m-tolyl isocyanate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Study period:

From 27 July 1987 To 27 July 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study - well documented

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Thirteen groups of 5 to 10 male and female rats each were exposed nose/head-only to 0, 25, 62, 74, 99, 111, 159, 169, 173, 176, 274, 331, or 492 mg/m³ m-tolylisocyanate (vapour) for 4 hours.

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

m-tolyl isocyanate

EC Number:

210-676-0

EC Name:

m-tolyl isocyanate

Cas Number:

621-29-4

Molecular formula:

C8H7NO

IUPAC Name:

1-isocyanato-3-methylbenzene

Details on test material:

m-tolylisocyanate: purity: 99.7 %

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable) n/a
- Source: Bayer AG.
- Females (if applicable) nulliparous and non-pregnant: [yes
- Rationale for use of males (if applicable) n/a
- Age at study initiation: 7 weeks
- Weight at study initiation: 160 gr 220 gr
- Fasting period before study: n/a
- Housing: Makrolon-Kafigen Type III cage
- Historical data: n/a
- Diet (e.g. ad libitum): n/a
- Water (e.g. ad libitum):n/a
- Acclimation period:n/a
- Microbiological status when known n/a
- Method of randomisation in assigning animals to test and control groups n/a

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50
- Air changes (per hr): 12, from 6 am to 6 pm.
- Photoperiod (hrs dark / hrs light): n/a

IN-LIFE DATES: From: To:n/a

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose/head only

Vehicle:

air

Details on inhalation exposure:

Chamber:
8 to 10 bars.
110 volumes automatically conditioned.
70% test atmosphere.

Environmental conditions without test animals:
Temperature: 24 °C
Humidity: 14 %

Environmental conditions with test animals:
Temperature: 25 °C
Humidity: 34%

Environmental conditions with test item:
Temperature: 21- 23°C (supply air)
Humidity: 10 to 40 % (supply air) 40 to 50 % (exhaust air)

Duration of exposure:

4 h

Concentrations:

0, 25, 62, 74, 99, 111, 159, 169, 173, 176, 274, 331, or 492 mg/m³

No. of animals per sex per dose:

5 to 10 male and 5 to 10 female rats/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 4 hours
- Frequency of observations and weighing:n/a
- Necropsy of survivors performed: no
- Clinical signs including body weight:serous and blood nasal discharge, breathing difficulties, cyanosis, dyspnea, reduced motility.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:n/a

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

33 mg/m³ air

Based on:

test mat.

95% CL:

26 - 44

Exp. duration:

4 h

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

30 mg/m³ air

Based on:

test mat.

95% CL:

24 - 39

Exp. duration:

4 h

Mortality:

during the post-exposure period which had no symtoms immediately after the exposition to m-tolylisocyanate.

Clinical signs:

irregular respiration

Remarks:

aggravated and slowed down breathing; Pulmonary edema and hydrothorax, hyperinflated lungs

Body weight:

Body-weight gain was noted from group 3 onwards.

Gross pathology:

Registered chages in the following organs:
Liver,
spleen,
and
kidneys.

Other findings:

Group 1 and Group 2::
All rats tolerated exposition symptomless.
Group 3: breathing difficulties, minor cyanosis and ruffled fur.
Group 4:breathing, tachypnea, Piloerection, cyanosis, emaciation, Motility issues, prostration (prefinal)
and flabbiness (lethargy).
Group 5:aggravated breathing, reduced motility ruffled fur, serous nasal discharge.
From 1st follow-up day also slowed breathing. End the follow-up week cyanosis and Emaciation,
slackness (lethargy).
From the middle of the 2nd week of follow-up, tachypnea.
Group 6: serous nasal discharge, sniffles, reduced breathing, Lethargy, reduced motility, tremors, scruffy and balked fur.
1st follow-up week= cyanosis, emaciation and wheezing.
Group 7:serous nasal discharge, reduced breathing, Lethargy, reduced motility, cyanosis, emaciation, scruffy fur, at the end of follow-up 1 rat was still presenting these symptoms.
Group 8:serous nasal discharge, reduced breathing, Lethargy, reduced motility, cyanosis, emaciation, scruffy fur, Motility issues, prostration.
Group 9:serous nasal discharge, reduced breathing, Lethargy, reduced motility, cyanosis, emaciation, scruffy fur, Motility issues, prostration. Symptoms more severe depending on the concentration of the test item.

