p-(trifluoromethoxy)phenyl isocyanate

Endpoint summary

Description of key information

Acute oral: Similar to OECD 401; Wistar rat; LD50(female): 1525 mg/kg bw, LD50(male): 2170 mg/kg bw

Acute inhalation: Similar to OECD 403; Wistar rat; LD50: 22.5 - 68.5 mg/m³ (0.0225 - 0.0685 mg/L)

Acute dermal: Similar to OECD 402; Wistar rat; LD50(female): ca. 670 mg/kg bw, LD50(male): ca. 268 mg/kg bw

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

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Seven or eight groups of 10 male and 10 female young adult Wister rats (weight 160 - 200 g) each received per gavage a single dose of 100, 1000, 1500, 1750, 2000, 2500, 3000, or 5000 mg/kg bw (male rats) and 100, 500, 1000, 1250, 1500, 2000, or 2500 mg/kg bw (female rats) 4-trifluormethoxyphenyl isocyanate. The animals were observed for mortality and clinical signs through day 14. A gross pathological examination was performed on animals which died during the observation period or were killed after termination of the study.

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: acetone/oil 2:10

Doses:

male rats: 100, 1000, 1500, 1750, 2000, 2500, 3000, or 5000 mg/kg bw
female rats: 100, 500, 1000, 1250, 1500, 2000, or 2500 mg/kg bw

No. of animals per sex per dose:

10 animals /sex/dose

Control animals:

no

Sex:

female

Dose descriptor:

LD50

Effect level:

1 525 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 320 - <= 1 761

Sex:

male

Dose descriptor:

LD50

Effect level:

2 170 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 906 - <= 2 469

Mortality:

The corresponding mortality for male rats was 0% (100 mg/kg bw), 0% (1000 mg/kg bw), 0% (1500 mg/kg bw), 20% (1750 mg/kg bw), 60% (2000 mg/kg bw), 70% (2500 mg/kg bw), 80% (3000 mg/kg bw) and 90% (5000 mg/kg bw) respectively.

The corresponding mortality for female rats was 0% (100 mg/kg bw), 0% (500 mg/kg bw), 0% (1000 mg/kg bw), 20% (1250 mg/kg bw), 40% (1500 mg/kg bw), 90% (2000 mg/kg bw) and 100% (2500 ml/kg bw) respectively.

Other findings:

necropsy on animals which died during post-observation period: lung spotted, partly slight emphysema, stomach empty, mucosa of forestomach wihite, hardened, intestine with dark, mucous content.

necropsy of animals killed of post-observation period: mucosa of the forestomach showed a slight hardness, other organs without findings

Signs of intoxication: Central nervous effects with laboured breathing, uncoordinated motions, cyanosis, decreased motility and in higher doses aggresivity and partly cramps.

Biginning of symptoms: 15 to 30 minutes in the lower dose groups and 5 to 10 minutes in the letal dose range.

Duration of symptoms: 2 to 6 days

A dose of 100 mg/kg bw was tolerated by male and female rats without symptoms.

The acute oral LD50 for male rats was 2170 mg/kg bw for male rats and 1525 mg/kg bw for female rats

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Based on EU GHS criteria

Conclusions:

Signs of intoxication were apathy. decreased motolity, cyanosis, laboured breathing and cramps. The LD50 for female rats was 1525 mg/kg bw and the LD50 for male rats was 2170 mg/kg bw.

Executive summary:

Seven or eight groups of 10 male and 10 female young adult Wister rats (weight 160 - 200 g) each reveived per gavage a single dose of 100, 1000, 1500, 1750, 2000, 2500, 3000, or 5000 mg/kg bw (male rats) and 100, 500, 1000, 1250, 1500, 2000, or 2500 mg/kg bw (female rats) 4-trifluormethoxyphenyl isocyanate. The animals were observed for mortality and clinical signs through day 14. A gross pathological examination was performed on animals which died during the observation period or were killed after termination of the study.

Signs of intoxication were apathy. decreased motolity, cyanosis, laboured breathing and cramps. The LD50 for female rats was 1525 mg/kg bw and the LD50 for male rats was 2170 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 525 mg/kg bw

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

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Five groups of 10 male and 10 female rats were exposed nose/head only to vapours of 4.5, 15.7, 22.5, 68.5, or 132 mg/m³ (analytical) 4-trifluoromethoxyphenyl isocyanate for 4 hours. The animals were observed for mortality, body weight and clinical signs up to day 21. A gross pathological examination was performed on animals which died intercurrent or were killed after termination of the study.

GLP compliance:

no

Test type:

standard acute method

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:

4.5, 15.7, 22.5, 68.5, or 132 mg/m³

No. of animals per sex per dose:

10 male and 10 female rats/dose

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LC50

Effect level:

22.5 - 68.5 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

The animals which died intercurrent showed strong inflated, edematous, pale grey or dark red decolored lungs. Livers were pale and spotted., spleen and kidneys had a pale colour. The gastro-intestinal tract was filled with a reddish-mucous content.

