signs of intoxication from 4 hrs up to 12 hrs p.a.: lacrimation, salivation,
hypersensitivity, convulsion, hypoactivity:
dermal
irritation: severely burned, severe edema
gross necropsy-survivors: no significant findings
gross necropsy-decedents: hyperemia of lungs and kidneys

Interpretation of results:
GHS criteria not met
Executive summary:

Dermal application of testsubstance to the skin of rabbits and an exposure observation time for 14 days yielded a LD50 of 2050 mg/kg bw and severe irritational effects.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 050 mg/kg bw

Additional information

There is no study according to the current OECD test guideline, but the given information is sufficient to evaluate this endpoint.

ORAL APPLICATION

Single oral application of undiluted test substance by < gavage to 5 rats/dose group and an observation time up to 14 days resulted in an LD50 value of 242 mg/kg bw. Clinical signs included hypoactivity, salivation, tremors and convulsions (Ind Bio-test Lab Inc 1969).

DERMAL APPLICATION

Following dermal application to rabbits of undiluted test substance and an observation time for 14 days the LD50 was 2050 mg/kg bw (Industr. Bio-test Lab Inc 1969). Clinical signs included hypoactivity, salivation, tremors and convulsions; the treated skin showed severe erythema and burns.

INHALATION EXPOSURE

No rat died during the 1 hour exposure against 710 mg/m³ (not further specified, Industr. Bio-tes Lab 1969). In an 8-hour inhalation study with saturated vapor, no ratl died and no signs of intoxication were observed (Mellon Inst Ind Res 1949). In Pereima 1975 cited in WHO 1995 the LC50 in rats was reported to be 58 mg/m³ but exposure period and other relevant data were not available.Clinical signs of intoxication included irritation of mucous membranes, neuromuscular excitation and convulsions.

Overall, the databases on acute inhalation toxicity of m-cresol is very limited and does not allow final conclusion. Nevertheless, further testing is not required because m-cresol is evaluated as corrosive and is classified /labelled accordingly. This is in accordance with the specific rules (Column 2) of Annex VIII No.8.5 of Regulation (EC) No. 1907/2006 (REACH), a study does not generally need to be conducted if the substance is classified as corrosive to the skin.

Justification for classification or non-classification

Based on the cited acute data with oral and dermal exposure a change in classification and labelling could be considered, but the data base is very limited. Therefore the present classification is accepted. Referring to acute inhalation exposure the given information is insufficient to evalutate the need for classification because important experimental details are not given. Therefore a classification is not required.

According to Regulation (EC) No. 1272/2008 the substance is allocated to category 3 for acute toxicity by oral and dermal route; Hazard Communication H301 and H311.