3,4-dichlorophenyl isocyanate

Endpoint summary

Description of key information

Acute toxicity via Oral route: Female rat LD50 = 91 mg/kg bw (Key, Rel.2).

Acute toxicity via Inhalation route: LC50 = 0.338 mg/L (Key, Rel.2)

Acute toxicity via Dermal route: Combined LD50 > 2000 mg/kg bw (Key, Rel2).

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: scientific acceptable

Principles of method if other than guideline:

3,4-dichlorophenyl isocyanate was diluted with Lutrol and administered, by intubation, to rats. The animals were given a volume equivalent to 0.5% of their body weight. Four groups of 5 males were given dose levels of 201, 342, 582 and 990 mg/kg and four groups of 5 females were given 41, 70, 118 and 201 mg/kg

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Doses:

male: 201, 342, 582 and 990 mg/kg bw
female: 41, 79, 118 and 201 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Sex:

male

Dose descriptor:

LD50

Effect level:

402 mg/kg bw

Sex:

female

Dose descriptor:

LD50

Effect level:

91 mg/kg bw

Mortality:

male:
201 mg/kg: 0/5/5 (deaths/symptoms/no. exposed)
342 mg/kg: 2/5/5
582 mg/kg: 4/5/5
990 mg/kg: 5/5/5

female:
41 mg/kg: 1/5/5 (deaths/symptoms/no. exposed)
70 mg/kg: 0/5/5
118 mg/kg: 5/5/5
201 mg/kg: 4/5/5

Clinical signs:

other: lethargy, pilo erection, convulsions at high dose levels - all death occured within 24 hours post-treatment

Gross pathology:

gastrointestinal inflammation

no data

Interpretation of results:

Category 3 based on GHS criteria

Executive summary:

method: 3,4 -Dichlorophenyl isocyanate was diluted with Lutrol and administered, by intubation, to rats. The animals were given a volume equivalent to 0.5% of their body weight. Four groups of 5 males were given dose levels of 201, 342, 582 and 990 mg/kg and four groups of 5 females were given 41, 70, 118 and 201 mg/kg.

result: LD50(male) = 402 mg/kg bw; LD50(female) = 91 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

91 mg/kg bw

Quality of whole database:

Three studies are available, all being pre-GLP and pre-guidelines. As a worst-case, the study giving the lowest LD50 value was selected as the key study.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guidelinestudy

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0, 91.7, 97.4, 150.7, 255.5, 452.3 mg/m³

No. of animals per sex per dose:

5

Control animals:

yes

Sex:

female

Dose descriptor:

LC50

Effect level:

338 mg/m³ air

Exp. duration:

4 h

Sex:

male

Dose descriptor:

LC50

Effect level:

452 mg/m³ air

Exp. duration:

4 h

Mortality:

male:
control 0/0/10
91.7 mg/m³ 0/0/5
97.4 mg/m³ 0/5/5
150.7 mg/m³ 0/5/5
255.5 mg/m³ 0/5/5
452.3 mg/m³ 1/5/5

female:
control 0/0/10
91.7 mg/m³ 0/0/5
97.4 mg/m³ 0/5/5
150.7 mg/m³ 1/5/5
255.5 mg/m³ 2/5/5
452.3 mg/m³ 3/5/5

Clinical signs:

other: up to and including 91.7 mg/kg no symptoms, >= 97.4 mg/m³ laboured breathing, bloddy and serous effluent of nose, reduced motility, ruffled coat, cyanosis, tachypnoe

Body weight:

loss of body weight

Gross pathology:

up to and including 97.4 mg/m³ no significant pulmonary change. animals which died during post observation period: inflated lung, liver, spleen and kidneys were pale, bloody content of gastro-intestinal tract, reddened intestine mucosa, hydrothorax and edema of the lung

no data

Interpretation of results:

Category 2 based on GHS criteria

Executive summary:

Rats were exposed nose/head to 0, 91.7, 97.4, 150.7, 255.5, 452.3 mg/m³ 3,4 -dichlorophenyl isocyanate during 4 h. LC50 (male) > 452 mg/m³. LC50 (female) = 338 mg/m³.

Animals treated with 91.7 mg/m³ showed no clinical symptoms and no significant pathological pulmonary change. Therefore 91 mg/m³ is considered as the NOAEL. A pronounced irritational potential of the substance to the respiratory system was found

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

338 mg/m³ air

Physical form:

inhalation: aerosol

Quality of whole database:

Inconsistent results were also obtained from the acute inhalation toxicity studies. The results obtained by Pauluhn (1988) was considered to be the most reliable due to methological deficiences or non-linear dose depency noted on the other studies.

