Isobutyl 4-chloro-3,5-diaminobenzoate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1970-09-24 - 1971-07-05

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1971

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Usual methods used at the laboratory, as described in the report

Deviations:

not specified

Principles of method if other than guideline:

The test item was applied as dust or vapour to the test animals

GLP compliance:

no

Remarks:

study conducted prior to GLP implementation

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isobutyl 4-chloro-3,5-diaminobenzoate

EC Number:

251-311-5

EC Name:

Isobutyl 4-chloro-3,5-diaminobenzoate

Cas Number:

32961-44-7

Molecular formula:

C11H15ClN2O2

IUPAC Name:

2-methylpropyl 3,5-diamino-4-chlorobenzoate

Test animals

Species:

other: rats, rabbits, mice, hamsters

Strain:

other: Wistar-II-rats, NMRI mice, Syrian goldhamster, non-pedigree rabbits

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeder Winkelmann, Kirchborchen (mice, rats, hamster)
- Females (if applicable) nulliparous and non-pregnant: n/a (only male mice, rats, hamsters used) / not stated for rabbits
- Weight at study initiation: 18-22 g (mice), 160-200 g (rats), 60-80 g (hamsters), 2.5-3.5 kg (rabbits)

Administration / exposure

Route of administration:

other: inhalation of either dust or vapour

Type of inhalation exposure:

other: nose only (dust) or whole body (dust or vapour)

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dust generator (homogenous dust generation without segregation) or heating of the substance up to 150°C and spreading of the vapour via propeller into exposure chamber
- Exposure chamber volume: 0.2m³ (dust, whole body) or 400l (vapour)

TEST ATMOSPHERE
- Brief description of analytical method used: For dust, the concentration was determined analytically. The test item was solved in methanol and determined spectrophotometically at 335 nm and 1 cm layer thickness. for absorption of the test item from the chamber cotton wool was used. It was possible to dissolve the test item quantitatively.
For vapours, concentration was calculated from the evaporized amount
- Samples taken from breathing zone: generally from exposure chamber

Analytical verification of test atmosphere concentrations:

yes

Remarks:

for dust atmosphere

Duration of exposure:

4 h

Remarks on duration:

4 hours single dose or 5 * 4 hours repeated dose

Concentrations:

0.024 or 2.30 mg/L (dust, 4h, rats, single dose, nose only)
2.94 mg/L (dust, 5*4h, rats, multiple dose, nose only)
0.975 mg/L (dust, 4h, rabbits, hamsters, mice, single dose, 0.2m³ chamber)
0.726 mg/L (dust, 5*4h, rabbits, hamsters, mice, multiple dose, 0.2m³ chamber)
4.6 mg/L (vapour, 4h, rats, mice, 400L chamber)
7.0 mg/L (vapour, 4h, rabbits, hamsters, 400L chamber)

No. of animals per sex per dose:

20 (rats, dust, nose only); 1 (rabbit, dust, 0.2m³ chamber); 5 (hamster, dust, 0.2m³ chamber); 20 (mice, dust, 0.2m³ chamber); 10 (rats, vapour); 20 (mice, vapour); 2 (rabbits, vapour); 5(hamster, vapour)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Other examinations performed: signs of toxicity, irritation of mucosa

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Remarks:

dust, rats, nose only, single exposure

Effect level:

> 2.3 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

no signs of toxicity or irritation observed

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LC0

Remarks:

dust, rats, nose only, single exposure

Effect level:

>= 2.3 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

no signs of toxicity or irritation observed

Effect levels 3

Sex:

male

Dose descriptor:

LC50

Remarks:

dust, rats, nose only, multiple exposure

Effect level:

> 2.94 mg/L air

Based on:

test mat.

Exp. duration:

20 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

exposure split into 5*4h; no signs of toxicity or irritation observed

Effect levels 4

Key result

Sex:

male

Dose descriptor:

LC0

Remarks:

dust, rats, nose only, multiple exposure

Effect level:

>= 2.94 mg/L air

Based on:

test mat.

Exp. duration:

20 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

exposure split into 5*4h; no signs of toxicity or irritation observed

Effect levels 5

Sex:

male

Dose descriptor:

LC0

Remarks:

dust, whole body, rabbit, hamsters, mice, single exposure

Effect level:

>= 0.975 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

no signs of toxicity or irritation observed

Effect levels 6

Sex:

male

Dose descriptor:

LC0

Remarks:

dust, whole body, rabbit, hamsters, mice, multiple exposure

Effect level:

>= 0.726 mg/L air

Based on:

test mat.

Exp. duration:

20 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

exposure split into 5*4h; no signs of toxicity or irritation observed

Effect levels 7

Key result

Sex:

male

Dose descriptor:

LC0

Remarks:

vapour, whole body, rats, mice

Effect level:

>= 4.6 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

no signs of toxicity or irritation observed

Effect levels 8

Key result

Sex:

male

Dose descriptor:

LC0

Remarks:

vapour, whole body, rabbits, hamsters

Effect level:

>= 7 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

no signs of toxicity or irritation observed

Mortality:

none observed

Clinical signs:

other: no signs of toxicity or irritation were observed

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

The study was performed in a scientifically reasonable method with sufficient documentation indicating that the study was well-performed. Hence, there is no doubt that the obtained results are reliable. No mortality was observed. During all experiments, no adverse effects, no signs of toxicity or irritation of mucosa of eyes or nose were observed. Most relevant LC0-values are 2.95 mg/L (rats, dust, over 5*4h) and 7.0 mg/L (rabbits, hamsters, vapour, over 4h) as those are the highest doses tested and also, one including a longer exposure duration. However, as those values are not above the limit values for classification according to Regulation 1272/2008 and no indication of an LC50 is given, the study cannot be used for classification, may however give the indication that the substance is not highly toxic by inhalation.

Executive summary:

The test item was applied both as dust and vapour to four species at the following concentrations and conditions:

0.024 or 2.30 mg/L (dust, 4h, rats, single dose, nose only)

2.94 mg/L (dust, 5*4h, rats, multiple dose, nose only)

0.975 mg/L (dust, 4h, rabbits, hamsters, mice, single dose, 0.2m³ chamber)

0.726 mg/L (dust, 5*4h, rabbits, hamsters, mice, multiple dose, 0.2m³ chamber)

4.6 mg/L (vapour, 4h, rats, mice, 400L chamber)

7.0 mg/L (vapour, 4h, rabbits, hamsters, 400L chamber)

Acute and subacute toxicity by inhalation of both dust and vapours is very low, the highest determined LC0 values are 2.95 mg/L (rats, dust, over 5*4h) and 7.0 mg/L (rabbits, hamsters, vapour, over 4h).