2,2',6,6'-tetra-tert-butyl-4,4'-methylenediphenol

Endpoint summary

Description of key information

Key study: Acute oral: Experimental results: Equivalent to OECD 401. GLP study. 
LD50 > 2000 mg/kg bw
Key study: Acute dermal: Experimental results: Equivalent to OECD 402. GLP study. 
LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited documentation

Qualifier:

no guideline followed

Principles of method if other than guideline:

Goups of 10 male Sprague-Dawlly CD rats received the test substance by gavage as a 10% W/W solution in peanut oil. The limit dose level was 3000 mg/kg bw. Observation peiod: 14 d

GLP compliance:

no

Remarks:

prior to GLP

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on oral exposure:

VEHICLE
Peanut oil
- Concentration in vehicle: 10% W/W
- Amount of vehicle (if gavage): not stated
- Justification for choice of vehicle: solubility


MAXIMUM DOSE VOLUME APPLIED: 3000 mg/kg bw

Doses:

3000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: probably daily, no details given
- Necropsy of survivors performed: yes

Sex:

male

Dose descriptor:

LD0

Effect level:

> 3 000 mg/kg bw

Based on:

test mat.

Mortality:

0/10

Clinical signs:

other: The animlas showed no clinical signs throughout the observation period.

Gross pathology:

Extensive dark aereas were observed in the liver. No details on incicidence etc. given.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 was greater than 3000 mg/kg bw. None of the 10 male rats died duing the study.

Executive summary:

An acute LD50 limit test was perfomed in a group of 10 male Sprague-Dawley rats receiving 3000 mg/kg bw of the test substance by gavage. Peanut oil sered as the vehicle. No deaths, clinical signs or effects on body weight gain were observed during the 14 -d obsevation period. At necropsy dark aereas of the liver were reported.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not a Guideline Study

Qualifier:

no guideline followed

Principles of method if other than guideline:

One male and one female beagle were treated orally with test article in gelatin capsules at each dose level and animals were monitored for 14 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

dog

Strain:

other: beagle

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Umbrian Farm Kennels
- Age at study initiation: 8-16 months
- Weight at study initiation: 7.5-16 kg
- Housing: Individual cages
- Diet: 1/2 LB of Wayne Food Krumettes (Allied Mills Inc.) moistened with water and mixed with a 1/50 lb. of evaporated milk replacer.
- Water: ad libitum

Route of administration:

oral: capsule

Vehicle:

unchanged (no vehicle)

Doses:

100, 251, 631, 1585, 2512 mg/kg

No. of animals per sex per dose:

2 animals, one female and one male

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Checked 3 times daily and weighed weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology and clinical chemistry.

Sex:

male/female

Dose descriptor:

LDLo

Effect level:

> 2.5 other: g/kg

Mortality:

No animal died in this study.

Clinical signs:

other: See tables and discussion below.

Gross pathology:

See tables and discussion below.

Observations: No vomiting was observed following dosing. There was no change in behavior or appearance of the animals during the 2 week observation period. The appetites remained good and the stools were well formed. Slight fluctuations in the body weight occurred at all levels, but were well within normal limits.

Clinical Chemistry: Biochemical parameters measured included glucose, BUN, SGPT, SGOT, alkaline phosphatase, and icteric index.. With occasional minor exceptions all values remained within normal limits throughout the study. Slight eleveations in BUN were noted in one animal during the middle portions of the study but the terminal reading was normal. Icteric indices above 5.0 units were due, in all cases, to varying degrees of hemolysis in many of the plasma samples, which appeared in small amounts despite all precautions. Unhemolyzed samples consistently gave readings under 4.0 units and no gross icterus was visible in the plasma of any animal. A trace of lipemia was noted grossly in the 14 day serum sample of one animal. Hemograms, consisting of hemocrit, hemoglobin, total WBC and differential counts, prothrombin time, and platelet count, all showed normal values throughout the study, and no significant changes were seen. Normal variations in pH and specific gravity of the urine was observed, no glucose was found in any specimen and individual reactions are not listed, and while traces of albuminuria were frequently noted in several of the animals, terminal readings were negative in all animals. Microscopic examination of the centrifuged sediment revealed no unusual findings. Tests for urobilinogen were negative in all specimens.

