m-tolyl isocyanate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Study period:

From 12 November 1979 to 20 October 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented and scientifically acceptable

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

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

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 n/a
- Source: Winkelmann, Borchen)
- Females (if applicable) nulliparous and non-pregnant: [yes, 5]
- Rationale for use of males (if applicable) n/a
- Age at study initiation:
- Weight at study initiation: 179 g
- Fasting period before study: n/a
- Housing: Mkrolonkafugen 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 ± 1.5
- Humidity (%): 60 ± 5
- Air changes (per hr): 12 hours , from 7 am to 7 pm
- Photoperiod (hrs dark / hrs light): n/a

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

1000, 1500, 2000, 2500, 3100, 4000 or 5000 µl/kg bw (= ca. 1060, 1590, 2120, 2650, 3286, 4240, 5300 mg/kg bw)

No. of animals per sex per dose:

5 male and 5 female rats/group

Control animals:

no

Details on study design:

Five male and 5 female young adult male Wistar rats (160 -180 g) per group reveived per gavage a single dose of 1000, 1500, 2000, 2500, 3100, 4000 or 5000 µl/kg bw m-tolylisocyanate. The animals were observed for mortality body weights and clinical signs through day 14.

Statistics:

calculation of LD50 according Fink and Hund, Arzneim Forsch 15, 624 (1965)

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 926 mg/kg bw

Based on:

test mat.

95% CL:

2 380 - 3 210

Mortality:

Males:
none for male rats at 1000 µl/kg bw, 1500 µg/kg bw doses.
20% at 2000 µl/kg bw dose
40% 2500 µg/kg bw dose
40 % 3100 µl/kg bw dose
100% 4000 µl/kg bw dose
100% 5000 µl/kg bw dose.

Females:
0% 1000 µl/kg bw dose
20% 1500 µg/kg bw dose
20% 2000 µl/kg bw dose
20% 2500 µg/kg bw dose
60 % at 3100 µl/kg bw dose
80% 4000 µl/kg bw dose
100% 5000 µl/kg bw dose respectively.

Body weight:

lower than 10% body weight loss

Remarks:

body weight reduction at 1500 µl/kg bw and above.

Other findings:

Signs of intoxication: Sedation, reduction of gerneral condition. Female rats showed a body weight reduction at 1500 µl/kg bw and above. A dose of 1000 µl/kg bw was tolerated by male and female rats without symptoms.

Any other information on results incl. tables

 

Dose mg/kg	Sex	Symptoms
1.0	M	-
1.5	M	Worsening General well-being; Sedation.
2.0	M	Worsening General well-being; Sedation.
2.5	M	Worsening General well-being; Sedation.
3.1	M	Worsening General well-being; Sedation.
4.0	M	Worsening General well-being; Sedation.
5.0	M	Worsening General well-being; Sedation.
1.0	F	-
1.5	F	Worsening General well-being; Sedation; Weight lost.
2.0	F	Worsening General well-being; Sedation.
2.5	F	Worsening General well-being; Sedation.
3.1	F	Worsening General well-being; Sedation; Weight lost.
4.0	F	Worsening General well-being; Sedation; Weight lost.
5.0	F	Worsening General well-being; Sedation.

 

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Moderately Toxic. No symptoms at 1000 µl/kg bw was tolerated by male and female rats without symptoms.

Executive summary:

Five male and 5 female young adult male Wistar rats (160 -180 g) per group were dosed undiluted at 1000, 1500, 2000, 2500, 3100, 4000 or 5000 µl/kg bw m-tolylisocyanate. The animals were observed for mortality body weights and clinical signs through day 14.

Signs of intoxication: Sedation, reduction of gerneral condition. Fermale rats showed a body weight reduction at 1500 µl/kg bw and above. A dose of 1000 µl/kg bw was tolerated by male and female rats without symptoms.

The symptoms appeared 1 hour after application low to moderately pronounced and partially held until the last test day. The deaths were recorded from the 4th hour to the 4th day of the experiment. There were none between males and females significant differences in the nature and intensity of the symptoms and the number of deaths. The acute oral LD50 for male rats is 2760 µl/kg bw (= ca. 2926 mg/kg bw).