m-toluidine

Endpoint summary

Description of key information

Oral application of 1350 -700 mg/kg bw m-toluidine dissolved in corn oil, resulted in a LD50 value of 922 mg/kg bw (DuPont De Nemours 1980).

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: only males and only 3 doses used instead of 5 as required.

Principles of method if other than guideline:

Method: other:
3 doses tested, 10 male animals/dose, single dose by gavage, observation period up to 14 d.
A range finding study was conducted to determine the initial dose.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male

Details on test animals or test system and environmental conditions:

young adult males, no further data

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

single oral application by gavage

Doses:

700, 1000, 1350 mg/kg bw diluted in corn oil

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

The range-finding study was run with 1 rat per dose for levels of 100-3500 mg/kg bw and produced death at 1500 mg/kg bw and above.
Main study:
Single oral application by gavage to 10 male rats and observation for 14 days. The surviving rats were weighed and observed during a 14-day recovery period and then sacrificed. The LD50 value was calculated from the mortality data using probit analysis of DJ Finney, 1971, Cambridge University Press.

Statistics:

Probit analylysis

Sex:

male

Dose descriptor:

LD50

Effect level:

922 mg/kg bw

95% CL:

>= 792 - <= 1 054

Remarks on result:

other: clinical signs included lacrimation, stained face, chromodacryorrhea, stained and wet perineal area, cyanosis, moribundity and moderate weight loss

Mortality:

1350 mg/kg bw: 10/10 all deaths occurred wintin 2 days after dosing
1000 mg/kg bw 6/10 all deaths occurred within 3 days after dosing
700 mg/kg bw 1/10 death occurred 2 days after dosing

Clinical signs:

other: 1350 mg/kg bw: lacrimation, chromodacryorrhea, cyanosis, moribundity and weight loss 1000 mg/kg bw lacrimation, chromodacryorrhea, cyanosis, labored breathing, diarrhea, stained and wet perineal area, stained face, weakness, moribunditss, and moderate

Gross pathology:

no data

Other findings:

no data

No further data.

Interpretation of results:

Category 4 based on GHS criteria

Executive summary:

Oral application of 1350 -700 mg/kg bw m-toluidine diluted in corn oil to male rats resulted in a LD50 value of 922 mg/kg bw (DuPont De Nemours 1980). Clinical signs observed at most dose levels included lacrimation, stained face, chromodacryorrhea, stained and wet perineal areas, cyanosis, morbundity and moderate weight loss. All deaths occurred within 3 days after dosing.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

922 mg/kg bw

Quality of whole database:

This is the only available study which is equal to the respective guideline and is there fore be evaluated with Klimisch score: 2.

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: Basic data given (comparable to standards)

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not applicable

GLP compliance:

yes

Species:

rat

Sex:

male/female

Sex:

female

Dose descriptor:

LD50

Effect level:

1 030 mg/kg bw

Remarks on result:

other: rat

Sex:

male

Dose descriptor:

LD50

Effect level:

1 000 mg/kg bw

Remarks on result:

other: rat

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Mean value LD50 = 1015 mg/kg bw (used for classification)
Risk of cutaneous absorption. Risk of methaemoglobin formation even after skin contact (leads to increased classification).
Symptoms may be delayed.

Executive summary:

As mention in chapter toxicikinetics read across to p-isopropyl aniline is appropriate and justified by ECB 2000 (peer reviewed data collection). p-Isopropyl aniline was applied to the skin of male and female rats as described by OECD TG 402 under GLP conditions to determine acute dermal toxicity.

The LD50 for males is 1000 mg/kg bw and for females 1030 mg/kg bw (Hoechst AG 1988)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 015 mg/kg bw

Quality of whole database:

The available study is performed according to OECD testguideline and therefore evaluated with Klimisch Score 2

Additional information

Acute Oral Toxixity

Groups of 10 male rats received single oral application of 1350 -700 mg/kg bw m-toluidine dissolved in corn oil, resulting in a LD50 value of 922 mg/kg bw (DuPont De Nemours 1980). Clinical signs included lacrimation, stained face, chromodacryorrhea, stained and wet perineal area, cyanosis, moribundity and moderate weight loss.

Acute Dermal Toxicity

As mentioned in toxicokinetics read across to p-isopropyl aniline and justified by ECB 2000 (peer reviewed data collection) the surrogate moleule p-isopropyl aniline was applied to the skin of male and female rats as described by OECD TG 402 under GLP conditions to determine acute dermal toxicity.

The LD50 for males is 1000 mg/kg bw and for females 1030 mg/kg bw (Hoechst AG 1988)

Justification for selection of acute toxicity – oral endpoint
This is the only available study which is equal to the respective guideline and is there fore be evaluated with Klimisch score: 2

Justification for selection of acute toxicity – dermal endpoint
the available study is performed according to OECD testguideline and therefore evaluated with Klimisch Score 2

Justification for classification or non-classification

Based on the available data and taking into account that m-toluidine (3 -Methyl-aniline) is known to be a methemoglobine forming molecule m-toluidine is classified according to Regulation (EC) 1972/2008 (GHS) as Category 3 for acute toxicity (H301, H311, H331).