Post Mortem Findings: The only significant pathology occurred in one animal in which a few small areas of calcification, thought to be parasitic in origin, were found in the liver. It was also noted that the whole kidneys were rather pale in this animal, but there was no pitting or other evidence of nephritis.

Histopathological Findings:Representative portions of liver, kidneys, heart, gall bladder, pancreas, adrenal glands and pituitary were processed and stained with hematoxylin-eosin. Additional liver portions were processed and stained with Oil Red O and Best’s Carmine for fat and glycogen respectively. Except for the occasional lesions reported on the attached chart, there was no evidence of inflammatory or degenerative changes in any of the tissues examined microscopically. The reported lesions are considered to be of spontaneous origin. Fat was not found in any of the liver sections, and the glycogen content was uniformly normal in amount and distribution. Kidney sections of one animal which showed slight elevations in the blood urea nitrogen values during the study revealed no evidence of any pathological changes.

Dose, body weights (kg) and terminal organ weights (g)
Treatment Group	Age in months	Body weights			Organ weights
		Pre-Treatment	1 week	2 week
					Kidneys	Liver
Controls
M 6-M	15.5	16	16.5	16.9	59.6	489.2
K92-F	14	11.6	12.0	12.2	41.4	455.2
100 mg/kg
M20-M	15	13.3	13.5	13.8	55.8	412.3
K89-F	14	11.5	11.5	11.3	43.7	343.4
251 mg/kg
N40-M	9.5	10.6	10.4	10.5	49.0	301.6
L72-F	14.75	6.5	6.5	6.3	37.5	257.6
631 mg/kg
N31-M	12	10.3	10.9	11.2	48.6	349.0
M51-F	9.25	8.8	8.6	8.7	41.1	252.2
1585 mg/kg
N24-M	11.75	9.7	10.1	10.3	55.4	343.6
L95-F	9.75	7.5	7.4	7.5	40.1	261.8
2512 mg/kg
M35-M	14	9.0	9.1	9.3	41.7	276.1
M66-F	7.75	10.8	10.7	10.9	52.3	318.2

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: not specified

Conclusions:

In single oral doses up to 2.5 g/kg body weight, the test material caused no changes in beagles observed for two weeks under the conditions of this
study.

Executive summary:

One male and one female beagle dog were treated orally at each of the following dose levels: 100, 251, 631, 1581 and 2512 mg/kg body weight and monitored for 14 days. There was no change observed in clinical behavior or appearance. Biochemical parameters measured remained normal except for an insignificant rise in BUN in one animal. Hemograms also remained normal and urine analysis showed only normal variations. At autopsy and on microscopic examination of selected tissue no significant pathology was found.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not a guideline study

Qualifier:

no guideline followed

Principles of method if other than guideline:

The purpose of this study was to determine the acute toxicity of the compound when it was administered orally in a single dose to rats.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10 to 14 weeks

Route of administration:

oral: unspecified

Vehicle:

peanut oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 24 g/kg

Doses:

0.18, 1.0, 1.6, 2.4, 3.2, 4.7, 7.0, 10.0, 16.0 and 24.0 g/kg

No. of animals per sex per dose:

1 per dose up to 2.4 g/kg and 2 per dose up to 10 g/kg in preliminary study; 10 per dose in definitive study

Control animals:

no

Sex:

male

Dose descriptor:

LD50

Effect level:

> 24 other: g/kg

Mortality:

see table below

Clinical signs:

other: see table below

Gross pathology:

All of the rats were killed and subjected to complete postmortem examinations and the viscera were examined microscopically. The viscera from all of the rats were normal. There were no alterations attributable to the compound.

The test material, as a 10% suspension in peanut oil, was administered orally to rats in graded doses ranging from 0.18 to 10 g/kg. Another suspension containing 30 g of the compound in peanut oil and diluted to 100 mL was administered orally to rats in doses ranging from 3.2 to 24 g/kg. The initial series of dosages was administered to a group of 12 rats. The second series of dosages was administered to a group of 60 male rats divided into groups of 10 rats.

