Carbamic acid ester

Endpoint summary

Description of key information

Acute oral
Rats (5/sex) were exposed by oral gavage to the test substance at 5000 mg/kg bw. No effects on mortality and body weight were seen during the 14 day observation period. Clinical signs were limited to nasal discharge (2 males on day 1) . Necropsy showed haemorraghes in the lungs of all animals. This finding is related to the use of CO2 in the euthanasia procedure The LD50 is > 5000 mg/kg bw.
Acute dermal
Rabbits (5/sex) were exposed dermally to the test substance at 2000 mg/kg bw for 24 hours. No effects on mortality and body weight were seen during the 14 day observation period. Clinical signs were limited to incidental erythema (2 animals) and raspy breathing (1 animal). Necropsy showed red foci in the lungs of 3 males and 2 females. The LD50 is > 2000 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:

May 6 to 20, 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study according to the guideline under GLP

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

report states 81-2

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Royalhart Colony New Hampton NY
- Age at study initiation: not indicated
- Weight at study initiation: males 236-262 g; females 211-239 g
- Fasting period before study: 18 hours
- Housing: individually in suspended stainless steel caging with mesh floors
- Diet Pelleted Purina Rat Chow #5012 (ad libitum)
- Water: tap water (ad libitum):
- Acclimation period: 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-27 °C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 90%

MAXIMUM DOSE VOLUME APPLIED: 1.3 mL

Doses:

5000 mg/kg bw (administered as 90% solution)

No. of animals per sex per dose:

5 males + 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality/clinical signs at 1,2,3,4 and 6 hours after application and daily thereafter, body weight on day 1, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and macroscopy

Statistics:

NA

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: it is not clear whether a correction for the purity of the substance was made

Mortality:

None

Clinical signs:

red-brown dry nasal discharge on day 1 in 2 males

Body weight:

within normal ranges

Gross pathology:

lung haemorraghes in all animals (related to the CO2 euthanasia method)
1 female with white patches on the lung

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the substance is > 5000 mg/kg bw

Executive summary:

Rats (5/sex) were exposed by oral gavage to the test substance at 5000 mg/kg bw. No effects on mortality and body weight were seen during the 14 day observation period. Clinical signs were limited to nasal discharge (2 males on day 1) . Necropsy showed haemorraghes in the lungs of all animals. This finding is related to the use of CO2 in the euthanasia procedure The LD50 is > 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

guideline study under GLP

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

May 21 to June 4 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study according to the guidelines and under GLP

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Davidson's Mill Farm, South Brunswick, NJ
- Age at study initiation: not indicated
- Weight at study initiation: males 2.3-2.6 kg; females 2.2-2.5 kg
- Housing: individually in suspended stainless steel caging with mesh floors
- Diet: Pelleted Purina Rabbit Chow (ad libitum)
- Water: tap water (ad libitum)
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-27 °C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 4-5 cm2
- % coverage: 10%
- Type of wrap if used: non-permeable adhesive-backed gauze patch wrapped with an elastic cloth

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none,
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

VEHICLE: none

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males + 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: bodyweight on day 1, 7 and 14; mortality/clinical signs at 1, 2, 4 and 5 hours after application and daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight

Statistics:

NA

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

moderate erythema in one male and one female (up to day 4)
raspy breathing in one male (day 1 and day 6-11)

Body weight:

within normal ranges

Gross pathology:

red foci in lungs of 3 males and 2 females
off-white coloured patches on left lung lobe in 1 female

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the substance is > 2000 mg/kg bw.

Executive summary:

Rabbits (5/sex) were exposed dermally to the test substance at 2000 mg/kg bw for 24 hours. No effects on mortality and body weight were seen during the 14 day observation period. Clinical signs were limited to incidental erythema (2 animales) and raspy breathing (1 animal). Necropsy showed red foci in the lungs of 3 males and 2 females. The LD50 is > 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:

guideline study under GLP

Additional information

Next to both key studies an acute study on the analogue of the metabolite, 1,6 -hexanediamine, is available. In this study an LD50 between 300 and 2000 mg/kg bw was reported. This is indicative of the fact that the metabolite may represent a worst case compared to the parent substance.

Justification for classification or non-classification

Based on the available data the substance does not need to be classified for acute toxicity according to the criteria of CLP (Regulation EC No 1272/2008).