Phenyl isocyanate

Endpoint summary

Description of key information

Several acute toxicity studies are available:
Acute oral toxicity: in the key study a LD50 = 887 mg/kg bw for rat (male+female) was found, in another study a LD50 = 2500 - 2750 mg/kg bw (male +female rats) was found and in a third study a LD50 = 1044 mg/kg bw for male rats and a LD50 = 172 mg/kg bw for female rats was determined. The reason for this discrepancy is unclear
Acute dermal toxicity: in one study a LD50 = ca. 5500 mg/kg bw for male rats and a LD50 > 5500 mg/kg bw for female rats was determined, in other studies on rabbits LD 50 values of > 2000 mg/kg bw or 7127 mg/kg bw (male/female rabbits) was found.
In the key acute inhalation study a LD50 = 22 mg/m³ (4h) was determined. The other studies were not regarded due to methodological deficiencies.

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:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Six groups of 5 male and 10 female young adult Wister rats (average weight 175 g) each received per gavage a single dose of 100, 500, 1000, 1500, 2000 or 2500 µl/kg bw (= ca. 109.5, 547.5, 1095, 1642.5, 2190, 2737.5 mg/kg) of undiluted phenyl isocyanate. The animals were observed for mortality, body weight and clinical signs through day 14.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

100, 500, 1000, 1500, 2000 or 2500 µl/kg (= ca. 109.5, 547.5, 1095, 1642.5, 2190, 2737.5 mg/kg)
density = 1,095 kg/L (20 °C)

No. of animals per sex per dose:

5 male and 5 female animals/sex/dose

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

0.81 mL/kg bw

Based on:

test mat.

Remarks on result:

other: 0.81 ml/kg bw = 887 mg/kg bw

Mortality:

Males: 0 (0.1 ml/kg bw), 2 (0.5 ml/kg bw), 3 (1.0 ml/kg bw), 4 (1.5 ml/kg bw), 4 (2.0 ml/kg bw), 5 (2.5 ml/kg bw)
Females: 0 (0.1 ml/kg bw), 2 (0.5 ml/kg bw), 2 (1.0 ml/kg bw), 3 (1.5 ml/kg bw), 4 (2.0 ml/kg bw), 5 (2.5 ml/kg bw)

Clinical signs:

other: A single dose of 0.5 to 2.5 ml/kg bw caused in all animals weight reduction, anesthesia and decrease of the general condition. At a dose of 1.0 to 2.5 ml/kg bw cyanosis and disordered breathing was additionally observed. The symptoms occurred after 10 min

Gross pathology:

No data

Other findings:

No data.

Signs of intoxication: Cyanosis, weight reduction, disordered breathing, reduction of general condition. No significant differences in male and female rats were observed.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

For male and female rats a LD50 = 0.81 ml/kg bw = 887mg/kg bw was found. According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Acute Tox. 4 is justified.

Executive summary:

Six groups of 5 male and 10 female young adult Wister rats (average weight 175 g) each received per gavage a single dose of 100, 500, 1000, 1500, 2000 or 2500 µl/kg bw of undiluted phenyl isocyanate. The animals were observed for mortality, body weight and clinical signs through day 14.

Signs of intoxication were cyanosis, weight reduction, disordered breathing and a reduction of the general condition.

For male and female rats a LD50 = 0.81 ml/kg bw = 887mg/kg bw was found.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

887 mg/kg bw

Quality of whole database:

Scientifically acceptable and sufficient documented.

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:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Seven groups of 5 male and 5 female rats were exposed nose/head only to vapours of 0, 0.7, 5.4, 15.2, 11.7, 27.9, 47.1 or 87.8 mg/m³ (analytical) phenyl isocyanate for 4 hours. The animals were observed for mortality, body weight and clinical signs through day 14. A gross pathological examination was performed on animals which died intercurrent or were killed after termination of the study.

GLP compliance:

yes

Test type:

standard acute method

Specific details on test material used for the study:

Content: 99.9%

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose/head only

Vehicle:

air

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0, 2, 19, 21, 31, 65, 83, 150 (nominal)
0, 0.7, 5.4, 15.2, 11.7, 27.9, 47.1 or 87.8 mg/m³ (analytical)

No. of animals per sex per dose:

5 rats/sex/dose

Control animals:

yes

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.022 mg/L air

Based on:

test mat.

95% CL:

>= 0.019 - <= 0.027

Exp. duration:

4 h

Mortality:

Males: 0 (control), 0 (0.7 mg/m³), 0 (5.4 mg/m³), 0 (15.2 mg/m³), 0 (11.7 mg/m³), 3 (27.9 mg/m³), 5 (47.1 mg/m³), 5 (87.8 mg/m³)
Females: 0 (control), 0 (0.7 mg/m³), 0 (5.4 mg/m³), 0 (15.2 mg/m³), 1 (11.7 mg/m³), 4 (27.9 mg/m³), 5 (47.1 mg/m³), 5 (87.8 mg/m³)

Clinical signs:

other: Beginning at 0.005 mg/l phenyl isocyanate in the test atmosphere a concentration dependent irritation of the respiratory tract und long lasting respiratory discomfort was evident.

Body weight:

A significant influence on body weight gain was seen beginning with group 5 (11.7 mg/m³).

Gross pathology:

Lungs inflated and edematous. Rhinarium and intestinal mucosa reddened. Spleen, liver and kidneys pale.

Other findings:

A delayed mortality occurred. The median of survival was 9 days.

Beginning at 0.005 mg/l phenyl isocyanate in the test atmosphere a concentration dependent irritation of the respiratory tract und long lasting respiratory discomfort was evident. The delayed mortality were caused by an irritative lung damage.

The NOEL was 0.0007 mg/l phenyl isocyanate

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

The LC50 was 0.022 mg/l (rat, male + female). According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Acute Tox. 1 is justified.

Executive summary:

Seven groups of 5 male and 5 female rats were exposed nose/head only to vapours of 0, 0.7, 5.4, 15.2, 11.7, 27.9, 47.1 or 87.8 mg/m³ (analytical) phenyl isocyanate for 4 hours. The animals were observed for mortality, body weight and clinical signs through day 14. A gross pathological examination was performed on animals which died intercurrent or were killed after termination of the study.

LC50 = 0.022 mg/l (rat, male + female). Beginning at 0.005 mg/l phenyl isocyanate in the test atmosphere a concentration dependent irritation of the respiratory tract und long lasting respiratory discomfort was evident. The delayed mortality was caused by an irritative lung damage.

The NOEL was 0.0007 mg/l phenyl isocyanate.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

22 mg/m³ air

Quality of whole database:

GLP guideline study.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

Scientifically acceptable and sufficient documented.

Additional information

The results from available acute oral toxicity studies are quite inconsistent. By a weight of evidence consideration a LD50 = 887 mg/kg bw is considered for risk assessment.

The LD50 for dermal application on rats was > 2000 mg/kg bw.

In the key study for acute inhalation toxicity (4 h exposure) the LC50 is 22 mg/m³

Justification for classification or non-classification

For male and female rats an acute oral LD50 = 0.81 ml/kg bw = 887 mg/kg bw was found. According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Acute Tox. 4 is justified.

The acute vapour inhalation LC50 was 22 mg/m³ (rat, male + female). According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Acute Tox. 1 is justified.

The acute dermal LD50 was > 5000 mg/kg bw (rat, male + female). According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.