o-toluidine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Although only adopted from OECD SIDS Report published by UNEP basic data are given and significant symptoms are reported to evaluate this toxicological endpoint

Data source

Reference

Reference 1

Reference Type:

publication

Title:

o-TOLUIDINE CAS No: 95-53-4 SIDS Initial Assessment Report.

Author:

OECD SIDS

Year:

2006

Bibliographic source:

UNEP Publications

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

LC50 was calculated with the Probit Analysis, Finney DJ, 3rd ed. Cambridge University Press.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

92-53-4

IUPAC Name:

92-53-4

Constituent 2

Reference substance name:

o-toluidine

EC Number:

202-429-0

EC Name:

o-toluidine

Cas Number:

95-53-4

Molecular formula:

C7H9N

IUPAC Name:

2-methylaniline

Test material form:

other: liquid

Details on test material:

IUCLID4 Test substance: other TS: 99.7 %

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 weeks
- Weight at study initiation: 230-260 g

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

head only

Vehicle:

other: air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE
The atmosphere was generated by passing nitrogen over o-toluidine liquid contained in a 3-neck round-bottom flask heated from 115 to 120°C. The vapor/aerosol was diluted with humified and O2-enriched houseline air and passed into the exposure chamber. Test atmosphere was regularly controlled.

Duration of exposure:

4 h

Concentrations:

492, 606, 722, 799, 848, 931, 1000 ppm (approx. 2184, 2691, 3206, 3548, 3765, 4134, 4440 mg/m³)

No. of animals per sex per dose:

10

Control animals:

other: not applicable

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights and clinical signs were observed daily

Statistics:

LC50 calculated with the Probit Analysis, Finney DJ, 3rd ed. Cambridge University Press.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

862 ppm

95% CL:

816 - 913

Exp. duration:

4 h

Remarks on result:

other: ca. 3827 mg/m³: clinical signs included cyanosis, labored breathing, lethargy

Mortality:

492 ppm: 0/10
606 ppm: 0/10
722 ppm: 1/10
799 ppm: 2/10
848 ppm: 6/10
931 ppm: 5/10
1000 ppm: 10/10

Clinical signs:

other: Compound related signs of intoxication, observed during and immediately following exposure, consisted of tremor, slight to moderate cyanosis, muscle spasm, labored breathing, slight to moderate corneal opacity, prostation and semi- prostation, and redd

Body weight:

Body weight losses of 6 to 22 % were observed 1 to 3 days post exposure, with normal weight gains occurring thereafter (individual animal data not given).

Applicant's summary and conclusion

Executive summary:

DuPont Chem, 1981, cited in OECS SIDS for o-toluidine in 2005, reported of groups of ten male rats that were exposed head-only to o-toluidine-vapor/aerosol for 4 hours in concentrations ranging from 492 up to 1000 ppm (corresponding to 2184 - 4440 mg/m3). Death occurred at 722 ppm (3206 mg/m3) in 1/10 rats on day 3 post exposure and the concentration of 1000 ppm (4440 mg/m3) was lethal to all animals within 24 hours post exposure. Major treatment related clinical signs included cyanosis, labored breathing, lethargy, prostration, reddish-brown nasal discharge and stained wet perinea, symptoms which show clear evidence for methemoglobinemia. In this study no histopathological investigations were performed. The calculated LC50 value is 862 ppm (3827 mg/m³).