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: well documented and scientifically acceptable

Principles of method if other than guideline:

Backs of 2 male and 2 female rabbits were shaved. Compound was applied undiluted to the skin at a dose level of 2000 mg/kg. The test area was loosely covered with plastic. After 24 hours, wrappings were removed and test areas cleaned. Animals were observed 14 days for symptoms and mortality

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

2

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no death occured

Clinical signs:

other: no symptoms occured

Gross pathology:

at the time of sacrifice, a gross necropsy revealed a darkened ring at the base of the cortex of the kidneys, grainy texture of the liver, and lungs with edema and small hemorrhagic areas.

The dermal toxicity for male and female rabbits was greated than 2000 milligram per kilogram. No symptoms or death occurred over a 14 -day observation period. At the time of sacrifice, a gross necropsy revealed a darkened ring at the base of the cortex of the kidneys, grainy texture of the liver, and lungs with edema and small hemorrhagic areas. Other internal organs appeared normal.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Executive summary:

Backs of 2 male and 2 female rabbits were shaved. Compound was applied undiluted to the skin at a dose level of 2000 mg/kg. The test area was loosely covered with plastic. After 24 hours, wrappings were removed and test areas cleaned. Animals were observed 14 days for symptoms and mortality. LD50 > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

>= 2 000 mg/kg bw

Quality of whole database:

Two studies are available, both being pre-GLP and pre-guidelines. The study of Lamb (1975) was identified as the key study as it well-documented and scientifically acceptable.

Additional information

- Acute toxicity via Oral route:

Three studies are available. In one study a LD50 = 91 mg/kg bw for rat (female) and a LD50 = 402 mg/kg bw rat (male) was found (Lamb, 1975), in another study a LD50 > 2500 mg/kg bw was found (Hoechst, 1974) and in a third study a LD50 = 9921 mg/kg bw for female rats was determined (Hecht/Kimmerle, 1960). The reason for this discrepancy is unclear.

As a worst case, the study giving the lowest LD50 value was selected as the key study (91 mg/kg bw).

 

- Acute toxicity via Inhalation route:

Inconsistent results were also obtained from the acute inhalation toxicity studies:

1/ Pauluhn, 1988: LC50 (aerosol, nose/head-only) = 0.338 (females) to 0.452 mg/L/4 hours (males);

2/ Brown, 1968: LC50 (aerosol of melted substance, whole body) = 2.70 mg/L/4 hours (male rats);

3/ Lamb, 1975: LC100 (vapour, whole body) LC100 < 0.22 mg/L/6 hours;

4/ Hofman, 1989: LC50 (vapour of melted substance, nose-only) = 0.102 mg/L/4 hours (male rats) ;

5/ Marhold, 1986: LC50 (unspecified route of administration) = 0.140 mg/L/2 hours (rats).

The results obtained by Pauluhn was considered to be the most reliable due to methological deficiences or non-linear dose depency noted on the other studies. The key result selected is thus 0.338 mg/L.

 

- Acute toxicity vie Dermal route:

The LD50 for dermal application on rabbits was > 2000 mg/kg bw (Lamb, 1975).

Justification for classification or non-classification

Harmonised classification:

The substance has no harmonised classification for acute toxicity according to the Regulation (EC) No. 1272/2008 (CLP). 

 

Self classification:

Acute toxicity via Oral route:

Based on the available information, the substance is for Acute Toxicity Category 3 (H301: Toxic if swallowed) according to the CLP and the GHS as the LD50 is 91 mg/kg bw (between 50 and 300 mg/kg bw).

Acute toxicity via Dermal route: 

Based on the available information, the test item is

- not classified according to the CLP as the LD50 is greater than 2000 mg/kg bw 

- not classified according to the GHS as the LD50 is greater than 2000 mg/kg bw and reliable evidence do not indicate the LD50 to be in the range of Category 5 values.

Acute toxicity via Inhalation:

Based on the available information, the substance is for Acute Toxicity Category 2 (H330: Fatal if inhaled) according to the CLP and the GHS as the LC50 is 0.338 mg/L (between 0.05 and 0.5 mg/L, aerosol).

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required. 

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity studies. 

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the CLP and the GHS as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (dermal) for a Category 1 classification (C ≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw ≥ C > 1000 mg/kg bw). No classification is required. 

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute dermal toxicity studies. 

Specific target organ toxicity: single exposure (Inhalation):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, inhalation are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (inhalation / aerosol) for a Category 1 classification (C≤ 1.0 mg/L/4h) and at the guidance value (inhalation / aerosol) for a Category 2 classification (5.0 mgL/4h ≥C > 1.0 mg/l/4h). No classification is required. 

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute inhalation toxicity studies. 

Aspiration hazard:

The substance is not a hydrocarbon and no effects were observed on lungs in oral studies, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.