m-cresol

Neurotoxicity

Description of key information

To examine probable neuro toxicity of m-cresol male and femaleCD rats received corn oil solutions of 0, 50, 150, 450 mg/kg bw/day by gavage once daily for 13 weeks. Dose related signs of toxicity and in high dosed rats neurobehavioural signs oftoxicity were reported.

A host of clinical observations indicative of neurotoxicity (including hypoactivity, rapid labored respiration, excessive salivation, and tremors) was reported at doses of 50 mg/kg/day or higher for all three isomers. However, the results of a number of neurobehavioral tests designed to assess demeanor and motor and reflex activity (testing was done 6 times throughout the 13 weeks prior to dosing) showed only sporadic differences with controls and/or alterations were not dose-related. No brain weight changes or histopathologic lesions in the brain or other nervous tissues were found for any isomer. Convulsions were reported at 450 mg/kg/day or higher (TRL 1986).

The NOAEL is 50 mg/kg bw (see TOXICOLOGICAL PROFILE FOR CRESOLS, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry).

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Link to relevant study records

Reference

Endpoint:

neurotoxicity: oral

Remarks:

13 week neurotoxicity study

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: only study summary is available: limited documentation

Principles of method if other than guideline:

10 male and 10 female CD rats/treatment group received corn oil solutions of 50, 175, 450 or 600 mg/kg bw/day by gavage once daily for 13 weeks. 20 male and 20 female CD rats received corn oil alone to serve as control. Rats were observed for body weight gain, food consumption, clinical signs and signs of neurobehavioral toxicity.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

no further data

Route of administration:

oral: gavage

Vehicle:

other: corn oil

Details on exposure:

no further data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

once daily, 13 weeks

Remarks:

Doses / Concentrations:
0, 50, 150, or 450 mg/kg bw dissolved in corn oil
Basis:

No. of animals per sex per dose:

10 animals /sex/dose, 20 animals per sex/dose served as controls

Control animals:

yes, concurrent vehicle

Details on study design:

Type: other: subchronic study
Observation period: 13 weeks

Observations and clinical examinations performed and frequency:

only summary available

Specific biochemical examinations:

only summary available, see section" any other information on malterials and methods"

Neurobehavioural examinations performed and frequency:

only summary available, see section" any other information on malterials and methods"

Sacrifice and (histo)pathology:

only summary available, see section" any other information on malterials and methods"

Other examinations:

only summary available, see section" any other information on malterials and methods"

Positive control:

only summary available, see section" any other information on malterials and methods"

Statistics:

only summary available, see section" any other information on malterials and methods"

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Clinical biochemistry findings:

not specified

Behaviour (functional findings):

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Neuropathological findings:

not specified

Other effects:

not examined

Description (incidence and severity):

Migrated information from 'Further observations for developmental neurotoxicity study'



Details on results (for developmental neurotoxicity):see section "Remarks on results";: this is no developmental neurotoxicity study (migrated information)

Details on results:

see section " Remarks on results"

Dose descriptor:

NOAEL

Effect level:

ca. 50 mg/kg bw/day (actual dose received)

Sex:

male/female

Basis for effect level:

other: dose related clinicl signs of toxicity, but only study abstract is available

Remarks on result:

other:

Mortality: 450 mg/kg bw: 1 female versus 1 female of controls gross and histopathological examination of the treated females revealed as cause of death: aspiration or inhalation of the test material or pulmonary edema.

Mean body weight: no difference to the controls.

Food consumption 450 mg/kg bw/day, males and females: significantly less than control during the initial portion of the study.

Clinical signs: from 50 mg/kg bw/day onwards: dose-related in incidence and included salivation, myotonus, tremors, urine wet abdomen, hypoactivity, rapid respiration, myoclonus, low body posture and labored respiration.

Neurobehavioral toxicity: 450 mg-group, males and females: initial part of the study: incidence of palpebral closure, rales, labored respiration at study termination, females: significantly increased urination Other differences from controls with regared to behavioural tests were evaluated as sporadic in nature by the authors (no further details given) Necropsy: brain weights of treated animals comparable to controls; gross and microscopic examination of tissues revealed no lesions which were attributable to treatment.

Executive summary:

According to an available stuy report summary:

CD rats/sex and treatment group received corn oil solutions of 0, 50, 150, 450 mg/kg bw/day by gavage once daily for 13 weeks to examine neurotoxicity of m-cresol resulting in dose related clinicl signs of toxicity and neurobehavioral signs of toxicity in high dosed animals. The NOAEL is 50 mg/kg bw/day.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

50 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

only abstact available

Effect on neurotoxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Effect on neurotoxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

To examine probable neuro toxicity of m-cresol male and femaleCD rats received corn oil solutions of 0, 50, 150, 450 mg/kg bw/day by gavage once daily for 13 weeks. Dose related signs of toxicity and in high dosed rats neurobehavioural signs oftoxicity were reported. The NOAEL is 50 mg/kg bw/day (abstract only, TRL 1986).

A host of clinical observations indicative of neurotoxicity (including hypoactivity, rapid labored respiration, excessive salivation, and tremors) was reported at doses of 50 mg/kg/day or higher for all three isomers. However, the results of a number of neurobehavioral tests designed to assess demeanor and motor and reflex activity (testing was done 6 times throughout the 13 weeks prior to dosing) showed only sporadic differences with controls and/or alterations were not dose-related. No brain weight changes or histopathologic lesions in the brain or other nervous tissues were found for any isomer. Convulsions were reported at 450 mg/kg/day or higher (TRL 1986).

Justification for selection of effect on neurotoxicity via oral route endpoint:
only study available

Justification for classification or non-classification

No classification is required.