Any other information on results incl. tables

A concentration of 6.6 mg/m³ m-tolylisocyanate for 4 hours was tolerated by the rats without clinical symptoms. A concentration of 13 mg/m³ influenced the body weight and was the beginning of the mortality range.

m-tolylisocyanate has a strong irritation potential on the respiratory tract. The duration of the symptoms are determined by the breathing discomfort, which have a low tendency to reversibility. In the lower concentration range the breathing discomfort was evident after 1 week. Therefore rats died during the post-exposure period which had no symtoms immediately after the exposition to m-tolylisocyanate.

 

 

N. animal	Nominal Concentration (mg/m^3)	SV Substance consumption (mg)	Primary Air (ml/min)	Diluted Air (l/min)	Mean S (l/min)
1	-	-	10000	-	10.00
2	25	60	33	10.0	10.03
3	62	150	123	10.0	10.12
4	74	180	148	10.0	10.15
5	99	240	100	10.0	10.10
6	111	270	150	10.0	10.15
7	159	390	200	10.0	10.20
8	169	420	360	10.0	10.36
9	173	430	350	10.0	10.35
10	176	430	200	10.0	10.20
11	274	690	500	10.0	10.50
12	331	850	700	10.0	10.70
13	492	1180	1000	9.0	10.00

 

 

Males:

N. animal	Nominal Concentration (mg/m^3)	Symptom duration	Time of death	Mortality (%)
1	-	-	-	0
2	25	-	-	0
3	62	14d-28d	-	0
4	74	7d-28d	8d-9d	30
5	99	4h-28d	8d-10d	30
6	111	4h-14d	2d-12d	100
7	159	4h-28d	8d-18d	70
8	169	4h-12d	2d-12d	100
9	173	4h-12d	7d-12d	100
10	176	4h-22d	8d-22d	100
11	274	4h-10d	7d-10d	100
12	331	4h-8d	1d-8d	100
13	492	4h-24h	<24h	100

 

Females:

N. animal	Nominal Concentration (mg/m^3)	Symptom duration	Time of death	Mortality (%)
1	-	-	-	0
2	25	8d-20d	-	0
3	62	7d-28d	13d	10
4	74	4h-28d	9d-15d	30
5	99	4h-28d	11d-16d	20
6	111	4h-28d	7d-12d	80
7	159	4h-16d	8d-17d	90
8	169	4h-12d	2d-16d	100
9	173	4h-12d	2d-12d	100
10	176	4h-19d	2d-19d	100
11	274	4h-12d	8d-12d	100
12	331	4h-14d	3d-14d	100
13	492	4h-3d	1d-3d	100

 

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

According to the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS), Fifth revised edition 2013, is classified under Category 1.
T+ = Very Toxic; Potential high acute hazard.

Executive summary:

Thirteen groups of 5 to 10 male and female rats each were exposed nose/head-only to 0, 25, 62, 74, 99, 111, 159, 169, 173, 176, 274, 331, or 492 mg/m³ m-tolylisocyanate (vapour) for 4 hours.

A concentration of 6.6 mg/m³ m-tolylisocyanate for 4 hours was tolerated by the rats without clinical symptoms. A concentration of 13 mg/m³ influenced the body weight and was the beginning of the mortality range.

m-tolylisocyanate has a strong irritation potential on the respiratory tract. The duration of the symptoms are determined by the breathing discomfort, which have a low tendency to reversibility. In the lower concentration range the breathing discomfort was evident after 1 week. Therefore rats died during the post-exposure period which had no symtoms immediately after the exposition to m-tolylisocyanate.

The NOEL for male and female rats is 6.6 mg/m³ m-tolylisocyanate in air.