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Description of key information

In three acute oral toxicity studies LD50 values of greater than 2000 mg/kg bw were determined for rats. A dermal LD50 of greater than 2000 mg/kg bw was determined for acute dermal toxicity in rabbits based on two studies.

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:
1980-06-27 to 1980-07-1
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented, scientifically acceptable study report
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males: 182 g; females: 162 g
- Fasting period before study: 15 - 20 hours before application
- Diet: ad libitum, "Herilan MRH-Haltung" (H. Eggersmann KG)
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 14.7, 21.5, 31.6, 46.4 and 50 % (g/V)

MAXIMUM DOSE VOLUME APPLIED: 13.6 mL/kg
Doses:
1470, 2150, 3160, 4640, 6810 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 700 mg/kg bw
Based on:
test mat.
Mortality:
Male animals: 1470 mg/kg: 1/5 after 14 days; 2150 mg/kg: 0/5 after 14 days; 3160 mg/kg: 3/5 after 14 days; 4640 mg/kg: 4/5 after 14 days; 6810 mg/kg: 5/5 after 14 days
Female animals: 1470 mg/kg: no deaths; 2150 mg/kg: 2/5 after 14 days; 3160 mg/kg: 5/5 after 14 days; 4640 mg/kg: 4/5 after 14 days; 6810 mg/kg: 5/5 after 14 days
Clinical signs:
other: Animals showed dyspnea, apathy, abnormal position, staggering, atony, missing pain- and corneal reflexes, narcotic-like state, spastic gait, ruffled fur, exsiccosis, salivation and a poor general state.
Gross pathology:
Animals that died before end of the study period showed an acute congestive hyperemia and an acute dilatation of the right side of the heart. The stomach was atonic and liquid content was observed. The liver showed a loam yellow colour and was reddish mottled. Furthermore partly severe broadened peripher loam-yellow lobular pattern was observed.
Sacrificed animals did not show any gross internal lesions during necropsy.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 700 mg/kg bw

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:
1997-07-24 to 1997-08-07
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant sudy report
Qualifier:
according to guideline
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Deviations:
no
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: Harlan lnterfauna UK Ltd, Huntingdon, Cambridgeshire, UK
- Age at study initiation: 10 - 12 wks
- Weight at study initiation: 2.2 - 2.7 kg
- Housing: individually
- Diet: ad libitum, standard laboratory rabbit diet (STANRAB (P) (SQC) Rabbit Diet from Special Diets Services)
- Water: ad libitum, tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22
- Humidity (%): 47 - 79
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorso-lumbar region (approx. 100 mm x 100 mm)
- Type of wrap if used: waterproof dressing

REMOVAL OF TEST SUBSTANCE
- Washing: with warm water (30 - 40 °C)
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amounts applied: 1.713 mL/kg bw
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: at least twice daily; weighing was performed once a week
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
other: One female showed soft to liquid feces on Days 10 and 11. No clinical signs were observed in the other animals.
Gross pathology:
No gross internal lesions were observed during necropsy.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity

key study

In the acute oral toxicity study similar to OECD guideline 401, groups of male and female Sprague Dawley rats (5/sex) were given a single oral dose of the test substance in carboxymethylcellulose per gavage at dose levels of 1470, 2150, 3160, 4640 and 6810 mg/kg bw (BASF, 80/199, 1981). Animals were then observed for 14 days.

On male died in the lowest dosing group. At 2150 mg/kg bw two female animals died. All animals died in the highest dosing group. At 3160 mg/kg bw all females and three male animals deceased. At 4640 mg/kg bw 3 animals of each sex died.

Animals showed dyspnea, apathy, abnormal position, staggering, atony, missing pain- and corneal reflexes, narcotic-like state, spastic gait, ruffled fur, exsiccosis, salivation and a poor general state. Animals gained weight throughout the study period.

Animals that died before end of the study period showed an acute congestive hyperemia and an acute dilatation of the right side of the heart. The stomach was atonic and liquid content was observed. The liver showed a loam yellow colour and was reddish mottled. Furthermore partly severe broadened peripheral loam-yellow lobular pattern was observed. Sacrificed animals did not show any gross internal lesions during necropsy.

An LD50 of 2700 mg/kg bw was determined.

supporting studies

In the first supporting acute oral toxicity study according to US EPA guideline 81-1 (subdivision F), groups of fasted, young (7-9 weeks old) CD rats (Sprague-Dawley) were given a single oral dose of the neat test substance (Hoechst-Celanese, 432/973416/AC, 1997). Five animals per sex were treated per group. Groups were dosed on individual days, starting at 5000 mg/kg bw to reduce animal usage and optimize results. Further concentrations that were tested were 1600, 2000 and 3200 mg/kg bw.