Body weight:

Body weight gain was normal in males at 15.7 mg/m³.
Higher concentrations in males and all concentrations in females had a markedly influence on body weight.

Other findings:

At a concentration of 15.7 mg/m³ air the rats showed an unspecific abnormal behaviour (lethargy, scruffy fur) and laboured breathing. up to 3 days after exposition. With higher concentrations these symptoms were present until death or termination of the study. Clear signs of irritation on the visible mucosa of the eyes and nose were evident.  

Up to a concentration of 15.7 mg/m³ no evidence of organ damages were found.

Animals killed after the post-observation period had pale or greyish discoloured, inflated lungs on concentrations above 22.5 mg/m³

Interpretation of results:

Category 1 based on GHS criteria

Remarks:

Based on EU GHS criteria

Conclusions:

Test item showed a strong irritating effect on the mucous membranes. The LC50 was 22.5 - 68.5 mg/m³ (0.0225 - 0.0685mg/L) for male and female rats.

Executive summary:

Five groups of 10 male and 10 female rats were exposed nose/head only to vapours of 4.5, 15.7, 22.5, 68.5, or 132 mg/m³ (analytical) 4-trifluoromethoxyphenyl isocyanat for 4 hours. The animals were observed for mortality, body weight and clinical signs up to day 21. A gross pathological examination was performed on animals which died intercurrent or were killed after termination of the study.

4-trifluoromethoxyphenyl isocyanate showed a strong irritating effect on the mucous membranes. The LC50 was 22.5 - 68.5 mg/m³ (0.0225 - 0.0685mg/L) for male and female rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

22.5 mg/m³ air

Physical form:

inhalation: vapour

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

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

4-Trifluoromethoxyphenyl isocyanate was applied semiocclusive 50 , 100, 150, 250, 500, 1000 or 1500 µl/kg bw (male rats) and 50, 100, 250, 500, 1500, or 2500 µl/kg bw (female rats) to five or ten male or female Wister rats for 24 hours. The animals were observed for mortality 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:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

other: undiluted or with cellulose powder

Duration of exposure:

24 hours

Doses:

male rats: 50 , 100, 150, 250, 500, 1000 or 1500 µl/kg bw = 67, 134, 201, 335, 670, 1340, 2010 mg/kg bw
female rats: 50, 100, 250, 500, 1500, or 2500 µl/kg bw = 67, 134, 335, 670, 20103350 mg/kg bw

No. of animals per sex per dose:

male rats: 50 µl/kg bw = 5 animals; 100, 150, 250, 500, 1000 or 1500 µl/kg bw = 10 animals
female rats: 50, 2500 µl/kg bw = 5 animals; 100, 250, 500, 1500 µl/kg bw = 10 animals

Control animals:

no

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 268 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 670 mg/kg bw

Based on:

test mat.

Other findings:

Signs of intoxiciation: increased motility, afterwards decreased motility, aggresivity, laboured breathing, weekness of hind limbs, partly strong weight loss.

Start of the symptoms: 5 to 20 minutes after application. Duration of the symptoms: 2 to 6 days. The surviving animals showed afterwards apathy up to 14 days

Necropsy findings on animals died intercurrent: , liver pale and mottled, kidneys pale, renal plevis partly reddened, in the urinary bladder partly red urine, intestine with dark, mucous content.

Necropsy findings on animals killed after post-observation period: on animals with weekness of hind limbs the renal pelvis was destroyed, bloody urine, other internal organs macroscopically without findings

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

Based on EU GHS criteria.

Conclusions:

Signs of intoxication were apathy, decreased motolity, cyanosis, laboured breathing and cramps. The LD50 for female rats was ca. 670 mg/kg bw and the LD50 for male rats was 238 mg/kg bw.

Executive summary:

Acute toxicity dermal test was done similarly to OECD guideline 402. 4-Trifluoromethoxyphenyl isocyanate was applied semiocclusive 50 , 100, 150, 250, 500, 1000 or 1500 µL/kg bw (male rats) and 50, 100, 250, 500, 1500, or 2500 µL/kg bw (female rats) to five or ten male or female Wister rats for 24 hours. The animals were observed for mortality 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.

Signs of intoxication were apathy, decreased motolity, cyanosis, laboured breathing and cramps. The LD50 for female rats was ca. 670 mg/kg bw and the LD50 for male rats was 238 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

268 mg/kg bw

Justification for classification or non-classification

Due to the results of the acute oral toxicity study a classification according to Regulation (EC) No 1272/2008 as Acute Tox.4; H302 is justified. For acute inhalation toxicity a classification as Acute Tox.1; H330 and for acute dermal toxicity Acute Tox.3; H311 applies.

In addition, respiration irritational effects were reported. Therefore H335 is applicable.