Dose g/kg	Mortality*		Changes in weights of the bodies (g)
	D	T	4 days	4 weeks
0.18	0	1	+5	+75
1.0	0	1	+5	+90
1.6	0	1	+2	+80
2.4	0	1	+10	+105
3.2	0	2	-6	+136
4.7	0	2	-8	+125
7.0	0	2	0	+125
10.0	0	2	-6	+140

Dose g/kg	Mortality^*		Average weights of the bodies (g) ± standard error
	D	T	Initial	2^ndday	5^thday
3.2	0	10	194±24	193±24	199±24
4.7	0	10	311±6	312±6	316±6
7.0	0	10	270±14	272±14	277±13
10.0	0	10	241±12	244±12	252±12
16.0	0	10	144±3	149±3	164±3
24.0	0	10	177±7	184±7	196±7
^*D = Number of deaths. T = Number of animals treated.

 

All the of the rats in both groups survived following the oral doses of the compound. There was no sign of intoxication and only mild transient diarrhea was observed at the higher dosages of the compound. The largest dose (24 g/kg) was the maximum amount which feasibly could be given to rats at one time. No deaths resulted and no signs of illness were observed even at this level.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: not specified

Conclusions:

At a maximum dose concentration of 24 g/kg the test material mortality was not observed.

Executive summary:

When 4,4’-methylenebis (2,6-di-tert-butylphenol) is administered orally in a single dose to rats the lethal level is in excess of 24 g/kg. At the level of 24 g/kg the compound did not induce any injury to the viscera of the rats.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not a guideline study

Qualifier:

no guideline followed

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

guinea pig

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gordon's Biological Supply
- Weight at study initiation: 282 g
- Fasting period before study: 18 h

Route of administration:

oral: gavage

Vehicle:

other: 20% (w/v) suspension in 0.5 methyl cellulose

Doses:

0, 1000, 1780, 3170, 5630 and 10000 mg/kg

No. of animals per sex per dose:

6 male animals per dose group

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days (or other?) 0
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights and histopathology

Sex:

male

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Mortality:

Three guinea pigs died, one at 1000 mg/kg, one at 10000 mg/kg and one control animal. At autopsy these animals showed evidence of pneumonia. Animals from all groups had pulmonary inflammation at the final autopsy. These deaths were not considered to be drug related.

Clinical Observations:No differences were observed clinically between groups, except for the reduced rate of body weight gain in animals at the highest dose.

Body Weight:The guinea pigs receiving 10000 mg/kg gained weight at a slightly slower rate than did the animals receiving any of the lower doses.

Mortality:Two deaths occurred in treated animals. One at 1000 mg/kg level died on the 10^thday; the other at the 10000 mg/kg level died on the 12^thday after dosing. Autolysis was advanced in both animals. One control animal died during the observation period (11^thday) and at autopsy , had pleurisy and pneumonia.

Gross Observations at Autopsy: Pneumonia occurred with random distribution in all groups. In the 5630 mg/kg group one animal had a large heart and one had adhesions between the pericardium and the lungs and diaphragm, and its heart appeared large. Liver weights showed no significant difference between treated groups and the untreated control.

Dose mg/kg	No. in group	Average Body Weights		Average Liver Weight	Died	Principle Findings
		Initial (g)	Terminal (g)	(g)
1000	6	271	361	17.7	1	Pneumonia.
1780	6	282	356	15.9	0	Pneumonia. One with pale kidneys.
3170	6	277	367	17.9	0	Pneumonia.
5630	6	295	371	20.1	0	Pneumonia. Two with enlarged heart, one of these with thoracic adhesions
10000	6	283	330	16.3	1	Pneumonia
Absolute Control	6	-	382	18.7	1	Pneumonia. Pleuritis.

Histopathological Examination: A portion of the liver from each of the five or 6 surviving animals in each dose group was processed and stained with hematoxylin-eosin. A kidney from one of the animals in the 1780 mg/kg dose group and a lung from an animal in the 5630 mg/kg group were similarly processed because they had exhibited gross lesions. Additional portions of each liver were processed and stained with Best’s Carmine for glycogen content, and with Oil Red O for fat content. A microscopic inspection of the prepared tissue slides revealed slight fat depositions, diffusely distributed, in one liver of the 1000 mg/kg group and in one liver of the 10000 mg/kg group. Liver glycogen appeared to be essentially equal between dose groups, although slight individual variations within groups were noted. The glycogen content of the control livers did not differ from that in the drug treated groups. There were no hepatic cell changes visible which might indicate a drug toxic effect.