One female at 1600 mg/kg, one male and two females at 2000 mg/kg and all rats at 3200 and 5000 mg/kg died during the study. All deaths occurred within approximately 30 hours of dosing. A slight bodyweight loss was recorded for the majority of decedents. Macroscopic examination revealed a generalized congestion in die majority of organs and tissues. Clinical signs of reaction to treatment included piloerection, hunched posture, waddling/unsteady gait, lethargy, respiratory distress, partially closed eyelids, pallid extremities, increased salivation, walking on toes, cold body surfaces, prostration and brown staining around muzzle, seen in rats at all doses. In addition, increased urine production, increased lacrimation, body tremors, protruding eyes, ungroomed appearance and sensitive to handling were seen among animals at one or more dose levels. Recovery of surviving rats was complete in all instances by Day 7. All surviving rats were considered to have achieved satisfactory weight gains throughout die study. No specific chemically-related target organ was identified in either decedent animals or in animals killed at study termination and in die latter there were no abnormalities revealed at the macroscopic examination on Day 15. The acute median lethal oral doses (LD50) and associated 95% confidence limits to male and female rats of were estimated to be:

Males only: 2298 (1898 to 3196) mg/kg bodyweight

Females only: 1983 (1693 to 2588) mg/kg bodyweight

Combined sexes: 2127 (1888 to 2724) mg/kg bodyweight.

In the second supporting study, 12 rats (6/dose group) were given a single oral dose of the unchanged test substance at dose levels of 500 and 5000 mg/kg bw (Celanese, C-802, 1985). Animals were only observed for one day. No gross signs of toxicity were observed. An LD50 of greater than 500 mg/kg bw was determined.

In a publication of Schafer et al. (1985) acute toxicity towards wild mammals was examined using 6 deer mice and a graduated dosage level. An approximate lethal dose (ALD) was determined. Using this single animal per level method, each succeeding treatment was 50 % higher than the preceding level and continued until mortality occurred. All chemicals were administered by gavage using water, corn oil, or 1.0% carbopol as carriers, followed by 3-days of observations for mortality. An ALD of 470 mg/kg was determined.

Acute inhalation toxicity

The test demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at 20 °C (BASF, 80/199, 1981). 12 young adult laboratory rats were exposed sequentially to the vapors generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 7 h. The exposure was subsequently repeated in the same manner. No analytical determination of the atmosphere concentrations was performed. The nominal concentration was calculated as quotient of the amount of test substance weight loss during exposure, and the amount of air used during exposure. Group-wise documentation of clinical signs was performed over a 14 day study period. Body weight of groups was determined before the start of the study (according to Smyth, H.F. et al.: Am. Ind. Hyg. Ass. J. 23, 95-107, 1962).

No mortality was observed. Animals attempted to escape and showed eyelid closure as well as dyspnea during the treatment. No gross internal lesions were observed during necropsy.

No LC50 can be derived from this type of study.

Acute dermal toxicity

key study

The acute dermal toxicity potential was determined according to US EPA guideline 82-1 (subdivision F).

Ten New Zealand White rabbits, five of each sex, were treated for 24 hours with 2000 mg/kg of neat test material under an occlusive wrapping (Hoechst-Celanese Corp, 433/973333/AC, 1997). The wrapping was removed after die 24 hour exposure period and the skin was washed with warm water and blotted dry. Animals were observed at frequent intervals on the day of dosing and then twice daily for mortality, clinical signs and skin condition. On the l4th day after administration, animals were killed and examined for signs of macroscopic chemically related adverse effects. No animal died during the study and all animals gained weight normally during the study except for one male who lost weight between day 8 and day 15. Systemic clinical signs were minimal and consisted of abnormal stools for one animal on only two days of the study. No skin reactions were noted. Chemically related macroscopic adverse effects were not found at necropsy. An LD50 of greater than 2000 mg/kg bw was determined under the conditions of the study.

supporting study

In the supporting study, 8 rabbits (4/dose group) were given a single oral dose of the unchanged test substance at dose levels of 2000 and 10300 mg/kg bw (Celanese, C-802, 1985). Animals were then observed for 7 days. One animal of the 2000 mg/kg bw group showed ocular discharge throughout most of the study period. No other gross signs of toxicity were observed. An LD50 of greater than 2000 mg/kg bw was determined.


Justification for selection of acute toxicity – oral endpoint
Well-documented, scientifically acceptable study report.

Justification for selection of acute toxicity – dermal endpoint
well-documented, scientifically acceptable study report

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled for acute toxicity under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EU) No 2015/1221.