Concerning histopathological lesions, one animal in the 1780 mg/kg group exhibited a slight subacute interstitial nephritis. Another, in the 5630 mg/kg group, showed a patchy bronchiolitis, while a third animal, in the 1000 mg/kg group, presented a discrete abscess in the liver. None of the lesions are considered to be drug related.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: not specified

Conclusions:

The maximum tolerated dose is in excess of 10 g/kg body weight.

Executive summary:

Thirty-six male albino guinea pigs were divided into 5 treatment groups and one control group. The following doses of the test material were administered: 1000, 1780, 3170, 5630 and 10000 mg/kg. Clinical difference were not observed between the groups except for some weight loss at higher doses. Two deaths occurred at dose concentrations of 1000 and 10000 mg/kg. The cause of death was most likely due to secondary infection rather than the test material. Gross pathology and histology examinations did not reveal pathology due to toxic effects from the test material. Therefore it can be concluded that the maximum tolerated dose is in excess of 10 g/kg body weight for guinea pigs.

Reference 5

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: Equivalent to OECD 401. GLP study.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Ltd.
- Age at study initiation: 9-11 weeks old
- Weight at study initiation: males: 181-197 g; females: 132-142 g
- Fasting period before study: All animals were fasted overnight (18 hours).
- Housing: On arrival, animals were housed in single sex groups of up to 12 to a cage; each cage measured 56 cm x 38 cm x 18 cm. Prior to experimentation the animals were rehoused (as single sex groups of four) in cages with stainless-steel wire-mesh floors and tops; each cage measured 38 cm x 25 cm x 18 cm. At least two days before dosing, the rats were housed in groups of two or three animals of the same sex per cage.
- Diet (e.g. ad libitum): PRD, Labsure Animal Foods, Dorset, ad libitum.
- Water (e.g. ad libitum): Filtered water from the public supply, ad libitum.
- Acclimation period: Two weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ºC
- Humidity (%): Not documented.
- Air changes (per hr): Not documented.
- Photoperiod (hrs dark / hrs light): Lighting was automatically switched on for the day (06.00 to 18.00 hours GMT) and off for the night (18.00 to 06.00 hours GMT)

Route of administration:

other: intraoesophageal intubation using a ballpoint needle fitted to a syringe

Vehicle:

corn oil

Details on oral exposure:

The test material was administered as a 20% m/v suspension in corn oil

Doses:

2000 mg/kg

No. of animals per sex per dose:

Five animals per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs three times a day for the first three days and daily thereafter. The initial (Day 1), Day 7 and Day 14 body weights were recorded.
- Necropsy of survivors performed: necropsy was not performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None of the rats died.

Clinical signs:

other: There were no clinical signs observed.

Table 7.2.1:      Summary of Acute Oral Toxicity

Males			Females
Dose	Mortality	Time of death	Dose	Mortality	Time of death
2000 mg/kg	0/5	--	2000 mg/kg	0/5	--

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 of the test material in rats administered as a 20% (m/v) suspension in corn oil was greater than 2000 mg/kg.

Executive summary:

Five rats per sex were orally dosed at 2000 mg/kg. Animals were observed for clinical signs three times a day for the first three days and daily thereafter for the remainder of the 14 day observation period. The initial (Day 1), Day 7 and Day 14 body weights were recorded. None of the rats died. There were no clinical signs observed. The acute oral LD50 of the test material in rats administered as a 20% (m/v) suspension in corn oil was greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 2. Equivalent to OECD 401. GLP study.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1976

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Limited reporting, limited number of animals

Qualifier:

no guideline followed

Principles of method if other than guideline:

A 10% solution of the test substance in peanut oil was administered to 2 rabbits with intact and 2 rabbits with abreaded skin. The dose level was 1500 mg/kg bw. The material was kept on the skin under occlusive conditions for 24 h. After removal the rabbits were observed for 14 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Weight at study initiation: 2.3 to 3 kg
- Fasting period before study: no
- Housing: not stated

Type of coverage:

occlusive

Vehicle:

peanut oil

Details on dermal exposure:

TEST SITE
- Area of exposure: trunk
- % coverage: not stated
- Type of wrap if used: plastic sleeves

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not stated
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1500 mg/kg bw
- Concentration (if solution): 10%

Duration of exposure:

24 h

Doses:

1500 mg/kg bw

No. of animals per sex per dose:

sex not stated, 4 animals, 2 with intact 2 with abraded skin

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days

Sex:

not specified

Dose descriptor:

LD0

Effect level:

> 1 500 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed within the 14-day observation period 0/4

Clinical signs:

other: The only clinical sign reported was a well defined erythema on day 1.

Gross pathology:

No data

Interpretation of results:

other: the study is too limited to draw firm conclusions.

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The study was limited to 4 animals, but even with abraded skin no deaths occured at a dose level of 1500 mg/kg bw. The study is insufficient to draw frim conclusions on a classification, but can be used as supporting eveidence for the low dermal toxicity of the test material.

Reference 2

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: Equivalent to OECD 402. GLP study.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Ltd.
- Age at study initiation: 9-11 weeks old
- Weight at study initiation: males: 204-227 g; females: 145-157 g
- Fasting period before study: All animals were fasted overnight (18 hours).
- Housing: On arrival, animals were housed in single sex groups of up to 12 to a cage; each cage measured 56 cm x 38 cm x 18 cm. Prior to experimentation the animals were rehoused (as single sex groups of four) in cages with stainless-steel wire-mesh floors and tops; each cage measured 38 cm x 25 cm x 18 cm. At least two days before dosing, the rats were housed in groups of two or three animals of the same sex per cage.
- Diet (e.g. ad libitum): PRD, Labsure Animal Foods, Dorset, ad libitum.
- Water (e.g. ad libitum): Filtered water from the public supply, ad libitum.
- Acclimation period: Two weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ºC
- Humidity (%): Not documented.
- Air changes (per hr): Not documented.
- Photoperiod (hrs dark / hrs light): Lighting was automatically switched on for the day (06.00 to 18.00 hours GMT) and off for the night (18.00 to 06.00 hours GMT)

Vehicle:

other: moistened

Details on dermal exposure:

The day before dosing, approximately 60% of the dorsal hair of all animals was closely shorn with fine electric clippers. Before application of the tst material, the skin was visually inspected to ensure that all micro-abrasions of the stratum corneum had healed.

The calculated dose was weighed onto a piece of aluminium foil lined with gauze and applied to the shorn skin. The foil was held in place by a double overwrap of waterproof adhesive tape.

After the 24 h exposure, the tape and foil were removed and the skin washed with warm dilute detergent solution and then dried.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

Five animals per sex

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for signs of toxicity three times a day for the first three days and daily thereafter for the remainder of the 14 day observation period. Initial (Day 1), Day 7 and Day 14 body weights were recorded.
- Necropsy of survivors performed: necropsies were not conducted.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None of the rats died.

Clinical signs:

other: There were no clinical signs observed.

Table 7.2.3:      Summary of Acute Dermal Toxicity

Males			Females
Dose	Mortality	Time of death	Dose	Mortality	Time of death
2000 mg/kg	0/5	--	2000 mg/kg	0/5	--

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute (24 h) percutaneous LD50 of the test powder in rats was greater than 2000 mg/kg.

Executive summary:

Five rats per sex were dermally dosed at 2000 mg/kg. Animals were observed for clinical signs three times a day for the first three days and daily thereafter for the remainder of the 14 day observation period. The initial (Day 1), Day 7 and Day 14 body weights were recorded. None of the rats died. There were no clinical signs observed. The acute dermal LD50 of the test material in rats was greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 2. Equivalent to OECD 402. GLP study.

Additional information

Key study: Acute oral: Experimental results: Equivalent to OECD 401. GLP study.

LD50 > 2000 mg/kg bw

Key study: Acute dermal: Experimental results: Equivalent to OECD 402. GLP study.

LD50 > 2000 mg/kg bw

Acute inhalation: Data waiving: In accordance with column 2 of REACH Annex VIII, the study does not need to be conducted since exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – inhalation endpoint
In accordance with column 2 of REACH Annex VIII, the study does not need to be conducted since exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Based on the available data, the substance is not classified for acute toxicity.